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

Abstract

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.

Age, Education Years, and Biochemical Factors Are Associated with Selective Neuronal Changes in the Elderly Hippocampus

“…In young individuals, the hippocampal GABAergic concentration is positively correlated with retrieval performance in an associative learning paradigm [ 55 ]. Additionally, a positive correlation between hippocampal GABA concentration and episodic memory scores was found in elderly women but not in men [ 56 ]. The concept of the cognitive reserve was proposed to account for factors that might explain why some elderly individuals are more susceptible to cognitive and physiological decline while others progress in a healthier manner.…”

Alterations of theta power and synchrony during encoding in young adult binge drinkers: Subsequent memory effects associated with retrieval after 48 h and 6 months

“…Indeed, recent evidence indicates that binge drinking is associated with lower GABA concentration ( Marinkovic et al, 2022 ) and neural hyperexcitability ( Correas et al, 2021 ). GABA reduction in the hippocampus is associated with neural hyperactivity and memory impairments in animal ( Li et al, 2021 ) and human studies ( Jiménez-Balado et al, 2021 ). Over time, alcohol-induced neurochemical changes may contribute to the allostatic neuroadaptations in limbic brain structures that are critical for memory consolidation ( Koob, 2003 ; Koob and Le Moal, 2008 ; Wise and Koob, 2014 ).…”

MRS in neurodegenerative dementias, prodromal syndromes and at‐risk states: A systematic review of the literature

“…Studies mostly had relatively large numbers of participants; the largest, with 594 participants, was also the only longitudinal study. 79 'At risk' was defined in a variety of ways and included: carriers of the apolipoprotein e4 allele (APOEe4) [78][79][80][81][82][83][84] increased Pittsburgh B compound (PiB) PET retention (a measure of brain amyloid) 79,82,85 CSF amyloid and tau 81,86 subjective and objective memory deficits in the absence of clinically significant impairment 87,88 and presence of nocturnal hypoxaemia (due to obstructive sleep apnoea). 87 Five studies compared MRS metabolites in cognitively normal participants with high or low brain amyloid.…”