Cognition or genetics? Predicting Alzheimer's disease with practice effects, APOE genotype, and brain metabolism

As practice effects are common in neuropsychological assessment, this study analyzed their utility to identify individuals with amnestic mild cognitive impairment (aMCI) at the greatest risk for Alzheimer's disease (AD-risk) and compared practice effects with APOE and brain metabolism biomarkers. We regressed Auditory Verbal Learning Test delayed recall (AVLT-DR) at 6 months on baseline AVLT-DR scores in 394 individuals with normal cognition from the Alzheimer's Disease Neuroimaging Initiative database and dichotomized 816 individuals with aMCI as showing practice effect or not showing practice effects (PE−) when the discrepancy between observed and predicted scores was found in less than 10%, 7%, and 5% of normal cognition. Cox regressions analyzed the AD-risk at 6 years. More than 60% of aMCI were showing practice effects. Controlling for age, sex, education, and baseline Mini-Mental State Examination and AVLT-DR scores, the AD-risk was associated with PE− [hazard ratio (HR) = 1.93], lower brain metabolism (HR = 0.95), and APOE genotype (HR = 1.92), with narrower risk estimates for PE−. The lack of practice effects during a 6-month period might be as precise as biomarkers for predicting the 6-year AD-risk.