Cohort Effects in Progression Rate on Cognitive and Functional Measures in an Alzheimer's Disease Clinical Cohort

Accurate prediction of Alzheimer's disease (AD) cognitive and functional outcomes in clinical research requires consistent underlying rates of change over time.

To examine cohort effects in AD progression rate over five years of follow-up using a clinical database of probable AD patients.

Baseline characteristics of three cohorts enrolled from 1995-1999, 2000-2004, and 2005-2009 were compared using ANOVA and chi-square tests. Differences in 5-year decline on the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), the Lawton and Brody Physical Self-maintenance Scale (PSMS), and Activities of Daily Living Scale (ADL) were assessed using longitudinal mixed effects regression, adjusting for age, sex, education, and other relevant clinical characteristics.

Cohorts 1 (n = 287), 2 (n = 257), and 3 (n = 374) did not differ on age, race, APOE genotype, or cognitive and functional measures. Educational attainment increased over time (13.4, 14.1, and 14.5 years, respectively, p < 0.001). Anti-dementia drug use at baseline was less common in Cohort 1 (32.2% versus 65.0%, and 66.8%, p < 0.001). The rate of decline in MMSE and CDR-SB did not differ across cohorts. ADAS-Cog scores for Cohort 2 declined more slowly than Cohort 3 (Btime ×cohort2 = -0.91 ± 0.35, p = 0.009), whereas Cohort 1 did not differ from cohort 3 (reference). Cohorts 1 and 2 differed from Cohort 3 in progression rate on the PSMS, but not the IADL.

There were no consistent temporal trends in progression rates over time. Longitudinal data over 15-20 years may be confidently pooled for outcomes analysis, but unexplained variability in rate of decline on some measures may occur.