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. 2023 Mar;38(3):474-479.
doi: 10.1002/mds.29306. Epub 2023 Jan 4.

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

Christopher Tan  1 , Huma Nawaz  2 , Sarah K Lageman  2 , Leslie J Cloud  2 , Amy W Amara  3 , Benjamin T Newman  4 , T Jason Druzgal  4 , Brian D Berman  2 , Nitai Mukhopadhyay  5 , Matthew J Barrett  2
Affiliations

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

Christopher Tan et al. Mov Disord. 2023 Mar.

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. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: cholinergic basal forebrain; cognitive impairment; magnetic resonance imaging; rapid eye movement sleep behavior disorder; voxel-based morphometry; working memory.

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Conflict of interest statement

Financial Disclosure/Conflict of Interest: None.

Figures

Figure 1.
Figure 1.
Cholinergic forebrain nuclei grey matter density in REM sleep behavior disorder and healthy controls. Horizontal lines indicate mean values of cholinergic nuclei grey matter density and error bars indicate 95% confidence interval for (A) Ch4 and (B) Ch123 for both 35 iRBD participants and 35 age- and sex-matched healthy controls. Abbreviations: Ch4 = cholinergic nucleus 4; Ch123 = cholinergic nucleus 1, 2, and 3; GMD = grey matter density; HC = healthy controls; iRBD = isolated REM sleep behavior disorder.
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