Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease

Brain. 2010 Jun;133(Pt 6):1747-54. doi: 10.1093/brain/awq079. Epub 2010 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Aged
  • Aged, 80 and over
  • Biogenic Monoamines / metabolism
  • Brain / diagnostic imaging
  • Brain / enzymology
  • Brain / metabolism*
  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / enzymology
  • Cognition Disorders / metabolism*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Olfactory Perception*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / enzymology
  • Parkinson Disease / metabolism*
  • Pattern Recognition, Physiological
  • Perceptual Disorders / diagnostic imaging
  • Perceptual Disorders / enzymology
  • Perceptual Disorders / metabolism*
  • Physical Stimulation
  • Positron-Emission Tomography
  • Vesicular Monoamine Transport Proteins / metabolism


  • Biogenic Monoamines
  • SLC18A2 protein, human
  • Vesicular Monoamine Transport Proteins
  • Acetylcholinesterase