Effects of Age, APOE ε4, Cognitive Reserve and Hippocampal Volume on Cognitive Intervention Outcome in Amnestic Mild Cognitive Impairment

Abstract

Here we studied intervention outcome and potential predictors for cognitive intervention effects in patients with amnestic mild cognitive impairment (aMCI), a population at risk of Alzheimer’s disease. We included 100 aMCI patients (cognitive intervention group, n=69; active control group, n=31) that underwent a previously established 6-month group-based multicomponent cognitive intervention or an active control condition. As a primary endpoint we defined changes in global cognition (Alzheimer’s Disease Assessment Scale – Cognitive Subscale, ADAS-Cog). Secondary endpoints were changes in verbal and visual episodic memory (California Verbal Learning Test, CVLT; Face Name Learning Test, FNL). Overall, we found no improvements in our primary outcome ADAS-Cog. Group by time interactions were found for CVLT learning (p=0.031), with improvements in the intervention group and deteriorations in the control group. The intervention group deteriorated in FNL learning (p=0.001) and the control group deteriorated in FNL recall (p=0.048). The main focus of the study was, however, whether intervention outcome was predicted by factors that are known to affect disease progression. As predictors we selected age, APOE carrier status, cognitive reserve, and hippocampal volume. In linear regression analyses, lower hippocampal volume predicted deteriorations in ADAS-Cog (p=0.035) and CVLT recall (p=0.016), whereas younger age (p=0.011) and APOE e4 non-carrier status (p=0.024) predicted improvements in CVLT learning. Lower cognitive reserve predicted deteriorations in FNL recall (p=0.008). Regarding the modest intervention effects, our results challenge a general recommendation of cognitive interventions in aMCI. Rather, our findings suggest that younger patients, APOE e4 non-carriers, and patients with higher CR and higher hippocampal volume have a higher likelihood to benefit from a cognitive intervention, which could be useful for the selection of patients for future intervention trials.