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Journal article
Neurophysiological correlates of modifiable dementia risk factors in cognitively unimpaired older adults
Cerebral Cortex, Vol.35(8), pp.1-7
2025
Appears in Thompson Institute Research Collection
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Abstract
The 2024 Lancet Commission on Dementia estimates that up to 45% of dementia cases could be prevented by addressing modifiable risk factors, emphasizing both prevention opportunities and the need to understand the biological mechanisms. This study investigated neurophysiological mechanisms underlying modifiable dementia risk factors in cognitively unimpaired older adults. Seventy-nine cognitively unimpaired older adults underwent magnetic resonance imaging brain scans, with spectroscopy measurements taken from the sensorimotor cortex (SMC) and prefrontal cortex (PFC), using a Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy sequence, optimized for measuring GABA+. Modifiable dementia risk scores were calculated using the Assessment for Cognitive Health and Dementia Risk (CogDrisk). Hierarchical linear regression analyses revealed a significant negative relationship within the SMC, with lower GABA+ (β = −0.249, P = 0.009) associated with higher risk scores. In the PFC, lower tNAA and tCho concentrations significantly predicted higher risk scores (β = −0.168 and −0.170, respectively). These findings suggest that GABAergic system alterations may underlie the pathophysiology of modifiable dementia risk in healthy aging, while changes in tNAA and tCho may reflect early alterations in neuronal integrity. These region-specific neurochemical findings may help identify potential early biomarkers for dementia risk and suggest new therapeutic pathways for preventive interventions.
Details
- Title
- Neurophysiological correlates of modifiable dementia risk factors in cognitively unimpaired older adults
- Authors
- Jacob M Levenstein (Corresponding Author) - University of the Sunshine Coast, Queensland, Thompson InstituteCiara Treacy - University of the Sunshine Coast, Queensland, Thompson InstituteSophie C Andrews - University of the Sunshine Coast, Queensland, Thompson Institute
- Publication details
- Cerebral Cortex, Vol.35(8), pp.1-7
- Publisher
- Oxford University Press
- Date published
- 2025
- DOI
- 10.1093/cercor/bhaf179
- ISSN
- 1460-2199; 1047-3211
- Copyright note
- © The Author(s) 2025. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
- Data Availability
- The datasets presented within this study are available from the corresponding author on reasonable request.
- Grants
- Naturalistic-fMRI Functional Connectivity Biomarkers Define Subtypes of Healthy Brain Aging and Cognitive Profiles, 0980028321, University of the Sunshine Coast (Australia, Sunshine Coast) - UniSC
- Organisation Unit
- Healthy Ageing Research Cluster; Thompson Institute
- Language
- English
- Record Identifier
- 991153838902621
- Output Type
- Journal article
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