Spatially convergent fMRI signatures of diabetes and male sex identify genetic vulnerabilities to accelerated brain aging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract Age-related cognitive decline results from complex interactions between neuroendocrine and neurometabolic processes that undergo lifelong degredation, yet the mechanisms underlying these remain poorly understood. This study examined effects of diabetes sex on functional brain networks across aging through analysis two large cohorts (N=1,621 total) using both 3T 7T MRI, complemented by spatial transcriptomic data over 14,000 genes six post-mortem brains. Four networks— cingulo-opercular, default mode, salience, lateral somatomotor—exhibited significant in individuals with independently males. Gene expression vulnerable revealed overexpression insulin-dependent glucose transporters, dopaminergic GABAergic synaptic genes, VEGFA-VEGFR2 pathway components. These findings suggest functionally-specific circuit vulnerability to metabolic hormonal dysregulation, potentially offering targets for early intervention before irreversible neurodegeneration occurs.

Language: Английский

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‘Critical Window’ for Brain Aging Is Ages 40 to 60

Neurology Today, Journal Year: 2025, Volume and Issue: 25(8), P. 12 - 14

Published: April 17, 2025

Language: Английский

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