The Impact of APOE Genotype on Neuropsychological Functioning in Mild Cognitive Impairment and Alzheimer’s Disease

The presence of the Apolipoprotein E (APOE) ε4 (epsilon 4) allele is the primary genetic risk factor for developing sporadic Alzheimer’s Disease (AD) and has recently been identified as a risk factor for Mild Cognitive Impairment (MCI). While previous research has repeatedly indicated the significance of APOEε4 in AD susceptibility, studies investigating the impact of APOEε4 on neuropsychological performance in AD and MCI have yielded contradictory results. Our study examined how the presence of APOEε4 impacts performance in individuals with MCI and AD on neuropsychological assessments evaluating memory, language, attention, executive, and visuospatial skills. Using archival data collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we assessed the impact of APOEε4 on cognitive functioning with a sample of 819 age-matched participants: 229 normal control, 397 MCI, and 193 probable AD. Groups were further split by APOE genotype, into APOEε4 carriers and noncarriers. Cognition was evaluated through 7 neuropsychological tests. Results revealed significant differences between noncarriers and carriers in the AD group on delayed recall and recognition measures within the Rey Auditory Verbal Learning Test, with carriers performing significantly worse than noncarriers. Significant differences were also present in the MCI group, with carriers performing significantly worse on Clock Drawing, Clock Copy, Category Fluency, Digit Span Forward, and immediate recall, learning, delayed recall, and recognition measures within the Rey Auditory Verbal Learning Test. No significant differences were noted in the NC group. Our results support previous literature in that the presence of APOEε4 impacts a variety of cognitive performance measures in both MCI and AD. The differences noted between APOEε4 carriers and noncarriers may have clinical utility for diagnosing and treating MCI and AD.