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A Prospective Community Study

Peijun Chen, MD, MPH, PhD; Graham Ratcliff, DPhil; Steven H. Belle, PhD; Jane A. Cauley, DrPH; Steven T. DeKosky, MD; Mary Ganguli, MD, MPH

Arch Gen Psychiatry. 2001;58:853-858.

Background  Specific patterns of decline over time were evaluated across a spectrum of cognitive measures in presymptomatic Alzheimer disease (AD) within a community sample.

Methods  A total of 551 individuals completed a battery of standard cognitive tests 3.5 and 1.5 years before outcome (clinical onset of AD vs continued nondemented status) within a prospective community-based study of AD. Test score changes in 68 cases (who subsequently developed symptomatic AD) and 483 controls (who remained nondemented) on each of 15 cognitive measures were transformed into z scores adjusted for age, sex, and education. A case-control rate ratio of the proportions of individuals who showed "cognitive decline" on each test was calculated, representing the relative magnitude of cognitive decline on each test in presymptomatic AD compared with normal aging.

Results  Declines in Trail-Making Tests A and B and Word List delayed recognition of originals and third immediate learning trial had the highest rate ratios, larger than 3.0 (P<.01). These were followed by Word List delayed recognition of foils and delayed recall, Consortium to Establish a Registry for Alzheimer's Disease Praxis, Clock Drawing, the Boston Naming Test, and Orientation, with rate ratios between 1.7 and 3.0 (P<.05).

Conclusions  Memory and executive dysfunction showed the greatest decline over time in individuals who would clinically manifest AD 1.5 years later. These findings might help us understand the underlying evolution of the early neurodegenerative process. They highlight the importance of executive dysfunction early in the disease process and might facilitate early detection of AD.

From the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health (Drs Chen, Belle, Cauley, and Ganguli), HealthSouth Harmarville Rehabilitation Hospital (Dr Ratcliff), and the Departments of Psychiatry (Drs Ratcliff, DeKosky, and Ganguli) and Neurology (Dr DeKosky) and the Alzheimer's Disease Research Center (Drs DeKosky and Ganguli), University of Pittsburgh School of Medicine, Pittsburgh, Pa. Dr Chen is now with the Department of Psychiatry, University of Michigan, Ann Arbor.

Corresponding author: Mary Ganguli, MD, MPH, Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213-2593 (e-mail: gangulim{at}msx.upmc.edu).

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