Effects of sex, age, and apolipoprotein E genotype on hippocampal parenchymal fraction in cognitively normal older adults

Early detection of Alzheimer’s disease (AD) is important for timely interventions and developing new treatments. Hippocampus atrophy is an early biomarker of AD. The hippocampal parenchymal fraction (HPF) is a promising measure of hippocampal structural integrity computed from structural MRI. It is important to characterize the dependence of HPF on covariates such as age and sex in the normal population to enhance its utility as a disease biomarker. We measured the HPF in 4239 structural MRI scans from 340 cognitively normal (CN) subjects aged 59-89 years from the AD Neuroimaging Initiative database, and studied its dependence on age, sex, apolipoprotein E (APOE) genotype, brain hemisphere, intracranial volume (ICV), and education using a linear mixed-effects model. In this CN cohort, HPF was inversely associated with ICV; was greater on the right hemisphere compared to left in both sexes with the degree of right > left asymmetry being slightly more pronounced in men; declined quadratically with age and faster in APOE ϵ4 carriers compared to non-carriers; and was significantly associated with cognitive ability. Consideration of HPF as an AD biomarker should be in conjunction with other subject attributes that are shown in this research to influence HPF levels in CN older individuals.