Geographical variation in dementia: systematic review with meta-analysis

Background Understanding geographical variation of dementia could highlight important modifiable socio-environmental risk factors. A previous systematic review (2012) identified an increased risk of Alzheimer dementia in in rural living in High-Income Countries (HICs), with a dearth of studies in Low to Middle-Income Countries (L-MICs). We updated this review to examine geographical variations in dementia, to encompass the growing number of studies in this field. Methods We systematically reviewed the literature for cross-sectional or longitudinal observational studies that compared dementia incidence or prevalence between two or more geographical areas including rural and urban settings. We conducted a narrative synthesis of included papers. Where possible, we undertook meta-analysis, generating odds ratios for rural versus urban dementia prevalence and stratified the analysis by HICs and L-MICs. Results We identified 38 relevant papers, encompassing approximately 98,502,147 people. Twenty-seven papers were included in the quantitative synthesis. Study methodologies varied widely. Dementia rates varied geographically (0.43-38.5%). Overall, rural living was associated with small increased odds of dementia (OR, 1.20, 95% CI 1.03-1.40; P value = 0.0182). Stratification by HICs and L-MICs demonstrated further variation, with increased odds of dementia in rural areas in L-MICs but not HICs. Conclusions There is some evidence of geographical variation of dementia. Rural living was associated with small increased odds of dementia, with stratification showing evidence in rural areas of L-MICs but not HICs. We believe this has not been reported previously. Future research must consider life course geographical exposure and addressing heterogeneity in definitions of ‘rural’ and ‘urban.’ What this study adds We confirm that rural living (compared to urban living) is associated with a small increased odds of dementia (OR 1.20, 95%CI 1.03-1.40). We demonstrate for the first time that this is driven by increased odds of dementia in rural areas in Low to Middle-Income Countries (L-MICs) rather than High Income Countries (HICs), and that the odds of dementia were higher in urban areas in large studies in HICs. Future studies need to carefully consider study setting, method of dementia ascertainment, when exposures may occur, and risk of bias, to understand the role of environment and geography in dementia risk. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement KEW was supported by clinical research fellowship from Alzheimer Scotland and the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing initiative (MR/L501530/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. KEW is also supported by Alzheimer Scotland Dementia Research Centre. JKB is supported by an NHS Education for Scotland/Chief Scientists Office Postdoctoral Clinical Lectureship (PCL/21/01). GMT is supported by the Osteopathic Heritage Foundation Ralph S. Licklider D.O. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Add data produced in the present study are available upon reasonable request to the authors.