Title: Social Isolation as a Modifiable Risk Factor for Physiological Decline in Midlife Women: Implications for Cognitive Health Prevention.

Poster Number: #4214

Authors: Gierke, C., Fernandez, M. M., Muñoz, P., Martinez, M., Morales, M., & Ferrer, N.

Abstract / Poster Summary

Background: Social isolation and loneliness represent critical, yet modifiable risk factors for physiological decline in midlife women. The menopausal transition, particularly perimenopause (approx. 40–51 years), represents a unique window of vulnerability. During this stage, social disconnection can accelerate biological mechanisms linked to cognitive impairment; for instance, isolated perimenopausal women show $40\%$ higher depression rates and elevated cardiovascular risk.

Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched (2020–2025) for literature evaluating the impact of objective social isolation and perceived loneliness on the physiological health of women aged 40–65 across different menopausal stages.

Results: The synthesized evidence demonstrates that social isolation during the menopausal transition drives distinct physiological pathways that converge on cognitive decline:

1) Cardiovascular Dysfunction: Induces elevated blood pressure, increased CVD risk, accelerated vascular aging, and endothelial dysfunction.

2) Chronic Inflammation: Activates pro-inflammatory cytokines, raising levels of IL-6, TNF-$\alpha$, and hs-CRP

3) HPA-Axis Dysregulation: Elevates cortisol levels, triggers glucocorticoid resistance, and impairs stress recovery

4) Sympathetic Overactivity: Increases catecholamines and SNS activity, impairing autonomic balance

These interconnected pathways lead to accelerated physiological aging (neuroendocrine and metabolic dysregulation) , increasing vulnerability to neurodegeneration via neural injury, synaptic dysfunction, and white matter changes , which ultimately drives cognitive decline and Alzheimer's disease risk.

Conclusions: Perimenopause is a critical preventive window. Strong social connections act as a biological resilience buffer that modulates these adverse pathways. Enhancing social connectedness provides a translational framework for multidomain interventions to strengthen physiological resilience and support lifetime Alzheimer's prevention

Email: christinegierke@uchile.cl