GBA and APOE Impact Cognitive Decline in Parkinson's Disease: A 10-Year Population-Based Study
Szwedo, Aleksandra Anna; Dalen, Ingvild; Pedersen, Kenn Freddy; Camacho, Marta; Bäckström, David; Forsgren, Lars; Tzoulis, Charalampos; Winder-Rhodes, Sophie; Hudson, Gavin; Liu, Ganqiang; Scherzer, Clemens R.; Lawson, Rachael A.; Yarnall, Alison J.; Williams-Gray, Caroline H.; Macleod, Angus D.; Counsell, Carl E.; Tysnes, Ole-Bjørn; Alves, Guido Werner; Maple-Grødem, Jodi
Journal article, Peer reviewed
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Date
2022Metadata
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- Department of Clinical Medicine [2213]
- Registrations from Cristin [11365]
Abstract
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