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Brain Advance Access originally published online on July 7, 2009
Brain 2009 132(9):2350-2355; doi:10.1093/brain/awp166
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© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Functional involvement of central cholinergic circuits and visual hallucinations in Parkinson's disease

Fiore Manganelli1, Carmine Vitale1,2,3, Gabriella Santangelo1,3,4, Chiara Pisciotta1, Rosa Iodice1, Autilia Cozzolino1, Raffaele Dubbioso1, Marina Picillo1, Paolo Barone1 and Lucio Santoro1

1 Department of Neurological Sciences, University Federico II of Naples, Naples, Italy 2 University Parthenope of Naples, Naples, Italy 3 Istituto di Diagnosi e Cura Hermitage Capodimonte, Naples, Italy 4 Second University of Naples, Neuropsychology Laboratory, Department of Psychology, Naples, Italy

Correspondence to: Lucio Santoro, MD, Department of Neurological Sciences, University Federico II of Naples, Via Sergio Pansini 5, 80131 Naples, Italy E-mail: lusantor{at}unina.it

Visual hallucinations (VHs) represent a frequent and disturbing complication of Parkinson's disease. Evidence suggests that VH can be related to central cholinergic dysfunction. Short-latency afferent inhibition (SAI) technique gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. This inhibition of motor-evoked potentials can be observed when transcranial magnetic stimulation is delivered with a delay ranging from 2 to 8 ms, after a peripheral nerve afferent input has reached the somatosensory cortex. We applied SAI technique in 10 non-demented patients with Parkinson's disease with VHs, in 12 non-demented patients with Parkinson's disease without VHs (NVH-pts) and in 11 age-matched normal controls. All patients with Parkinson's disease underwent a battery of neuropsychological tests to assess frontal and visuospatial functions, memory and attention. SAI was significantly reduced in patients with VHs compared with controls and patients without VHs. Neuropsychological examination showed a mild cognitive impairment in 16 out of 22 patients with Parkinson's disease. In addition, we found that in our patients with VHs, performance of some tasks evaluating visuospatial functions and attentional/frontal lobe functions was significantly more impaired than in patients without VHs. SAI abnormalities, presence of VH and neuropsychological results strongly support the hypothesis of cholinergic dysfunction in some patients with Parkinson's disease, who will probably develop a dementia. A follow-up study of our patients is required to verify whether SAI abnormalities can predict a future severe cognitive decline. Moreover, SAI can also be very useful to follow-up the efficacy of anti-cholinesterase therapies.

Key Words: Parkinson's disease; TMS; short-latency afferent inhibition; cognitive deficits; visual hallucinations

Abbreviations: MCI, mild cognitive impairment; NBM, nucleus basalis of Meynert; NVH-pts, patients without visual hallucination; Parkinson's disease-CogNL, cognitively normal Parkinson's disease; SAI, short-latency afferent inhibition; VH-pts, patients with visual hallucination

Received February 27, 2009. Revised April 16, 2009. Accepted May 15, 2009.


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