Abstract
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 |
|---|---|
| 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 |
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Keywords
- Parkinson's disease
- Parkinson's disease with dementia
- GBA
- Longitudinal
- genetic association
Cite this
Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease. / Lunde, Kristin Aaser; Chung, Janete; Dalen, Ingvild; Pedersen, Kenn Freddy; Linder, Jan; Domellöf, Magdalena E.; Elgh, Eva; MacLeod, Angus; Tzoulis, Charalampos; Larsen, Jan Petter; Tysnes, Ole-Bjørn; Forsgren, Lars; Counsell, Carl E.; Alves, Guido; Maple-Grødem, Jodi (Corresponding Author).
In: Alzheimer's and Dementia, Vol. 14, No. 10, 10.2018, p. 1293-1301.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease
AU - Lunde, Kristin Aaser
AU - Chung, Janete
AU - Dalen, Ingvild
AU - Pedersen, Kenn Freddy
AU - Linder, Jan
AU - Domellöf, Magdalena E.
AU - Elgh, Eva
AU - MacLeod, Angus
AU - Tzoulis, Charalampos
AU - Larsen, Jan Petter
AU - Tysnes, Ole-Bjørn
AU - Forsgren, Lars
AU - Counsell, Carl E.
AU - Alves, Guido
AU - Maple-Grødem, Jodi
N1 - PINE was supported by Parkinson’s UK (grant numbers G0502, G0914, G1302), Scottish Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The Norwegian ParkWest study has been funded by the Research Council of Norway (grant number 177966), the Western Norway Regional Health Authority (grant number 911218), Stavanger University Hospital Research Funds (grant number 501611), and the Norwegian Parkinson’s Disease Association. Janete Chung and Kristin Aaser Lunde are supported by the Western Norway Regional Health Authority (grant numbers 911859 and 911830). The NYPUM study has been funded by the Swedish Medical Research Council, the Swedish Parkinson’s Disease Association, the Swedish Parkinson Foundation, Erling Persson Foundation, Kempe Foundation and the Västerbotten County Council. The funding sources had no role in the design and conduct of the study: collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript: and decision to submit the manuscript for publication.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - Parkinson's disease with dementia
KW - GBA
KW - Longitudinal
KW - genetic association
U2 - 10.1016/j.jalz.2018.04.006
DO - 10.1016/j.jalz.2018.04.006
M3 - Article
VL - 14
SP - 1293
EP - 1301
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 10
ER -