Association between lifetime depression history, hippocampal volume and memory in non-amnestic mild cognitive impairment

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non-amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated FreeSurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143) = 7.84, p < 0.001, R² = 0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p = 0.008), and right hippocampal body (p = 0.004) and better performance on structured encoding (p = 0.011) and unstructured memory retention (p = 0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.