Robert P. Friedland, MD; Elisabeth Koss, PhD; James V. Haxby, PhD; Cheryl L. Grady, PhD; Jay Luxenberg, MD; Mark B. Schapiro, MD; Jeffrey Kaye, MD
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.
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Friedland RP, Koss E, Haxby JV, Grady CL, Luxenberg J, Schapiro MB, et al. Alzheimer Disease: Clinical and Biological Heterogeneity. Ann Intern Med. 1988;109:298–311. doi: 10.7326/0003-4819-109-4-298
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Published: Ann Intern Med. 1988;109(4):298-311.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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