Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

Kristin Aaser Lunde, Janete Chung, Ingvild Dalen, Kenn Freddy Pedersen, Jan Linder, Magdalena E. Domellöf, Eva Elgh, Angus MacLeod, Charalampos Tzoulis, Jan Petter Larsen, Ole-Bjørn Tysnes, Lars Forsgren, Carl E. Counsell, Guido Alves, Jodi Maple-Grødem (Corresponding Author)

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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.
Original languageEnglish
Pages (from-to)1293-1301
Number of pages9
JournalAlzheimer's and Dementia
Volume14
Issue number10
Early online date21 May 2018
DOIs
Publication statusPublished - Oct 2018

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Keywords

  • Parkinson's disease
  • Parkinson's disease with dementia
  • GBA
  • Longitudinal
  • genetic association

Cite this

Lunde, K. A., Chung, J., Dalen, I., Pedersen, K. F., Linder, J., Domellöf, M. E., ... Maple-Grødem, J. (2018). Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease. Alzheimer's and Dementia, 14(10), 1293-1301. https://doi.org/10.1016/j.jalz.2018.04.006