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Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease
Author(s) -
Lunde Kristin Aaser,
Chung Janete,
Dalen Ingvild,
Pedersen Kenn Freddy,
Linder Jan,
Domellöf Magdalena E.,
Elgh Eva,
Macleod Angus D.,
Tzoulis Charalampos,
Larsen Jan Petter,
Tysnes OleBjørn,
Forsgren Lars,
Counsell Carl E.,
Alves Guido,
MapleGrødem Jodi
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.04.006
Subject(s) - glucocerebrosidase , dementia , hazard ratio , confidence interval , parkinson's disease , allele , medicine , disease , oncology , proportional hazards model , genetics , biology , gene
Both polymorphisms and mutations in glucocerebrosidase ( GBA ) may influence the development of dementia in patients with Parkinson's disease. Methods Four hundred forty‐two patients and 419 controls were followed for 7 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) of them progressed to dementia during follow‐up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers. 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 with other risk alleles.