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The Dementias: Neuropsychiatric Syndromes of the 21st Century

The Dementias: Neuropsychiatric Syndromes of the 21st Century

Psychiatric Times - Category 1 Credit

To earn AMA PRA Category 1 Credit(s)™:
Read the article "The Dementias: Neuropsychiatric Syndromes of the 21st Century" from the October 2008 issue of Psychiatric Times, complete the posttest and the evaluation. (Note: A score of at least 70% must be achieved in order to be awarded credit.)

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Sponsored by CME LLC for 1.5 Category 1 credits.
Original release date 10/08. Approved for CME credit through April 2009.

Educational Objectives

After reading this article, you will be familiar with:

• The classifications of cognitive loss syndromes.
• The clinical features of these syndromes.
• The neurobiology of these disorders.
• Current treatment approaches.

Who will benefit from reading this article?
Psychiatrists, neurologists, primary care physicians, geriatricians, nurse practitioners, and other health care professionals. Continuing medical education credit is available for most specialists. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing board.

In the new century, the dementias will probably become 1 of the 2 or 3 dominant behavioral health problems in the United States. This article provides an overview of the major clinical features of these cognitive loss syndromes and emphasizes the perspective of the practicing psychiatrist. In addition, some of what is known about the neurobiology of these disorders is summarized and a brief review of current treatment approaches is provided.

The challenge for psychiatry

The sheer numbers of persons with cognitive loss disorders, as well as their attendant behavioral implications, will require the attention of practicing psychiatrists:

• Alzheimer disease (AD), 6 million.
• Alzheimer spectrum, milder syndromes, 6 million.
• Lewy body syndromes, 1 million.
• Vascular syndromes, 1 million.
• Frontotemporal dementias, 0.5 million.

Indeed, current prevalence estimates of this burgeoning epidemic are thought to be on the low end. The number of people affected by these syndromes is expected to rise steadily as diagnostic processes improve and the population ages.

All of the syndromes share certain features. They are all age-related. Rarely do any of them present before age 50. They present clinically with the insidious onset of behavioral change, although some of them demonstrate secondary findings in neuromotor and movement domains. Their clinical features are dominated by cognitive loss, but all of them have signature changes in other behavioral domains as well. They progress relentlessly. None of them have laboratory or imaging diagnostic tests that can replace the judgment of a skilled behavioral clinician. In addition, all of them, or at least most of them, have treatments that may confer modest but significant benefit to those with the disorders and their families.

Classification of the cognitive loss syndromes

Cognitive loss disorders can be classified along 2 axes, according to severity and neuropathology (Table 1). Classification of these cognitive loss disorders by severity is based on expert clinical-medical opinion that follows current diagnostic criteria. The judgment of an experienced clinician that a cognitive loss syndrome is present and that it has (or has not) generated psychosocial or vocational impairment is the gold standard. Neuropsychological testing, imaging, and ancillary medical testing confirm the diagnosis.

Dementia is a generic term for cognitive loss syndromes of such severity that they produce psychosocial or vocational functional impairment.1,2 Any of the neuropathologies listed in Table 1 can produce dementia, once the disease has advanced sufficiently.

Mild cognitive impairment (MCI) is an evolving concept. It signifies a cognitive loss syndrome that is milder than dementia and does not (yet) cause functional impairment.3 MCI may affect 1 or more cognitive domains. When 1 of the domains affected is memory, the syndrome is called MCI amnestic type. When nonmemory domains are affected, it is called MCI nonamnestic type. The determination that a cognitive domain is affected is based on a comparison of the patient’s neuropsychological test performance against age- and education-adjusted norms.

A diagnosis of MCI is grounded more strongly in neuropsychological test performance than is the dementia syndrome, where diagnosis remains more strongly in the realm of medical judgment. These issues can create problems in the clinical application of the MCI diagnosis because no single neuropsychological test invokes or determines a cognitive domain. In addition, the age- and education-adjusted norms for neuropsychological testing in older adults may have been skewed by the inclusion of MCI-like syndromes among the populations studied.

Age-associated cognitive impairment and related terms refer to cognitive loss syndromes that are milder than MCI. In age-associated cognitive impairment, the patient complains of cognitive loss, usually in 1 of the memory domains, but neuropsychological testing fails to show impairment compared with adjusted performance norms. The boundary between patients with age-associated cognitive impairment and “normal” controls is still unclear.

Normality is a more problematic clinical concept with regard to cognitive function than one might think. Sometimes, in cognitive research protocols where we seek “normals,” we are in an analogous situation to the ancient Archimedes, who spent his life searching for an honest man and was never quite sure that he had found one.

The core problem with defining normal cognition is that we presently accept a pattern of steady and robust cognitive deterioration across the life span as normal aging. This may be a form of cognitive prejudice. Neuropsychological test performance is adjusted against population norms that may have included many persons with MCI and age-associated cognitive impairment–type syndromes. We presently diagnose normal cognition when a reliable informant states that the patient has not shown evidence of cognitive loss—a somewhat vague and unsatisfying concept of normality.

It could be said that in our evolving understanding of neuropathologies of the dementias, these disorders remain poised part way between neurology and psychiatry. In neurology, we expect objective neuropathological confirmation of clinical syndromes. In psychiatry, we find subtle neuropathological changes in the major psychosyndromes, but we do not fully understand them. The neuropathological features of the degenerative disorders, especially AD, are weakly correlated with clinical symptoms according to severity, and the great majority of persons older than 65 have some of these neuropathological features.

Some persons have dementia without any characteristic neuropathological findings. There is a great deal of overlap across the pathological boundaries of the disorders. Almost all patients with AD also have vascular pathology. Furthermore, almost all patients with dementia with Lewy bodies have AD changes in their brain as well. Some of the key terms, such as neurodegenerative, come from an earlier era, and are likely to be replaced by more specific molecular-genetic language soon.


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