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