Hippocampal volumes in UK Biobank are associated with APOE only in older adults.

Introduction: The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and genotype on total hippocampal volume.

Methods: Utilizing neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and with hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling.

Results: Total hippocampal volume declined with age, with significant differences by genotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at age 76.

Discussion: The association of and hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance of genotype in determining when to begin screening for AD.