Identifying risk factors of young-onset dementia and evaluating evidence hierarchy: a meta-analysis and umbrella review.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of observational epidemiological studies
PubMed 41478824 · doi:10.1016/j.tjpad.2025.100467
What was done
Researchers conducted a systematic review, meta-analysis, and umbrella review searching PubMed, Embase, Web of Science, and Ovid Medline through May 22, 2025, for epidemiological studies examining non-genetic risk factors for young-onset dementia (YOD). They pooled relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses with the inverse variance method and categorized the strength of evidence into convincing, highly suggestive, suggestive, or weak tiers based on statistical criteria.
What was found
From 36 included studies evaluating 31 non-genetic risk factors, 21 associations reached nominal statistical significance (P < 0.05). Prior stroke was supported by convincing evidence for increased YOD risk. Highly suggestive evidence was found for alcohol use disorders, diabetes, depression, mood disorders, Parkinson's disease, multiple sclerosis, asthma, and the use of antidepressants/antipsychotics. Specific numerical effect sizes (RRs) and 95% CIs were not reported in the abstract.
Why it matters
This review establishes a graded hierarchy of modifiable and clinical risk factors specifically for young-onset dementia, highlighting cerebrovascular disease, psychiatric conditions, and alcohol use disorders as key targets for early intervention.
Limits
The abstract does not provide numerical effect estimates, confidence intervals, heterogeneity statistics, or the total number of individual participants across the 36 included studies. Inherent to observational study reviews, associations (particularly for psychiatric symptoms and psychotropic medications) may reflect reverse causality or residual confounding rather than direct causal pathways.
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