The impact of common genetic variants in cognitive decline in the first seven years of Parkinson’s disease: A longitudinal observational study,Neuroscience Letters

当前位置： X-MOL 学术 › Neurosci. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

The impact of common genetic variants in cognitive decline in the first seven years of Parkinson’s disease: A longitudinal observational study
Neuroscience Letters ( IF 2.5 ) Pub Date : 2021-09-10 , DOI: 10.1016/j.neulet.2021.136243
Janete Chung ₁ , Anastasia Ushakova ₂ , Maria Doitsidou ₃ , Charalampos Tzoulis ₄ , Ole-Bjørn Tysnes ₅ , Ingvild Dalen ₂ , Kenn Freddy Pedersen ₆ , Guido Alves ₇ , Jodi Maple-Grødem ₈

Affiliation

The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
Department of Research, Section of Biostatistics, Stavanger University Hospital, Stavanger, Norway.
Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK.
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Norway.
The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway.
The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.

Introduction

Cognitive impairment is a common feature of Parkinson’s disease and is a significant determinant of patients’ quality of life and dependence. The pattern and progression of cognitive symptoms vary greatly between individuals, and genetic biomarkers may help to predict the severity and trajectory of cognitive impairment in groups of patients.

Methods

The study included 171 patients from a longitudinal population-based incident Parkinson’s disease study from South Western Norway. All participants were followed from the time of diagnosis for up to seven years, undertaking repeated batteries of clinical and neuropsychological tests, measuring global cognitive impairment, executive function, attention, verbal learning and memory, and visuospatial skills. We used linear mixed regression analyses to explore associations between the function in specific cognitive domains over time and common genetic variants in APOE, MAPT, COMT and BDNF.

Results

The COMT¹⁵⁸Val/Val allele was associated with faster decline in executive function (p = 0.028), verbal learning and memory (p = 0.029), and visuospatial skills (p = 0.027). The BDNF, MAPT and APOE genotypes were not significantly associated with longitudinal changes in individual cognitive domains, however carriers of the APOE-ε4 allele were shown to be at increased risk of mild cognitive impairment and dementia within the study period (OR 3.03; p = 0.006).

Conclusions

This population-based study of newly diagnosed patients provides new evidence that COMT Val¹⁵⁸Met effects cognitive outcomes limited to discrete domains and APOE-ε4 status predicts a poor overall cognitive prognosis. Together, these data contribute to our understanding of the biology underlying the heterogeneity observed in the progression of PD.

中文翻译：

常见遗传变异对帕金森病前七年认知衰退的影响：一项纵向观察研究

介绍

认知障碍是帕金森病的共同特征，是患者生活质量和依赖性的重要决定因素。认知症状的模式和进展在个体之间差异很大，遗传生物标志物可能有助于预测患者群体认知障碍的严重程度和轨迹。

方法

该研究包括来自挪威西南部的一项纵向人群帕金森病事件研究的 171 名患者。从诊断之日起对所有参与者进行长达七年的随访，反复进行临床和神经心理学测试，测量整体认知障碍、执行功能、注意力、语言学习和记忆以及视觉空间技能。我们使用线性混合回归分析来探索特定认知领域的功能随时间推移与APOE、MAPT、COMT和BDNF中常见遗传变异之间的关联。

结果

COMT ¹⁵⁸ Val/Val 等位基因与执行功能 (p = 0.028)、语言学习和记忆 (p = 0.029) 以及视觉空间技能 (p = 0.027)的快速下降有关。BDNF、MAPT和APOE基因型与个体认知领域的纵向变化没有显着相关性，但APOE -ε4 等位基因的携带者在研究期间显示出轻度认知障碍和痴呆的风险增加（OR 3.03；p = 0.006)。