“Surviving and Thriving”: evidence for cortical GABA stabilization in cognitively-intact oldest-old adults

• DOI: 10.1038/s41398-025-03302-w
• Publication Date: 2025-03-13T09:17:37Z
• Authors: Mark K. Britton; Greg Jensen; Richard AE Edden; Nicolaas AJ Puts; Sara A. Nolin; Stacy Suzanne Mer...; Roxanne F. Rezaei; Megan Forbes; Keyanni Joy Johnson; Pradyumna K. Bhar...; Mary Kathryn Fran...; David A. Raichlen; Cortney J. Jessup; G. Alex Hishaw; Emily J. Van Etten; Aaron T. Gudmundson; Saipavitra Murali...; Hannah Cowart; Theodore P. Trouard; David S. Geldmacher; Virginia G. Wadley; Noam Alperin; Bonnie E. Levin; Tatjana Rundek; Kristina M. Visscher; Adam J. Woods; Gene E. Alexander; Ronald A. Cohen; Eric C. Porges

Abstract Age-related alterations in GABAergic function, including depletion of cortical GABA concentrations, is likely associated with declining cognitive performance in normative aging. However, the extent to which GABAergic function is perturbed in the highest-functioning stratum of the oldest-old (85+) population is unknown. For the first time, we report the stability of cortical GABA in this population. We extend our previously-reported Individual Participant Data Meta-Analysis of GABA levels across the lifespan, integrating four large cross-sectional datasets sampling cognitively-intact oldest-old adults. Within our lifespan model, the slope of age-related GABA differences in cognitively-intact oldest-old adults flattens after roughly age 80; within oldest-old adults only, inclusion of age does not improve the fit of models predicting GABA. We interpret these findings as an effect of survivorship: inclusion in the study required intact cognition, and too great a reduction of GABA levels may not be compatible with neurophysiological function needed for intact cognition. This work contributes to a growing body of evidence suggesting that successful cognitive aging may require intact GABAergic function, as well as further characterizing successful aging amongst oldest-old adults and emphasizing GABA as a potential target for interventions to prolong cognitive health in aging.