High-resolution MRI evidence for age- and sex-related changes in hippocampal subfield volume during healthy aging

Hippocampal volume is associated with memory and is critical in Alzheimer's disease, but few studies have examined hippocampal subfield volume changes during healthy aging. Herein, we utilize submillimeter MRI to examine age- and sex-specific subfield volumetric changes in 206 participants (M_age = 53.05 years, range = 21-87, N_female = 110). Total intracranial volume was regressed out and hierarchical regression was performed to examine subfield volume changes with age. To identify inflection points per subfield, piecewise regression was used with bootstrapped confidence intervals to distinguish whether these significantly differed by subfield and sex after multiple comparisons correction. Partial correlations controlling for age were performed to identify relationships between subfield volume and cognitive domains. We identified significant quadratic relationships for all subfields (qs < .05). Volumetric inflection points did not differ by subfield, but significantly differed by sex, such that age-related CA1 and CA4-DG volume decline began later for males than for females (CA1: 1 year; CA4-DG: 5 years), whereas the opposite was observed in the subiculum and presubiculum (subiculum: 6 years; presubiculum: 4 years). Further, CA4-DG volume declined more quickly in males relative to females after the inflection point. Finally, we found associations between attention and CA1 and CA4-DG volume, and between language and CA1. These findings indicate significant age and sex effects on subfield volume across the adult lifespan and subfield-specific relationships with cognitive performance. Understanding the factors that may lead to these sex-specific volumetric losses by subfield is critical given the implications for preserved cognitive function into later life.