APOEε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

Abstract

ObjectiveTo determine ifAPOEε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) and dementia with Lewy bodies (DLB).MethodsA total of 289 patients (AD = 239; DLB = 50) underwent volumetric MRI, neuropsychological testing, andAPOEε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis to identify cognitive domains encompassing attention/executive functions, learning/memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH andAPOEε4 in the full sample, we tested associations of WMH with factor scores using linear regression models inAPOEε4 carriers (n = 167) and noncarriers (n = 122). We hypothesized that greater WMH volume would relate to worse cognition more strongly inAPOEε4 carriers. Findings were replicated in 198 patients with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed.ResultsA significant interaction was observed between WMH andAPOEε4 for language, but not for memory or executive functions. Separate analyses inAPOEε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language inAPOEε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language inAPOEε4 carriers only. No significant associations were observed in noncarriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains inAPOEε4 carriers only.ConclusionAPOEε4 may influence the association between WMH and cognitive performance in AD and DLB.