Identifying risk factors of young-onset dementia and evaluating evidence hierarchy: a meta-analysis and umbrella review - 01/01/26

Doi : 10.1016/j.tjpad.2025.100467

Jiayu Zhang ^a, Dandan Yang ^a, Jian Liang ^a, Yin Hu ^a, Liping Rao ^a, Jun Huang ^a, Qijun Wu ^b,^⁎ , Bo Jiang ^a,^⁎
^a Center of Clinical Pharmacology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
^b Department of Clinical Epidemiology, Clinical Research Center, Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China

^⁎Corresponding author at: Center of Clinical Pharmacology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88, Jiefang Road, Hangzhou 310009, China.Center of Clinical PharmacologyThe Second Affiliated HospitalZhejiang University School of MedicineNo. 88, Jiefang RoadHangzhou310009China^⁎⁎Corresponding author at: Department of Clinical Epidemiology, Clinical Research Center, Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang 110004, China.Department of Clinical EpidemiologyClinical Research CenterKey Laboratory of Precision Medical Research on Major Chronic DiseaseShengjing Hospital of China Medical UniversityNo. 36, San Hao StreetShenyang110004China

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Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 01 January 2026

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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