NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study Raffaele Nardone • Ju ¨ rgen Bergmann • Francesco Brigo • Monica Christova • Alexander Kunz • Martin Seidl • Frediano Tezzon • Eugen Trinka • Stefan Golaszewski Received: 26 April 2012 / Accepted: 3 August 2012 / Published online: 19 August 2012 Ó Springer-Verlag 2012 Abstract Central cholinergic dysfunction has been reported in patients with Parkinson& s disease (PD) and hallucinations by evaluating short latency afferent inhibi- tion (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients with- out RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age- matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neu- ropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD. Keywords Parkinson& s disease Á REM sleep behavior disorder Á Transcranial magnetic stimulation Á Short latency afferent inhibition Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is a clinical condition characterized by an inter- mittent or complete loss of muscle atonia and an increase of phasic muscular activity during REM sleep, leading to complex nocturnal motor behaviors (Mahowald and Schenck 2000). RBD affects mainly older men and may occur alone (idiopathic form) or in association with a variety of neu- rological disorders. In particular, RBD is frequently asso- ciated with synucleinopathies (Boeve et al. 2001; Iranzo et al. 2006; Postuma et al. 2009), including Parkinson& s disease (PD) (Schenck et al. 1996a; Comella et al. 1998; Gagnon et al. 2002a, b). RBD often precedes the clinical onset of the neurodegenerative disease. The pathophysiological mechanisms of RBD are still matter of debate. Animal models studies (Jouvet and R. Nardone Á A. Kunz Á M. Seidl Á E. Trinka Á S. Golaszewski Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria R. Nardone (&) Á F. Brigo Á F. Tezzon Department of Neurology, Franz Tappeiner Hospital, Merano, Via Rossini, 5, 39012 Meran/o, BZ, Italy e-mail: raffaele.nardone@asbmeran-o.it J. Bergmann Neuroscience Institute, Christian Doppler Klinik, Salzburg, Austria F. Brigo Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Verona, Italy M. Christova Department of Physiology, Medical University of Graz, Graz, Austria 123 J Neural Transm (2013) 120:413–422 DOI 10.1007/s00702-012-0888-6