Sex Differences in Stress Reactivity and Dementia Risk Across the Lifespan: A Social Safety Theory Perspective

07/11/2026

AI Summary

Sex differences in psychological, neural and biological stress reactivity drive systemic chronic inflammation, disproportionately elevating dementia risk in females across the life course.
Lifestyle behaviours and biological pathways including sleep, physical activity, diet and sex steroid hormone dynamics modify stress-related dementia risk.
Early health monitoring and targeted interventions to reduce stress can bolster cognitive resilience and improve brain health into older age.

TL;DR (AI Generated)

Examining this topic through the lens of Social Safety Theory, we first summarize known sex differences in psychological, neural, and biological stress reactivity, with a focus on how stress occurring across the lifespan can promote systemic chronic inflammation and lead to inflammation-related health problems, particularly for females.

Next, we describe known sex differences in lifestyle behaviors and biological pathways that can both increase and decrease risk for stress-related health problems including dementia-namely, sleep, physical activity, diet, and sex steroid hormone dynamics.

Basic summary

Front Neuroendocrinol. 2026 Nov 6:101297. doi: 10.1016/j.yfrne.2026.101297. Online ahead of print.

ABSTRACT

Brain health is a key predictor of morbidity and mortality across the life course, and as the proportion of individuals experiencing cognitive decline grows larger, understanding sex differences in processes that drive cognitive aging in each sex is becoming increasingly important. To address this pressing need, we review research focusing on a central but frequently underappreciated factor: biopsychosocial stress reactivity. Examining this topic through the lens of Social Safety Theory, we first summarize known sex differences in psychological, neural, and biological stress reactivity, with a focus on how stress occurring across the lifespan can promote systemic chronic inflammation and lead to inflammation-related health problems, particularly for females. Next, we describe known sex differences in lifestyle behaviors and biological pathways that can both increase and decrease risk for stress-related health problems including dementia-namely, sleep, physical activity, diet, and sex steroid hormone dynamics. Finally, based on this research, we discuss several strategies for reducing stress-related dementia risk and improving cognitive resilience across the life course, highlighting the health monitoring approaches that will inform early intervention, and in turn, improved brain health for the older adults of tomorrow.

PMID:42994703 | DOI:10.1016/j.yfrne.2026.101297

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