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GBA and APOE impact...
GBA and APOE impact cognitive decline in Parkinson's disease : A 10-year population-based study
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Szwedo, Aleksandra A (author)
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Dalen, Ingvild (author)
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Pedersen, Kenn Freddy (author)
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Camacho, Marta (author)
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- Bäckström, David C, M.D. 1978- (author)
- Umeå universitet,Neurovetenskaper,Department of Neurology, and Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut, USA
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- Forsgren, Lars (author)
- Umeå universitet,Neurovetenskaper
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Tzoulis, Charalampos (author)
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Winder-Rhodes, Sophie (author)
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Hudson, Gavin (author)
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Liu, Ganqiang (author)
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Scherzer, Clemens R (author)
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Lawson, Rachael A (author)
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Yarnall, Alison J (author)
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Williams-Gray, Caroline H (author)
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Macleod, Angus D (author)
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Counsell, Carl E (author)
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Tysnes, Ole-Bjørn (author)
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Alves, Guido (author)
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Maple-Grødem, Jodi (author)
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(creator_code:org_t)
- 2022-02-02
- 2022
- English.
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In: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 37:5, s. 1016-1027
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Abstract
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- BACKGROUND: Common genetic variance in apolipoprotein E (APOE), β-glucocerebrosidase (GBA), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.OBJECTIVES: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non-selective, population-based cohorts of newly diagnosed PD patients.METHODS: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE-ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini-Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini-Hochberg corrections.RESULTS: Carriers of APOE-ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE-ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non-carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219.CONCLUSIONS: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- APOE
- GBA
- Parkinson's disease
- cognitive decline
- dementia
- Human Anatomy
- anatomi
- nanomaterials
- nanomaterial
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Szwedo, Aleksand ...
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Dalen, Ingvild
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Pedersen, Kenn F ...
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Camacho, Marta
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Bäckström, David ...
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Forsgren, Lars
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show more...
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Tzoulis, Charala ...
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Winder-Rhodes, S ...
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Hudson, Gavin
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Liu, Ganqiang
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Scherzer, Clemen ...
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Lawson, Rachael ...
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Yarnall, Alison ...
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Williams-Gray, C ...
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Macleod, Angus D
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Counsell, Carl E
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Tysnes, Ole-Bjør ...
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Alves, Guido
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Maple-Grødem, Jo ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Movement Disorde ...
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Umeå University