Modifiable risk factors for cognitive impairment in Parkinson's disease: A systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Cognitive impairment is a common and devastating manifestation in Parkinson's disease (PD). We aimed to identify modifiable risk factors for PD with cognitive impairment. METHODS: We systematically searched PubMed and the Cochrane Library from June 1937 to September 2018 and included prospective cohort studies with random-effects model used to combine estimates. Primary analyses for all types of cognitive impairments and subgroup analyses for separate outcomes were conducted. RESULTS: A total of 31,298 articles were identified, of which 32 articles with 18 factors met the inclusion criteria for meta-analysis. In the primary analysis, 9 modifiable risk factors were found to increase the risk of PD with cognitive impairment, including postural-instability-gait disorder (relative risk = 3.76, 95% confidence interval = 1.36-10.40), hallucinations (relative risk = 3.09, 95% confidence interval = 1.61-5.93), orthostatic hypotension (relative risk = 2.98, 95% confidence interval = 1.41-6.28), cerebrovascular disease (relative risk = 1.52, 95% confidence interval = 1.01-2.28), diabetes mellitus (relative risk = 1.47, 95% confidence interval = 1.13-1.92), obesity (relative risk = 1.38, 95% confidence interval = 1.15-1.65), cardiac disease (relative risk = 1.35, 95% confidence interval = 1.17-1.56), alcohol consumption (relative risk = 1.32, 95% confidence interval = 1.15-1.52), and smoking (relative risk = 1.31, 95% confidence interval = 1.14-1.50). In the subgroup analysis, postural-instability-gait disorder subtype, orthostatic hypotension and hallucinations may increase the risk of dementia in PD. A total of 37 articles were included in the systematic review, in which 9 risk factors and 1 protective factor were additionally associated in single studies with the risk of PD with cognitive impairment, and 5 factors were associated with specific cognition domains. CONCLUSIONS: Effective interventions in the management of PD symptoms, comorbidities, and lifestyles may be promising to reduce PD with cognitive impairment risk. © 2019 International Parkinson and Movement Disorder Society.