Predicting longitudinal basal forebrain volume in the Alzheimer’s disease spectrum: the role of sex and ApoE epsilon 4 genotype

BACKGROUND: Imaging studies showed early atrophy of the cholinergic basal forebrain already at prodromal stages of sporadic Alzheimer’s disease (AD). Women and carriers of the ApoE epsilon 4 (ApoE ε4) allele are more likely to develop the disease; however, the underlying mechanisms are still unclear.OBJECTIVE: Explore the impact of sex and ApoE ε4 genotype in the AD spectrum.DESIGN: Longitudinal and multi-centered studySETTING: From the German DELCODE cohort we analyzed 710 individuals (median age: 71.25 years, interquartile range [IQR]=9.22) with follow-up MRI scans (median time: 1 year, IQR= 3).MEASUREMENTS: Volume segmentation and a linear mixed-effect model were used to calculate the effect of ApoE ε4 genotype, sex, diagnosis, age, time and their interactions over normalized basal forebrain and hippocampal volumes.RESULTS: The hippocampus, but not the basal forebrain, showed atrophy over time (b = -0.01, p= 0.0008, 95%CI [-0.02, -0.00]). Female participants had significantly larger baseline basal forebrain (b = 0.30,p =