Cerebral small vessel disease in middle age and genetic predisposition to late-onset Alzheimer's disease

Abstract

Introduction: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E ε4 (APOE ε4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD.

Methods: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study.

Results: Microbleed prevalence was 14.5%, and mean ± standard deviation white matter hyperintensity percentage of total brain volume was 0.41 ± 0.28%. There was no significant association between APOE ε4 carrier status or history of parental dementia and white matter hyperintensity volume (P = .713, .912 respectively) or microbleeds (P = .082, .562 respectively) on multiple regression.

Discussion: Genetic predisposition to LOAD, through APOE genotype or AD family history, is not associated with CSVD in middle age.

Keywords: Cerebral microbleed; Cerebral small vessel disease; Dementia; MRI; Middle age; Risk factors; White matter hyperintensity.