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Predictors of cognitive impairment in Parkinson’s disease: a systematic review and meta-analysis of prospective cohort studies

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Abstract

Introduction

Cognitive impairment is a debilitating manifestation in Parkinson’s disease (PD). We sought to investigate predictors of PD-CI (PD with cognitive impairment).

Methods

We systematically searched PubMed and Cochrane Library for prospective cohort studies and pooled estimates via random-effects models. Primary analyses for all types of cognitive impairments and subgroup analyses by separate outcomes were conducted.

Results

A total of 28,009 studies were identified, of which 57 studies with 31 factors were included in the meta-analysis. In the primary analysis, 13 factors were associated with PD-CI, comprising advanced age [relative risk (RR) = 1.07, 95% confidence interval (CI) = 1.03–1.12], age at onset (RR = 4.43, 95% CI = 1.87–10.54), postural-instability-gait disorder (RR = 3.76, 95% CI = 1.36–10.40), higher Hoehn and Yahr stage (RR = 1.83, 95% CI = 1.35–2.47), higher UPDRS III score (RR = 1.04, 95% CI = 1.01–1.08), rapid eye movement sleep behavior disorder (RR = 3.72, 95% CI = 1.20–11.54), hallucinations (RR = 3.09, 95% CI = 1.61–5.93), orthostatic hypotension (RR = 2.98, 95% CI = 1.41–6.28), anxiety (RR = 2.59, 95% CI = 1.18–5.68), APOE ε2 (RR = 6.47, 95% CI = 1.29–32.53), APOE ε4 (RR = 3.04, 95% CI = 1.88–4.91), electroencephalogram theta power > median (RR = 2.93, 95% CI = 1.61–5.33), and alpha power < median (RR = 1.77, 95% CI = 1.07–2.92). In the subgroup analysis, MAPT H1/H1 genotype increased the risk of dementia in PD. Sixty-four studies were included in the systematic review, of which 12 factors were additionally correlated with PD-CI using single studies.

Conclusions

Advanced age, genetic variation in APOE and MAPT, gait disturbance, motor assessments, non-motor symptoms, and electroencephalogram may be promising predictors for PD-CI.

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Acknowledgements

This study was supported by Grants from the National Key R&D Program of China (2018YFC1314700), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01) and ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, 266071, China

    Yu Guo, Xiao-He Hou, Jie-Qiong Li, Xi-Peng Cao & Lan Tan

  2. Department of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai, 200040, China

    Feng-Tao Liu, Jian Wang & Jin-Tai Yu

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  1. Yu Guo
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Contributions

JTY conceptualized and designed the study. YG, FTL, and XHH conducted the study. YG, XHH, and JTY analyzed and extracted data. YG, XHH, FTL, LT, JW, and JTY wrote the first draft of the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Lan Tan, Jian Wang or Jin-Tai Yu.

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None authors have financial disclosures and conflicts of interest.

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The manuscript does not contain clinical studies or patient data. No additional ethics approval was required for this systematic review and meta-analysis.

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Guo, Y., Liu, FT., Hou, XH. et al. Predictors of cognitive impairment in Parkinson’s disease: a systematic review and meta-analysis of prospective cohort studies. J Neurol 268, 2713–2722 (2021). https://doi.org/10.1007/s00415-020-09757-9

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  • DOI: https://doi.org/10.1007/s00415-020-09757-9

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