Hippocampal Atrophy Is Associated with Subjective Memory Decline: The PATH Through Life Study

Objective: To investigate whether subjective memory decline (SMD) in cognitively healthy individuals is associated with hippocampal atrophy. Methods: Multiple regression analyses assessing the relationship between hippocampal atrophy over 4 years and SMD at baseline and follow-up in 305 cognitively healthy individuals aged 60-64 years free from dementia, mild cognitive impairment, and other neurological disorders. Results: SMD at baseline was not a significant predictor of hippocampal atrophy. However, SMD at follow-up was associated with greater hippocampal atrophy. Associations were reduced but remained significant after controlling for anxiety and depression symptomatology. Conclusion: Hippocampal atrophy was associated with incident/persisting SMD and this association was not, or only partly, explained by anxiety and depression symptomatology. These results are consistent with a biological origin to subjective memory decline. SMD should be included in screening and neuropsychological batteries.