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A 22-Year Prospective Study of the Framingham Cohort

Merrill F. Elias, PhD, MPH; Alexa Beiser, PhD; Philip A. Wolf, MD; Rhoda Au, PhD; Roberta F. White, PhD; Ralph B. D'Agostino, PhD

Arch Neurol. 2000;57:808-813.

Objectives  To relate performance on tests of cognitive ability to the subsequent development of probable Alzheimer disease (pAD) and to identify the pattern of earliest changes in cognitive functioning associated with a diagnosis of pAD.

Design  From May 1975 to November 1979, a screening neuropsychological battery was administered to Framingham Study participants. They were followed up prospectively for 22 years and examined at least every 2 years for the development of pAD.

Setting  A community-based center for epidemiological research.

Participants  Subjects were 1076 participants of the Framingham Study aged 65 to 94 years who were free of dementia and stroke at baseline (initial) neuropsychological testing.

Main Outcome Measure  Presence or absence of pAD during a 22-year surveillance period was related to test performance at initial neuropsychological testing.

Results  Lower scores for measures of new learning, recall, retention, and abstract reasoning obtained during a dementia-free period were associated with the development of pAD. Lower scores for measures of abstract reasoning and retention predicted pAD after a dementia-free period of 10 years.

Conclusions  The "preclinical phase" of detectable lowering of cognitive functioning precedes the appearance of pAD by many years. Measures of retention of information and abstract reasoning are among the strongest predictors of pAD when the interval between initial assessment and the development of pAD is long.

From the Statistical Consulting Unit, Department of Mathematics and Statistics, Boston University College of Arts and Sciences, Boston, Mass (Drs Elias and D'Agostino); Department of Psychology, University of Maine, Orono (Dr Elias); Department of Epidemiology and Biostatistics, Boston University School of Public Health (Dr Beiser); Department of Neurology, Boston University School of Medicine (Drs Wolf, Au, and White); Department of Psychology, Boston Environmental Hazards Center, Boston Department of Veterans Affairs Medical Center (Dr White); and Odense University, Odense, Denmark (Dr White).

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