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Table 1 Protective factors that are common in non-communicable neurological disorders (i.e., found in more than one disease under consideration)

From: Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews

Factor

Effect size metric

Effect size (95% CI)

Neurological condition (systematic review/meta-analysis)

Level of evidence

Umbrella review study

Mediterranean diet

RR

0.83 (0.75–0.93)

Mild cognitive impairment incidence (Wu, 2017) @

IV

Galbete, 2018 [84]; Dinu, 2018# [81]

RR

0.60 (0.48–0.77)

Alzheimer disease (Wu, 2017) @

IV

Galbete, 2018 [84]; Dinu, 2018# [81]

RR

0.69 (0.57–0.84)

Mild cognitive impairment incidence/Dementia (Cao, 2016) @

IV

Galbete, 2018 [84]

HR

0.73 (0.56–0.96)

Mild cognitive impairment incidence (Singh, 2014) @

IV

Galbete, 2018 [84]

RR

0.64 (0.46–0.89)

Alzheimer disease incidence (Singh, 2014) @

IV

Galbete, 2018 [84]

RR

0.84 (0.74–0.95)

Stroke (Psaltopoulou, 2013; Cohort studies) @

IV

Galbete, 2018 [84]

Dinu, 2018# [81]

RR

0.20 (0.10–0.41)

Stroke (Psaltopoulou, 2013; Case-control studies) @

Weak

Dinu, 2018 [81]

RR

0.83 (0.66–1.06)

Stroke (Psaltopoulou, 2013; Cross-sectional studies) @

No evidence

Dinu, 2018 [81]

RR

0.76 (0.60–0.96)

Stroke (Grosso, 2014; Cohort studies) @

Weak

Dinu, 2018 [81]

RR

0.87 (0.81–0.94)

Neurodegenerative diseases (Sofi, 2014) @

Convincing

Dinu, 2018 [81]

RR

0.79 (0.70–0.90)

Neurodegenerative diseases (Wu, 2017) @

Highly suggestive

Dinu, 2018 [81]

RR

0.72 (0.58–0.88)

Cognitive impairment (Psaltopoulou, 2013; Cohort studies) @

Suggestive

Dinu, 2018 [81]

HR

0.67 (0.55–0.81)

Cognitive impairment (Singh, 2014; High-vs.-low MeDi score) @

Suggestive

Dinu, 2018 [81]

HR

0.92 (0.88–0.97)

Cognitive impairment (Singh, 2014; 1-point increase in MeDi score) @

Suggestive

Dinu, 2018 [81]

RR

0.31 (0.16–0.59)

Cognitive impairment (Psaltopoulou, 2014; Case-control) @

Weak

Dinu, 2018 [81]

RR

0.83 (0.75–0.93)

Cognitive impairment (Wu, 2017) @

Highly suggestive

Dinu, 2018 [81]

RR

0.69 (0.57–0.84)

Dementia

Convincing

Dinu, 2018 [81]

RR

0.64 (0.47–0.86)

Stroke (Grosso, 2014; Randomized trials) @

Weak

Dinu, 2018 [81]

Caffeine

RR

0.67 (0.57–0.80)

Parkinson disease

Probable

Grosso, 2017 [76]

N/SP

0.78 (0.50–1.22)

Alzheimer disease

Limited

Grosso, 2017 [76]

N/SP

0.79 (0.61–1.04)

Cognitive impairment

Limited

Grosso, 2017 [76]

N/SP

0.82 (0.67–1.01)

Cognitive disorders

Possible

Grosso, 2017 [76]

Coffee consumption

RR

0.97 (0.85–1.11)

Cognitive decline

6*

Poole, 2017 [79]

RR

0.96 (0.83–1.11)

Stroke

8*

Poole, 2017 [79]

RR

0.98 (0.79–1.23)

Glioma

5*

Poole, 2017 [79]

RR

0.64 (0.53–0.76)

Parkinson disease (Qi, 2014) @

5*

Poole, 2017 [79]

RR

0.64 (0.53–0.77)

Parkinson disease (Noyce, 2012) @

7*

Poole, 2017 [79]

RR

0.73 (0.54–0.99)

Alzheimer disease (Barranco Quintana, 2017) @

3*

Poole, 2017 [79]

RR

0.70 (0.56–0.88)

Parkinson disease (Hernan, 2002) @

Probable

Grosso, 2017 [76]

RR

0.73 (0.55–0.97)

Alzheimer disease (Liu, 2016) @

Possible

Grosso, 2017 [76]

RR

0.67 (0.58–0.76)

Parkinson disease (Noyce, 2012)@

III

Bellou, 2016 [50]

Alcohol intake

RR

0.74 (0.61–0.91)

Dementia

Weak

Bellou, 2017 [49]

RR

0.75 (0.57–0.98)

Vascular dementia

Weak

Bellou, 2017 [49]

RR

0.72 (0.61–0.86)

Alzheimer disease

Weak

Bellou, 2017 [49]

RR

0.75 (0.66–0.85)

Parkinson disease

III

Bellou, 2016 [50]

Physical activity

RR

0.76 (0.66–0.86)

Dementia

Suggestive

Bellou, 2017 [49]

RR

0.62 (0.42–0.92)

Vascular dementia

Weak

Bellou, 2017 [49]

HR

0.66 (0.57–0.78)

Parkinson disease

I

Bellou, 2016 [50]

HR

0.62 (0.52–0.72)

Alzheimer disease

Highly suggestive

Bellou, 2017 [49]

Bone mineral density in femoral neck

OR

0.36 (0.21–0.61)

Multiple sclerosis

Weak

Belbasis, 2015 [18, 51]

OR

0.25 (0.09–0.66)

Parkinson disease

IV

Bellou, 2016 [50]

Bone mineral density in hip

OR

0.33 (0.18–0.60)

Multiple sclerosis

Weak

Belbasis, 2015 [18, 51]

OR

0.55 (0.38–0.80)

Parkinson disease

IV

Bellou, 2016 [50]

Bone mineral density in lumbar spine

OR

0.34 (0.24–0.50)

Multiple sclerosis

Weak

Belbasis, 2015 [18, 51]

OR

0.29 (0.16–0.54)

Parkinson disease

IV

Bellou, 2016 [50]

Serum vitamin D

SMD to RR

0.08 (0.01–0.63)

Alzheimer disease

No conclusion

Theodoratou, 2014 [52]

OR

0.42 (0.34–0.53)

Cognition

Suggestive

Theodoratou, 2014 [52]

RR

0.61 (0.50–0.75)

Stroke

Suggestive

Theodoratou, 2014 [52]

HR

0.66 (0.55–0.80)

Ischemic stroke

Suggestive

Theodoratou, 2014 [52]

OR

0.52 (0.44–0.61)

Ischemic stroke

Suggestive

Theodoratou, 2014 [52]

OR

0.16 (0.05–0.50)

Parkinson disease

IV

Bellou, 2016 [50]

OR

0.44 (0.24–0.70)

Multiple sclerosis

Weak

Belbasis, 2015 [18, 51]

Serum vitamin B12

OR

0.64 (0.44–0.93)

Multiple sclerosis

Suggestive

Belbasis, 2015 [18, 51]

OR

0.50 (0.40–0.63)

Parkinson disease

IV

Bellou, 2016 [50]

Vitamin E dietary intake

RR

0.80 (0.67–0.95)

Alzheimer disease

Weak

Bellou, 2017 [49]

OR

0.81 (0.67–0.98)

Parkinson disease

IV

Bellou, 2016 [50]

Statins

RR

0.83 (0.76–0.91)

Dementia

Suggestive

Bellou, 2017 [49]

RR

0.72 (0.59–0.89)

Alzheimer disease

Weak

Bellou, 2017 [49]

RR

0.77 (0.64–0.92)

Parkinson disease

IV

Bellou, 2016 [50]

Antihypertensive drugs

HR

0.84 (0.75–0.94)

Dementia

Weak

Bellou, 2017 [49]

RR

0.64 (0.42–0.98)

Vascular dementia

Weak

Bellou, 2017 [49]

Non-aspirin NSAIDS

RR

0.85 (0.77–0.94)

Parkinson disease

IV

Bellou, 2016 [50]

RR

0.65 (0.49–0.86)

Alzheimer disease

Weak

Bellou, 2017 [49]

  1. Abbreviations: N/A not available, OR odds ratio, RR relative risk, HR hazard ratio, SMD standardized mean difference, N/SP not specified (either OR or RR), 95% CI 95% confidence interval
  2. *According to AMSTAR classification. # Overlapping studies. @These refer to metrics (e.g., RRs, HRs) of the original systematic reviews included in the umbrella reviews. The full citations of these original systematic reviews/meta-analyses are included in the corresponding umbrella reviews
  3. Note: In this table, only statistically significant risk factors that appeared in more than two studies are included