Abstract Details

Title Parkinson’s Disease Mild Cognitive Impairment with MRI evidence of Cholinergic Nucleus 4 Degeneration: A New Subtype?

Topic Movement Disorders

Presentation(s) S32 - Movement Disorders: Neuroimaging and Neuromodulation (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Subtyping PD-MCI into clinically- and pathologically-homogenous subtypes could enhance clinical trial design and support personalized treatment approaches. Prior studies have revealed that Ch4 volume correlates with the severity of cognitive impairment and predicts future cognitive decline in PD.

Objective To determine if Parkinson’s disease (PD) with mild cognitive impairment (PD-MCI) patients and MRI evidence of cholinergic nucleus 4 (Ch4) degeneration represent a distinct subtype of PD-MCI.

Design/Methods We analyzed baseline MRI scans for 148 PD-MCI participants from the Parkinson’s Progression Markers Initiative (PPMI). Ch4 grey matter density (GMD) was calculated using voxel-based morphometry and probabilistic maps. PD-MCI participants were divided into those with low Ch4 and normal Ch4 based on a normed z-score cutoff of 1 SD below the mean. We compared motor and non-motor symptoms and data-driven subtype frequencies between PD-MCI with and without low Ch4. We also constructed Kaplan-Meier survival analysis curves to compare the time to reach the cognitive domain milestones.

Results Of the 148 PPMI participants analyzed, 116 had normal Ch4 GMD while 32 had low Ch4 GMD. PD-MCI patients with low Ch4 GMD had significantly worse Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) total, MDS-UPDRS-I, MDS-UPDRS-II, and MDS-UPDRS-III scores (all P<0.05), as well as worse autonomic symptoms and olfaction as measured by the Scales for Outcomes in Parkinson’s disease - Autonomic Dysfunction and University of Pennsylvania Smell Identification Test (all P<0.05). The PD-MCI participants with low Ch4 GMD also were more likely to have diffuse malignant PD (51.6% vs. 23.4%, respectively; P<0.01) and had faster time to reach cognitive milestones (log rank P=0.0046).

Conclusions PD-MCI with low Ch4 GMD represents a distinct subtype characterized by more severe motor and non-motor symptoms and faster progression to dementia. These findings suggest that this group should be considered in PD-MCI clinical trials, particularly those investigating cholinergic therapies.

Authors/Disclosures
Ahmed Negida, MD, PhD (Virginia Commonwealth University) PRESENTER	Dr. Negida has nothing to disclose.
Hiba Z. Vohra	Ms. Vohra has nothing to disclose.
Sarah Lageman (Virginia Commonwealth University)	Sarah Lageman has received personal compensation in the range of $0-$499 for serving as a Content Validator of online materials with CurePSP.
Nitai Mukhopadhyay (Virginia Commonwealth University)	Nitai Mukhopadhyay has nothing to disclose.
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. The institution of Dr. Berman has received research support from Neurocrine Biosciences.
Daniel Weintraub	Daniel Weintraub has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Clintrex. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion. Daniel Weintraub has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Modality.ai. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CuraSen. Daniel Weintraub has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer Ingelheim. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Daniel Weintraub has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorder Society. The institution of Daniel Weintraub has received research support from NIH. The institution of Daniel Weintraub has received research support from Fox Foundation. The institution of Daniel Weintraub has received research support from IPMDS. Daniel Weintraub has received intellectual property interests from a discovery or technology relating to health care.
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.

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