Objective: To determine if there is evidence of cholinergic basal forebrain degeneration, i.e., reduced cholinergic nucleus 4 (Ch4) volume on MRI, in patients with REM sleep behavior disorder (RBD) compared to healthy controls (HC) and whether Ch4 degeneration is associated with cognitive impairment in RBD.

Background: Cholinergic dysfunction is an important contributor to cognitive impairment in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). REM sleep behavior disorder (RBD) often presents prior to diagnosis of PD and DLB and is also associated with cognitive impairment. Imaging studies using positron emission topography (PET) have shown reduced cholinergic innervation of the neocortex in RBD, but it is unclear whether cholinergic dysfunction in RBD correlates with the cognitive impairment observed in RBD.

Method: We analyzed a cohort of 35 RBD and 35 age- and gender-matched healthy controls (HC) from the Parkinson’s Progression Markers Initiative who had brain MRIs at baseline. Following application of standard voxel-based morphometry methods, regional grey matter density (GMD) was calculated for Ch4 and cholinergic nuclei 1, 2, and 3 (Ch123) using probabilistic maps. Both the RBD and HC participants completed cognitive assessments including the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test-Revised, Letter Number Sequencing (LNS), Symbol Digit Modalities Test, Judgement of Line Orientation (short form), and Semantic Fluency Animals Test (SFT-animals).

Results: There were 30 men and 5 women in each group. The mean age for RBD participants was 69.2 years (SD=5.7), and the mean age of healthy controls was 69.1 years (SD=5.8). RBD participants performed worse on all cognitive tests compared to HC (all p<0.006), with the exception of SFT-animals (p=0.96). Ch4 GMD was significantly lower in the RBD group compared to HC (0.417 vs. 0.441; p=0.02). There was no significant difference in Ch123 GMD between the 2 groups (p=0.85). Ch4 GMD was not significantly correlated with cognitive performance on any of the tasks in the HC group. In the RBD group, Ch4 GMD was significantly correlated with MoCA score (r=0.41, p=0.01), LNS scaled score (r=0.37, p=0.04) and SFT-animals scaled score (r=0.39, p=0.03).

Conclusion: RBD is associated with greater Ch4 degeneration compared to HC. Ch4 degeneration in RBD is correlated with impairment in global cognition and tasks of executive function and working memory.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-nucleus-4-degeneration-and-cognitive-impairment-in-rem-sleep-behavior-disorder/