Midlife Vascular and Lifestyle Determinants of Late-Life Cognitive Decline and Dementia: A Life-Course Prevention Framework with a Gulf (GCC) Perspective

Dementia is a growing global health challenge, yet many determinants of late-life cognitive decline emerge decades before symptoms appear. Midlife is a practical window for prevention because hypertension, diabetes, obesity, dyslipidemia, smoking, physical inactivity, unhealthy diet, sleep disturbance, and social isolation can be identified and modified before substantial brain injury becomes apparent. This narrative review synthesizes evidence linking midlife vascular and lifestyle exposures to late-life cognitive impairment and dementia. The most consistent data support a life-course model in which cumulative vascular, metabolic, inflammatory, and behavioral risks interact with neurodegenerative pathology and cognitive reserve. Vascular and metabolic factors act largely through small-vessel disease, endothelial dysfunction, and inflammation, whereas physical activity, healthy diet, sleep, and social engagement may strengthen resilience. Although observational evidence is vulnerable to confounding and single-risk trials may underestimate cumulative benefit, multidomain prevention remains biologically plausible and clinically actionable, as recent trials reaffirm. These priorities are especially salient in the rapidly transitioning Gulf Cooperation Council (GCC) countries, where midlife cardiometabolic risk is high and local evidence is limited. Dementia prevention should be embedded in routine midlife care, with vascular risk management and sustained lifestyle support treated as core elements of lifelong brain health.