Abstract Details

Title Cholinergic Nucleus 4 Degeneration and Cognitive Impairment in isolated REM Sleep Behavior Disorder

Topic Sleep

Presentation(s) S6 - Sleep Medicine Highlights (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

Background

Cholinergic dysfunction is an important contributor to cognitive impairment in Parkinson’s disease and dementia with Lewy bodies. REM sleep behavior disorder (RBD) is also associated with cognitive impairment and often presents prior to diagnosis of Parkinson’s disease or dementia with Lewy bodies. Imaging studies using positron emission topography have shown reduced cholinergic innervation of the neocortex in RBD, but it is unclear whether there is cholinergic degeneration in iRBD and if present whether this is associated with cognitive impairment in iRBD.

Objective

To determine if there is evidence of cholinergic nucleus 4 (Ch4) degeneration in patients with isolated REM sleep behavior disorder (iRBD) and whether Ch4 degeneration is associated with cognitive impairment in iRBD.

Design/Methods

We analyzed data for 35 iRBD patients and 35 age- and sex-matched healthy controls (HC) from the Parkinson’s Progression Markers Initiative. Both groups completed cognitive assessments including Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test, Letter Number Sequencing (LNS), Symbol Digit Modalities Test, Judgement of Line Orientation, and Semantic Fluency Animals Test (SFT-animals). Regional grey matter density (GMD) was calculated for Ch4 and cholinergic nuclei 1, 2, and 3 (Ch123) from high-resolution structural MRI scans using probabilistic maps applied to brain MRIs.

Results

Ch4 GMD was significantly lower in the iRBD group compared to HC (0.417 vs. 0.441; p=0.02). There was no significant difference in Ch123 GMD between groups (p=0.85). In the iRBD 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). After adjustment for age, sex, scanner type, and TIV in a multivariate linear regression model, Ch4 GMD was found to be a significant predictor of LNS (β-coefficient=58.31, p=0.026, 95% CI [7.47, 109.15]), a measure of working memory.

Conclusions

iRBD is associated with Ch4 degeneration and this degeneration may contribute to impairment in working memory.

Authors/Disclosures
Christopher Tan, MD PRESENTER	Mr. Tan has nothing to disclose.
	No disclosure on file
Sarah Lageman (Virginia Commonwealth University)	No disclosure on file
Leslie Cloud, MD (VCU)	The institution of Dr. Cloud has received research support from NIH. Dr. Cloud has received personal compensation in the range of $500-$4,999 for serving as a Community leader with Paltown.
Amy W. Amara, MD PhD (University of Colorado Anschutz Medical Center)	The institution of Dr. Amara has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Photopharmics, Inc. The institution of Dr. Amara has received research support from Michael J Fox Foundation for Parkinson's Research . The institution of Dr. Amara has received research support from Biogen Idec. The institution of Dr. Amara has received research support from NIH.
	No disclosure on file
Brian Berman, MD, MS, FAAN (Virginia Commonwealth University)	Dr. Berman has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for International Parkinson and Movement Disorder Society. The institution of Dr. Berman has received research support from Dystonia Medical Research Foundation. The institution of Dr. Berman has received research support from Administration for Community Living. The institution of Dr. Berman has received research support from The Parkinson Foundation. The institution of Dr. Berman has received research support from National Institutes of Health.
Nitai Mukhopadhyay (Virginia Commonwealth University)	No disclosure on file
Matthew J. Barrett, MD (Virginia Commonwealth University)	Dr. Barrett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Healthcare LLC. The institution of Dr. Barrett has received research support from Kyowa Kirin. The institution of Dr. Barrett has received research support from NIH.