DEMENTIA

The syndrome of dementia is an irreversible decline in cognitive abilities that causes significant dysfunction. Like most syndromes, dementia can be caused by a number of diseases. In the nineteenth century, for example, a main cause of dementia was syphilis. As a result of dramatic increases in average human life expectancy, dementia is caused primarily by a number of neurological diseases associated with old age. Dementia is distinguished from pseudo-dementia because the latter is reversible—for example, depression, extreme stress, and infection can cause dementia but with treatment a return to a former cognitive state is likely (Oizilbash et al.). Dementia is also distinguished from normal age-related memory loss, which effects most people by about age seventy in the form of some slowing of cognitive skills and a deterioration in various aspects of memory. But senior moments of forgetfulness do not constitute dementia, which is a precipitous and diseaserelated decline resulting in remarkable disability. Since 1997, a degree of cognitive impairment that is greater than normal age-related decline but not yet diagnosable as dementia has been labeled mild cognitive impairment (MCI), with about one-third of those in this category converting to dementia each year. These cognitive conditions from normal age-related forgetfulness to dementia form a continuum. Specialized clinics that were once called Alzheimer's Centers are increasingly changing their name to Memory Disorders Centers in order to begin to treat patients at various points along the continuum prior to the onset of dementia.

Although dementia can have many causes, the primary cause of dementia in our aging societies is Alzheimer disease (AD). Approximately 60 percent of dementia in the American elderly and worldwide in industrialized nations is secondary to AD (U.S. General Accounting Office). This discussion will focus on so-called Alzheimer's dementia in order to illustrate ethical issues that pertain to all progressive dementias. One epidemiological study in the United States estimated that 47 percent of persons eighty-five years and older (the old-old) had probable AD, although this is a widely considered inflated (Evans et al). Epidemiologists differ in their estimates of late-life AD prevalence, but most studies agree roughly on the following: about 1 percent to 2 percent of older adults at age sixty have probable AD, and this percentage doubles every five years so that 3 percent are affected at age sixty-five, 6 percent at age seventy, 12 percent at age seventy-five, and 24 percent by age eighty. While some argue that those who live into their nineties without being affected by AD will usually never be affected by it, this is still speculative. According to a Swiss study, 10 percent of non-demented persons between the ages of eighty-five and eighty-eight become demented each year (Aevarsson). There are very few people in their late forties and early fifties who are diagnosed with AD. Without delaying or preventive interventions, the number of people with AD, in the United States alone, will increase to 14.3 million by 2050 (Evans et al). These numbers represent a new problem of major proportions and immense financial consequences for medicine, families, and society (Binstock et al).

There is a second very rare form of AD which is early onset that is clearly familial. About 3 percent of AD cases are caused by rare autosomal dominant (or causative) single gene mutations, of which three are clearly defined. In these cases of familial AD, symptoms usually occur in the early forties or mid- to late-thirties, and death occurs within five years of diagnosis, in contrast to the more typical seven to eight years for ordinary late-onset disease (Post and Whitehouse).

Various stage theories of disease progression have been developed. However, in clinical practice, professionals speak roughly of three stages. In mild stage dementia, the newly diagnosed patient has significant cognitive losses resulting in disorientation and dysfunction, and often displays affective flatness and possibly depression. In moderate stage dementia, the patient forgets that he or she forgets, thereby gaining relief from insight into losses. Some patients will at this point adjust well emotionally to a life lived largely in the pure present, although some long-term memories are still in place. The recognition of loved ones is usually still possible. However, as many as one-third of patients in the moderate stage will struggle with emotional and behavior problems, including agitation, combativeness, paranoia, hallucinations, wandering, and depression. A small percentage becomes sexually disinhibited. The advanced stage of dementia includes a loss of all or nearly all ability to communicate by speech, inability to recognize loved ones in most cases, loss of ambulation without assistance, incontinence of bowel and/or bladder, and some weight loss due to swallowing difficulties. The advanced stage is generally considered terminal, with death occurring on average within two years. AD, however, is heterogeneous in its manifestations, and defies simplistic staging. For example, while most people with advanced AD will have no obvious ability to recognize loved ones, this is not always the case. In late December 2000, for example, the daughter of a man recently deceased sent an e-mail note to the AD networks around the world:

Hello Dear Friends: As many of you know, my father has been suffering from Alzheimer's disease for the past 4.5. years. It has been a long and often very hard road for him, for my mom, and for me too. However, as of 7 p.m. last night, my father no longer has to struggle with the disease that robbed him of every part of his being, except one. He never once stopped recognizing my mom and never, ever stopped reaching out to her and wanting to give her a kiss. No matter how many parts of his personality were lost, no matter how many hospital visits full of needles and catheters, no matter how many diapers, he always retained his kind, gentle sweetness and his European manners as a gentleman. In the end, things went very quickly for him. He simply closed his eyes and closed his mouth, indicating no more food or water.

The gentleman described above was in the advanced and therefore terminal stage of AD. Yet he retained the ability to recognize loved ones.

The Fundamental Moral Question: Do People with Dementia Count?

Despite the seriousness of dementia and the responsibilities it creates for caregivers, it is ethically important that the person with dementia not be judged by hypercognitive values (Post, 1995, 2000a). The self is not cognition alone, but is rather a complex entity with emotional and relational aspects that should be deemed morally significant and worthy of affirmation (Sabat). A bias against the deeply forgetful is especially pronounced in personhood theories of moral status in which persons are defined by the presence of a set of cognitive abilities (Kitwood). After discussion of the disparities in bioethical thinking about what constitutes a person, Stanley Rudman concludes, "It is clear that the emphasis on rationality easily leads to diminished concern for certain human beings such as infants, … and the senile, groups of people who have, under the influence of both Christian and humanistic considerations, been given special considerations" (Rudman, p. 47). Often, the personhood theorists couple their exclusionary rationalistic views with utilitarian ethical theories that are deeply incoherent with regard to life and death. As Rudman summarizes the concern, rationality is too severe a ground for moral standing, "allowing if not requiring the deaths of many individuals who may, in fact, continue to enjoy simple pleasures despite their lack of rationality …" (Rudman, p. 57). Of course, in the real world of families, love, and care, personhood theories have no practical significance.

The philosophical tendency to diminish the moral status or considerability of people with dementia is also related to a radical differentiation between the formerly intact or then self and the currently demented or now self. The reality is that until the very advanced and even terminal stage of AD, the person with dementia will usually have sporadically articulated memories of deeply meaningful events and relationships ensconced in long-term memory. It is wrong to bifurcate the self into then and now, as if continuities are not at least occasionally striking (Kitwood, Sabat). This is why it is essential that professional caregivers be aware of the person's life story, making up for losses by providing cues toward continuity in self-identity. Even in the advanced stage of dementia, as in the case presented at the outset of this entry, one finds varying degrees of emotional and relational expression, remnants of personality, and even meaningful nonverbal communication as in the reaching out for a hug.

The fitting moral response to people with dementia, according to western ethical thought as informed by Judaism and Christianity, is to enlarge our sense of human worth to counter an exclusionary emphasis on rationality, efficient use of time and energy, ability to control distracting impulses, thrift, economic success, self-reliance, self-control, language advantage, and the like. As Alasdair MacIntyre argues, too much has been made of the significance of language, for instance, obscuring the moral significance of species who lack linguistic abilities, or human beings who have lost such abilities (MacIntyre). It is possible to distinguish two fundamental views of persons with dementia. Those in the tradition of Stoic and Enlightenment rationalism have achieved much for universal human moral standing by emphasizing the spark of reason (logos) in us all; yet when this rationality dissipates, so does moral status. Those who take an alternative position see the Stoic heritage as an arrogant view in the sense that it makes the worth of a human being entirely dependent on rationality, and then gives too much power to the reasonable. This alternative view is generally associated with most Jewish and Christian thought, as well as that of other religious traditions in which the individual retains equal value regardless of cognitive decline. As the Protestant ethicist Reinhold Niebuhr wrote, "In Stoicism life beyond the narrow bonds of class, community, and race is affirmed because all life reveals a unifying divine principle. Since the principle is reason, the logic of Stoicism tends to include only the intelligent in the divine community. An aristocratic condescension, therefore, corrupts Stoic universalism." (p. 53). This rationalistic inclusivity lacks the deep universalism of other-regarding or unlimited love (Post, 2000a).

The perils of forgetfulness are especially evident in our culture of independence and economic productivity that so values intellect, memory, and self-control. AD is a quantifiable neurological atrophy that objectively assaults normal human functioning; on the other hand, as medical anthropologists's highlight, AD is also viewed within the context of socially constructed images of the human self and its fulfillment. A longitudinal study carried out in urban China, for example, by Charlotte Ikels, which was published in 1998, indicates that dementia does not evoke the same level of dread there as it does among Americans. Thus, the stigma associated with the mental incapacitation of dementia varies according to culture. Peter Singer, for example, is part of a preference utilitarian philosophical culture that happens to believe that those who do not project preferences into the future and implement them are not persons. According to Singer, those with memory impairment must then ultimately be devalued. While this devaluation is plausible for those human beings in the persistent vegetative state where the essentially human capacities—cognitive, emotional, relational, or aesthetic—no longer survive, people with dementia can experience many forms of gratification. The challenge is to work with remaining capacities. The first principle of care for persons with dementia is to reveal to them their value by providing attention and tenderness in love (Kitwood).

Enhancing Quality of Life

Emotional, relational, aesthetic, and symbolic well-being are possible to varying degrees in people with progressive dementia (Kitwood). Quality of life can be much enhanced by working with these aspects of the person. The aesthetic well-being available to people with AD is obvious to anyone who has watched art or music therapy sessions. In some cases, a person with advanced AD may still draw the same valued symbol, as though through art a sense of self is retained (Firlik).

A sense of purpose or meaning on the part of caregivers can enhance quality of life for the person with dementia. In an important study by Peter V. Rabinsand and his colleagues, thirty-two family caregivers of persons with AD and thirty caregivers of persons with cancer were compared cross-sectionally to determine whether the type of illness cared for affected the emotional state of the caregiver and to identity correlates of both undesirable and desirable emotional outcomes. While no prominent differences in negative or positive states were found between the two groups, correlates of negative and positive emotional status were identified. These include caregiver personality variables, number of social supports, and the feeling that one is supported by one's religious faith. Specifically, "emotional distress was predicted by self-reported low or absent religious faith" (Rabins et al., p. 335). Moreover, spirituality predicted positive emotional states in caregiving. Interestingly, the study suggests that it was "belief, rather than social contact, that was important" (Rabins et al., p. 332) Spirituality and religion are especially important to the quality of life of African-American caregivers, for whom it is shown to protect against depression (Picot et al.). Spirituality is also a means of coping with the diagnosis of AD for many affected individuals (Elliot).

In general, quality of life is a self-fulfilling prophesy. If those around the person with dementia see the glass as half empty and make no efforts to relate to the person in ways that enhance his or her experience, then quality of life is minimal. Steven R. Sabat, who has produced the definitive observer study of the experience of dementia, underscores the extent to which the dignity and value of the person with dementia can be maintained through affirmation and an existential perspective.

Specific Clinical Ethical Issues

Nearly every major issue in clinical ethics pertains to AD (Post, 2000b). The Alzheimer's Disease and Related Disorders Association issued an authoritative 2001 publication on ethics issues that covers truth in diagnosis, therapeutic goals, genetic testing, research ethics, respect for autonomy, driving and dementia, end-of-life care, assisted oral feeding and tube feeding, and suicide and assisted suicide. This work borrowed considerably from focus group work that led to the Fairhill Guidelines on Ethics of the Care of People with Alzheimer's Disease (Post and Whitehouse). The Fairhill Guidelines were also the acknowledged baseline for the Alzheimer Canada's national ethics guidelines entitled "Tough Issues" (Cohen et al). The most relevant work on ethics and AD emerges in a grounded way from the affected individuals, their families, and those who serve them in loyal care.

The Association recommends truthtelling in diagnosis because this allows the affected individual, while still competent, to make plans for the future with regard to finances, healthcare, and activities. Most clinicians in the United States and Canada do disclose the probable diagnosis of AD, even though it is only about 90 percent accurate and must be verified upon autopsy. This transition has been encouraged by the emergence of new treatments (Alzheimer's Disease Association).

Genetic testing is frowned on by the Association, except in the early-onset familial cases where a single gene mutation causes the disease. AD is the object of intense genetic analysis. It is a genetically heterogeneous disorder—to date, it is associated with three determinative or causal gene mutations (i.e., someone who has the mutation will definitely get the disease) and one susceptibility or risk gene. The three causal AD genes mutations (located on chromosomes 21, 14, and 1) were discovered in the 1990s. These are autosomal-dominant genes and pertain to early-onset familial forms of AD (usually manifesting between the early 40s and mid-50s) which, according to one estimate, account for possibly fewer than 3 percent of all cases. These families are usually well aware of their unique histories. Only in these relatively few unfortunate families is genetic prediction actually possible, for those who carry the mutation clearly know that the disease is an eventuality. Many people in these families do not wish to know their genetic status, although some do get tested. Currently, there is no clearly predictive test for ordinary late-onset AD that is associated with old age. There is one well-defined susceptibility gene, an apolipoprotein E [.element]4 allele on chromosome 19 (apoE=protein; APOE=gene), which was discovered in 1993 and found to be associated with susceptibility to late-onset AD (after fifty-five years). A single [.element]4 gene (found in about one-third of the general population) is not predictive of AD in asymptomatic individuals—it does not come close to fore-telling disease, and many people with the gene will never have AD. Among those 2 percent of people with two of the [.element]4 genes, AD does not necessary occur either (Post et al). Such susceptibility testing can be condoned in a research setting, but is not encouraged in clinical practice because it provides no reliable predictive information upon which to base decisions, it has no medical use, and it may result in discrimination in obtaining disability or long-term care insurance (Post et al., Alzheimer's Disease Association).

The Association's 2001 statement includes the important argument that disclosing the diagnosis early in the disease process allows the person to "be involved in communicating and planning for end-of-life decisions." Diagnostic truthtelling is the necessary beginning point for an ethics of precedent autonomy for those who wish to implement control over their futures through advance directives such as durable power of attorney for healthcare, which allows a trusted loved one to make any and all treatment decisions once the person with dementia becomes incompetent. This can effectively be coupled with a living will or some other specific indication of the agent's material wishes with regard to endof-life care. Unless the person knows the probable diagnosis in a timely way while still competent to file such legal instruments, the risk of burdensome medical technologies is increased. Even in the absence of such legal forms, however, many technologically advanced countries will allow next of kin to decide against efforts to extend life in severe dysfunction. This is important because many patients suffer incapacitating cognitive decline long before having a diagnostic work up; those who are diagnosed early enough to exercise their autonomy can become quickly incapacitated.

The Association does not support mandatory reporting of a probable diagnosis of AD to the Department of Motor Vehicles. There are a number of reasons for this caution, one of which is patient confidentiality. Reporting requirements might discourage some persons from coming into the clinic for early diagnosis at a time early in the course of disease when drug treatments are most clearly indicated. Eventually all people with AD must stop driving when they are a serious risk to self or others. Family members must know that if a loved one drives too long and injures others, they may even be held financially liable and insurers may not be obliged to cover this liability. Ideally, a privilege is never limited without offering the person ways to fill in the gaps and diminish any sense of loss. An all or nothing approach can and should be avoided. Compromise and adjustments can be successfully implemented by those who are informed and caring, especially when the person with AD has insight into diminishing mental abilities and loss of competence. The affected person should retain a sense of freedom and self-control if possible (Alzheimer's Disease Association).

AD is on the leading edge of the debate over physician-assisted suicide (PAS) and euthanasia. The policies that emerge from this debate will have monumental significance for people with dementia, and for social attitudes toward the task of providing care when preemptive death is cheaper and easier. The Association affirms the right to dignity and life for every Alzheimer patient, and cannot condone suicide (Alzheimer's Disease Association).

The Association asserts that the refusal or withdrawal of any and all medical treatment is a moral and legal right for all competent Americans of age, and this right can be asserted by a family surrogate acting on the basis of either substituted judgement (what would the patient when competent have wanted) or best interests (what seems the most humane and least burdensome option in the present).

The Association concludes that AD in its advanced stage should be defined as a terminal disease, as roughly delineated by such features as the inability to recognize loves ones, to communicate by speech, to ambulate, or to maintain bowel and/or bladder control. When AD progresses to this stage, weight loss and swallowing difficulties will inevitably emerge. Death can be expected for most patients within a year or two, or even sooner, regardless of medical efforts. One useful consequence of viewing the advanced stage of AD as terminal is that family members will better appreciate the importance of palliative (pain medication) care as an alternative to medical treatments intended to extend the dying process. All efforts at life extension in this advanced stage create burdens and avoidable suffering for patients who could otherwise live out the remainder of their lives in greater comfort and peace. Cardiopulmonary resuscitation, dialysis, tube-feeding, and all other invasive technologies should be avoided. The use of antibiotics usually does not prolong survival, and comfort can be maintained without antibiotic use in patients experiencing infections. Physicians and other healthcare professionals should recommend this less burdensome and therefore more appropriate approach to family members, and to persons with dementia who are competent, ideally soon after initial diagnosis. Early discussions of a peaceful dying should occur between persons with dementia and their families, guided by information from healthcare professionals on the relative benefits of a palliative care approach (Alzheimer's Disease Association).

Avoiding hospitalization will also decrease the number of persons with advanced AD who receive tube-feeding, since many long-term care facilities send residents to hospitals for tube placement, after which they return to the facility. It should be remembered that the practice of long-term tube-feeding in persons with advanced dementia began only in the mid-1980s after the development of a new technique called percutaneous endoscopic gastrostomy (PEG). Before then, such persons were cared for through assisted oral feeding. In comparison with assisted oral feeding, however, long-term tube-feeding has no advantages, and a number of disadvantages (Alzheimer's Disease Association).

In closing this entry, attention will be directed in greater depth to three representative areas of special concern to family and professional caregivers: cognitive enhancing compounds, research risk, and tube feeding.

COGNITIVE ENHANCING COMPOUNDS. Persons with AD and their families greet the emergence of new compounds to mitigate the symptoms of dementia with great hope. These compounds, known as cholinesterase inhibitors, slightly elevate the amount of acetylcholine in the brain, slightly boosting communication between brain cells. In the earlier stages of the disease, while enough brain cells are still functional, these drugs can improve word finding, attentiveness to tasks, and recognition of others for a brief period in the range of six months to two years. Thus, some symptoms can be mitigated for a while, but these drugs have no impact on the underlying course of the disease, and neither reverse nor cure dementia. Some affected individuals, after taking any new compound whether artificial or natural, may exude a burst of renewed self-confidence in their cognitive capacities. But how much of this is due to the compound itself remains unclear. Presumably each person with AD is a part of some relational network that inevitably plays a role in the self-perception of cognitive improvement—indeed, self-perception is dependent on the perceptions of others and their need for a glimmer of hope as caregivers. Realistically, a medication may bring the self-perception of a renewed sense of mental clarity, as though a fog has lifted, yet none of the available cognitive enhancing compounds slow the progression of disease.

It is hard for professionals to know how to respond to the passion for the possible. Should unrealistic hopes be indulged for emotional reasons (Post, 1998, 2000b)? Should the money expended for new compounds of relatively marginal efficacy be spent on environmental and relational opportunities? Many clinicians caution both persons with AD and their family caregivers against thinking that the new compound is a miracle cure. Many still remain somewhat skeptical of studies of cognitive testing indicating significant but always minor benefit; no such studies take into account confounding factors such as the quality of relationships, environment, and emotional well-being. Nevertheless, reports of a fog lifting are interesting anecdotally. Are statements of future expectations so excessive among some desperate caregivers that hope is easily exploited by pharmaceutical profiteers? Medication needs to be placed within a full program of dementia care (including emotional, relational, and environmental interventions) so as not to be excessively relied on; family members should be respected when they desire to stop medication; even when medication is desired, families need to appreciate the limits of current compounds.

It is possible as well, that the anti-dementia compounds can, in those cases where they may have some capacity to give what is always at best a modest and fleeting cognitive boost,—fleeting because the underlying cognitive decline is intractable—be double-edged swords. While some slight cognitive improvements may occur, these may come at the cost of renewed insight into the disease process on the part of the affected individual, and of relational difficulties in the context of affected individuals and their caregivers. If the kindest point in the progression of AD is when the person with dementia forgets that he or she forgets, and is therefore able to get free of insight and related anxiety, then a little cognitive enhancement is not obviously a good thing for quality of life and quality of lives. Is it possible, then, to speak of detrimental benefits?

Decisions about these compounds are ethically and financially complex because their efficacy is quite limited, the affected individual remains on the inevitable downward trajectory of irreversible progressive dementia, and there may be nonchemical interventions focusing on emotional, relational, and spiritual well-being that are both cheaper and more effective. This is not to suggest that we should all be pharmacological Calvinists rather than pharmacological hedonists, but does anyone doubt that the pharmaceuticals wield a great deal of power across the spectrum of AD support groups? In the future, as compounds emerge that can actually alter the underlying progression of AD, affected individuals and caregivers will be faced with difficult tradeoffs between length of life and quality of life (Post, 1997, 2001a).

Research Risks

The crucial unanswered question in AD research is this: What should be the maximal or upper limit for permissible potential risks in any AD research, regardless of whether the research is characterized as potentially therapeutic for the subject or not? A secondary unanswered question is this: Should proxy consent be permitted in higher risk research, even when there is no potential therapeutic benefit for the participant, just as it is permitted when the research is considered potentially therapeutic? Without agreement on these fundamental questions, the upcoming treatments, promising both greater benefit and greater risk, will not expeditiously reach those in most need.

The Association's 2001 statement is as follows:

(A) For minimal risk research all individuals should be allowed to enroll, even if there is no potential benefit to the individual. In the absence of an advance directive, proxy consent is acceptable.

(B) For greater than minimal risk research and if there is a reasonable potential for benefit to the individual, the enrollment of all individuals with Alzheimer disease is allowable based on proxy consent. The proxy's consent can be based on either a research specific advance directive or the proxy's judgment of the individual's best interests.

(C) For greater than minimal risk research and if there is no reasonable potential for benefit to the individual only those individuals who (1) are capable of giving their own informed consent, or (2) have executed a research specific advance directive are allowed to participate. In either case, a proxy must be available to monitor the individual's involvement in the research. (Note: this provision means that individuals who are not capable of making their own decisions about research participation and have not executed an advance directive or do not have a proxy to monitor their participation, cannot participate in this category of research.)

The Association's statement is laudable because of its endorsement of surrogate consent in all research of potential benefit to the subject, even if there is potentially a greater than minimal risk. Surrogate consent should always be based on accurate facts about the risks and potential benefits of the clinical research or trial, rather than on understatement of risks or burdens and exaggerated claims of benefit. Participants in all research should be protected from significant pain or discomfort. It is the responsibility of all investigators and surrogates to monitor the well-being of participants.

The Association indicates that surrogates must not allow their hopes for effective therapies to overtake their critical assessment of the facts, or to diminish the significance of participant expressions of dissent. Subject dissent or other expressions of agitation should be respected, although a surrogate can attempt reasonable levels of persuasion or assistance. People with dementia, for example, may initially refuse to have blood drawn or to take medication; once a family member helps calm the situation and explains things, they may change their minds. This kind of assistance is acceptable. Continued dissent, however, requires withdrawal of the participant from the study, even though surrogates would prefer to see the research participation continue.

At this point in time, the most important unresolved issue in dementia research is how much potential risk to those affected by AD should society allow? Research in AD is becoming increasingly physically invasive and biologically complex. Is there any maximal threshold of potential risk beyond which research should be disallowed? Furthermore, how can actual discomforts in research be properly monitored, and what degree of discomfort requires that research be halted? In general, research ethics has not addressed these issues, focusing instead on matters of subject and proxy consent.

END OF LIFE AND PEG TUBES. Gastrostomy tube feeding became common in the context of advanced dementia and in elderly patients more generally after 1981, secondary to the development of the PEG procedure. The PEG procedure was developed by Dr. Michael Gauderer and his colleagues at Rainbow Babies and Children's Hospital in Cleveland from 1979 to 1980 for use in young children with swallowing difficulties. The procedure required only local anesthesia, thus eliminating the significant surgical risk associated with general anesthesia and infection (Gauderer and Ponsky). Gauderer wrote two decades later that while PEG use has benefited countless patients, "in part because of its simplicity and low complication rate, this minimally invasive procedure also lends itself to over-utilization" (p.879). Expressing moral concerns about the proliferation of the procedure, Gauderer indicates that as the third decade of PEG use begins to unfold, "much of our effort in the future needs to be directed toward ethical aspects …" (p. 882). PEG is being used more frequently even in those patients for whom these procedures were deemed too risky in the past.

For over a decade, researchers have underscored the burdens and risks of PEG tube-feeding in persons with advanced dementia. The mounting literature was well summarized by Finucane and his research colleagues, who found no published evidence that tube-feeding prevents aspiration pneumonia, prolongs survival, reduces risks of pressure sores or infections, improves function, or provides palliation in this population (Finucane, et al.; Gillick; Post, 2001b).

Families often perceive tube-feeding as preventing pneumonia or skin breakdown, and many assume that it extends survival. These perceptions are erroneous. The main benefit of PEG is that it makes life easier for the informal family caregiver who, for reason of competing duties or perhaps physical limitation, cannot find the time or energy to engage in assisted oral feedings. Yet PEG use is not really easy, because it has its technological complexities, and the recipient will usually have diarrhea. In some cases, physical restraints are used to keep a person from pulling on the several inches of tube that extend out of the abdomen. One wonders if assisted oral feeding is not easier after all. Regardless, purported technical ease and efficiency do not mean that these technologies should be applied. Should persons with advanced progressive dementia ever be provided with PEGs? In the general, assisted oral feeding and hospice are the better alternative to tube-feeding, although in practice there will be some cases in which the limited capacities of an informal family caregiver do justify tube-feeding as the ethically imperative alternative to starvation when the ability to swallow has begun to diminish. Ideally home health aides would make assisted oral feeding possible even in these cases, but this is not a priority in the healthcare system. Institutions, however, should uniformly provide assisted oral feeding as the desired alternative to tube-feeding, a measure that would profoundly obviate the overuse of this technology.

There will be many family caregivers who have no interest in PEG use and who feel that they are being loyal to their loved one's prior wishes. A physician should expect this response. A study included in-person interviews of eighty-four cognitively normal men and women aged sixty-five years and older from a variety of urban and suburban settings (including private homes, assisted-living apartments, transitional care facilities, and nursing homes). Three-fourths of the subjects would not want cardiopulmonary resuscitation, use of a respirator, or parenteral or enteral tube nutrition with the milder forms of dementia; 95 percent or more would not want any of these procedures with severe dementia (Gjerdingen et al.). These subjects were adequately informed of the burdens and benefits of such interventions.

Physicians and other healthcare professionals should recommend this less burdensome and therefore more appropriate approach to family members, and to persons with dementia who are competent, ideally soon after initial diagnosis. Early discussions of a peaceful dying should occur between persons with dementia and their families, guided by information from healthcare professionals on the relative benefits of a palliative care approach (Volicer and Hurley).

stephen g. post

SEE ALSO: Abuse, Interpersonal: Elder Abuse; Advance Directives and Advance Care Planning; Aging and the Aged;Artificial Nutrition and Hydration; Autonomy; Beneficence; Care; Christianity, Bioethics in; Compassionate Love; Competence; Confidentiality; Genetic Testing and Screening; Grief and Bereavement; Human Dignity; Informed Consent; Judaism, Bioethics in; Life, Quality of; Life, Sanctity of; Long-Term Care; Medicaid; Medicare; Moral Status; Neuroethics; Palliative Care and Suffering; Research, Unethical; Right to Die, Policy and Law

BIBLIOGRAPHY

Aevarsson, O Skoog I. 1996. "A Population-Based Study on the Incidence of Dementia Disorders Between 85 and 88 Years of Age." Journal of the American Geriatrics Society 44: 1455–1460.

Alzheimer Canada. 1997. Tough Issues: Ethical Guidelines of the Alzheimer Society of Canada. Toronto: Alzheimer Canada.

Alzheimer's Disease Association. 2001. Ethical Issues in Alzheimer's Disease. Chicago: Alzheimer Disease Association.

Binstock, Robert H.; Post, Stephen G.; and Whitehouse, Peter J.; eds. 1992. Dementia and Aging: Ethics, Values and Policy Choices. Baltimore, MD: The Johns Hopkins University Press.

Cohen, Carol A.; Whitehouse, Peter J.; Post, Stephen G.; et al. 1999. "Ethical Issues in Alzheimer Disease: The Experience of a National Alzheimer Society Task Force." Alzheimer Disease and Associated Disorders 13(2): 66–70.

Elliot, Hazel. 1997. "Religion, Spirituality and Dementia: Pastoring to Sufferers of Alzheimer's Disease and Other Associated Forms of Dementia." Disability and Rehabilitation 19(10): 435–441.

Evans, D. A.; Funkenstein, H. H.; Albert, M. S.; et al. 1989. "Prevalence of Alzheimer's Disease in a Community Population of Older Persons: Higher than Previously Reported." Journal of the American Medical Association 262: 2551–2556.

Finucane, Thomas E.; Christmas, Colleen; and Travis, Kathy. 1999. "Tube Feeding in Patients with Advanced Dementia: A Review of the Evidence." Journal of the American Medical Association 282: 1365–1370.

Firlik, Andrew D. 1991. "Margo's Logo." Journal of the American Medical Association 265: 201

Gauderer, Michael. 1999. "Twenty Years of Percutaneous Endoscopic Gastrostomy: Origin and Evolution of a Concept and its Expanded Applications." Gastrointestinal Endoscopy 50: 879–882.

Gauderer, Michael, and Ponsly, Jeffrey L. 1981. "A Simplified Technique for Constructing a Tube Feeding Gastrostomy." Surgery in Gyncology and Obstetrics 152: 83–85.

Gillick, Muriel R. 2000. "Rethinking the Role of Tube Feeding in Patients with Advanced Dementia." New England Journal of Medicine 342(3): 206–210.

Gjerdingen, Dwenda K.; Neff, Jennifer A.; Wang, Marie; et al. 1999. "Older Persons' Opinions About Life-Sustaining Procedures in the Face of Dementia." Archives of Family Medicine 8: 421–425.

Ikels, Charlotte. 1998. "The Experience of Dementia in China." Culture, Medicine and Psychiatry 3: 257–283.

Kitwood, Tom. 1997. Dementia Reconsidered: The Person Comes First. Buckingham, Eng.: Open University Press.

Kitwood, Tom, and Bredin, Kathleen. 1992. "Towards a Theory of Dementia Care: Personhood and Well-being." Ageing and Society 12: 269–297.

MacIntyre, Alasdair. 1999. Dependent Rational Animals: Why Human Beings Need the Virtues. Chicago: Open Court.

Niebuhr, Reinhold. 1956. An Interpretation of Christian Ethics. New York: Meridian Books.

Oizilbash, Nawab; Schneider, Lon S.; Tariot, Pierre; et al., eds. 2002. Evidence-Based Dementia Practice. Oxford: Blackwell Press.

Picot, Sandra J.; Debanne, Sara M.; Namazi, Kevin; et al. 1997. "Religiosity and Perceived Rewards of Black and White Caregivers." Gerontologist 37(1): 89–101.

Post, Stephen G. 1997. "Slowing the Progression of Dementia: Ethical Issues." Alzheimer Disease and Associated Disorders 11(supplement 5): 34–36.

Post, Stephen G. 1998. "The Fear of Forgetfulness: A Grassroots Approach to Alzheimer Disease Ethics." Journal of Clinical Ethics 9(1): 71–80.

Post, Stephen G. 2000a. The Moral Challenge of Alzheimer Disease: Ethical Issues from Diagnosis to Dying, 2nd edition. Baltimore, MD: The Johns Hopkins University Press.

Post, Stephen G. 2000b. "Key Issues in the Ethics of Dementia Care." Neurological Clinics 18(4): 1011–1022.

Post, Stephen G. 2001a. "Anti-Dementia Compounds, Hope, and Quality of Lives." Alzheimer's Care Quarterly 2(3): 75–77.

Post, Stephen G. 2001b. "Tube-Feeding and Advanced Progressive Dementia." The Hastings Center Report 31(1): 36–42.

Post, Stephen G., and Whitehouse, Peter J. 1995. "Fairhill Guidelines on Ethics of the Care of People with Alzheimer Disease: A Clinician's Summary." Journal of the American Geriatrics Society 43(12): 1423–1429.

Post, Stephen G., and Whitehouse, Peter J., eds. 1998. Genetic Testing for Alzheimer Disease: Ethical and Clinical Issues. Baltimore, MD: The Johns Hopkins University Press.

Post, Stephen G.; Whitehouse, Peter J.; Binstock, Robert H.; et al. 1997. "The Clinical Introduction of Genetic Testing for Alzheimer Disease: An Ethical Perspective." Journal of the American Medical Association 277(10): 832–836.

Rabins, Peter V.; Fitting, Melinda D.; Eastham, James; et al. 1990. "The Emotional Impact of Caring for the Chronically Ill." Psychosomatics 31(3): 331–336.

Rudman, Stanley. 1997. Concepts of Persons and Christian Ethics. Cambridge, Eng.: Cambridge University Press.

Sabat, Steven R. 2002. The Experience of Alzheimer's Disease: Life Through a Tangled Veil. Oxford: Blackwell Publishers.

Singer, Peter. 1993. Practical Ethics. Cambridge, Eng.: Cambridge University Press.

U.S. General Accounting Office. 1998. Alzheimer's Disease: Estimates of Prevalence in the U.S., Pub. No. HEHS–98–16. Washington, D.C.: Author.

Volicer, Ladislav, and Hurley, Ann, eds. 1998. Hospice Care for Patients with Advanced Progressive Dementia. New York: Springer Publishing.

Dementia

Definition

Description

Causes and symptoms

Demographics

Diagnosis

Treatments

Prognosis

Prevention

Definition

Dementia is not a specific disorder or disease. It is a syndrome (group of symptoms) associated with a progressive loss of memory and other intellectual functions that is serious enough to interfere with performing the tasks of daily life. Dementia can occur to anyone at any age from an injury or from oxygen deprivation, although it is most commonly associated with aging. It is the leading cause of institutionalization of older adults.

Description

The definition of dementia has become more inclusive over the past several decades. Whereas earlier descriptions of dementia emphasized memory loss, the last three editions of the professional’s diagnostic handbook, Diagnostic and Statistical Manual of Mental Disorders (also known as the DSM) define dementia as an overall decline in intellectual function, including difficulties with language, simple calculations, planning and judgment, and motor (muscular movement) skills, as well as loss of memory. Although dementia is not caused by aging itself—most researchers regard it as resulting from injuries, infections, brain diseases, tumors, or other disorders—it is quite common in older people. The prevalence of dementia increases rapidly with age; it doubles every five years after age 60. Dementia affects only 1% of people aged 60-64 but 30%-50% of those older than 85. About four to five million persons in the United States are affected by dementia as of 2006. Surveys have indicated that dementia is the condition most feared by older adults in the United States.

Causes and symptoms

Causes

Dementia can be caused by almost 40 different diseases and conditions, ranging from dietary deficiencies and metabolic disorders to head injuries and inherited diseases. The possible causes of dementia can be categorized as follows:

• Primary dementia. These dementias are characterized by damage to or wasting away of the brain tissue itself. They include Alzheimer’s disease (AD), frontal lobe dementia (FLD), and Pick’s disease. FLD is dementia caused by a disorder (usually genetic) that affects the front portion of the brain, and Pick’s disease is a rare type of primary dementia that is characterized by a progressive loss of social skills,

language, and memory, leading to personality changes and sometimes loss of moral judgment.

• Multi-infarct dementia (MID). Sometimes called vascular dementia, this type is caused by blood clots in the small blood vessels of the brain. When the clots cut off the blood supply to the brain tissue, the brain cells are damaged and may die. (An infarct is an area of dead tissue caused by obstruction of the circulation.)
• Lewy body dementia. Lewy bodies are areas of injury found on damaged nerve cells in certain parts of the brain. They are associated with AD and Parkinson’s disease, but researchers do not yet know whether dementia with Lewy bodies is a distinct type of dementia or a variation of AD or Parkinson’s disease.
• Dementia related to alcoholism or exposure to heavy metals (arsenic, antimony, bismuth).
• Dementia related to infectious diseases. These infections may be caused by viruses (HIV, viral encephalitis); spirochetes (Lyme disease, syphilis); or prions (Creutzfeldt-Jakob disease). Spirochetes are certain kinds of bacteria, and prions are protein particles that lack nucleic acid.
• Dementia related to abnormalities in the structure of the brain. These may include a buildup of spinal fluid in the brain (hydrocephalus); tumors; or blood collecting beneath the membrane that covers the brain (subdural hematoma).

Dementia may also be associated with depression , low levels of thyroid hormone, or niacin or vitamin B₁₂ deficiency. Dementia related to these conditions is often reversible.

Genetic factors in dementia

Genetic factors play a role in several types of dementia, but the importance of these factors in the development of the dementia varies considerably. AD is known, for example, to have an autosomal (non-sex-related) dominant pattern in most early-onset cases as well as in some late-onset cases, and to show different degrees of penetrance (frequency of expression) in late-life cases. Recently, two forms of a gene responsible for recycling the proteins thought to be involved in forming the neuron-destroying amyloid plaques of AD were identified and associated with late-onset disease. Researchers have not yet discovered how the genes associated with dementia interact with other risk factors to produce or trigger the dementia. One non-genetic risk factor presently being investigated is toxic substances in the environment.

EARLY-ONSET ALZHEIMER’S DISEASE

In early-onset AD, which accounts for 2%-7% of cases of AD, the symptoms develop before age 60. It is usually caused by an inherited genetic mutation. Early-onset AD is also associated with Down syndrome (trisomy 21), in that persons with trisomy 21 (three forms of human chromosome 21 instead of a pair) often develop early-onset AD. Development of AD in persons with Down syndrome has been traced to the presence of BACE1, which increases under low oxygen conditions in mice. The researchers had investigated the effects of low oxygen because of the relationship between a history of stroke , which cuts off oxygen to the brain, and AD.

LATE-ONSET ALZHEIMER’S DISEASE

Recent research indicates that late-onset AD is a polygenic disorder; that is, its development is influenced by more than one gene. It has been known since 1993 that a specific form of a gene (the APOE gene) on human chromosome 19 is a genetic risk factor for late-onset AD. In 1998 researchers at the University of Pittsburgh reported on another gene that controls the production of bleomycin hydrolase (BH) as a second genetic risk factor that acts independently of the APOE gene. In December 2000, three separate research studies reported that a gene on chromosome 10 that may affect the processing of a protein (called amyloid-beta protein) is also involved in the development of late-onset AD. When this protein is not properly broken down, a starchy substance builds up in the brains of people with AD to form the plaques that are characteristic of the disease. The most recent development is the confirmation of the involvement of variant forms of a gene called SORL1. The proteins controlled by this gene are related to the production of amyloidbeta protein. Low levels of the SORL1 protein cause amyloid-beta levels near cells to rise.

MULTI-INFARCT DEMENTIA (MID)

While the chief risk factors for MID are high blood pressure, advanced age, and male sex, there is an inherited form of MID called CADASIL, which stands for cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy. CADASIL can cause psychiatric disturbances and severe headaches as well as dementia.

FRONTAL LOBE DEMENTIAS

Researchers think that between 25% and 50% of cases of frontal lobe dementia involve genetic factors. Pick’s dementia appears to have a much smaller genetic component than FLD. It is not yet known what other risk factors combine with inherited traits to influence the development of frontal lobe dementias.

FAMILIAL BRITISH DEMENTIA (FBD)

FBD is a rare autosomal dominant disorder that was first reported in the 1940s in a large British family extending over nine generations. FBD resembles AD in that the patient develops a progressive dementia related to amyloid deposits in the brain. In 1999, a mutated gene that produces the amyloid responsible for FBD was discovered on human chromosome 13. Studies of this mutation may yield further clues to the development of AD as well as FBD itself.

CREUTZFELDT-JAKOB DISEASE

Although Creutzfeldt-Jakob disease is caused by a prion (a proteinaceous infectious particle consisting only of protein, as opposed to a virus, which consists of protein and nucleic acid, or a virion, which consists of nucleic acid), researchers think that 5%-15% of cases may have a genetic component.

Symptoms

DSM-IV-TR identifies certain symptoms as criteria that must be met for a patient to be diagnosed with dementia. One criterion is significant weakening of the patient’s memory with regard to learning new information as well as recalling previously learned information. In addition, the patient must be found to have one or more of the following disturbances:

• aphasia. Aphasia refers to loss of language function. A person with dementia may use vague words like “it” or “thing” often because he or she cannot recall the exact name of an object; the affected person may echo what other people say, or repeat a word or phrase over and over. People in the later stages of dementia may stop speaking at all.
• apraxia. Apraxia refers to loss of the ability to perform intentional movements even though the person is not paralyzed, has not lost the sense of touch, and knows what he or she is trying to do. For example, a patient with apraxia may stop brushing his teeth, or have trouble tying his shoelaces.
• agnosia. Agnosia refers to loss of the ability to recognize objects even though the person’s sight and sense of touch are normal. People with severe agnosia may fail to recognize family members or even their own face reflected in a mirror.
• problems with abstract thinking and complex behavior. This criterion refers to the loss of the ability to make plans, carry out the steps of a task in the proper order, make appropriate decisions, evaluate situations, show good judgment, etc. For example, a patient might light a stove burner under a saucepan before putting food or water in the pan, or be unable to record checks and balance a checkbook.

DSM-IV-TR also specifies that these disturbances must be severe enough to cause problems in the person’s daily life, and that they must represent a decline from a previously higher level of functioning.

In addition to the changes in cognitive functioning, the symptoms of dementia may also include personality changes and emotional instability. Patients with dementia sometimes become mildly paranoid because their loss of short-term memory leads them to think that mislaid items have been stolen. About 25% of patients with dementia develop a significant degree of paranoia , that is, generalized suspiciousness or specific delusions of persecution. Mood swings, anxiety , and irritability or anger are also frequent occurrences, particularly when patients with dementia are in situations that force them to recognize the extent of their impairment.

The following signs and symptoms are used to differentiate among the various types of dementia during a diagnostic evaluation.

ALZHEIMER’S DISEASE

Dementia related to AD often progresses slowly; it may be accompanied by irritability, wide mood swings, and personality changes in the early stage. Many patients, however, retain their normal degree of sociability in the early stages of AD. In second-stage AD, the patient typically gets lost easily, is completely disoriented with regard to time and space, and may become angry, uncooperative, or aggressive. Patients in second-stage AD are at high risk for falls and other accidents. In final-stage AD, the patient is completely bedridden, has lost control over bowel and bladder functions, and may be unable to swallow or eat. The risk of seizures increases as the patient progresses from early to end-stage AD. Death usually results from an infection or from malnutrition.

MULTI-INFARCT DEMENTIA

In MID, the symptoms are more likely to occur after age 70. In the early stages, the patient retains his or her personality more fully than a patient with AD. Another distinctive feature of this type of dementia is that it often progresses in a stepwise fashion; that is, the patient shows rapid changes in functioning, then remains at a plateau for a while rather than showing a continuous decline. The symptoms of MID may also have a “patchy” quality; that is, some of the patient’s mental functions may be severely affected while others are relatively undamaged. Other symptoms of MID include exaggerated reflexes, an abnormal gait (manner of walking), loss of bladder or bowel control, and inappropriate laughing or crying.

DEMENTIA WITH LEWY BODIES

This type of dementia may combine some features of AD, such as severe memory loss and confusion, with certain symptoms associated with Parkinson’s disease, including stiff muscles, a shuffling gait, and trembling or shaking of the hands. Visual hallucinations may be one of the first symptoms of dementia with Lewy bodies.

FRONTAL LOBE DEMENTIAS

The frontal lobe dementias are gradual in onset. Pick’s dementia is most likely to develop in persons between 40 and 60, while FLD typically begins before the age of 65. The first symptoms of the frontal lobe dementias often include socially inappropriate behavior (rude remarks, sexual acting-out, disregard of personal hygiene, etc.). Patients are also often obsessed with eating and may put non-food items in their mouths or making frequent sucking or smacking noises. In the later stages of frontal lobe dementia or Pick’s disease, the patient may develop muscle weakness, twitching, and delusions or hallucinations.

CREUTZFELDT-JAKOB DISEASE

The dementia associated with Creutzfeldt-Jakob disease occurs most often in persons between 40 and 60. It is typically preceded by a period of several weeks in which the patient complains of unusual fatigue, anxiety, loss of appetite, or difficulty concentrating. This type of dementia also usually progresses much more rapidly than other dementias, resulting in the death of the affected person within a few months to one year.

Demographics

The demographic distribution of dementia varies somewhat according to its cause. Moreover, recent research indicates that dementia in many patients has overlapping causes, so that it is not always easy to assess the true rates of occurrence of the different types. For example, AD and MID are found together in about 15%-20% of cases.

Alzheimer’s disease

AD is by far the most common cause of dementia in the elderly, accounting for 60%-80% of cases. It is estimated that four million adults in the United States have AD. The disease strikes women more often than men, but researchers do not know yet whether the sex ratio simply reflects the fact that women in developed countries tend to live longer than men, or whether female sex is itself a risk factor for AD. One well-known long-term study of Alzheimer’s in women is the Nun Study, begun in 1986 and presently conducted at the University of Kentucky. The researchers have identified numerous relationships between factors from early, mid-, and late life and the risk of AD.

Multi-infarct dementia

MID is responsible for between 15% and 20% of cases of dementia (not counting cases in which it coexists with AD). Unlike AD, MID is more common in men than in women. Diabetes, high blood pressure, a history of smoking, and heart disease are all risk factors for MID. Researchers in Sweden have suggested that MID is underdiagnosed, and may coexist with other dementias more frequently than is presently recognized.

Dementia with Lewy bodies

Dementia with Lewy bodies is now thought to be the second most common form of dementia after AD. But because researchers do not completely understand the relationship between Lewy bodies, AD, and Parkinson’s disease, the demographic distribution of this type of dementia is also unclear.

Other dementias

FLD, Pick’s disease, Huntington’s disease, Parkinson’s disease, HIV infection, alcoholism, head trauma, etc. account for about 10% of all cases of dementia. In FLD and Pick’s dementia, women appear to be affected slightly more often than men.

Diagnosis

In some cases, a patient’s primary physician may be able to diagnose the dementia; in many instances, however, the patient will be referred to a neurologist or a gerontologist (specialist in medical care of the elderly). Distinguishing one disorder from other similar disorders is a process called differential diagnosis. The differential diagnosis of dementia is complicated because of the number of possible causes; because more than one cause may be present at the same time; and because dementia can coexist with such other conditions as depression and delirium. Delirium is a temporary disturbance of consciousness marked by confusion, restlessness, inability to focus one’s attention, hallucinations, or delusions. In elderly people, delirium is frequently a side effect of surgery, medications, infectious illnesses, or dehydration. Delirium can be distinguished from dementia by the fact that delirium usually comes on fairly suddenly (in a few hours or days) and may vary in severity—it is often worse at night. Dementia develops much more slowly, over a period of months or years, and the patient’s symptoms are relatively stable. It is possible for a person to have delirium and dementia at the same time.

Another significant diagnostic distinction in elderly patients is the distinction between dementia and age-associated memory impairment (AAMI), which is sometimes called benign senescent forgetfulness. Older people with AAMI have a mild degree of memory loss; they do not learn new information as quickly as younger people, and they may take longer to recall a certain fact or to balance their checkbook. But they do not experience the degree of memory impairment that characterizes dementia, and they do not get progressively worse.

Clinical interview

In making a diagnosis, the doctor will begin by taking a full history, including the patient’s occupation and educational level as well as medical history. The occupational and educational history allows the examiner to make a more accurate assessment of the extent of the patient’s memory loss and intellectual decline. In some cases, the occupational history may indicate exposure to heavy metals or other toxins. A complete medical history allows the doctor to assess such possibilities as delirium, depression, alcohol-related dementia, dementia related to head injury, or dementia caused by infection. It is particularly important for the doctor to have a list of all the patient’s medications, including over-the-counter and alternative herbal preparations, because of the possibility that the patient’s symptoms are related to side effects of these substances.

Whenever possible, the examiner will consult the patient’s family members or close friends as part of the history-taking process. In many cases, friends and relatives can provide more detailed information about the patient’s memory problems and loss of function.

Mental status examination

A mental status examination (MSE) evaluates the patient’s ability to communicate, follow instructions, recall information, perform simple tasks involving movement and coordination. The MSE also gives information about the patient’s emotional state and general sense of space and time. The MSE includes the doctor’s informal evaluation of the patient’s appearance, vocal tone, facial expressions, posture, and gait as well as formal questions or instructions. A common form that has been used since 1975 is the so-called Folstein Mini-Mental Status Examination, or MMSE. Questions that are relevant to diagnosing dementia include asking the patient: to count backward from 100 by 7s, to make change, to name the current President of the United States, to repeat a short phrase after the examiner (e.g., “no ifs, ands, or buts”); to draw a clock face or geometric figure, and to follow a set of instructions involving movement (e.g., “Show me how to throw a ball” or “Fold this piece of paper and place it under the lamp on the bookshelf.”) The examiner may test the patient’s abstract reasoning ability by asking him or her to explain a familiar proverb (e.g., “People who live in glass houses shouldn’t throw stones”) or test the patient’s judgment by asking about a problem with a common-sense solution, such as what one does when a prescription runs out.

Neurological examination

A neurological examination includes an evaluation of the patient’s cranial nerves and reflexes. The cranial nerves govern the ability to speak as well as sight, hearing, taste, and smell. The patient will be asked to stick out her tongue, follow the examiner’s finger with her eyes, raise her eyebrows, etc. The patient is also asked to perform certain actions (e.g., touching the nose with the eyes closed) that test coordination and spatial orientation. The doctor will usually touch or tap certain areas of the body, such as the knee or the sole of the foot, to test the patient’s reflexes. Failure to respond to the touch or tap may indicate damage to certain parts of the brain.

Laboratory tests

Blood and urine samples may be collected in order to rule out such conditions as thyroid deficiency, niacin or vitamin B₁₂ deficiency, heavy metal poisoning, liver disease, HIV infection, syphilis, anemia, medication reactions, or kidney failure. A lumbar puncture (spinal tap) may be done to rule out neurosyphilis.

Diagnostic imaging

The patient may be given a computed tomography (CT) scan or magnetic resonance imaging (MRI) to detect evidence of strokes, disintegration of the brain tissue in certain areas, blood clots or tumors, a buildup of spinal fluid, or bleeding into the brain tissue. Positron-emission tomography (PET) or single-emission computed tomography (SPECT) imaging is not used routinely to diagnose dementia, but may be used to rule out AD or frontal lobe degeneration if a patient’s CT scan or MRI is unrevealing.

Treatments

Reversible and responsive dementias

Some types of dementia are reversible, and a few types respond to specific treatments related to their causes. Dementia related to dietary deficiencies or metabolic disorders is treated with the appropriate vitamins or thyroid medication. Dementia related to HIV infection often responds well to zidovudine (Retrovir), a drug given to prevent the AIDS virus from replicating. Multi-infarct dementia is usually treated by controlling the patient’s blood pressure and/or diabetes; while treatments for these disorders cannot undo damage already caused to brain tissue, they can slow the progress of the dementia. Patients with alcohol-related dementia often improve over the long term if they are able to stop drinking. Dementias related to head injuries, hydrocephalus, and tumors are treated by surgery.

It is important to evaluate and treat elderly patients for depression, because the symptoms of depression in older people often mimic dementia. This condition is sometimes called pseudodementia. In addition, patients who have both depression and dementia often show some improvement in intellectual functioning when the depression is treated. The medications most often used for depression related to dementia are the selective serotonin reuptake inhibitors (SSRIs ) paroxetine and sertraline. The mental status examination should be repeated after 6-12 weeks of antidepressant medication.

Irreversible dementias

As of 2006, there were no medications or surgical techniques that can cure AD, the frontal lobe dementias, MID, or dementia with Lewy bodies. There are also no “magic bullets” that can slow or stop the progression of these dementias. There are, however, several medications that are used to slow cognitive deterioration in AD. Four of these medications are cholinesterase inhibitors, which increase levels of acetylcholine in the brain, and these medications are effective in some people who have mild or moderate AD. Acetylcholine is a neurotransmitter (nerve signaling molecule) that facilitates communication among neurons. Another type of drug is the NMDA receptor antagonist memantine (available in the U.S. under the trade name Namenda), which may help stabilize memory in people with moderate to severe AD.

In April 2005, the U.S. Food and Drug Administration (FDA) issued a public health advisory regarding unapproved, “off-label” use of certain antipsychotic drugs that were approved for treatment of schizophrenia and mania. Clinical studies showed that use of these atypical antipsychotic medications in elderly patients with dementia to treat behavioral disorders is associated with increased mortality.

Patients may be given medications to ease the depression, anxiety, sleep disturbances, and other behavioral symptoms that accompany dementia, but most physicians prescribe relatively mild dosages in order to minimize the troublesome side effects of these drugs. Dementia with Lewy bodies appears to respond better to treatment with the newer antipsychotic medications than to treatment with such older drugs as haloperidol (Haldol).

Patients in the early stages of dementia can often remain at home with some help from family members or other caregivers, especially if the house or apartment can be fitted with safety features (handrails, good lighting, locks for cabinets containing potentially dangerous products, nonslip treads on stairs, etc.). Patients in the later stages of dementia, however, usually require skilled care in a nursing home or hospital.

Prognosis

The prognosis for reversible dementia related to nutritional or thyroid problems is usually good once the cause has been identified and treated. The prognoses for dementias related to alcoholism or HIV infection depend on the patient’s age and the severity of the underlying disorder.

The prognosis for the irreversible dementias is gradual deterioration of the patient’s functioning

KEY TERMS

Age-associated memory impairment (AAMI) — A condition in which an older person has some memory loss and takes longer to learn new information. AAMI is distinguished from dementia in that it is not progressive and does not represent a serious decline from the person’s previous level of functioning. Benign senescent forgetfulness is another term for AAMI.

Agnosia — Loss of the ability to recognize familiar people, places, and objects. Amyloid—A waxy translucent substance composed mostly of protein, that forms plaques (abnormal deposits) in the brain during the progression of Alzheimer’s disease.

Aphasia — Loss of previously acquired ability to understand or use written or spoken language, due to brain damage or deterioration.

Apraxia — Inability to perform purposeful movements that is not caused by paralysis or loss of feeling.

Creutzfeldt-Jakob disease — A degenerative disease of the central nervous system caused by a prion, or “slow virus.”

Delirium — A disturbance of consciousness marked by confusion, difficulty paying attention, delusions, hallucinations, or restlessness. It can be distinguished from dementia by its relatively sudden onset and variation in the severity of the symptoms.

Diagnostic and Statistical Manual of Mental

Disorders —A handbook for mental health professionals that includes lists of symptoms that indicate different mental disorders.

Frontal lobe dementia — Dementia caused by a disorder, usually genetic, that affects the front portion of the brain.

Hematoma — An accumulation of blood, often clotted, in a body tissue or organ, usually caused by a break or tear in a blood vessel.

Huntington’s disease — A hereditary disorder that appears in middle age and is characterized by gradual brain deterioration, progressive dementia, and loss of voluntary movement. It is sometimes called Huntington’s chorea.

Hydrocephalus — The accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain.

Lewy bodies — Areas of injury found on damaged nerve cells in certain parts of the brain associated with dementia.

Multi-infarct dementia — Dementia caused by damage to brain tissue resulting from a series of blood clots or clogs in the blood vessels. It is also called vascular dementia.

Parkinson’s disease — A disease of the nervous system most common in people over 60, characterized by a shuffling gait, trembling of the fingers and hands, and muscle stiffness. It may be related in some way to Lewy body dementia.

Pick’s disease — A rare type of primary dementia that affects the frontal lobes of the brain. It is characterized by a progressive loss of social skills, language, and memory, leading to personality changes and sometimes loss of moral judgment.

Prion — A protein particle that lacks nucleic acid.

Pseudodementia — A term for a depression with symptoms resembling those of dementia. The term “dementia of depression” is now preferred.

ending in death. The length of time varies somewhat. Patients with AD may live 2-20 years with the disease, with an average of seven years. Patients with frontal lobe dementia or Pick’s disease live on average 5-10 years after diagnosis. The course of Creutzfeldt-Jakob disease is much more rapid, with patients living 5-12 months after diagnosis.

Prevention

The reversible dementias related to thyroid and nutritional disorders can be prevented in many cases by regular physical checkups and proper attention to diet. Dementias related to toxic substances in the workplace may be prevented by careful monitoring of the work environment and by substituting less hazardous materials or substances in manufacturing processes. Dementias caused by infectious diseases are theoretically preventable by avoiding exposure to the prion, spirochete, or other disease agent. Multi-infarct dementia may be preventable in some patients by attention to diet and monitoring of blood pressure. Dementias caused by abnormalities in the structure of the brain are not preventable as of 2006.

With regard to genetic factors, tests are now available for the APOE gene implicated in late-onset AD, but these tests are used primarily in research instead of clinical practice. One reason is that the test results are not conclusive; about 20% of people who eventually develop AD do not carry this gene. Another important reason is the ethical implications of testing for a disease that presently has no cure. These considerations may change, however, if researchers discover better treatments for primary dementia, more effective preventive methods, or more reliable genetic markers.

See alsoRespite care.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, text revised. Washington, DC: American Psychiatric Association, 2000.

“Dementia.” The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, M.D., and Robert Berkow, M.D. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Lyon, Jeff, and Peter Gorner. Altered Fates: Gene Therapy and the Retooling of Human Life. New York and London: W. W. Norton & Co., Inc., 1996.

Marcantonio, Edward, M.D. “Dementia.” Chapter 40 in The Merck Manual of Geriatrics, edited by Mark H. Beers, M.D., and Robert Berkow, M.D. Whitehouse Station, NJ: Merck Research Laboratories, 2000.

Morris, Virginia. How to Care for Aging Parents. New York: Workman Publishing, 1996.

PERIODICALS

“Alzheimer’s Disease: Recent Progress and Prospects.” Harvard Mental Health Letter (Parts 1, 2, and 3) 18 (October-December 2001).

Rogaeva, Ekaterina, et al. “The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.” Nature Genetics Advance online publication; doi:10.1038/ng1943.

Sun, Xiulian, Guiqiong He, Hong Qing, Zhou Wiehui, Frederick Dobie, Cai Fang, Matthias Staufenbiel, L. Eric Huang, and Weihong Song. “Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating BACE1 gene expression.” Proceedings of the National Academy of Science 103 (2006): 18727-18732.

ORGANIZATIONS

Alzheimer’s Association. 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611. Toll Free: (800) 272-3900.

Alzheimer’s Disease International. 45/46 Lower Marsh, London SE1 7RG, United Kingdom. Telephone: (+44 20) 7620 3011. E-mail: adi@alz.co.uk. <http://www.alz.co.uk>.

National Family Caregivers Association. 10400 Connecticut Avenue, Suite 500, Kensington, MD, 20895-3944. Toll Free: (800) 896-3650. Telephone: (301)942-6430. Fax: (301) 942-2302. Website: http://www.nfcacares.org/>.

National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. Telephone: (301) 443-4513. <http://www.nimh.nih.gov>

National Institute of Neurological Disorders and Stroke (NINDS). Building 31, Room 8A06, 9000 Rockville Pike, Bethesda, MD 20892. Telephone: (301) 496-5751. <http://www.ninds.nih.gov>.

National Institute on Aging Information Center. P.O. Box 8057, Gaithersburg, MD 20898. Telephone: (800) 222-2225 or (301) 496-1752.

National Organization for Rare Disorders (NORD). P. O. Box 8923, New Fairfield, CT 06812. Telephone: (800) 447-6673 or (203) 746-6518.

OTHER

Alzheimer’s Disease Education and Referral (ADEAR). <http://www.alzheimers.org>.

The Nun Study. <http://www.coa.uky.edu/nunnet>.

National Library of Medicine. “Dementia.” <http://www.nlm.nih.gov/medlineplus/dementia.html> (accessed January 16, 2007).

National Guideline Clearinghouse. <http://www.guideline.gov/> (accessed January 16, 2007).

Rebecca Frey, Ph.D.
Emily Jane Willingham, Ph.D.

Dementia

Diagnosis

Causes

Resources

Dementia, which is from the Latin word dement meaning away mind, is a progressive deterioration and eventual loss of mental ability that is severe enough to interfere with normal activities of daily living, lasts more than six months, not present since birth, and not associated with a loss or alteration of consciousness. Dementia is a group of symptoms caused by gradual death of brain cells. Dementia is usually caused by degeneration in the cerebral cortex, the part of the brain responsible for thoughts, memories, actions, and personality. Death of brain cells in this region leads to the cognitive impairment that characterizes dementia. Statistics widely vary, but some estimates make the number of people in the United States who have some form of dementia at about 2.5 to 5 million. That number will increase as the average age of the U.S. population increases.

To distinguish true dementia from more limited difficulties due to localized brain damage, the strict medical definition requires that this decline affect at least two distinct spheres of mental activity; examples of such spheres include memory, verbal fluency, calculating ability, and understanding of time and location.

Some definitions of dementia also require that it interfere with a person’s work and social life. However, this may be difficult to show when a person’s work and social life is already limited, either by choice or by another mental or physical disorder. As a result, the most recent and most authoritative definition (that was developed jointly by the National Institute for Neurological and Communicative Disorders and Stroke [NINCDS]—part of the National Institutes of Health—and the Alzheimer Disease and Related Disorders Association [ADRDA]) does not include this criterion. The NINCDS-ADRDA definition focuses strictly on a decline from a previously higher level of mental function.

The term dementia goes back to antiquity, but was originally used in the general sense of being ‘out of one’s mind.’ Identification specifically with difficulties in thinking and learning occurred in the late eighteenth and early nineteenth centuries. Even then, however, the term was used for almost any sort of thinking, learning, or memory problem, whether temporary or permanent and without regard to cause. The most typical picture was of a young adult suffering from insanity or a disease affecting the brain.

This picture changed later in the nineteenth century, as psychiatrists (then called alienists) sought to group disorders in ways that would help reveal their causes. Temporary stupor, dementia associated with insanity, and memory problems resulting from damage to a specific area of the brain were all reclassified. The central core of what was left was then senile dementia: the substantial, progressive loss of mental function sometimes seen in older people and now recognized as resulting from one or more specific, identifiable diseases. Current definitions still recognize the existence of dementia in younger people, however.

Diagnosis

The first step in diagnosing dementia is to show that the person’s ability to think and learn has in fact declined from its earlier level. His or her current ability in different spheres of mental activity can be measured by any of a variety of mental status tests. The difficulty comes in comparing these current ability levels with those at earlier times. A patient’s own reports cannot be relied upon, since memory loss is typically part of dementia. Frequently, however, family members’ descriptions of what the person once could do establish that a decline has occurred. In other cases, comparison with what a person has accomplished throughout his or her life is enough to show that a decline has occurred. If neither source of information provides a clear answer, it may be necessary to re-administer the mental status test several months later and compare the two results.

Is any decline, no matter how small, sufficient to establish a diagnosis of dementia? The answer is not entirely clear. Research has shown that a majority of older people suffer a small but measurable decrease in their mental abilities. For example, one recent study followed 5, 000 people, some for as many as 35 years. This study found that scores on tests of mental abilities did not change between ages of 25 and 60 years, but declined about 10% between ages of 60 and 70 years. More significantly, people in their late eighties had scores more than 25% below those seen earlier.

Since none of the people tested were considered demented, one might assume that these declines are normal. It is still possible, however, that some tested individuals were in the early stages of dementia; these people’s results may then have pulled down the average scores for the group as a whole and created a false impression of a sizable normal drop in IQ (intelligence quotient). This ambiguity is particularly unfortunate because it has significant implications at the individual level: No one knows whether, if an older person’s mental sharpness starts to decline, this a normal part of aging or a possible signal of approaching dementia.

Once the existence of dementia has been established, the next question is: What is causing the condition? Alzheimer disease is by far the most common cause of dementia, especially in older adults. One recent study found that it directly caused 54% of dementias in people over 65 years of age, and may have been partially responsible for up to 12% more.

Unfortunately, there is no direct way to diagnose Alzheimer disease in a living person; only microscopic examination of the brain after death can conclusively establish that a person had this disorder. The same is true for the second most common cause, multi-infarct dementia. Both diagnoses are made by excluding other causes of dementia.

It is particularly crucial to exclude causes for which appropriate treatment might prove helpful. Among the most common and important of these are side effects of medications an individual may be taking—for example, sleeping pills, antidepressants, certain types of high bloodpressure medications, or others to which a person may be particularly sensitive. Medications are particularly likely to be responsible when the affected person is not only confused and forgetful, but also is not alert to what is going on around him or her.

Older individuals—the group most likely to suffer dementia from other causes—are particularly likely to be taking multiple drugs for their various disorders. Sometimes these drugs interact, producing side effects such as dementia that would not occur with any single drug at the same dosage. Drug side effects, including dementia, may also be more common in older people because their body’s ability to eliminate the drug often declines with age. Reduced speed of elimination calls for a corresponding reduction in dosage that does not always occur.

Another common, but treatable, cause of dementia, or of what looks like dementia, is depression. Some psychiatrists refer to the slowed thinking and confusion sometimes seen in people with depression as pseudodementia because of its psychological origin. Others believe the distinction does not reflect a meaningful difference. In any case, effective treatment of the depression will relieve the dementia it has produced.

Causes

Dementia can result from a wide variety of disorders and conditions. Some are quite rare, while others are moderately common. In some cases (measles, for example) dementia may be a rare complication of an otherwise common disease; in other cases, such as infection with Human Immunodeficiency Virus (HIV), an impact on mental function well known to medical specialists may not be widely recognized by the general public.

Non-Alzheimer degenerative dementias

In addition to Alzheimer disease, dementia may result from several other conditions characterized by progressive degeneration of the brain. The three most common of these are Pick’s disease, Parkinson disease, and Huntington’s disease (Huntington’s chorea).

Like Alzheimer disease, Pick’s disease affects the brain’s cortex—that is, the outer part where most of the higher mental functions take place. In other respects, however, the disorders are quite different. In Pick’s disease, for example, microscopic examination of the brain reveals dense inclusions (Pick bodies) within the nerve cells, while the cells themselves are inflated like blown-up balloons. This does not at all resemble the neurofibrillary tangles and beta-amyloid plaques seen in Alzheimer disease. However, since microscopic examination of a living person’s brain is rare, symptoms are used to distinguish the two diseases in practice.

Typically, Pick’s disease affects different parts of the cortex than does Alzheimer disease. This influences the order in which symptoms appear. The earliest symptoms of Pick’s disease include personality changes such as loss of tact and concern for others, impaired judgment, and loss of the ability to plan ahead. Loss of language skills occurs later, while memory and knowledge of such things as where one is and the time of day are preserved until near the end. In contrast, memory and time-space orientation are among the first things lost in Alzheimer disease, while personality changes and loss of language skills are late symptoms.

Both Parkinson disease and Huntington’s chorea initially affect deeper brain structures, those concerned with motor functions (that is, movement of the voluntary muscles). Indeed, most descriptions of Parkinson disease focus on the muscular rigidity that the disorder produces. In the later stages, however, nearly all patients with the disease will develop some degree of dementia as well.

Shortly after appearance of the choreiform movements that typify Huntington disease, most patients will begin to have trouble thinking clearly and remembering previous events. By the time they die, Huntington patients are intellectually devastated.

Vascular dementias

Although degenerative disorders account for the majority of dementia cases, a respectable minority result from interference with blood flow in or to the brain. Most such cases are due to a series of small strokes. Each stroke in the series may be unnoticeable, but the long-term result is a continuing and eventually severe decline in mental function.

A stroke, known technically as an infarct, is a failure of blood flow beyond a certain point in an artery. Usually this is due to a blood clot at that point, but sometimes it results from a break in the artery allowing much or all of the blood to escape. Although the fundamental causes are almost diametrically opposite—a clot at the wrong place versus no clot where one is needed—the effects are virtually the same. Unlike the degenerative dementias, which follow a relatively predictable course, vascular dementias can be quite variable. When and precisely where the next stroke occurs will determine both how quickly the dementia progresses and the extent to which different mental abilities are affected. Typically, however, vascular dementias are characterized by sudden onset, step-wise progression, and occurrence of motor symptoms early in the disorder. High blood pressure is usually present as a predisposing factor. Most, but not all, physicians believe that other heart attack risk factors, such as diabetes, cigarette smoking, and high cholesterol, also increase the risk of developing vascular dementia.

Traditionally, physicians have distinguished two major types of vascular dementia. In multiple-infarct dementia, examination of the brain after death shows a number of small but individually identifiable areas where strokes have destroyed the brain tissue. In Binswanger’s disease, individual areas of destruction cannot be identified. Almost the entire white matter of the brain—the portion occupied primarily by axons rather than nerve cell bodies—is affected to some degree. There is no sharp line between the two disorders, however, just as there is none between multiple-infarct dementia and the effect of two or three large strokes.

Dementia may also result from a reduction in blood flow to the brain as a whole. The most common cause is a severe narrowing of the carotid arteries in the neck. This may be considered analogous to partial plugging of an automobile’s fuel line, whereas the local damage resulting from a stroke is more like knocking out a piston. Most other dementias similarly represent damage to the engine itself. (Alzheimer disease might perhaps be likened to cylinder-wall deposits causing the pistons to stick, although scientists do not know enough about the origin of the disease to be sure this analogy is entirely accurate.)

Infectious dementias

Many infections either attack the brain as their primary target or can spread to it. If enough brain tissue is destroyed as a result, the outcome may be dementia. Brain infections can be due to viruses, bacteria, fungi, or parasites. For example, the measles virus will occasionally attack the brain, producing a condition known as subacute sclerosing panencephalitis that causes dementia and eventually death. The herpes (cold sore) virus can also cause dementia if it attacks the brain.

Infection by mosquito-borne encephalitis virus may leave survivors with significantly reduced mental function. The frequency with which this occurs depends, however, both on the particular virus involved and the age of the individual. Dementia is rare following infection with Western encephalitis virus, but is found in more than half those under five years of age who survive an Eastern encephalitis virus attack. Similarly, equine encephalitis virus produces severe illness, often leading to serious brain damage or death, in children under 15 years of age; in older people, however, the disease is typically quite mild and causes no lasting problems.

Nevertheless, serious viral infections of the brain are relatively uncommon. The one exception is infection with the human immunodeficiency virus (HIV)— the virus that causes AIDS. This is the most common infectious cause of dementia in the United States today, and the number of people affected continues to grow.

Although popular accounts of HIV infection focus on the damage it causes to the immune system, the virus also typically attacks the brain. Nearly all HIV-infected people will develop dementia at some time during their illness. However, how soon this dementia occurs and how severe it may become varies widely. About 20% of people with HIV infection develop dementia before they develop the opportunistic infections that define progression to full-blown AIDS.

Over the last half of the twentieth century and now into the twenty-first century, antibiotics have greatly reduced the threat from bacterial infection of the brain or the meninges that surround it. In one respect, however, the situation may be said to have worsened. Formerly, 95% of those with acute bacterial meningitis died; today, most survive, but the disease often leaves them with reduced mental capacities or other central nervous system problems.

On the other hand, tuberculous meningitis, which once accounted for up to 5% of children’s hospital admissions, has now been almost eliminated. There has also been a major reduction in syphilis of the central nervous system, a disease whose effects once resulted in 15 to 30% of mental hospital admissions. Unfortunately, both diseases are undergoing resurgences. The incidence of tuberculosis has increased over 20% since 1985, while estimates suggest that 50, 000 undetected and untreated new cases of syphilis occur each year. In the absence of treatment, 25 to 30% of syphilis cases will spread to the brain or meninges and result, over the course of years, in paralysis and dementia.

Fungal infections of the brain and meninges are generally rare except in people with weakened immune systems. Parasitic infections are also rare in this country. Elsewhere, however, the well-known African sleeping sickness, spread by a type of biting fly found only in equatorial Africa, is due to a parasite known as a trypanosome. Malaria, a mosquito-born parasitic disease, may also at times attack the brain and result in dementia.

Two infectious dementias that are quite rare but of tremendous scientific interest are Creutzfeldt-Jakob disease and kuru. The probable cause of these diseases are prions, infectious agents made up of gene-lacking proteins.

Miscellaneous causes

The dementia that can result from medication side effects or overdoses has been discussed in connection with diagnosis. Certain vitamin deficiencies may also cause dementia. The only one that is not extremely rare

KEY TERMS

Pick’s disease— A degenerative brain disorder causing progressive dementia.

Vascular dementia— Loss of mental function due to a number of small, individually unnoticeable, strokes or to some other problem with the blood vessels in or supplying blood to the brain.

in developed countries, however, is Korsakoff’s syndrome. This results from thiamine deficiency produced by intense, prolonged alcohol abuse. Yet another potential cause of dementia is deficiency of thyroid hormone; unlike many other dementias, this is usually reversible once adequate amounts of the hormone are available.

In yet other cases, diseases of the kidney or liver may lead to build-up of toxic materials in the blood; dementia then becomes one symptom that these materials have reached poisonous levels. Chronic hypoglycemia (low blood sugar), often due to disorders of the pancreas, may also impair mental function.

Although both head injuries and brain tumors usually affect only a single sphere of mental activity (and thus, by definition, do not produce dementia) this is not always the case. Prize fighters and boxers in particular are likely to have experienced multiple blows to the head, and as a result often suffer from a generalized dementia. Conditions such as near-drowning, in which the brain is starved of oxygen for several minutes, may also result in dementia.

Almost 3% of dementia cases are due to hydro-cephalus (literally, water on the brain; more precisely, an accumulation within the brain of abnormal amounts of cerebrospinal fluid). This usually results from an injury that makes it difficult for the fluid to reach the areas where it is supposed to be reabsorbed into the bloodstream. In the most common form, and the one most easily overlooked, pressure within the brain remains normal despite the fluid build-up. The extra fluid nevertheless distorts the shape of the brain and impairs its function. Installing shunts that allow the fluid to reach its proper place usually cures the dementia.

Resources

BOOKS

Burns, Alistair, and Bengt Winblad, eds. Severe Dementia. Chichester, UK, and Hoboken, NJ: John Wiley & Sons, 2006.

Burns, Alistair, John O’Brien, and David Ames, eds. Dementia. London, UK: Hodder Arnold, 2005.

Mendez, Mario F., and Jeffrey L. Cummings, eds. Dementia: A Clinical Approach. 3rd ed. Philadelphia, PA: Butterworth-Heinemann, 2003.

Weiner, Myron F., and Anne M. Lipton. The Dementias: Diagnosis, Treatment, and Research. Washington, DC: American Psychiatric Pub., 2003.

W. A. Thomasson

Dementia

Definition

Dementia is not a specific disorder or disease. It is a syndrome (group of symptoms) associated with a progressive loss of memory and other intellectual functions that is serious enough to interfere with performing the tasks of daily life. Dementia can occur to anyone at any age from an injury or from oxygen deprivation, although it is most commonly associated with aging. It is the leading cause of institutionalization of older adults.

Description

The definition of dementia has become more inclusive over the past several decades. Whereas earlier descriptions of dementia emphasized memory loss, the last three editions of the professional's diagnostic handbook, Diagnostic and Statistical Manual of Mental Disorders (also known as the DSM ) define dementia as an overall decline in intellectual function, including difficulties with language, simple calculations, planning and judgment, and motor (muscular movement) skills as well as loss of memory. Although dementia is not caused by aging itself— most researchers regard it as resulting from injuries, infections, brain diseases, tumors, or other disorders— it is quite common in older people. The prevalence of dementia increases rapidly with age; it doubles every five years after age 60. Dementia affects only 1% of people aged 60–64 but 30%–50% of those older than 85. About four to five million persons in the United States are affected by dementia as of 2002. Surveys indicate that dementia is the condition most feared by older adults in the United States.

Causes and symptoms

Causes

Dementia can be caused by nearly forty different diseases and conditions, ranging from dietary deficiencies and metabolic disorders to head injuries and inherited diseases. The possible causes of dementia can be categorized as follows:

• Primary dementia. These dementias are characterized by damage to or wasting away of the brain tissue itself. They include Alzheimer's disease (AD), frontal lobe dementia (FLD), and Pick's disease. FLD is dementia caused by a disorder (usually genetic) that affects the front portion of the brain, and Pick's disease is a rare type of primary dementia that is characterized by a progressive loss of social skills, language, and memory, leading to personality changes and sometimes loss of moral judgment.
• Multi-infarct dementia (MID). Sometimes called vascular dementia , this type is caused by blood clots in the small blood vessels of the brain. When the clots cut off the blood supply to the brain tissue, the brain cells are damaged and may die. (An infarct is an area of dead tissue caused by obstruction of the circulation.)
• Lewy body dementia. Lewy bodies are areas of injury found on damaged nerve cells in certain parts of the brain. They are associated with Alzheimer's and Parkinson's disease, but researchers do not yet know whether dementia with Lewy bodies is a distinct type of dementia or a variation of Alzheimer's or Parkinson's disease.
• Dementia related to alcoholism or exposure to heavy metals (arsenic, antimony, bismuth).
• Dementia related to infectious diseases. These infections may be caused by viruses (HIV, viral encephalitis); spirochetes (Lyme disease, syphilis); or prions (Creutzfeldt-Jakob disease). Spirochetes are certain kinds of bacteria, and prions are protein particles that lack nucleic acid.
• Dementia related to abnormalities in the structure of the brain. These may include a buildup of spinal fluid in the brain (hydrocephalus); tumors; or blood collecting beneath the membrane that covers the brain (subdural hematoma).

Dementia may also be associated with depression, low levels of thyroid hormone, or niacin or vitamin B ₁₂deficiency. Dementia related to these conditions is often reversible.

Genetic factors in dementia

Genetic factors play a role in several types of dementia, but the importance of these factors in the development of the dementia varies considerably. Alzheimer's disease (AD) is known, for example, to have an autosomal (non-sex-related) dominant pattern in most early-onset cases as well as in some late-onset cases, and to show different degrees of penetrance (frequency of expression) in late-life cases. Moreover, researchers have not yet discovered how the genes associated with dementia interact with other risk factors to produce or trigger the dementia. One non-genetic risk factor presently being investigated is toxic substances in the environment.

EARLY-ONSET ALZHEIMER'S DISEASE. In early-onset AD, which accounts for 2%–7% of cases of AD, the symptoms develop before age 60. It is usually caused by an inherited genetic mutation. Early-onset AD is also associated with Down syndrome, in that persons with trisomy 21 (three forms of human chromosome 21 instead of a pair) often develop early-onset AD.

LATE-ONSET ALZHEIMER'S DISEASE. Recent research indicates that late-onset Alzheimer's disease is a polygenic disorder; that is, its development is influenced by more than one gene. It has been known since 1993 that a specific form of a gene (the APOE gene) on human chromosome 19 is a genetic risk factor for late-onset AD. In 1998 researchers at the University of Pittsburgh reported on another gene that controls the production of bleomycin hydrolase (BH) as a second genetic risk factor that acts independently of the APOE gene. In December 2000, three separate research studies reported that a gene on chromosome 10 that may affect the processing of a protein (called amyloid-beta protein) is also involved in the development of late-onset AD. When this protein is not properly broken down, a starchy substance builds up in the brains of people with AD to form the plaques that are characteristic of the disease.

MULTI-INFARCT DEMENTIA (MID). While the chief risk factors for MID are high blood pressure, advanced age, and male sex, there is an inherited form of MID called CADASIL, which stands for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL can cause psychiatric disturbances and severe headaches as well as dementia.

FRONTAL LOBE DEMENTIAS. Researchers think that between 25% and 50% of cases of frontal lobe dementia involve genetic factors. Pick's dementia appears to have a much smaller genetic component than FLD. It is not yet known what other risk factors combine with inherited traits to influence the development of frontal lobe dementias.

FAMILIAL BRITISH DEMENTIA (FBD). FBD is a rare autosomal dominant disorder that was first reported in the 1940s in a large British family extending over nine generations. FBD resembles Alzheimer's in that the patient develops a progressive dementia related to amyloid deposits in the brain. In 1999, a mutated gene that produces the amyloid responsible for FBD was discovered on human chromosome 13. Studies of this mutation may yield further clues to the development of Alzheimer's disease as well as FBD itself.

CREUTZFELDT-JAKOB DISEASE. Although Creutzfeldt-Jakob disease is caused by a prion, researchers think that 5%–15% of cases may have a genetic component.

Symptoms

The fourth edition, text revised version of the DSM was published in 2000, and is known as DSM-IV-TR. DSM-IV-TR identifies certain symptoms as criteria that must be met for a patient to be diagnosed with dementia. One criterion is significant weakening of the patient's memory with regard to learning new information as well as recalling previously learned information. In addition, the patient must be found to have one or more of the following disturbances:

• Aphasia. Aphasia refers to loss of language function. A person with dementia may use vague words like "it" or "thing" often because he or she can't recall the exact name of an object; the affected person may echo what other people say, or repeat a word or phrase over and over. People in the later stages of dementia may stop speaking at all.
• Apraxia. Apraxia refers to loss of the ability to perform intentional movements even though the person is not paralyzed, has not lost the sense of touch, and knows what he or she is trying to do. For example, a patient with apraxia may stop brushing their teeth, or have trouble tying their shoelaces.
• Agnosia. Agnosia refers to loss of the ability to recognize objects even though the person's sight and sense of touch are normal. People with severe agnosia may fail to recognize family members or even their own face reflected in a mirror.
• Problems with abstract thinking and complex behavior. This criterion refers to the loss of the ability to make plans, carry out the steps of a task in the proper order, make appropriate decisions, evaluate situations, show good judgment, etc. For example, a patient might light a stove burner under a saucepan before putting food or water in the pan, or be unable to record checks and balance their checkbook.

DSM-IV-TR also specifies that these disturbances must be severe enough to cause problems in the person's daily life, and that they must represent a decline from a previously higher level of functioning.

In addition to the changes in cognitive functioning, the symptoms of dementia may also include personality changes and emotional instability. Patients with dementia sometimes become mildly paranoid because their loss of short-term memory leads them to think that mislaid items have been stolen. About 25% of patients with dementia develop a significant degree of paranoia , that is, generalized suspiciousness or specific delusions of persecution. Mood swings, anxiety, and irritability or anger are also frequent occurrences, particularly when patients with dementia are in situations that force them to recognize the extent of their impairment.

The following sections describe the signs and symptoms that are used to differentiate among the various types of dementia during a diagnostic evaluation.

ALZHEIMER'S DISEASE. Dementia related to AD often progresses slowly; it may be accompanied by irritability, wide mood swings, and personality changes in the early stage. Many patients, however, retain their normal degree of sociability in the early stages of Alzheimer's. In second-stage AD, the patient typically gets lost easily, is completely disoriented with regard to time and space, and may become angry, uncooperative, or aggressive. Patients in second-stage AD are at high risk for falls and other accidents. In final-stage AD, the patient is completely bedridden, has lost control over bowel and bladder functions, and may be unable to swallow or eat. The risk of seizures increases as the patient progresses from early to end-stage Alzheimer's. Death usually results from an infection or from malnutrition.

MULTI-INFARCT DEMENTIA. In MID, the symptoms are more likely to occur after age 70. In the early stages, the patient retains his or her personality more fully than a patient with AD. Another distinctive feature of this type of dementia is that it often progresses in a stepwise fashion; that is, the patient shows rapid changes in functioning, then remains at a plateau for a while rather than showing a continuous decline. The symptoms of MID may also have a "patchy" quality; that is, some of the patient's mental functions may be severely affected while others are relatively undamaged. Other symptoms of MID include exaggerated reflexes, an abnormal gait (manner of walking), loss of bladder or bowel control, and inappropriate laughing or crying.

DEMENTIA WITH LEWY BODIES. This type of dementia may combine some features of AD, such as severe memory loss and confusion, with certain symptoms associated with Parkinson's disease, including stiff muscles, a shuffling gait, and trembling or shaking of the hands. Visual hallucinations may be one of the first symptoms of dementia with Lewy bodies.

FRONTAL LOBE DEMENTIAS. The frontal lobe dementias are gradual in onset. Pick's dementia is most likely to develop in persons between 40 and 60, while FLD typically begins before the age of 65. The first symptoms of the frontal lobe dementias often include socially inappropriate behavior (rude remarks, sexual acting-out, disregard of personal hygiene, etc.). Patients are also often obsessed with eating and may put non-food items in their mouths as well as making frequent sucking or smacking noises. In the later stages of frontal lobe dementia or Pick's disease, the patient may develop muscle weakness, twitching, and delusions or hallucinations.

CREUTZFELDT-JAKOB DISEASE. The dementia associated with Creutzfeldt-Jakob disease occurs most often in persons between 40 and 60. It is typically preceded by a period of several weeks in which the patient complains of unusual fatigue , anxiety, loss of appetite, or difficulty concentrating. This type of dementia also usually progresses much more rapidly than other dementias, frequently over a span of a few months.

Demographics

The demographic distribution of dementia varies somewhat according to its cause. Moreover, recent research indicates that dementia in many patients has overlapping causes, so that it is not always easy to assess the true rates of occurrence of the different types. For example, AD and MID are found together in about 15%–20% of cases.

Alzheimer's disease

AD is by far the most common cause of dementia in the elderly, accounting for 60%–80% of cases. It is estimated that four million adults in the United States suffer from AD. The disease strikes women more often than men, but researchers don't know yet whether the sex ratio simply reflects the fact that women in developed countries tend to live longer than men, or whether female sex is itself a risk factor for AD. One well-known long-term study of Alzheimer's in women is the Nun Study, begun in 1986 and presently conducted at the University of Kentucky.

Multi-infarct dementia

MID is responsible for between 15% and 20% of cases of dementia (not counting cases in which it coexists with AD). Unlike AD, MID is more common in men than in women. Diabetes, high blood pressure, a history of smoking, and heart disease are all risk factors for MID. Researchers in Sweden have suggested that MID is underdiagnosed, and may coexist with other dementias more frequently than is presently recognized.

Dementia with Lewy bodies

Dementia with Lewy bodies is now thought to be the second most common form of dementia after Alzheimer's disease. But because researchers don't completely understand the relationship between Lewy bodies, AD, and Parkinson's disease, the demographic distribution of this type of dementia is also unclear.

Other dementias

FLD, Pick's disease, Huntington's disease, Parkinson's disease, HIV infection, alcoholism, head trauma, etc. account for about 10% of all cases of dementia. In FLD and Pick's dementia, women appear to be affected slightly more often than men.

Diagnosis

In some cases, a patient's primary physician may be able to diagnose the dementia; in many instances, however, the patient will be referred to a neurologist or a gerontologist (specialist in medical care of the elderly). Distinguishing one disorder from other similar disorders is a process called differential diagnosis . The differential diagnosis of dementia is complicated because of the number of possible causes; because more than one cause may be present at the same time; and because dementia can coexist with such other conditions as depression and delirium . Delirium is a temporary disturbance of consciousness marked by confusion, restlessness, inability to focus one's attention, hallucinations, or delusions. In elderly people, delirium is frequently a side effect of surgery, medications, infectious illnesses, or dehydration. Delirium can be distinguished from dementia by the fact that delirium usually comes on fairly suddenly (in a few hours or days) and may vary in severity— it is often worse at night. Dementia develops much more slowly, over a period of months or years, and the patient's symptoms are relatively stable. It is possible for a person to have delirium and dementia at the same time.

Another significant diagnostic distinction in elderly patients is the distinction between dementia and ageassociated memory impairment (AAMI), which is sometimes called benign senescent forgetfulness. Older people with AAMI have a mild degree of memory loss; they do not learn new information as quickly as younger people, and they may take longer to recall a certain fact or to balance their checkbook. But they do not suffer the degree of memory impairment that characterizes dementia, and they do not get progressively worse.

Clinical interview

The doctor will begin by taking a full history, including the patient's occupation and educational level as well as medical history. The occupational and educational history allows the examiner to make a more accurate assessment of the extent of the patient's memory loss and other evidence of intellectual decline. In some cases, the occupational history may indicate exposure to heavy metals or other toxins. A complete medical history allows the doctor to assess such possibilities as delirium, depression, alcohol-related dementia, dementia related to head injury, or dementia caused by infection. It is particularly important for the doctor to have a list of all the patient's medications, including over-the-counter and alternative herbal preparations, because of the possibility that the patient's symptoms are related to side effects of these substances.

Whenever possible, the examiner will consult the patient's family members or close friends as part of the history-taking process. In many cases, friends and relatives can provide more detailed information about the patient's memory problems and loss of function.

Mental status examination

A mental status examination (MSE) evaluates the patient's ability to communicate, follow instructions, recall information, perform simple tasks involving movement and coordination, as well as his or her emotional state and general sense of space and time. The MSE includes the doctor's informal evaluation of the patient's appearance, vocal tone, facial expressions, posture, and gait as well as formal questions or instructions. A common form that has been used since 1975 is the so-called Folstein Mini-Mental Status Examination, or MMSE. Questions that are relevant to diagnosing dementia include asking the patient to count backward from 100 by 7s, to make change, to name the current President of the United States, to repeat a short phrase after the examiner (such as, "no ifs, ands, or buts"); to draw a clock face or geometric figure, and to follow a set of instructions involving movement (such as, "Show me how to throw a ball" or "Fold this piece of paper and place it under the lamp on the bookshelf.") The examiner may test the patient's abstract reasoning ability by asking him or her to explain a familiar proverb ("People who live in glass houses shouldn't throw stones," for example) or test the patient's judgment by asking about a problem with a common-sense solution, such as what one does when a prescription runs out.

Neurological examination

A neurological examination includes an evaluation of the patient's cranial nerves and reflexes. The cranial nerves govern the ability to speak as well as sight, hearing, taste, and smell. The patient will be asked to stick out the tongue, follow the examiner's finger with the eyes, raise the eyebrows, etc. The patient is also asked to perform certain actions (such as touching the nose with the eyes closed) that test coordination and spatial orientation. The doctor will usually touch or tap certain areas of the body, such as the knee or the sole of the foot, to test the patient's reflexes. Failure to respond to the touch or tap may indicate damage to certain parts of the brain.

Laboratory tests

Blood and urine samples may be collected in order to rule out such conditions as thyroid deficiency, niacin or vitamin B₁₂deficiency, heavy metal poisoning, liver disease, HIV infection, syphilis, anemia, medication reactions, or kidney failure. A lumbar puncture (spinal tap) may be done to rule out neurosyphilis.

Diagnostic imaging

The patient may be given a computed tomography (CT) scan or magnetic resonance imaging (MRI) to detect evidence of strokes, disintegration of the brain tissue in certain areas, blood clots or tumors, a buildup of spinal fluid, or bleeding into the brain tissue. Positron-emission tomography (PET) or single-emission computed tomography (SPECT) imaging is not used routinely to diagnose dementia, but may be used to rule out Alzheimer's disease or frontal lobe degeneration if a patient's CT scan or MRI is unrevealing.

Treatments

Reversible and responsive dementias

Some types of dementia are reversible, and a few types respond to specific treatments related to their causes. Dementia related to dietary deficiencies or metabolic disorders is treated with the appropriate vitamins or thyroid medication. Dementia related to HIV infection often responds well to zidovudine (Retrovir), a drug given to prevent the AIDS virus from replicating. Multi-infarct dementia is usually treated by controlling the patient's blood pressure and/or diabetes; while treatments for these disorders cannot undo damage already caused to brain tissue, they can slow the progress of the dementia. Patients with alcohol-related dementia often improve over the long term if they are able to stop drinking. Dementias related to head injuries, hydrocephalus, and tumors are treated by surgery.

It is important to evaluate and treat elderly patients for depression, because the symptoms of depression in older people often mimic dementia. This condition is sometimes called pseudodementia. In addition, patients who suffer from both depression and dementia often show some improvement in intellectual functioning when the depression is treated. The medications most often used for depression related to dementia are the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline . The mental status examination should be repeated after six–12 weeks of antidepressant medication.

Irreversible dementias

As of 2001, there are no medications or surgical techniques that can cure Alzheimer's disease, the frontal lobe dementias, MID, or dementia with Lewy bodies. There are also no "magic bullets" that can slow or stop the progression of these dementias. There is, however, one medication, Aricept, that is being used to halt the progression of Alzheimer's disease. In addition, another medication called galantamine (Reminyl) is also being used to treat the symptoms of Alzheimer's disease. Patients may be given medications to ease the depression, anxiety, sleep disturbances, and other behavioral symptoms that accompany dementia, but most physicians prescribe relatively mild dosages in order to minimize the troublesome side effects of these drugs. Dementia with Lewy bodies appears to respond better to treatment with the newer antipsychotic medications than to treatment with such older drugs as haloperidol (Haldol).

Patients in the early stages of dementia can often remain at home with some help from family members or other caregivers, especially if the house or apartment can be fitted with safety features (handrails, good lighting, locks for cabinets containing potentially dangerous products, nonslip treads on stairs, etc.). Patients in the later stages of dementia, however, usually require skilled care in a nursing home or hospital.

Prognosis

The prognosis for reversible dementia related to nutritional or thyroid problems is usually good once the cause has been identified and treated. The prognoses for dementias related to alcoholism or HIV infection depend on the patient's age and the severity of the underlying disorder.

The prognosis for the irreversible dementias is gradual deterioration of the patient's functioning ending in death. The length of time varies somewhat. Patients with Alzheimer's disease may live from two–20 years with the disease, with an average of seven years. Patients with frontal lobe dementia or Pick's disease live on average between five and 10 years after diagnosis. The course of Creutzfeldt-Jakob disease is much more rapid, with patients living between five and 12 months after diagnosis.

Prevention

The reversible dementias related to thyroid and nutritional disorders can be prevented in many cases by regular physical checkups and proper attention to diet. Dementias related to toxic substances in the workplace may be prevented by careful monitoring of the work environment and by substituting less hazardous materials or substances in manufacturing processes. Dementias caused by infectious diseases are theoretically preventable by avoiding exposure to the prion, spirochete, or other disease agent. Multi-infarct dementia may be preventable in some patients by attention to diet and monitoring of blood pressure. Dementias caused by abnormalities in the structure of the brain are not preventable as of 2002.

With regard to genetic factors, tests are now available for the APOE gene implicated in late-onset Alzheimer's, but these tests are used primarily in research instead of clinical practice. One reason is that the test results are not conclusive; about 20% of people who eventually develop AD do not carry this gene. Another important reason is the ethical implications of testing for a disease that presently has no cure. These considerations may change, however, if researchers discover better treatments for primary dementia, more effective preventive methods, or more reliable genetic markers.

See also Respite care

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, text revised. Washington, DC: American Psychiatric Association, 2000.

"Dementia." The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, M.D., and Robert Berkow, M.D. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Lyon, Jeff, and Peter Gorner. Altered Fates: Gene Therapy and the Retooling of Human Life. New York and London: W. W. Norton & Co., Inc., 1996.

Marcantonio, Edward, M.D. "Dementia." Chapter 40 in The Merck Manual of Geriatrics, edited by Mark H. Beers, M.D., and Robert Berkow, M.D. Whitehouse Station, NJ: Merck Research Laboratories, 2000.

Morris, Virginia. How to Care for Aging Parents. New York: Workman Publishing, 1996. A good source of information about caring for someone with dementia as well as information about dementia itself.

PERIODICALS

"Alzheimer's Disease: Recent Progress and Prospects." Harvard Mental Health Letter (Parts 1, 2, and 3) 18 (October–December 2001).

ORGANIZATIONS

Alzheimer's Association. 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611. (800) 272-3900.

Alzheimer's Disease International. 45/46 Lower Marsh, London SE1 7RG, United Kingdom. (+44 20) 7620 3011. E-mail: adi@alz.co.uk. <www.alz.co.uk>.

National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. <www.nimh.nih.gov>.

National Institute of Neurological Disorders and Stroke (NINDS). Building 31, Room 8A06, 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-5751. <www.ninds.nih.gov>.

National Institute on Aging Information Center. P.O. Box 8057, Gaithersburg, MD 20898. (800) 222-2225 or (301) 496-1752.

National Organization for Rare Disorders (NORD). P. O. Box 8923, New Fairfield, CT 06812. (800) 447-6673 or (203) 746-6518.

OTHER

Alzheimer's Disease Education and Referral (ADEAR). <www.alzheimers.org>.

The Nun Study. <www.coa.uky.edu/nunnet>.

Rebecca J. Frey, Ph.D.

Dementia

Definition

Dementia is not a specific disorder or disease. It is a syndrome (group of symptoms) associated with a progressive loss of memory and other intellectual functions that is serious enough to interfere with the tasks of daily life. Dementia can occur to anyone at any age from an injury or oxygen deprivation, although it is most commonly associated with aging.

Description

The definition of dementia has become more inclusive over the past several decades. Whereas earlier descriptions of dementia emphasized memory loss, the last two editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R in 1987 and DSMIV in 1994) define dementia as an overall decline in intellectual function, including difficulties with language, simple calculations, planning and judgment, and motor (muscular movement) skills as well as loss of memory. Although dementia is not caused by aging itself—most researchers regard it as resulting from injuries, infections, brain diseases, tumors, or other disorders—it is quite common in older people. Common estimates are that over 15% of people in North America over the age of 65 suffer from dementia, and 40% of people over 80. Surveys indicate that dementia is the condition most feared by older adults in the United States.

Dementia can be caused by nearly forty different diseases and conditions, ranging from dietary deficiencies and metabolic disorders to head injuries and inherited diseases. The possible causes of dementia can be categorized as follows:

• Primary dementia. These dementias are characterized by damage to or wasting away of the brain tissue itself. They include Alzheimer disease (AD), Pick disease, and frontal lobe dementia (FLD).
• Multi-infarct dementia (MID). Sometimes called vascular dementia, this type is caused by blood clots in the small blood vessels of the brain. When the clots cut off the blood supply to the brain tissue, the brain cells are damaged and may die.
• Lewy body dementia. Lewy bodies are areas of injury found on damaged nerve cells in certain parts of the brain. They are associated with Alzheimer and Parkinson disease , but researchers do not yet know whether dementia with Lewy bodies is a distinct type of dementia or a variation of Alzheimer or Parkinson disease.
• Dementia related to alcoholism or exposure to heavy metals (arsenic, antimony, bismuth).
• Dementia related to infectious diseases. These infections may be caused by viruses (HIV, viral encephalitis); spirochetes (Lyme disease, syphilis); or prions (Creutzfeldt-Jakob disease).
• Dementia related to abnormalities in the structure of the brain. These may include a buildup of spinal fluid in the brain (hydrocephalus ); tumors; or blood collecting beneath the membrane that covers the brain (subdural hematoma).

Dementia may also be associated with depression , low levels of thyroid hormone, or niacin or vitamin (B12) deficiency. Dementia related to these conditions is often reversible.

Genetic profile

Genetic factors play a role in several types of dementia, but the importance of these factors in the development of the dementia varies considerably. Alzheimer disease (AD) is known, for example, to have an autosomal (non-sex-related) dominant pattern in most early-onset cases as well as in some late-onset cases, and to show different degrees of penetrance (frequency of expression) in late-life cases. Moreover, researchers have not yet discovered how the genes associated with dementia interact with other risk factors to produce or trigger the dementia. One non-genetic risk factor presently being investigated is toxic substances in the environment.

Early-onset Alzheimer disease

In early-onset AD, which accounts for 2-7% of cases of AD, the symptoms develop before age 60. It is usually caused by an inherited genetic mutation. Early-onset AD is also associated with Down syndrome , in that persons with trisomy 21 (three forms of human chromosome 21 instead of a pair) often develop early-onset AD.

Late-onset Alzheimer disease

Recent research indicates that late-onset Alzheimer disease is a polygenic disorder; that is, its development is influenced by more than one gene . It has been known since 1993 that a specific form of a gene for apolipoprotein E (APOE) on human chromosome 19 is a genetic risk factor for late-onset AD. In 1998 researchers at the University of Pittsburgh reported on another gene that controls the production of bleomycin hydrolase (BH) as a second genetic risk factor that acts independently of the APOE gene. In December 2000, three separate research studies reported that a gene on chromosome 10 that may affect the processing of amyloid-beta protein is also involved in the development of late-onset AD.

Multi-infarct dementia (MID)

While the chief risk factors for MID are high blood pressure, advanced age, and male sex, there is an inherited form of MID called CADASIL , which stands for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL can cause psychiatric disturbances and severe headaches as well as dementia.

Frontal lobe dementias

Researchers think that between 25% and 50% of cases of frontal lobe dementia involve genetic factors. Pick's dementia appears to have a much smaller genetic component than FLD. It is not yet known what other risk factors combine with inherited traits to influence the development of frontal lobe dementias.

Familial British dementia (FBD)

FBD is a rare autosomal dominant disorder that was first reported in the 1940s in a large British family extending over nine generations. FBD resembles Alzheimer in that the patient develops a progressive dementia related to amyloid deposits in the brain. In 1999 a mutated gene that produces the amyloid responsible for FBD was discovered on human chromosome 13. Studies of this mutation may yield further clues to the development of Alzheimer disease as well as FBD itself.

Creutzfeldt-Jakob disease

Although Creutzfeldt-Jakob disease is caused by a prion, researchers think that 5-15% of cases may have a genetic component.

Demographics

The demographic distribution of dementia varies somewhat according to its cause. Moreover, recent research indicates that dementia in many patients has overlapping causes, so that it is not always easy to assess the true rates of occurrence of the different types. For example, AD and MID are found together in about 15-20% of cases.

Alzheimer disease

AD is by far the most common cause of dementia in the elderly, accounting for 60-80% of cases. It is estimated that 4 million adults in the United States suffer from AD. The disease strikes women more often than men, but researchers do not know yet whether the sex ratio simply reflects the fact that women tend to live longer than men, or whether female sex is itself a risk factor for AD. One well-known long-term study of Alzheimer in women is the Nun Study, begun in 1986 and presently conducted at the University of Kentucky.

Multi-infarct dementia

MID is responsible for between 15% and 20% of cases of dementia (not counting cases in which it coexists with AD). Unlike AD, MID is more common in men than in women. Diabetes , high blood pressure, a history of smoking, and heart disease are all risk factors for MID. Researchers in Sweden have suggested that MID is underdiagnosed, and may coexist with other dementias more frequently than is presently recognized.

Dementia with Lewy bodies

Dementia with Lewy bodies is now thought to be the second most common form of dementia after Alzheimer disease. But because researchers do not completely understand the relationship between Lewy bodies, AD, and Parkinson disease, the demographic distribution of this type of dementia is also unclear.

Other dementias

FLD, Pick disease, Huntington disease , Parkinson's disease, HIV infection, alcoholism, head trauma, etc. account for about 10% of all cases of dementia. In FLD and Pick dementia, women appear to be affected slightly more often than men.

Signs and symptoms

DSM-IV specifies that certain criteria must be met for a patient to be diagnosed with dementia. One criterion is significant weakening of the patient's memory with regard to learning new information as well as recalling previously learned information. In addition, the patient must be found to have one or more of the following disturbances:

• Aphasia. Aphasia refers to loss of language function. A person with dementia may use vague words like "it" or "thing" a lot because they cannot recall the exact name of an object; they may echo what other people say, or repeat a word or phrase over and over. People in the later stages of dementia may stop speaking at all.
• Apraxia. Apraxia refers to loss of the ability to perform intentional movements even though the person is not paralyzed, has not lost their sense of touch, and knows what they are trying to do. For example, a patient with apraxia may stop brushing their teeth, or have trouble tying their shoelaces.
• Agnosia. Agnosia refers to loss of the ability to recognize objects even though the person's sight and sense of touch are normal. People with severe agnosia may fail to recognize family members or their own face reflected in a mirror.
• Problems with abstract thinking and complex behavior. This criterion refers to the loss of the ability to make plans, carry out the steps of a task in the proper order, make appropriate decisions, evaluate situations, show good judgment, etc. For example, a patient might light a stove burner under a saucepan before putting food or water in the pan, or be unable to record checks and balance his or her checkbook.

DSM-IV also specifies that these disturbances must be severe enough to cause problems in the person's daily life, and that they must represent a decline from a previously higher level of functioning.

The following sections will focus on the signs and symptoms that are used to differentiate among the various types of dementia during a diagnostic evaluation.

Alzheimer disease

Dementia related to AD often progresses slowly; it may be accompanied by irritability, wide mood swings, and personality changes in the early stage. In second-stage AD, the patient typically gets lost easily, is completely disoriented with regard to time and space, and may become angry, uncooperative, or aggressive. In final-stage AD, the patient is completely bedridden, has lost control over bowel and bladder functions, and may be unable to swallow or eat. The risk of seizures increases as the patient progresses from early to end-stage Alzheimer disease. Death usually results from an infection or malnutrition.

Multi-infarct dementia

In MID, the symptoms are more likely to occur after age 70. In the early stages, the patient retains his or her personality more fully than a patient with AD. Another distinctive feature of this type of dementia is that it often progresses in a stepwise fashion; that is, the patient shows rapid changes in functioning, then remains at a plateau for awhile rather than showing a continuous decline. The symptoms of MID may also have a "patchy" quality; that is, some of the patient's mental functions may be severely affected while others are relatively undamaged. Other symptoms of MID include exaggerated reflexes, an abnormal gait (manner of walking), loss of bladder or bowel control, and inappropriate laughing or crying.

Dementia with Lewy bodies

This type of dementia may combine some features of AD, such as severe memory loss and confusion, with certain symptoms associated with Parkinson disease, including stiff muscles, a shuffling gait, and trembling or shaking of the hands. Visual hallucinations may be one of the first symptoms of dementia with Lewy bodies.

Frontal lobe dementias

The frontal lobe dementias are gradual in onset. Pick's dementia is most likely to develop in persons between 40 and 60, while FLD typically begins before the age of 65. The first symptoms of the frontal lobe dementias often include socially inappropriate behavior (rude remarks, sexual acting-out, lack of personal hygiene, etc.). Patients are also often obsessed with eating and may put non-food items in their mouths as well as making frequent sucking or smacking noises. In the later stages of frontal lobe dementia or Pick's disease, the patient may develop muscle weakness, twitching, and delusions or hallucinations.

Creutzfeldt-Jakob disease

The dementia associated with Creutzfeldt-Jakob disease occurs most often in persons between 40 and 60. It is typically preceded by a period of several weeks in which the patient complains of unusual tiredness, anxiety, loss of appetite, or difficulty concentrating. This type of dementia also usually progresses much more rapidly than other dementias, usually over a span of a few months.

Diagnosis

In some cases, a patient's primary physician may be able to diagnose the dementia; in many instances, however, the patient will be referred to a neurologist or a specialist in geriatric medicine. The differential diagnosis of dementia is complicated because of the number of possible causes; because more than one cause may be present; and because dementia can coexist with other conditions such as depression and delirium. Delirium is a temporary disturbance of consciousness marked by confusion, restlessness, inability to focus one's attention, hallucinations, or delusions. In elderly people, delirium is frequently a side effect of surgery, medications, infectious illnesses, or dehydration. Delirium can be distinguished from dementia by the fact that delirium usually comes on fairly suddenly (in a few hours or days) and may vary in severity—it is often worse at night. Dementia develops much more slowly, over a period of months or years, and the patient's symptoms are relatively stable. It is possible for a person to have delirium and dementia at the same time. Another significant diagnostic distinction in elderly patients is the distinction between dementia and age-associated memory impairment (AAMI). Older people with AAMI have a mild degree of memory loss; they do not learn new information as quickly as younger people, and they may take longer to recall a certain fact or to balance their checkbook. But they do not suffer the degree of memory impairment that characterizes dementia, and they do not get progressively worse.

Patient history

The doctor will begin by taking a full history, including the patient's occupation and educational level as well as medical history. The occupational and educational history allows the examiner to make a more accurate assessment of the extent of the patient's memory loss and other evidence of intellectual decline. In some cases the occupational history may indicate exposure to heavy metals or other toxins. A complete medical history allows the doctor to assess possibilities such as delirium, depression, alcohol-related dementia, dementia related to head injury, or dementia caused by infection. It is particularly important for the doctor to have a list of all the patient's medications, including over-the-counter preparations, because of the possibility that the patient's symptoms are related to side effects.

Mental status examination

A mental status examination (MSE) evaluates the patient's ability to communicate, follow instructions, recall information, perform simple tasks involving movement and coordination, as well as his or her emotional state and general sense of space and time. The MSE includes the doctor's informal evaluation of the patient's appearance, vocal tone, facial expressions, posture, and gait as well as formal questions or instructions. A common form that has been used since 1975 is the socalled Folstein Mini-Mental Status Examination, or MMSE. Questions that are relevant to diagnosing dementia include asking the patient to count backward from 100 by 7s, to make change, to name the current President, to repeat a short phrase after the examiner (e.g., "no ifs, ands, or buts") to draw a clock face or geometric figure, and to follow a set of instructions involving movement (e.g., "Show me how to throw a ball" or "Fold this piece of paper and place it under the lamp on the bookshelf"). The examiner may test the patient's abstract reasoning ability by asking him or her to explain a familiar proverb (e.g., "People who live in glass houses shouldn't throw stones") or test the patient's judgment by asking about a problem with a common-sense solution, such as what one does when a prescription runs out.

Neurological examination

A neurological examination includes an evaluation of the patient's cranial nerves and reflexes. The cranial nerves govern the ability to speak as well as sight, hearing, taste, and smell. The patient will be asked to stick out the tongue, follow the examiner's finger with the eyes, raise the eyebrows, etc. The patient is also asked to perform certain actions (e.g., touching the nose with the eyes closed) that test coordination and spatial orientation. The doctor will usually touch or tap certain areas of the body, such as the knee or the sole of the foot, to test the patient's reflexes. Failure to respond to the touch or tap may indicate damage to certain parts of the brain.

Laboratory tests

Blood and urine samples are collected in order to rule out such conditions as thyroid deficiency, niacin (vitamin B12) deficiency, heavy metal poisoning, liver disease, HIV infection, syphilis, anemia, medication reactions, or kidney failure. A lumbar puncture (spinal tap) may be done to rule out neurosyphilis.

Diagnostic imaging

The patient may be given a CT (computed tomography) scan or MRI (magnetic resonance imaging) to detect evidence of strokes, disintegration of the brain tissue in certain areas, blood clots or tumors, a buildup of spinal fluid, or bleeding into the brain tissue. PET (positron-emission tomography) or SPECT (single-emission computed tomography) imaging is not used routinely to diagnose dementia, but may be used to rule out Alzheimer disease or frontal lobe degeneration if a patient's CT scan or MRI is unrevealing.

Treatment and management

Reversible and responsive dementias

Some types of dementia are reversible, and a few types respond to specific treatments related to their

causes. Dementia related to dietary deficiencies or metabolic disorders is treated with the appropriate vitamins or thyroid medication. Dementia related to HIV infection often responds well to zidovudine (Retrovir), a drug given to prevent the AIDS virus from replicating. Multi-infarct dementia is usually treated by controlling the patient's blood pressure and/or diabetes; while treatments for these disorders cannot undo damage already caused to brain tissue, they can slow the progress of the dementia. Patients with alcohol-related dementia often improve over the long term if they are able to stop drinking. Dementias related to head injuries, hydrocephalus, and tumors are treated by surgery.

It is important to evaluate and treat elderly patients for depression, because the symptoms of depression in older people often mimic dementia. This condition is sometimes called pseudodementia. In addition, patients who suffer from both depression and dementia often show some improvement in intellectual functioning when the depression is treated.

Irreversible dementias

There are no medications or surgical techniques that can cure Alzheimer disease, the frontal lobe dementias, MID, or dementia with Lewy bodies. There are also no "magic bullets" that can slow or stop the progression of these dementias. Patients may be given medications to ease the depression, anxiety, sleep disturbances, and similar symptoms that accompany dementia, but most physicians prescribe relatively mild dosages in order to minimize the troublesome side effects of these drugs. Dementia with Lewy bodies appears to respond better to treatment with the newer antipsychotic medications than to treatment with such older drugs as haloperidol (Haldol).

Patients in the early stages of dementia can often remain at home with some help from family members or other caregivers, especially if the house or apartment can be fitted with safety features (handrails, good lighting, locks for cabinets containing potentially dangerous products, nonslip treads on stairs, etc.). Patients in the later stages of dementia, however, usually require skilled care in a nursing home or hospital.

Prognosis

The prognosis for reversible dementia related to nutritional or thyroid problems is usually good once the cause has been identified and treated. The prognoses for dementias related to alcoholism or HIV infection depend on the patient's age and the severity of the underlying disorder.

The prognosis for the irreversible dementias is gradual deterioration of the patient's functioning ending in death. The length of time varies somewhat. Patients with Alzheimer disease may live from two to 20 years with the disease, with an average of seven years. Patients with frontal lobe dementia or Pick's disease live on average between five and 10 years after diagnosis. The course of Creutzfeldt-Jakob disease is much more rapid, with patients living between five and 12 months after diagnosis.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Washington, DC: American Psychiatric Association, 1994.

"Delirium and Dementia." Section 5 in The Merck Manual of Geriatrics. Whitehouse Station, NJ: Merck Research Laboratories, 1995.

"Dementia." The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Lyon, Jeff, and Peter Gorner. Altered Fates: Gene Therapy and the Retooling of Human Life. New York and London: W. W. Norton & Co., Inc., 1996.

Morris, Virginia. How to Care for Aging Parents. New York: Workman Publishing, 1996. A good source of information about caring for someone with dementia as well as information about dementia itself.

ORGANIZATIONS

Alzheimer's Association. 919 North Michigan Ave., Suite 1000, Chicago, IL 60611-1676. (800) 272-3900.

Alzheimer's Disease International. 45/46 Lower Marsh, London, SE1 7RG. UK (+44 20) 7620 3011. adi@alz.co.uk. <http://www.alz.co.uk.>.

National Institute of Mental Health. 6001 Executive Blvd., Rm. 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. Fax: (301) 443-4279. <http://www.nimh.nih.gov/publicat/index.cfm>.

National Institute of Neurological Disorders and Stroke. 31 Center Drive, MSC 2540, Bldg. 31, Room 8806, Bethesda, MD 20814. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov>.

National Institute on Aging Information Center. PO Box 8057, Gaithersburg, MD 20898. (800) 222-2225 or (301) 496-1752.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.

WEBSITES

Alzheimer's Disease Education and Referral (ADEAR): <http://www.alzheimers.org>.

National Institute of Mental Health (NIMH): <http://www.nimh.nih.gov>.

National Institute of Neurological Disorders and Stroke (NINDS): <http://www.ninds.nih.gov>.

National Institute on Aging (NIA): <http://www.nih.gov/nia>.

The Nun Study: <http://www.coa.uky.edu/nunnet>.

Rebecca J. Frey, PhD