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
Peer reviewed, Journal article
Published version

Date
2022Metadata
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Original version
Szwedo, A. A., Dalen, I., Pedersen, K. F., Camacho, M., Bäckström, D., Forsgren, L., ... & Parkinson's Incidence Cohorts Collaboration. (2022). GBA and APOE impact cognitive decline in Parkinson's disease: a 10‐year population‐based study. Movement Disorders, 37(5), 1016-1027. 10.1002/mds.28932Abstract
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.