Lower GABA levels in the posterior cingulate are linked with poorer episodic memory in healthy older adults

Lalwani, P.; Vanderlip, C.; Stark, C. E.

doi:10.1101/2025.03.18.643988

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bioRxiv · 10.1101/2025.03.18.643988

Lower GABA levels in the posterior cingulate are linked with poorer episodic memory in healthy older adults

Lalwani, P.·Vanderlip, C.·Stark, C. E.

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Abstract

Age-related deficits in episodic memory and mnemonic discrimination are associated with an increased risk of neurodegenerative diseases, such as Alzheimers disease (AD) (Stark et al., 2013). While much research has focused on hippocampal contributions to these age-related changes (Stark et al., 2019), less is known about the role of posterior cingulate cortex (PCC) especially reduced inhibition in episodic memory deficit. PCC has connections to the medial temporal lobe and is linked to memory declines (Greicius et al., 2004). It is also one of the most vulnerable regions to amyloid deposition in AD (Yokoi et al., 2018). This study hypothesized and found that age-related declines in GABAergic function (brains major inhibitory neurotransmitter) within the PCC contributes to individual differences in memory performance in healthy older adults. Using Magnetic Resonance Spectroscopy, we measured GABA levels in the PCC in 22 healthy younger and 30 older adults. We assessed episodic memory using Rey Delayed Auditory Verbal Learning Test (RAVLT) and Mnemonic Similarity Task (MST). We found that both raw GABA levels and episodic memory performance are lower in older adults compared to young. This reduction in GABA levels is subserved by age-related changes in tissue-composition as evidenced by no age-group differences in corrected GABA levels. More importantly, lower GABA levels (independent of tissue-correction) were associated with poorer episodic performance including delayed recall and mnemonic discrimination. This research suggests that therapeutically targeting posterior cingulate GABA levels might help slow or alleviate memory decline. Significance StatementThis study provides novel insights into the role of posterior cingulate cortex (PCC) GABA+ levels in age-related memory deficits. Our findings demonstrate that lower PCC GABA+ levels in older adults are associated with poorer performance on episodic memory tasks, particularly those involving mnemonic discrimination and word-list learning. This research expands on the growing body of literature linking GABAergic dysfunction to age-related cognitive impairments and suggests that GABAergic changes in the PCC contribute to episodic memory deficits. Importantly, our results highlight the potential of targeting PCC GABA levels as a therapeutic strategy to slow or mitigate memory decline in aging. These findings also offer promising avenues for future research into early biomarkers for Alzheimers disease and other neurodegenerative conditions.

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Lalwani, P., Vanderlip, C., Stark, C. E.. 2025-03-18. Lower GABA levels in the posterior cingulate are linked with poorer episodic memory in healthy older adults. https://doi.org/10.1101/2025.03.18.643988

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