Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease.
Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease.
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DOI：
10.1093/brain/awq079
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Frey KA
中科院分区：
文献类型：
--
作者：
Bohnen NI;Müller ML;Kotagal V;Koeppe RA;Kilbourn MA;Albin RL;Frey KA
嗅觉功能障碍在帕金森氏症患者中很常见。然而，这种功能障碍的病理生理学仍然知之甚少。参与气味感知的中枢神经退行性变可能导致帕金森病的嗅觉功能障碍。中枢胆碱能缺陷发生在帕金森氏症，胆碱能神经元支配的神经区域，如边缘皮质，参与气味感知。我们研究了帕金森病无痴呆受试者在气味识别任务中的表现与前脑胆碱能去神经支配之间的关系。58例无痴呆的帕金森病患者（平均Hoehn和Yahr分期2.5±0.5）（平均Mini-Mental State Examination分期29.0±1.4）接受了临床评估、[11C]甲基-4-哌啶酰丙酸乙酰胆碱酯酶脑正电子发射断层扫描和嗅觉测试，并采用宾夕法尼亚大学嗅觉识别测试。[11C]二氢四苯那嗪水泡单胺转运体2型正电子发射断层扫描证实帕金森病的诊断。我们发现，气味识别测试分数与海马区（r = 0.56, P < 0.0001）、杏仁核（r = 0.50, P < 0.0001）和新皮层（r = 0.46, P = 0.0003）的乙酰胆碱酯酶活性呈正相关。纹状体单胺能活性与气味识别评分呈正相关（r = 0.30, P < 0.05）。以气味识别分数为因变量，包括大脑边缘（海马和杏仁核）和新皮层乙酰胆碱酯酶活性以及纹状体单胺能活性进行多元回归分析，结果表明，大脑边缘乙酰胆碱酯酶活性（F = 10.1, P < 0.0001）、纹状体单胺能活性（F = 1.6, P = 0.13）存在显著的回归效应，但皮质乙酰胆碱酯酶活性不显著（F = 0.3, P = 0.75）。气味识别得分与情景性言语学习认知测试得分呈正相关（r = 0.30, P < 0.05）。这些发现表明，在中重度帕金森病患者中，边缘皮质胆碱能去神经支配比黑质纹状体多巴胺能去神经支配更能决定低氧。气味识别的更大缺陷可能会使帕金森病患者面临临床显著认知障碍的风险。
Olfactory dysfunction is common in subjects with Parkinson’s disease. The pathophysiology of such dysfunction, however, remains poorly understood. Neurodegeneration within central regions involved in odour perception may contribute to olfactory dysfunction in Parkinson’s disease. Central cholinergic deficits occur in Parkinson’s disease and cholinergic neurons innervate regions, such as the limbic archicortex, involved in odour perception. We investigated the relationship between performance on an odour identification task and forebrain cholinergic denervation in Parkinson’s disease subjects without dementia. Fifty-eight patients with Parkinson’s disease (mean Hoehn and Yahr stage 2.5 ± 0.5) without dementia (mean Mini-Mental State Examination, 29.0 ± 1.4) underwent a clinical assessment, [11C]methyl-4-piperidinyl propionate acetylcholinesterase brain positron emission tomography and olfactory testing with the University of Pennsylvania Smell Identification Test. The diagnosis of Parkinson’s disease was confirmed by [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 positron emission tomography. We found that odour identification test scores correlated positively with acetylcholinesterase activity in the hippocampal formation (r = 0.56, P < 0.0001), amygdala (r = 0.50, P < 0.0001) and neocortex (r = 0.46, P = 0.0003). Striatal monoaminergic activity correlated positively with odour identification scores (r = 0.30, P < 0.05). Multiple regression analysis including limbic (hippocampal and amygdala) and neocortical acetylcholinesterase activity as well as striatal monoaminergic activity, using odour identification scores as the dependent variable, demonstrated a significant regressor effect for limbic acetylcholinesterase activity (F = 10.1, P < 0.0001), borderline for striatal monoaminergic activity (F = 1.6, P = 0.13), but not significant for cortical acetylcholinesterase activity (F = 0.3, P = 0.75). Odour identification scores correlated positively with scores on cognitive measures of episodic verbal learning (r = 0.30, P < 0.05). These findings indicate that cholinergic denervation of the limbic archicortex is a more robust determinant of hyposmia than nigrostriatal dopaminergic denervation in subjects with moderately severe Parkinson's disease. Greater deficits in odour identification may identify patients with Parkinson's disease at risk for clinically significant cognitive impairment.
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影响因子：
9.9
作者：
Hilker, R;Thomas, AV;Heiss, WD
通讯作者：
Heiss, WD
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
3.8
作者：
DOTY, RL;REYES, PF;GREGOR, T
通讯作者：
GREGOR, T
影响因子：
2.9
作者：
DOTY, RL;SHAMAN, P;DANN, M
通讯作者：
DANN, M
影响因子：
9.9
作者：
Aarsland, D.;Bronnick, K.;Alves, G.
通讯作者：
Alves, G.