Overlapping effects of age on associative memory and the anterior hippocampus from middle to older age

• We assessed age-effects in associative memory and the hippocampus.
• Compared middle-aged and older adults and assessed sex-differences.
• Older adults had worse memory and less hippocampal volume and activation.
• Age-differences in memory were mirrored specifically in the anterior hippocampus.
• Age-effects in all modalities were more pronounced in men as compared to women.

The anterior hippocampus has been implicated in associative memory, and along with hippocampal volume, this type of memory declines with age. However, few cross-sectional studies include middle-aged samples, making it unclear at what point these age-related changes occur. In addition, although men and women have been shown to differ in associative memory and rates of age-related hippocampal atrophy, sex-differences in aging are rarely studied. To address these issues, we assessed memory for word-pairs, hippocampal volume and activation during encoding and retrieval, across middle-aged (n = 39) and older (n = 44) participants, specifically in relation to sex. Older adults showed significantly poorer associative memory compared to middle-aged adults, paralleled by smaller anterior hippocampi and less activation during successful retrieval. The age-by-sex interaction observed in memory performance was also mirrored in the volume and activation of the hippocampus, indicating more pronounced age-effects in men as compared to women. These results indicate a specific role of the anterior hippocampus in verbal associative memory and suggest they both decline between middle-age and older age.