Funder: Academy of Medical Sciences; Id: http://dx.doi.org/10.13039/501100000691
Funder: American Parkinson Disease Association Center for Advanced Parkinson Research
Funder: BMA Doris Hillier award
Funder: Bupa Foundation; Id: http://dx.doi.org/10.13039/501100000355
Funder: Cure Parkinson's Trust
Funder: Erling‐Persson Foundation
Funder: European Research Council; Id: http://dx.doi.org/10.13039/501100000781
Funder: Hjärnfonden; Id: http://dx.doi.org/10.13039/501100003792
Funder: John and Lucille Van Geest Foundation; Id: http://dx.doi.org/10.13039/501100020410
Funder: Kempestiftelserna; Id: http://dx.doi.org/10.13039/501100007067
Funder: Knut och Alice Wallenbergs Stiftelse; Id: http://dx.doi.org/10.13039/501100004063
Funder: Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse; Id: http://dx.doi.org/10.13039/501100006129
Funder: Lockhart Parkinson's Disease Research Fund
Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100007155
Funder: Medicinska Forskningdet
Funder: NIHR Newcastle Biomedical Research Unit and Centre
Funder: NHS Grampian endowments
Funder: Norwegian Health Association; Id: http://dx.doi.org/10.13039/501100013263
Funder: Norwegian Parkinson's Research Foundation
Funder: Patrick Berthoud Trust
Funder: Rebergs Legacy
Funder: RS Macdonald Trust
Funder: SPRING; Id: http://dx.doi.org/10.13039/100001869
Funder: Swedish Parkinson Foundation
Funder: Umeå Universitet; Id: http://dx.doi.org/10.13039/501100004885
Funder: Västerbotten Läns Landsting; Id: http://dx.doi.org/10.13039/501100002960
Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269
Background: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson’s disease (PD), although studies have yielded mixed results. Objectives: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non‐selective, population‐based cohorts of newly diagnosed PD patients. Methods: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE ‐ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini‐Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini−Hochberg corrections. Results: Carriers of APOE‐ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE‐ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non‐carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. Conclusions: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society