Meyer Philipp M, Strecker Karl, Kendziorra Kai, Becker Georg, Hesse Swen, Woelpl Dominique, Hensel Anke, Patt Marianne, Sorger Dietlind, Wegner Florian, Lobsien Donald, Barthel Henryk, Brust Peter, Gertz Hermann J, Sabri Osama, Schwarz Johannes
Department of Nuclear Medicine, University of Leipzig, Liebigstr 18, 04103 Leipzig, Germany.
Arch Gen Psychiatry. 2009 Aug;66(8):866-77. doi: 10.1001/archgenpsychiatry.2009.106.
Cognitive or depressive disorders are frequently noted in patients with Parkinson disease (PD) and may be related to altered signaling through alpha4beta2*-nicotinic acetylcholine receptors (alpha4beta2*-nAChRs).
To assess the availability of alpha4beta2*-nAChRs and their relationship to mild cognitive and mild depressive symptoms in vivo in patients with PD.
Crossover comparison between patients with PD and healthy volunteers (control group) using the alpha4beta2*-nAChR-specific radioligand 2-[(18)F]fluoro-3-(2[S]-2-azetidinylmethoxy)-pyridine (2-[(18)F]FA-85380) and positron emission tomography.
Departments of Neurology and Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Twenty-two nonsmoking patients with PD and 9 nonsmoking healthy volunteers.
Level of 2-[(18)F]FA-85380 binding potential (2-FA BP), a measure of alpha4beta2*-nAChR availability. The relationship between severity of cognitive symptoms as rated using the Mini-Mental State Examination and DemTect scale and the level of depressive symptoms as indicated using the Beck Depression Inventory, and 2-FA BP were assessed.
In patients with PD compared with healthy volunteers, there was widespread reduced 2-FA BP, especially in the midbrain, pons, anterior cingulate cortex, frontoparietal cortex, and cerebellum. In subgroups of patients with PD with possible depression, reduced 2-FA BP was most pronounced in the cingulate cortex and frontoparieto-occipital cortex, whereas in patients with PD with mild cognitive impairment, 2-FA BP was reduced in the midbrain, pons, and cerebellum. In patients with PD, the strongest associations between depressive symptoms and reduced 2-FA BP were noted in the anterior cingulate cortex, putamen, midbrain, and occipital cortex. In contrast, cognitive symptoms correlated only weakly with reduced 2-FA BP in the thalamus, midbrain, temporal cortex, hippocampus, and cerebellum.
There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced alpha4beta2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.
认知或抑郁障碍在帕金森病（PD）患者中经常出现，可能与通过α4β2* - 烟碱型乙酰胆碱受体（α4β2* - nAChRs）的信号改变有关。
评估PD患者体内α4β2* - nAChRs的可用性及其与轻度认知和轻度抑郁症状的关系。
使用α4β2* - nAChR特异性放射性配体2 - [（18）F]氟 - 3 - （2[S] - 2 - 氮杂环丁烷基甲氧基） - 吡啶（2 - [（18）F]FA - 85380）和正电子发射断层扫描，对PD患者和健康志愿者（对照组）进行交叉比较。
德国莱比锡大学神经病学和核医学系。
22名不吸烟的PD患者和9名不吸烟的健康志愿者。
2 - [（18）F]FA - 85380结合潜力（2 - FA BP）水平，这是一种衡量α4β2* - nAChR可用性的指标。评估了使用简易精神状态检查表和DemTect量表评定的认知症状严重程度与使用贝克抑郁量表指示的抑郁症状水平以及2 - FA BP之间的关系。
与健康志愿者相比，PD患者中2 - FA BP普遍降低，尤其是在中脑、脑桥、前扣带回皮质、额顶叶皮质和小脑。在可能患有抑郁症的PD患者亚组中，2 - FA BP降低在扣带回皮质和额顶枕叶皮质最为明显，而在患有轻度认知障碍的PD患者中，2 - FA BP在中脑、脑桥和小脑中降低。在PD患者中，抑郁症状与2 - FA BP降低之间最强的关联见于前扣带回皮质、壳核、中脑和枕叶皮质。相比之下，认知症状与丘脑、中脑、颞叶皮质、海马体和小脑中2 - FA BP降低的相关性较弱。
与健康志愿者相比，无临床明显痴呆或抑郁的PD患者中α4β2* - nAChR可用性广泛降低。PD患者皮质下和皮质区域内α4β2* - nAChR结合减少与轻度认知或抑郁症状的严重程度相关。这些结果为胆碱能神经传递在PD精神共病中的作用提供了新的体内证据。
