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Editorial   |    
Dementia in the Twenty-First Century
SUSAN K. SCHULTZ, M.D.
Am J Psychiatry 2000;157:666-668. doi:10.1176/appi.ajp.157.5.666

It has always been the burden of psychiatrists to broach topics that patients and families may be reticent in discussing, such as suicidal or delusional ideation. With the aging of our society, however, the psychiatrist must increasingly inquire about another type of "taboo" symptom: memory impairment. Dementia syndromes are moving to the forefront of public health concern, yet their recognition and treatment are often unfortunately delayed until well into the course. While many psychiatrists are very familiar with other stigmatized illnesses, the diagnosis of dementia is particularly difficult to talk about directly, perhaps because of its foreboding implications. Loss of autonomy, loss of dignity, loss of the self are all wrapped into the diagnosis, engendering a sense of despair that is only compounded by the absence of effective treatment. It is not surprising then that families seem to suppress the awareness of a loved one’s impairment. So frequently they offer rationales for functional losses, make excuses, and fill in the gaps in communication because they "know what Mom meant to say." And so on it goes until the impairment becomes so great that the diagnosis is finally made in the context of an episode of delirium, agitation, or psychosis. At this point, if a psychiatrist becomes involved at all, the clinical management of the dementia syndrome largely consists of "damage control" efforts, as the waves of psychiatric symptoms begin and the family grieves a loss that has long been hiding among them. There are many reasons for psychiatry as a profession to become more proactive in this process. We can do better for our patients, and our patients are aging.

Worldwide, nearly 70 million people were age 80 or older in 1998. This number is expected to reach 370 million persons by 2050, an almost sixfold increase (1). When one considers that the incidence of dementia approaches 50% among the oldest-old, the importance of cognitive screening becomes increasingly clear. The aging of our society is not limited to the oldest-old but rather represents a population-wide shift associated with lower birthrates. As a reflection of this shift, the median age of the North American population has increased from 29.8 years in 1950 to 42.1 years in 1998 (1). With the leading edge of the U.S. "baby boomers" reaching late life in the next decade, this "median shift" will continue to move upward in an unprecedented manner. While aging is the greatest risk factor for dementia, other contributing factors include the presence of head trauma, substance abuse, HIV or other CNS infection, vascular disease, chronic hypoxemia, hepatic and renal insufficiency, and other chronic illnesses. These conditions are managed by present-day medical technology with such growing proficiency that individuals with multiple vulnerabilities for dementia are surviving into late-life at a rate greater than any other period in history.

The clinical management of dementia syndromes has long hovered between the auspices of neurology, internal and family medicine, and psychiatry. Perhaps as a result of this "homelessness," or perhaps because of its insidious nature, dementia is among the most underrecognized of psychiatric syndromes. Most psychiatrists, with an ample workload emanating from the general adult and child disorders, do not necessarily incorporate a cognitive screen in daily practice. Furthermore, the geriatric patient is likely to shun mental health services entirely and seek care from providers in family practice or internal medicine. Yet clinicians in the primary care setting are even less inclined to incorporate cognitive screening in routine clinical assessments (2). For example, Callahan et al. (3) reported that among primary care outpatients age 60 years old or older who made a routine visit, 15.7% had at least mild cognitive impairment that was not recognized; among moderately to severely impaired patients, only 25% had dementia recorded as a chart diagnosis. This may be due to the time constraints of general practice, but may also be due to a lack of training in this area. However, even the very brief assessment tools (e.g., the Mini-Mental State examination) have been shown to have high sensitivity for the detection of cognitive impairment (4). While these tools admittedly lack specificity, detection of the presence of any type of impairment is essential to optimize patient care and safety. The general practitioner need not worry about discerning the nuances of dementia variants but rather should focus on incorporating a very brief instrument into standard follow-up visits for elderly patients. Unfortunately, the incentive for such practice is minimal, given the paucity of effective interventions for cognitive impairment at present. However, the development of successful preventive strategies depends on research that involves individuals in early stages of illness. Until we learn to recognize and treat the earliest signs, we resign ourselves to be damage-control interventionists.

Geriatric interventions are highlighted in five papers presented in this issue. In one of these, Lyketsos et al. report on the topic of dementia diagnoses in elderly hospitalized patients. Computer-generated ICD-9-CM chart diagnoses were retrospectively examined from 21,251 elderly patients discharged from the medical-surgical unit of Johns Hopkins Hospital over a 2-year period. Differences in care-burden that were associated with dementia were examined through comparisons of length of stay, inpatient costs, and mortality between the 823 subjects diagnosed with dementia and the 20,428 without a dementia diagnosis. Notably, the patients with dementia had longer stays, higher costs, and a greater frequency of medication-induced psychosis and delirium. These differences were impressive, and the fact that statistically significant findings were discerned despite the likelihood that many cases of dementia were unrecognized reflects the substantial impact of dementia on clinical services. The authors did note that their observed frequency of chart diagnoses may have underestimated the actual dementia cases, e.g., they reported a frequency of only 8.9% in the inpatients who were 85 years old or older. This highlights the importance of routine cognitive screening of elderly patients in the medical-surgical environment.

A related study also reported in this issue targets perhaps the most challenging aspect of dementia care, i.e., the management of neuropsychiatric symptoms such as delusions, hallucinations, depressive symptoms, and aggression. In this study, the elderly population of a county in Utah was screened for cognitive impairment, with more detailed assessments obtained from a subgroup with dementia as well as from a stratified probability sample of the population. Psychiatric symptoms were found to be present in the majority (61%) of subjects with dementia. Of these, apathy, depression, and aggression were seen most commonly. The authors make the excellent point that there is a critical need for research that explores more complex interventions that incorporate both medication and other strategies. Undeniably, research that addresses these interventions is extremely important, since psychiatric sequelae affect a multitude of individuals with dementia and incur a tremendous burden to caregivers.

Yet it is clear that the ideal intervention is prevention. Amelioration of symptoms once the illness has wreaked its havoc is far too little, far too late. The most challenging aspect of dementia research is that by the time symptoms are recognized, the disease pathology has likely been present for decades, beginning in mid-life or earlier. It is possible that successful interventions may rely on interceding in pathologic processes that are unique to specific phases of the illness. For example, it has been reported that neuritic plaques are among the earliest lesions observable in Alzheimer’s disease, while other neuropathologic markers become more evident later in the course (5). Detection and intervention at the earliest vantage point is perhaps the ultimate goal for dementia management, affording the greatest hope for future generations.

Neuroimaging studies have suggested that patients with mild cognitive impairment display a number of structural and functional imaging abnormalities (6, 7). The continued use of neuroimaging techniques in research may improve detection early in the course of dementia. These techniques, in conjunction with detailed neuropsychological assessments in the pre-syndromal period, will be instrumental in the development of preventive interventions. Further work in other areas such as CSF markers of neurodegeneration will also help researchers to distinguish and map early pathologic changes. Early detection appears all the more crucial when one considers the recent work that has demonstrated that inhibition of transmembrane aspartic proteases and presenilin proteins may directly intercede in the cleavage of amyloid precursor protein, i.e., prevent beta-amyloid formation (810).

As the baby boomers continue to move toward late-life, their future awaits the combined efforts of researchers in psychiatry, psychology, neuroimaging, and neuropathology to discern the progenitors of cognitive decline and apply this knowledge to the development of preventive interventions. This will take the field of dementia research to a place where new agents such as the aforementioned secretase inhibitors, perhaps with a combination of anti-inflammatory, antioxidant, hormonal, or neurotrophic agents, will obviate the disease entirely. A tall order for researchers of the new millennium.

Address reprint requests to Dr. Schultz, University of Iowa Department of Psychiatry, Psychiatry Research, 1-189A Medical Education Building, Iowa City, IA 52242.

"Ageing" and "The Oldest Old." Geneva, United Nations, Population Division, Department of Economic and Social Affairs, 1998
 
Knopman DS: The initial recognition and diagnosis of dementia. Am J Med  1998; 104:2S–12S; discussion 39S–42S
 
Callahan CM, Hendrie HC, Tierney WM: Documentation and evaluation of cognitive impairment in elderly primary care patients. Ann Intern Med  1996; 124:273–274
 
Nadler JD, Relkin NR, Cohen MS, Hodder RA, Reingold J, Plum F: Mental status testing in the elderly nursing home population. J Geriatr Psychiatry Neurol  1995; 8:177–183
 
Haroutunian V, Perl DP, Purohit DP, Marin D, Khan K, Lantz M, Davis KL, Mohs RC: Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 1998; 55:1185–  1191
 
Bottino CM, Almeida OP: Can neuroimaging techniques identify individuals at risk of developing Alzheimer’s disease? Int Psychogeriatr  1997; 9:389–403
 
Small GW: Differential diagnosis and early detection of dementia. Am J Geriatr Psychiatry 1998; 6(suppl 1):S26–S33
 
Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME: Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity. Nature  1999; 402:533–537
 
Haass C, De Strooper B: The presenilins in Alzheimer’s disease—proteolysis holds the key. Science  1999; 286:916–919
 
Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M: Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science  1999; 286:735–741
 
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References

"Ageing" and "The Oldest Old." Geneva, United Nations, Population Division, Department of Economic and Social Affairs, 1998
 
Knopman DS: The initial recognition and diagnosis of dementia. Am J Med  1998; 104:2S–12S; discussion 39S–42S
 
Callahan CM, Hendrie HC, Tierney WM: Documentation and evaluation of cognitive impairment in elderly primary care patients. Ann Intern Med  1996; 124:273–274
 
Nadler JD, Relkin NR, Cohen MS, Hodder RA, Reingold J, Plum F: Mental status testing in the elderly nursing home population. J Geriatr Psychiatry Neurol  1995; 8:177–183
 
Haroutunian V, Perl DP, Purohit DP, Marin D, Khan K, Lantz M, Davis KL, Mohs RC: Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 1998; 55:1185–  1191
 
Bottino CM, Almeida OP: Can neuroimaging techniques identify individuals at risk of developing Alzheimer’s disease? Int Psychogeriatr  1997; 9:389–403
 
Small GW: Differential diagnosis and early detection of dementia. Am J Geriatr Psychiatry 1998; 6(suppl 1):S26–S33
 
Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME: Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity. Nature  1999; 402:533–537
 
Haass C, De Strooper B: The presenilins in Alzheimer’s disease—proteolysis holds the key. Science  1999; 286:916–919
 
Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M: Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science  1999; 286:735–741
 
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