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

doi:10.1016/j.jalz.2018.04.006

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 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	https://doi.org/10.1016/j.jalz.2018.04.006
Publication status	Published - Oct 2018

Keywords

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

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© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 4.51 MBLicence: CC BY-NC-ND

Carl Counsell
Person: Clinical Academic
Angus MacLeod
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Senior Lecturer (Clinical)
- School of Medicine, Medical Sciences & Nutrition, Chronic Disease Research Group
Person: Clinical Academic

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Lunde, K. A., Chung, J., Dalen, I., Pedersen, K. F., Linder, J., Domellöf, M. E., Elgh, E., MacLeod, A., Tzoulis, C., Larsen, J. P., Tysnes, O-B., Forsgren, L., Counsell, C. E., Alves, G., & 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

Lunde, KA, Chung, J, Dalen, I, Pedersen, KF, Linder, J, Domellöf, ME, Elgh, E, MacLeod, A, Tzoulis, C, Larsen, JP, Tysnes, O-B, Forsgren, L, Counsell, CE, Alves, G & Maple-Grødem, J 2018, 'Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease', Alzheimer's and Dementia, vol. 14, no. 10, pp. 1293-1301. https://doi.org/10.1016/j.jalz.2018.04.006

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title = "Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease",

abstract = "INTRODUCTION: Both polymorphisms and mutations in GBA may influence the development of dementia in patients with Parkinson{\textquoteright}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{\textquoteright}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{\textquoteright}s disease, especially due to the relatively higher frequency of these alleles compared to other risk alleles.",

keywords = "Parkinson's disease, Parkinson's disease with dementia, GBA, Longitudinal, genetic association",

author = "Lunde, {Kristin Aaser} and Janete Chung and Ingvild Dalen and Pedersen, {Kenn Freddy} and Jan Linder and Domell{\"o}f, {Magdalena E.} and Eva Elgh and Angus MacLeod and Charalampos Tzoulis and Larsen, {Jan Petter} and Ole-Bj{\o}rn Tysnes and Lars Forsgren and Counsell, {Carl E.} and Guido Alves and Jodi Maple-Gr{\o}dem",

note = "PINE was supported by Parkinson{\textquoteright}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{\textquoteright}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{\textquoteright}s Disease Association, the Swedish Parkinson Foundation, Erling Persson Foundation, Kempe Foundation and the V{\"a}sterbotten 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.",

year = "2018",

month = oct,

doi = "10.1016/j.jalz.2018.04.006",

language = "English",

volume = "14",

pages = "1293--1301",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "10",

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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 -

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

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Angus MacLeod

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