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Systematic review of genetic variants associated with cognitive impairment and depressive symptoms in Parkinson’s disease

Published online by Cambridge University Press:  27 August 2019

Tyrra D’Souza  and
Anto P. Rajkumar Open the ORCID record for Anto P. Rajkumar [Opens in a new window]
Tyrra D’Souza
Affiliation:
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King’s College London, 16, De Crespigny Park, London-SE5 8AF, UK
Anto P. Rajkumar*
Affiliation:
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King’s College London, 16, De Crespigny Park, London-SE5 8AF, UK Mental Health of Older Adults and Dementia Clinical Academic Group, South London and Maudsley NHS foundation Trust, 115, Denmark Hill, London-SE5 8AQ, UK
*
Author for correspondence: Anto P. Rajkumar, E-mail: [email protected]
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Abstract

Objective:

Cognitive impairment and depression are among the most prevalent and most disabling non-motor symptoms in Parkinson’s disease (PD). The genetic factors that are associated with these symptoms remain uncertain. This systematic review aims to summarise the prevailing evidence from all genetic association studies investigating the genetic variants associated with cognitive impairment and depressive symptoms in people with PD.

Method:

A systematic review using five online databases: PubMed, PsycINFO, CINAHL, EMBASE and OpenGrey (PROSPERO protocol: CRD42017067431). We completed the quality assessment using the Q-Genie tool.

Results:

2353 articles were screened, and 43 articles were found to be eligible to be included. A meta-analysis of studies investigating LRRK2 rs34637584 confirmed that the minor allele carriers had significantly less cognitive impairment (p = 0.015). Further meta-analyses showed that GBA variants rs76763715 (p < 0.001) and rs421016 (p = 0.001) were significantly associated with more cognitive impairment in people with PD. Minor alleles of GBA variants rs76763715, rs421016, rs387906315 and rs80356773 were associated with more depressive symptoms in PD. Moreover, APOE ε4 allele has been associated with more cognitive impairment in PD. BDNF (rs6265) and CRY1 (rs2287161) variants have been associated with more depressive symptoms in people with PD.

Conclusions:

PD carriers of GBA variants are at high risk for cognitive decline and depression. Screening for these variants may facilitate early identification and effective management of these non-motor symptoms. The molecular mechanisms underlying favourable cognitive functioning in LRRK2 rs34637584 variant carriers warrant further investigation.

Keywords

cognitiondepressionParkinson’s diseasesystematic review
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 1 , February 2020 , pp. 10 - 22
Copyright
© Scandinavian College of Neuropsychopharmacology 2019 

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