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

Ya-Ru Zhang; Wei Xu; Wei Zhang; Hui-Fu Wang; Ya-Nan Ou; Yi Qu; Xue-Ning Shen; Shi-Dong Chen; Kai-Min Wu; Qian-Hua Zhao; Hai-Ning Zhang; Li Sun; Qiang Dong; Lan Tan; Lei Feng; Can Zhang; Evangelos Evangelou; A David Smith; Jin-Tai Yu

doi:10.1016/j.jad.2022.07.008

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

J Affect Disord. 2022 Oct 1:314:160-167. doi: 10.1016/j.jad.2022.07.008. Epub 2022 Jul 19.

Authors

Ya-Ru Zhang¹, Wei Xu², Wei Zhang³, Hui-Fu Wang², Ya-Nan Ou², Yi Qu², Xue-Ning Shen¹, Shi-Dong Chen¹, Kai-Min Wu¹, Qian-Hua Zhao¹, Hai-Ning Zhang⁴, Li Sun⁴, Qiang Dong¹, Lan Tan², Lei Feng⁵, Can Zhang⁶, Evangelos Evangelou⁷, A David Smith⁸, Jin-Tai Yu⁹

Affiliations

¹ Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
² Department of Neurology, Qingdao Municipal Hospital Group, Qingdao University, Qingdao, China.
³ The Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.
⁴ Department of Neurology and Neuroscience Center, First Hospital of Jilin University, Changchun, China.
⁵ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁶ Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
⁷ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁸ Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
⁹ Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: jintai_yu@fudan.edu.cn.

PMID: 35863541
DOI: 10.1016/j.jad.2022.07.008

Abstract

Background: 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.

Methods: 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.

Results: 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.

Limitations: Low quality of the studies included.

Conclusions: 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.

Keywords: Alzheimer's disease; Cognitive impairment; Dementia; Risk factors; Umbrella review.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / epidemiology
Alzheimer Disease* / etiology
Blood Glucose
Cognitive Dysfunction* / epidemiology
Humans
Prospective Studies
Risk Factors
Systematic Reviews as Topic

Substances

Blood Glucose