Abstract
INTRODUCTION: Both polymorphisms and mutations in GBA may influence the development of dementia in patients with Parkinson’s disease.
METHODS: 442 patients and 419 controls were followed for seven years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.
RESULTS: A total of 12.0% of patients with Parkinson’s disease carried a GBA variant, and nearly half (22/53) progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted HR 3.81, 95% CI 1.35 to 10.72; P = .011) or polymorphisms (adjusted HR 1.79; 95% CI 1.07 to 3.00; P = .028) progressed to dementia more rapidly than non-carriers.
DISCUSSION: GBA variants are of great clinical relevance for the development of dementia in Parkinson’s disease, especially due to the relatively higher frequency of these alleles compared to other risk alleles.
METHODS: 442 patients and 419 controls were followed for seven years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.
RESULTS: A total of 12.0% of patients with Parkinson’s disease carried a GBA variant, and nearly half (22/53) progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted HR 3.81, 95% CI 1.35 to 10.72; P = .011) or polymorphisms (adjusted HR 1.79; 95% CI 1.07 to 3.00; P = .028) progressed to dementia more rapidly than non-carriers.
DISCUSSION: GBA variants are of great clinical relevance for the development of dementia in Parkinson’s disease, especially due to the relatively higher frequency of these alleles compared to other risk alleles.
Original language | English |
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Pages (from-to) | 1293-1301 |
Number of pages | 9 |
Journal | Alzheimer's and Dementia |
Volume | 14 |
Issue number | 10 |
Early online date | 21 May 2018 |
DOIs | |
Publication status | Published - Oct 2018 |
Keywords
- Parkinson's disease
- Parkinson's disease with dementia
- GBA
- Longitudinal
- genetic association
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Profiles
-
Carl Counsell
- Clinical Medicine
- School of Medicine, Medical Sciences & Nutrition, Data Safe Haven
- School of Medicine, Medical Sciences & Nutrition, Chronic Disease Research Group
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Reader (Clinical)
- Institute of Applied Health Sciences
Person: Clinical Academic
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Angus MacLeod
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Senior Lecturer (Clinical)
- Clinical Medicine
- School of Medicine, Medical Sciences & Nutrition, Chronic Disease Research Group
Person: Clinical Academic