Aging, Practice Effects, and Genetic Risk in the Wisconsin Registry for Alzheimer's Prevention

In the last five years, a consensus has developed that Alzheimer's disease (AD) may begin years before overt cognitive impairment. Accordingly, the focus has shifted to identifying preclinical disease in order to match treatments to those most likely to benefit. Subtle cognitive changes, including reduced benefit from practice, may be one such preclinical sign. In this study, we explore cognitive aging trajectories within a large cohort of clinically intact late middle-aged adults.

Longitudinal cognitive data were analyzed from 594 participants in the Wisconsin Registry for Alzheimer's Prevention. Mixed models were used to examine trajectories, adjusting for prior exposure, and the moderation thereof by markers of dementia risk, APOE-ε4 status, and family history of AD.

Practice effects were observed for Verbal Learning & Memory, Working Memory, Speed & Flexibility, and Visual Learning. However, for Working Memory and Speed & Flexibility, these effects were attenuated for FH + subjects.

Reduced practice effects have previously been observed in clinical groups. These results in middle-aged adults suggest that they may also indicate preclinical changes on the path to AD.