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Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease

From the Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (I.P., D.P.P., K.L.D., V.H.); Bronx VA Medical Center, Bronx, NY (I.P., V.H.); and the Jewish Home and Hospital, New York, NY (L.L., G.L.).

Address correspondence and reprint requests to Dr. Isak Prohovnik, MIRECC (00MH), Bronx VAMC, 130 West Kingsbridge Road, Bronx, NY 10468; e-mail: isak.prohovnik{at}mssm.edu

Background: Little is known about Alzheimer disease at advanced ages, although its incidence continues to increase at least through the ninth decade of life.

Objective: To examine the effects of age on the relationship between clinical dementia severity and neuropathologic hallmarks in a large sample spanning the full age range.

Methods: The authors assessed 81 subjects during life for dementia severity, and examined their brains. They analyzed plaque and tangle burden, as well as the activities of the cholinergic marker enzymes acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), in relation to age at death and the clinical severity of dementia.

Results: Dementia severity was strongly related to plaque and tangle burden in relatively young patients (aged <75 years), but this correlation diminished with age and disappeared in the ninth decade of life. Among the oldest patients studied, there was no difference in plaque and tangle load between the mild and severe dementia cases. This interaction (p < 0.0001 for plaque density) was not observed for the cholinergic markers ChAT and AChE.

Conclusion: The nature or expression of Alzheimer disease may be different in severely demented older patients, who have equal cholinergic deficits but significantly lower plaque and tangle burden. If confirmed in a prospective study, these findings have diagnostic and therapeutic implications.

Supported in part by NIH grants P01-AG02219 and P50-AG05138.

Disclosure: The authors report no conflicts of interest.

These data were partially presented at the First Congress of the International Society for Vascular Behavioral and Cognitive Disorders, Goteborg, Sweden, August 28 through 31, 2003.

Received February 17, 2005. Accepted in final form September 29, 2005.

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