Epidemiology and risk factors of Alzheimer's disease and related dementias in South and Southeast Asia: a systematic review and meta-analysis protocol

Abstract

Background: Alzheimer's disease (AD) impacts over 55 million individuals worldwide and remains the leading cause of dementia (60-70% of cases). By 2050, South and Southeast Asia are projected to have an older adult population more than double, bearing a major share of Alzheimer's disease burden. This will exert a heavy strain on healthcare systems, particularly in resource-limited countries where support and infrastructure are already stretched. Despite this, no review has yet explored the regional epidemiology and associated risk factors in this context. Thus, this study protocol outlines to synthesise prevailing evidence from these densely populated regions, particularly low- and middle-income nations within South and Southeast Asia.

Methods: This review will include studies that reported epidemiological characteristics including prevalence, age of onset, mortality, and risk factors of AD and related dementias comprising in South and Southeast Asian regions. Studies published in any language from inception to date will be extracted from PubMed, Scopus, CINAHL, EMBASE and APA PsycNet, following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We will also search grey literature sources and screen the reference lists of the articles selected for full-text review to identify additional relevant studies. Observational studies including case-control, cohort, and cross-sectional designs reporting desired outcomes will be included and appraised for quality assessment with the modified Newcastle-Ottawa Scale (mNOS). The included articles will be appraised by two independent reviewers, with a third resolving any conflicts. Pooled estimates of prevalence, age of onset and mortality will be analysed using random effect meta-analysis (REML) model. Associated risk factors, including modifiable and non-modifiable will be narratively synthesised. Forest plots will be used to visualise the findings, and heterogeneity across the included studies will be assessed using the I² and Cochrane's Q statistics. Potential publication bias will be assessed using a funnel plot along with the Begg's and Egger's tests. Sensitivity and subgroup analyses will also be conducted to assess the robustness of pooled estimates and to explore potential sources of heterogeneity. Statistical analysis will be conducted using Rstudio (v.4.3.2) and GraphPad Prism V.9.0.2.

Ethics and disseminations: The systematic review is focused on the analysis of secondary data from published literature; thus, no ethical approval will be needed. The protocol will follow international standard guidelines, findings will be reported in a reputed journal and disseminated through (inter)national conferences, webinars and key stakeholders to inform policy, research and AD management strategies.

Prospero registration number: CRD 420251047105.

Keywords: Dementia; EPIDEMIOLOGY; Meta-Analysis; Risk Factors; Systematic Review.

Figure 1. Distribution of Alzheimer’s disease rates across South and Southeast Asian countries. The map showing the geographic variation of Alzheimer’s disease prevalence rates (cases per 10 000 population) from the World Population Review Databases, 2025, highlighting differences across South and Southeast Asian countries as well as high-, upper-middle- and low-middle-income countries in these regions.

Figure 2. PRISMA flow diagram for overall study procedure. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram outlining the selection process of studies included in the systematic review searched from six (PubMed, Scopus, CINAHL, EMBASE and APA PsycNet) electronic databases from inception to 1^st May 2025.

Figure 3. Systematic process of articles screening for final inclusion. The down-drop flowchart illustrating stepwise depiction of the article screening procedure leading to final study inclusion.

Figure 4. Forest and funnel plot for meta-analysis. Forest and funnel plots demonstrating the meta-analysis of selected outcomes across a sample of 10 included studies. (A) Forest plot showing Odds Ratios (ORs) comparison. (B) Funnel plot showing publication bias detection.

Figure 5. PICO (P: Population, I: Intervention, C: Condition, and O: Outcome) framework and co-occurrence network of key search terms. Cluster illustration of PICO framework highlighting the key components of the research question, alongside a co-occurrence network of key search terms used during the systematic search process.