Modifiable risk factors for incident dementia and cognitive impairment: An umbrella review of evidence

Dementia and cognitive impairment can be attributed to genetic and modifiable factors. Considerable evidence emerged in modifiable factors and urgently requires standardized evaluation. We conducted an umbrella review to evaluate the strength and validity of the existing evidence.We searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors. For each association, we analyzed the summary effect size, 95 % confidence interval, 95 % prediction interval, heterogeneity, small study effect and excess significance bias. Mendelian randomization studies were descriptively reviewed further exploring the causality of the associations.In total, 12,015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, BMI, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for that of midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified causal relationships of education and plasma glucose with Alzheimer's disease.Low quality of the studies included.Modifiable risk factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Our results support a valuable rationale for future experimental designs to establish further evidence for the associations in larger populations.