The course of cognitive impairment in preclinical Alzheimer disease - Three- and 6-year follow-up of a population-based sample

Objectives: To examine the ability of the total score and individual items from the Mini-Mental State Examination in predicting the development of Alz heimer disease (AD) across a 3- and 6-year period in a population-based sam ple, and to describe the longitudinal changes in these measures across the same follow-up periods. Design: Prospective follow-up of a community-based cohort, with 3 times of testing across a 6-year period. At each time of measurement, participants w ere clinically examined by physicians to identify demented and nondemented participants according to Diagnostic ann Statistical Manual of Mental Disor ders, Revised Third Edition, criteria. Participants: The study population consisted of all participants who were n ondemented at the first follow-up and participated in the second follow-up examination. Among those, 459 remained nondemented and 73 developed AD duri ng the second follow-up period. Results: Baseline differences in the total Mini-Mental State Examination sc ore and the delayed memory item were seen 6 years before eventual dementia diagnosis (P<.01). Analysis of the longitudinal changes showed no differenc es in the rate of decline for the incident AD or nondemented group between time 1 and time 2 (P>.10). However, the incident AD group exhibited precipi tous declines in 8 of the 10 subscales between time 2 and time 3, the point at which they were clinically diagnosed (P<.01). Logistic regression analy ses showed that only the delayed memory item was a significant predictor of who would develop AD, independent of age, sex, and years of education, at both of the first 2 times of measurement (P<.001). Conclusions: The diagnosis of AD is preceded by a long preclinical phase in which deficits in memory performance are most common. These deficits remai n relatively stable up until the time that a dementia diagnosis can be rend ered.