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Alzheimer Disease: Clinical and Biological Heterogeneity
- Robert P. Friedland, MD;
- Elisabeth Koss, PhD;
- James V. Haxby, PhD;
- Cheryl L. Grady, PhD;
- Jay Luxenberg, MD;
- Mark B. Schapiro, MD; and
- Jeffrey Kaye, MD
Abstract
The clinical and biological features of Alzheimer disease are not uniform in their expression; heterogeneity is evident in the disease's clinical, anatomic, and physiologic characteristics. The presence of considerable intersubject and intrasubject heterogeneity suggests that subtypes of the disease exist. We define subtypes of Alzheimer disease in regard to the behavioral features (for example, predominant right or left hemisphere, or symmetrical impairment), inheritance (familial or sporadic), dosage of chromosome 21 (presence of the Down syndrome), time course of progression, age of onset (presenile or senile), and presence or absence of motor deficit (myoclonus or signs of an extrapyramidal syndrome). Studies of regional cerebral glucose metabolism with positron emission tomography and [18-fluorine] fluorodeoxyglucose show focal alterations in glucose use, with cerebral metabolic asymmetries in patients with Alzheimer disease that are related to the nature of the cognitive deficit. Serial roentgenographic computed tomographic studies show heterogeneous rates of lateral ventricle enlargement in the disease that are related to rates of cognitive decline. Similar anatomic and physiologic abnormalities are also found in persons 45 years of age or older who have the Down syndrome. Furthermore, patients with Alzheimer disease who have extrapyramidal dysfunction or myoclonus are a distinct subgroup, with specific abnormalities of central monoamine markers of dopamine metabolism, serotonin metabolism, and the hydroxylation cofactor, biopterin. The concept of subtypes in Alzheimer disease serves as a model with which the interactions of genetic influences with environmental factors can be examined.
Article and Author Information
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An edited summary of a combined Clinical Staff Conference held 29 April 1987 at the Amphitheater, Building 10, Bethesda, Maryland, sponsored by the National Institutes of Health, U.S. Department of Health and Human Services.
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Authors who wish to cite a section of the conference and specifically indicate its author can use this example for the form of reference:
Haxby JV. Evidence of metabolic heterogeneity from positron emission tomography studies, pp 300-302. In: Friedland RP, moderator. Alzheimer disease: clinical and biological heterogeneity. Ann Intern Med. 1988;109:298-311.
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Requests for Reprints: Robert P. Friedland, MD, Brain Aging and Dementia Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Building 10, Room 12S207, 9000 Rockville Pike, Bethesda, MD 20892.
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Current Author Addresses: Drs. Friedland, Koss, Haxby, Grady, Schapiro, and Kaye: Brain Aging and Dementia Section, Laboratory of Neurosciences, National Institute of Aging, National Institutes of Health, Bethesda, MD 20892.
Dr. Luxenberg: 2340 Sutler St., San Francisco, CA 94115.
