Structural and molecular cholinergic imaging markers of cognitive decline in Parkinson's disease.
Structural and molecular cholinergic imaging markers of cognitive decline in Parkinson's disease.
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帕金森病认知能力下降的结构和分子胆碱能成像标志物。
DOI：
10.1093/brain/awad226
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Grothe,MichelJ
中科院分区：
文献类型：
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作者：
Schumacher,Julia;Kanel,Prabesh;Dyrba,Martin;Storch,Alexander;Bohnen,NicolaasI;Teipel,Stefan;Grothe,MichelJ
帕金森氏病患者的认知功能减退与胆碱能系统的退化有关，这可以通过活体结构MRI标记物的基底前脑体积和皮质胆碱能活动的PET测量来评估。这项横断面研究包括143名非痴呆性帕金森病患者和52名健康对照受试者，他们接受了结构磁共振成像，用11C-甲基-4-哌啶丙酸酯(PMP)进行了PET扫描，作为皮质乙酰胆碱酯酶活性的测量指标，并进行了详细的认知评估。根据对照组大脑皮质PMP PET信号的第五个百分位数，帕金森病患者被细分为正常胆碱能组(n=94)和低胆碱能组(n=49)。使用基于胆碱能前脑基底核团立体定向图谱的自动MRI体积测量方法提取功能性定义的前脑后部和前部亚区体积。在排除年龄、性别和教育年限后，我们使用贝叶斯检验来比较对照组、正常胆碱能和低胆碱能帕金森病患者之间的基础前脑体积。使用贝叶斯相关性在所有帕金森氏病患者中评估了两种胆碱能成像指标之间的关联，并使用贝叶斯方差分析评估了它们与不同认知领域表现的各自关系。作为一项特异性分析，海马体体积被添加到分析中。我们发现，与胆碱能正常的帕金森病[针对零模型的贝叶斯因子(BF10)=8.2]和对照组(BF10=6.0)相比，低胆碱能组的后部基底前脑体积减少的证据是不确定的(BF10和lt；3)。在连续相关性分析中，后部基底前脑体积与皮质PMP PET信号在时间-后方分布上显著相关。预测认知分数的联合模型显示，两种胆碱能标记物(后基底前脑体积和皮质PMP PET信号)与多领域认知缺陷独立相关，并且对包括记忆分数在内的所有认知分数的预测作用比对海马体体积更重要。我们得出结论：帕金森病患者后基底前脑的变性伴随着皮层乙酰胆碱酯酶活性的功能变化，PET和MRI胆碱能成像标记物与帕金森病非痴呆患者的多领域认知缺陷独立相关。相比之下，在帕金森氏症早期认知障碍的发展过程中，海马体萎缩似乎只有很少的参与。
Cognitive decline in Parkinson’s disease is related to cholinergic system degeneration, which can be assessedin vivousing structural MRI markers of basal forebrain volume and PET measures of cortical cholinergic activity. In the present study we aimed to examine the interrelation between basal forebrain degeneration and PET-measured depletion of cortical acetylcholinesterase activity as well as their relative contribution to cognitive impairment in Parkinson’s disease.This cross-sectional study included 143 Parkinson’s disease participants without dementia and 52 healthy control participants who underwent structural MRI, PET scanning with11C-methyl-4-piperidinyl propionate (PMP) as a measure of cortical acetylcholinesterase activity, and a detailed cognitive assessment. Based on the fifth percentile of the overall cortical PMP PET signal from the control group, people with Parkinson’s disease were subdivided into a normo-cholinergic (n= 94) and a hypo-cholinergic group (n= 49). Volumes of functionally defined posterior and anterior basal forebrain subregions were extracted using an established automated MRI volumetry approach based on a stereotactic atlas of cholinergic basal forebrain nuclei. We used Bayesiant-tests to compare basal forebrain volumes between controls, and normo- and hypo-cholinergic Parkinson’s participants after covarying out age, sex and years of education. Associations between the two cholinergic imaging measures were assessed across all people with Parkinson’s disease using Bayesian correlations and their respective relations with performance in different cognitive domains were assessed with Bayesian ANCOVAs. As a specificity analysis, hippocampal volume was added to the analysis.We found evidence for a reduction of posterior basal forebrain volume in the hypo-cholinergic compared to both normo-cholinergic Parkinson’s disease [Bayes factor against the null model (BF10) = 8.2] and control participants (BF10= 6.0), while for the anterior basal forebrain the evidence was inconclusive (BF10< 3). In continuous association analyses, posterior basal forebrain volume was significantly associated with cortical PMP PET signal in a temporo-posterior distribution. The combined models for the prediction of cognitive scores showed that both cholinergic markers (posterior basal forebrain volume and cortical PMP PET signal) were independently related to multi-domain cognitive deficits, and were more important predictors for all cognitive scores, including memory scores, than hippocampal volume.We conclude that degeneration of the posterior basal forebrain in Parkinson’s disease is accompanied by functional cortical changes in acetylcholinesterase activity and that both PET and MRI cholinergic imaging markers are independently associated with multi-domain cognitive deficits in Parkinson’s disease without dementia. Comparatively, hippocampal atrophy only seems to have minimal involvement in the development of early cognitive impairment in Parkinson’s disease.