Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study

Abstract

Central cholinergic dysfunction has been reported in patients with Parkinson's disease (PD) and hallucinations by evaluating short latency afferent inhibition (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 without 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 neuropsychological 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.

Effects of lorazepam and baclofen on short‐ and long‐latency afferent inhibition

“…In those with REM sleep behaviour disorder, SAI is positively correlated with greater executive function, verbal memory and visuospatial abilities (Nardone et al . , ). Furthermore, in healthy individuals, SAI has been shown to be enhanced only during the retrieval phase and not the encoding or consolidation phase of memory (Bonni et al .…”

TMS and drugs revisited 2014

“…SAI increases with the intensity of the conditioning stimulus (Fischer and Orth, 2011). SAI decreases with normal aging (Young-Bernier et al, 2012a, Young-Bernier et al, 2012b and in neurodegenerative disorders of the central cholinergic system, such as Alzheimer's disease (Di Lazzaro et al, 2005aNardone et al, 2008Nardone et al, , 2011 and Parkinson's disease (Celebi et al, 2012;Nardone et al, 2013;Rochester et al, 2012;Yarnall et al, 2013). Accordingly, it was proposed that SAI is a physiological marker of the integrity and excitability of central cholinergic pathways.…”

A systematic review of the literature on disorders of sleep and wakefulness in Parkinson's disease from 2005 to 2015

“…(iv) contribution of various neurotransmitter pathways to RBD pathophysiology and implications (such as association between cholinergic denervation[353,354] and cognitive function)…”