Cold Climate Exposure and Alzheimer’s Disease: A Systematic Review Demonstrating Epidemiological Associations and Biological Mechanisms

Background: Growing evidence suggests cold climate exposure may influence Alzheimer's disease (AD) pathogenesis through vascular, inflammatory, and metabolic pathways.

Objective: To systematically evaluate the association between cold exposure and AD risk/progression through epidemiological and mechanistic evidence.

Methods: A systematic search of PubMed, Scopus, and Web of Science (2000–2023) was conducted following PRISMA guidelines.  Included studies examined: 1) epidemiological associations between cold climates and AD incidence and 2) biological mechanisms linking cold exposure to AD pathology.

Results: From 1,200 identified records, 48 studies met inclusion criteria.  Meta-analysis of 12 epidemiological studies showed colder regions had 20% higher AD incidence (RR=1.20, 95%CI:1.12-1.28).  Mechanistic studies revealed cold exposure:

·         Reduces cerebral blood flow (15-30% decrease)

·         Increases blood-brain barrier permeability (2-fold in animal models)

·         Elevates pro-inflammatory cytokines (IL-6↑40-60%)

·         Impairs amyloid-β clearance (glymphatic function↓25-50%)

Conclusion: Cold climate is associated with increased AD risk through multiple biological pathways.  These findings highlight the need for climate-adaptive prevention strategies in vulnerable populations.