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A 13-Year Prospective Study of the Framingham Cohort

Richard T. Linn, PhD; Philip A. Wolf, MD; David L. Bachman, MD; Janice E. Knoefel, MD; Janet L. Cobb, MPH; Albert J. Belanger, MS; Edith F. Kaplan, PhD; Ralph B. D'Agostino, PhD

Arch Neurol. 1995;52(5):485-490.

Abstract
Objective
To evaluate the interval between the onset of detectable cognitive impairment and clinical diagnosis in individuals with probable Alzheimer's disease (AD), and to identify the pattern of the earliest changes in cognition in probable AD.

Design
Longitudinal follow-up of a community-based cohort sample. In 1976 through 1978, a screening neuropsychological examination was administered to Framingham Study participants. These subjects were then followed up prospectively for development of probable AD for up to 13 years.

Setting
This study was conducted at a communitybased center for epidemiologic research.

Participants
The surveillance sample consisted of 1045 participants in the Framingham Study aged 65 to 88 years who were free of dementia at the time of the neuropsychological screening examination.

Main Outcome Measures
Scores on a group of neuropsychological tests were entered into a series of age-and education-adjusted multiple regression procedures, with the presence or absence of probable AD as the outcome variable.

Results
Considered individually, most of the screening neuropsychological measures were significantly related to later AD diagnosis. When stepwise regression procedures were employed, only measures of verbal memory and immediate auditory attention span remained significantly related to AD diagnosis. Of note, subjects later diagnosed with probable AD performed at higher levels than normal subjects on the Digit Span test at initial screening. Regression results were essentially unchanged even when the AD sample was restricted to those individuals for whom the screening examination preceded the clinical onset of dementia by 7 years or more.

Conclusions
These findings support previous contentions that a "preclinical phase" of detectable cognitive deficits can precede the clinical diagnosis of probable AD by many years, and they also support the hypothesis that problems with secondary verbal memory are among the first signs of AD.

Author Affiliations
From the Department of Neurology, Boston (Mass) University School of Medicine (Drs Linn, Wolf, Bachman, Knoefel, and Kaplan); and Department of Mathematics, Boston University (Ms Cobb, Mr Belanger, and Dr D'Agostino). Dr Linn is now with the Department of Rehabilitation Medicine, State University of New York at Buffalo; Dr Bachman is now with the Department of Neurology, Medical University of South Carolina, Charleston.

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