Abstract
BackgroundThe etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.MethodsWe performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.ResultsWe identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.ConclusionsWe identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
Highlights
The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated
Search strategy and eligibility criteria Using a standardized search strategy, which was specified according to each database, we systematically explored the following databases: MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO, registered up to September 20th, 2018, in order to identify umbrella reviews analyzing associations of non-purely genetic risk and protective factors with multiple chronic neurological disorders or umbrella reviews of single such factors with multiple clinical outcomes, in alignment with the WHO definition of neurological disorders [61] (Appendix 2)
In the single umbrella review comparing meta-analyses of observational studies with randomized controlled trials, there was no discordant direction of results with regard to neurological disorders [52]
Summary
The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases. Despite the high contribution of these nosological entities to the Global Burden of Disease, there has been only partial elucidation of their etiologies (for a discussion, which extends this study’ aims on the potential communicable etiology of such non-communicable diseases, see [4]). This important gap lies in contrast to other diseases, such as cancer and cardiovascular disorders, where research efforts have been far more prolific. The aging process encompasses the (patho) physiological unfolding of life, as well as the contribution of genetic and lifestyle determinants [33]
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