Document Detail


Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease.
MedLine Citation:
PMID:  20413575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nicolaas I Bohnen; Martijn L T M Müller; Vikas Kotagal; Robert A Koeppe; Michael A Kilbourn; Roger L Albin; Kirk A Frey
Related Documents :
17012935 - The neurobiology of neuropsychiatric syndromes in dementia.
18046875 - Vascular dementia: prevention and treatment.
2088085 - The diagnosis of alzheimer's disease.
11186595 - Medicare expenditures associated with alzheimer disease.
21907175 - Apolipoprotein e and lrp1 increase early in parkinson's disease pathogenesis.
15177535 - Treatment of inflammatory bowel disease with azathioprine and 6-mercaptopurine.
Publication Detail:
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:
Title:  Brain : a journal of neurology     Volume:  133     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-06-22     Revised Date:  2010-12-17    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  1747-54     Citation Subset:  AIM; IM    
Affiliation:
Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI 48109, USA. nbohnen@umich.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetylcholinesterase / 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:
P01 NS015655/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biogenic Monoamines; 0/SLC18A2 protein, human; 0/Vesicular Monoamine Transport Proteins; EC 3.1.1.7/Acetylcholinesterase
Comments/Corrections
Comment In:
Brain. 2010 Dec;133(Pt 12):e160; author reply e161   [PMID:  20805099 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  EULAR/PRINTO/PRES criteria for Henoch-Sch?nlein purpura, childhood polyarteritis nodosa, childhood W...
Next Document:  Implementation of Measurement Instruments in Physical Therapist Practice: Development of a Tailored ...