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Patterns of Cognitive Decline in Presymptomatic Alzheimer Disease
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).
RELATED ARTICLE
Canaries in a Coal Mine: Cognitive Markers of Preclinical Alzheimer Disease
Brent J. Small, Laura Fratiglioni, and Lars Bäckman
Arch Gen Psychiatry. 2001;58(9):859-860.
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