Cholinergic Nucleus 4 Degeneration and Cognitive Impairment in Isolated Rapid Eye Movement Sleep Behavior Disorder

Abstract

Background: Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD). Objective: The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment. Methods: We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age-and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI). Results: Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (β-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory. Conclusions: iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory.

Quantitative sleep electroencephalogram and cognitive performance in Parkinson’s disease with and without rapid eye movement sleep behavior disorder

“…Although cholinergic activity in NREM sleep is reduced, cholinergic signaling increases during and regulates REM sleep ( 38 ). Studies have also demonstrated reduced volumes of cholinergic basal forebrain nuclei in PD patients with cognitive impairment ( 39 – 41 ), possibly leading to an upregulation of cholinergic receptors in response to cholinergic neuron loss ( 42 – 44 ). Additionally, the role of GABAergic neurons in the basal forebrain deserves mention, as they play a significant role in influencing theta oscillations ( 45 ) and spindle activity ( 46 , 47 ).…”

Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson’s Disease

“…Increasing cortical cholinergic dysfunction specifically characterised a group of iRBD patients with cognitive decline in another study with a small sample [70]. Grey matter density of the basal nucleus of Meynert, the main origin of cortical cholinergic innervation, was significantly reduced in 35 iRBD patients and reduction was associated with poorer performance in a working memory task [71].…”