Cold Climate and Alzheimer's Disease: A Narrative Review of Biomedical and Environmental Mechanisms.

Emerging evidence suggests that exposure to cold environments may influence Alzheimer's disease (AD) pathogenesis through interconnected vascular, inflammatory, metabolic, and thermoregulatory mechanisms. Aging impairs physiological resilience to cold stress, which may exacerbate neurodegenerative processes in vulnerable individuals. This narrative review summarizes findings from epidemiological, mechanistic, and interventional studies on the relationship between cold exposure and AD. This article is a narrative review informed by a structured literature search conducted in PubMed and Scopus databases up to July 2025. Boolean operators such as ("cold exposure" OR "cold climate") AND ("Alzheimer's disease" OR "neurodegeneration") were applied. While not a systematic review, a PRISMA-style flowchart was solely for transparency, illustrating how the literature was screened. No meta-analytic methods or formal bias assessment tools were applied. Cold exposure is associated with cerebral vasoconstriction, glucose hypometabolism, sleep disruption, mitochondrial stress, and increased permeability of the blood-brain barrier. These changes promote neuroinflammation and oxidative stress, which are key contributors to the pathology of AD. Reduced brown adipose tissue with aging makes people more sensitive to cold. Apolipoprotein E (APOE) ε4 allele carriers seem to be more susceptible to these stresses. Epidemiological data support a higher dementia risk in colder climates, with seasonal and regional variations persisting after adjustment for confounders. Exposure to cold environments may act as a modifiable risk factor for AD, particularly in aging populations with impaired thermoregulation. While evidence points to plausible mechanistic links, further longitudinal and experimental studies are required. Integrating environmental variables into neurodegenerative risk models may enhance prevention strategies and support personalized interventions.