Depression and Hippocampal Subfield Volume in Older Adults

Abstract

AbstractBackgroundMajor Depressive Disorder (MDD) is associated with higher risk for developing Alzheimer’s Disease (AD), (Bennett & Thomas, 2014). Both conditions are associated with smaller hippocampal subfield volumes, and both preferentially affect females (Shi et al., 2021). We examined the relationship between depression diagnosis and hippocampal subfield volume, by carrier status for AD genetic risk variant APOE4 and sex. We hypothesized that the association between depression and subfield volume would be stronger in females due to the higher rate of depression.MethodWe examined 1726 cognitively intact older adults from the Health and Aging Brain Study ‐ Health Disparities (HABS‐HD) cohort (Table1) who had available hippocampal high resolution MRI scans (Siemens Skyra or Vida‐3T). Scans were segmented into CA1, CA23DG, and subiculum using Automatic Segmentation of Hippocampal Subfields (ASHS) software and subfield volume was averaged bilaterally. We used separate multiple linear regressions to assess the association between depression and each hippocampal subfield volume, covarying for age, sex, years of education, number of MRI slices segmented, intracranial volume, and scanner. We corrected for multiple comparisons across regions using FDR correction. We also evaluated CA1 and CA23DG volume to depression diagnosis, stratifying by APOE4 positivity and sex and testing for formal interactions.ResultSee Table 2 for results. Depression was associated with smaller CA1 and CA23DG volume across all participants. Depression was associated with smaller CA1 and CA23DG in the APOE4 negative group, but not the APOE4 positive group. The depression by APOE4 interaction was significant for CA23DG volume (𝛽 = 0.25, p = 0.049). Depression was associated with smaller CA1 and CA23DG volumes in males, but not in females, with trend level interaction effects in the CA1 (𝛽 = 0.13, p = 0.095) and CA23DG (𝛽 = 0.17, p = 0.067).ConclusionDepression was associated with smaller CA1 and CA23DG volumes in older adults consistent with past literature. In contrast to our hypotheses, depression was associated with lower hippocampal subregional volumes more in those with lower risk for Alzheimer’s disease (male and APOE4‐ adults).Variability induced by other AD risk factors may mask the relationship between depression and hippocampal subregion volume when AD risk is higher.