Systematic evaluation of the associations between environmental risk factors and dementia: An umbrella review of systematic reviews and meta-analyses.
BACKGROUND
Dementia is a heterogeneous neurodegenerative disease, whose etiology results from a complex interplay between environmental and genetic factors.


METHODS
We searched PubMed to identify meta-analyses of observational studies that examined associations between nongenetic factors and dementia. We estimated the summary effect size using random-effects and fixed-effects model, the 95% CI, and the 95% prediction interval. We assessed the between-study heterogeneity (I-square), evidence of small-study effects, and excess significance.


RESULTS
A total of 76 unique associations were examined. By applying standardized criteria, seven associations presented convincing evidence. These associations pertained to benzodiazepines use, depression at any age, late-life depression, and frequency of social contacts for all types of dementia; late-life depression for Alzheimer's disease; and type 2 diabetes mellitus for vascular dementia and Alzheimer's disease.


CONCLUSIONS
Several risk factors present substantial evidence for association with dementia and should be assessed as potential targets for interventions, but these associations may not necessarily be causal.
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
Vanesa
V
Bellou
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
Lazaros
L
Belbasis
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; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Ioanna
I
Tzoulaki
Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London, UK.
Lefkos T
LT
Middleton
Department of Medicine, Stanford Prevention Research Center, Stanford, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA; Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA.
John P A
JPA
Ioannidis
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. Electronic address: vangelis@cc.uoi.gr.
Evangelos
E
Evangelou
D003704:Dementia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015201:Meta-Analysis as Topic; D012307:Risk Factors; D000078202:Systematic Reviews as Topic
Alzheimer's disease; Dementia; Epidemiology; Risk factors; Umbrella review