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Background : The current pilot study was designed to examine the association between hippocampal γ-aminobutyric acid (GABA) concentration and episodic memory in older individuals, as well as the impact of two major risk factors for Alzheimer’s disease (AD)—female sex and Apolipoprotein ε4 ( ApoE  ε4) genotype—on this relationship.   Methods : Twenty healthy, community-dwelling individuals aged 50–71 (11 women) took part in the study. Episodic memory was evaluated using a Directed Forgetting task, and GABA+ was measured in the right hippocampus using a Mescher-Garwood point-resolved magnetic resonance spectroscopy (MRS) sequence. Multiple linear regression models were used to quantify the relationship between episodic memory, GABA+,  ApoE ɛ4 , and sex, controlling for age and education.   Results : While GABA+ did not interact with  ApoE  ɛ4 carrier status to influence episodic memory ( p  = 0.757), the relationship between GABA+ and episodic memory was moderated by sex: lower GABA+ predicted worse memory in women such that, for each standard deviation decrease in GABA+ concentration, memory scores were reduced by 11% ( p  = 0.001).   Conclusions : This pilot study suggests that sex, but not  ApoE  ɛ4 genotype, moderates the relationship between hippocampal GABA+ and episodic memory, such that women with lower GABA+ concentration show worse memory performance. These findings, which must be interpreted with caution given the small sample size, may serve as a starting point for larger studies using multimodal neuroimaging to understand the contributions of GABA metabolism to age-related memory decline.

Reduced Hippocampal GABA+ Is Associated With Poorer Episodic Memory in Healthy Older Women: A Pilot Study