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From the Department of Neurology (H. Shimada, A.A., M.A., S.K., and T.H.), Graduate School of Medicine, Chiba University; and the Molecular Imaging Center (H.S., H. Shinotoh, K.S., N.T., T.O., K.F., T.S., T.I.), National Institute of Radiological Sciences, Chiba, Japan.
Address correspondence and reprint requests to Dr. Hitoshi Shinotoh, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 260-8555, Japan BQV10131{at}nifty.ne.jp
Objective: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB).
Methods: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis.
Results: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = –12%) (false discovery rate–corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = –27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced.
Conclusions: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.
Abbreviations: AChE = acetylcholinesterase; ANOVA = analysis of variance; BA = Brodmann area; DLB = dementia with Lewy bodies; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; FDR = false discovery rate; FWE = family-wise error; HC = healthy controls; LBD = Lewy body disease; MMSE = Mini-Mental State Examination; MNI = Montreal Neurological Institute; PD = Parkinson disease; PDD = Parkinson disease with dementia; VOI = volume of interest.
Supplemental data at www.neurology.org
Editorial, page 256
e-Pub ahead of print on May 27, 2009, at www.neurology.org.
Dr. Asahina is funded by a Grant-in-Aid for Scientific Research (17590861).
Disclosure: The authors report no disclosures.
Received November 27, 2008. Accepted in final form March 30, 2009.
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  N. I. Bohnen and R. L. Albin Cholinergic denervation occurs early in Parkinson disease Neurology, July 28, 2009; 73(4): 256 - 257. [Full Text] [PDF]
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