# Identifying risk factors of young-onset dementia and evaluating evidence hierarchy: a meta-analysis and umbrella review

## TL;DR

This study identifies risk factors for young-onset dementia and evaluates how strong the evidence is for each.

## Contribution

The study is the first to systematically evaluate the strength of evidence for modifiable risk factors specific to young-onset dementia.

## Key findings

- Prior stroke was convincingly linked to increased risk of young-onset dementia.
- Alcohol use disorders, diabetes, and depression showed highly suggestive evidence of association with YOD.

## Abstract

Young-onset dementia (YOD) directly affects the working-age population. The premature onset of dementia intensifies peer caregiving responsibilities and diverts medical and nursing resources. While modifiable risk factors for late-onset dementia have been well established, uncertainty remains regarding the applicability of these findings to YOD. We aim to identify modifiable risk factors for YOD and evaluate the strength of evidence.

We searched PubMed, Embase, Web of Science, and Ovid Medline from inception to 22 May 2025 for epidemiological studies on non-genetic risk factors for YOD. We used random-effects meta-analyses with the inverse variance method to pool relative risks (RRs) and 95% confidence intervals (CIs). A series of statistical tests were designed to classify the strength of evidence of significant associations as convincing, highly suggestive, suggestive, or weak evidence.

From 25,731 initial and 2289 updated search records, 36 studies examining 31 non-genetic risk factors for YOD were identified. Of the 31 associations examined, 21 were nominally statistically significant at P < 0.05 based on random-effects models. Prior stroke was convincingly associated with an increased risk of YOD. Evidence of association was highly suggestive for alcohol use disorders, diabetes, depression, mood disorders, Parkinson's disease, multiple sclerosis, use of antidepressants/antipsychotics, and asthma.

We found that the risk of dementia in young individuals may be closely related to neuropsychiatric symptoms and clinical alcohol disorders. Future research should further validate these findings and explore intervention strategies to reduce dementia risk in younger individuals.

Image, graphical abstract