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在无痴呆的帕金森病中,局部脑区淀粉样β蛋白积聚与特定领域的认知表现相关。

Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

作者信息

Akhtar Rizwan S, Xie Sharon X, Chen Yin J, Rick Jacqueline, Gross Rachel G, Nasrallah Ilya M, Van Deerlin Vivianna M, Trojanowski John Q, Chen-Plotkin Alice S, Hurtig Howard I, Siderowf Andrew D, Dubroff Jacob G, Weintraub Daniel

机构信息

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Center for Neurodegenerative Disease Research and Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

出版信息

PLoS One. 2017 May 25;12(5):e0177924. doi: 10.1371/journal.pone.0177924. eCollection 2017.

Abstract

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

摘要

帕金森病患者在其病程的不同时间会出现具有临床意义的认知障碍,在此之前通常会出现记忆、视觉空间和执行功能领域较轻微的缺陷。淀粉样蛋白β积聚对这些问题的影响尚不清楚。我们假设,使用检测纤维状淀粉样蛋白β斑块沉积的放射性示踪剂18F-氟代贝他吡进行淀粉样蛋白β正电子发射断层扫描(PET)成像,将能够识别非痴呆帕金森病患者中存在整体认知障碍或在个体认知领域表现不佳的受试者。我们对61名非痴呆帕金森病患者进行了详细的认知评估和18F-氟代贝他吡PET脑成像。扫描结果由两名对临床数据不知情的独立核医学医生进行定性解读(阳性或阴性),并通过一种新的体积加权方法进行定量分析。通过使用运动障碍协会的1级标准,经专家共识确定是否存在轻度认知障碍。19名参与者(31.2%)被诊断为轻度认知障碍,其余参与者认知正常。15名参与者(24.6%)的18F-氟代贝他吡PET成像定性结果为阳性。年龄增加和APOE ε4等位基因的存在与18F-氟代贝他吡的综合结合水平较高相关。在多变量模型中,专家评级的18F-氟代贝他吡扫描异常与轻度认知障碍的诊断无关。然而,后扣带回中的18F-氟代贝他吡保留值与言语记忆表现呈负相关。额叶皮质、楔前叶和前扣带回中的保留值与命名表现呈负相关。通过18F-氟代贝他吡PET测量的区域皮质淀粉样蛋白β可能是非痴呆帕金森病患者特定认知缺陷的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da2/5444629/a4a7cbc72a09/pone.0177924.g001.jpg

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