Sex Matters: Hippocampal Volume Predicts Individual Differences in Associative Memory in Cognitively Normal Older Women but Not Men

Abstract

The hippocampus plays a prominent role in associative memory by supporting relational binding and recollection processes. Structural atrophy in the hippocampus is likely to induce associative memory deficits in older adults. Previous studies have primarily focused on average age-related differences in hippocampal structure and memory performance. To date, however, it remains unclear whether individual differences in hippocampal morphometry underlie differential associative memory performance, and whether there are sex differences in the structural correlates of associative memory in healthy older adults. Here, we used voxel-based morphometry (VBM) to examine the extent to which gray matter volume (GMV) of the hippocampus predicts associative memory performance in cognitively normal older adults. Seventy-one participants completed a cued recall paired-associative learning test (PALT), which consists of novel associations and semantically related associations, and underwent magnetic resonance imaging (MRI). We observed worse associative memory performance and larger variability for novel associations than for semantically related associations. The VBM results revealed that higher scores on associative memory for novel associations were related to greater hippocampal GMV across all older adults. When considering men and women separately, the correlation between hippocampal GMV and associative memory performance for novel associations reached significance only in older women. These findings suggest that hippocampal structural volumes may predict individual differences in novel associative memory in older women but not men.

Keywords: associative memory; elderly; hippocampus; sex differences; voxel-based morphometry (VBM).

Figure 1

Bilateral hippocampal regions of interest (yellow) defined using the automated anatomical labeling (AAL) atlas.

Figure 2

A scatter plot of the associative memory performance across all older adults for each measure of the paired-associative learning test (PALT).

Figure 3

Region of interest (ROI) correlation analyses between gray matter volume (GMV) and scores on associative memory for novel associations. The left panel shows that GMV of the left hippocampus (peak Montreal Neurological Institute (MNI) coordinate: −27, −36, −2; number of voxels: 334) (A) and the right hippocampus (peak MNI coordinate: 26, −10, −23; number of voxels: 425) (B) are significantly correlated with scores on associative memory for novel associations across all older adults. Bars at the top show the correlation values. The right panel shows the partial regression plots between the GMV of the peak coordinate in the left hippocampus (A) and the right hippocampus (B) and scores on associative memory for novel associations after controlling age, gender, education level and montreal cognitive assessment (MoCA).

Figure 4

ROI correlation analyses between GMV and scores on associative memory for novel associations in older women. The left panel shows that GMV of the left hippocampus (peak MNI coordinate: −27, −40, 0; number of voxels: 309) is significantly correlated with scores on associative memory for novel associations in older women. Bars at the top show the correlation values. The right panel shows the partial regression plots between the GMV of peak coordinate in the left hippocampus and scores on associative memory for novel associations in older men and women after controlling age, education level and MoCA.

Figure 5

Whole-brain correlation analyses between GMV and scores on associative memory for novel associations. The left panel shows that GMV in anatomical clusters that mainly include the left hippocampus and parahippocampal gyrus (peak MNI coordinate: −27, −36, −2; number of voxels: 1441) (A) and the right hippocampus and parahippocampal gyrus (peak MNI coordinate: 17, 2, −20; number of voxels: 2033) (B) are significantly correlated with scores on associative memory for novel associations in older adults. Bars at the top show the correlation values. The right panel shows the partial regression plots between the GMV of the peak coordinate in anatomical clusters that mainly include the left hippocampus and parahippocampal gyrus (A) and the right hippocampus and parahippocampal gyrus (B) and scores on associative memory for novel associations after controlling age, gender, education level and MoCA.

Figure 6

Whole-brain correlation analyses between GMV and scores on associative memory for novel associations in older women. The left panel shows that GMV in anatomical cluster that mainly include the left hippocampus and parahippocampal gyrus (peak MNI coordinate: −15, −34, −11; number of voxels: 2393) is significantly correlated with scores on associative memory for novel associations in older women. The right panel shows the partial regression plots between the GMV of the peak coordinate in the anatomical cluster that mainly include the left hippocampus and parahippocampal gyrus and scores on associative memory for novel associations in men and women after controlling age, education level and MoCA.