| Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease. | |
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MedLine Citation:
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PMID: 20413575 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 + or - 0.5) without dementia (mean Mini-Mental State Examination, 29.0 + or - 1.4) underwent a clinical assessment, [(11)C]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 [(11)C]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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Authors:
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Nicolaas I Bohnen; Martijn L T M Müller; Vikas Kotagal; Robert A Koeppe; Michael A Kilbourn; Roger L Albin; Kirk A Frey |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-04-22 |
Journal Detail:
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Title: Brain : a journal of neurology Volume: 133 ISSN: 1460-2156 ISO Abbreviation: Brain Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-06-22 Revised Date: 2010-12-17 |
Medline Journal Info:
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Nlm Unique ID: 0372537 Medline TA: Brain Country: England |
Other Details:
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Languages: eng Pagination: 1747-54 Citation Subset: AIM; IM |
Affiliation:
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Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI 48109, USA. nbohnen@umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholinesterase
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metabolism Aged Aged, 80 and over Biogenic Monoamines / metabolism Brain / enzymology, metabolism*, radionuclide imaging Cognition Disorders / enzymology, metabolism*, radionuclide imaging Cross-Sectional Studies Female Humans Male Middle Aged Neuropsychological Tests Olfactory Perception* Parkinson Disease / enzymology, metabolism*, radionuclide imaging Pattern Recognition, Physiological Perceptual Disorders / enzymology, metabolism*, radionuclide imaging Physical Stimulation Positron-Emission Tomography Vesicular Monoamine Transport Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P01 NS015655/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biogenic Monoamines; 0/SLC18A2 protein, human; 0/Vesicular Monoamine Transport Proteins; EC 3.1.1.7/Acetylcholinesterase |
| Comments/Corrections | |
Comment In:
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Brain. 2010 Dec;133(Pt 12):e160; author reply e161
[PMID:
20805099
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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