Influence of apolipoprotein E ε4 on rates of cognitive and functional decline in mild cognitive impairment

Background: Apolipoprotein E epsilon 4 (APOE epsilon 4) allele carrier status has been well established as a risk factor for developing Alzheimer's disease. However, the specific influence of APOE epsilon 4 allele status on cognitive and functional rates of decline in mild cognitive impairment (MCI) is poorly understood. We examine the prospective association of APOE epsilon 4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI). Methods: A total of 516 aMCI participants aged 55-90 years who received placebo or vitamin E from the Alzheimer's Disease Cooperative Study's MCI treatment trial were evaluated. During the 36-month study period, neurocognitive and functional measures were collected. These measures were assessed over time for change and association with APOE epsilon 4 status. Generalized Estimating Equations were performed to model each outcome measure over the study period. Results: APOE epsilon 4 status had a significant impact on cognitive and functional decline on multiple measures: those who were APOE epsilon 4 positive had significantly more rapid decline in performance on all cognitive and functional measures except Number Cancellation and Maze tracing (P < .05). The greatest decline was seen in global measures of cognition and function including the Clinical Diagnostic Rating scale, followed by the Mini-Mental State Examination, Global Deterioration scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Conclusions: These findings demonstrate that APOE epsilon 4 genotype is predictive of increased general rates of decline with global measures of cognition and function most affected. With accelerated declines in common clinical trial primary efficacy measures, APOE epsilon 4 status needs to be accounted for in treatment trials of MCI. (c) 2010 The Alzheimer's Association. All rights reserved.