ABSTRACT
Objective
To assess the relationship of subtle preclinical cognitive changes with white matter microstructure and cortical volume in middle-aged adults at high AD risk due to a parental history.
Methods
Participants (n = 278) were AD patients’ offspring from the Israel Registry for Alzheimer’s Prevention study. Cognitively unimpaired-decliners (CU-D) were based on a linear regression model. In a subsample with MRI (n = 220), we examined relationships of CU-D with white matter (WM) microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) and cortical volume in brain regions commonly affected in AD.
Results
CU-D participants had lower FA in the superior longitudinal fasciculus (SLF) (p = < 0.001) and higher MD in the SLF (p = < 0.001), and cingulum adjacent to the corpus callosum (p = < 0.001) and genu (p = 0.006) compared to cognitively unimpaired-stable (CU-S) participants. The groups did not differ in cortical brain volumes.
Conclusions
CU-D participants had poorer WM microstructure in brain tracts affected early in AD. Early interventions can target individuals that fit the CU-D criteria.