Abstract Details

Title Parkinson Disease Phenotype in Ashkenazi Jews with and without LRRK2 Mutations

Topic Movement Disorders

Presentation(s) S13 - (-)

Poster/Presentation
Number 004

Background Parkinson's disease (PD) phenotype of carriers of LRRK2 carriers is often similar to non-carriers.

Objective

Design/Methods The study included 456 AJ PD probands from three centers: Columbia University (n=141), Beth Israel (n=129), NY, and Tel-Aviv (n=186), Israel. Participants were either newly recruited (n=393; including 77 LRRK2 G2019S mutation carriers, 19.6%), or previously recruited (n=63). A total of 122 carriers were examined. Carriers of glucocerebrosidase mutations were excluded. Participants' phenotype was characterized by treating-physicians and self report questionnaires as well as the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the geriatric depression scale (GDS) and the non motor symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features (predictor) and LRRK2 status (outcome).

Results Carriers and non carriers of LRRK2 G2019S were similar in age (67.5yrs versus 67.7yrs), gender distribution (59.7% versus 57.7% male), UPDRS-III (20.8 versus 19.5), MoCA (24.9 versus 24.8), GDS (5.7 versus 5.8) and NMS (8.4 versus 8.1) scores. However, mean age-at-onset (AAO) was lower among carriers (57.8yrs versus 61.4yrs, p=0.004), disease duration longer (9.4yrs versus 6.6yrs, p<0.001) and carriers' disease onset more often involved the legs (31.3% versus 10.7% p=0.001). In logistic models adjusted for age, disease-duration, gender and recruitment site, carriers were more likely to have lower extremity onset (p=0.003), persistent levodopa response for >5 years (p<0.001) and dyskinesia (p=0.041), as assessed by their treating clinicians. Performance on UPDRS, MoCA, GDS and NMS did not differ by mutation status in the adjusted model.

Conclusions LRRK2 PD in AJ is characterized by earlier AAO and frequent lower extremity involvement at onset, persistent response to levodopa and dyskinesia.

Authors/Disclosures
Roy Alcalay, MD (Columbia University) PRESENTER	Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.
	No disclosure on file
Rachel J. Saunders-Pullman, MD (Mount Sinai Beth Israel, Neurology, Downtown Union Square)	The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program.
Harold Moses, MD (Vanderbilt Multiple Sclerosis Center)	No disclosure on file
Mingxin Tang, PhD (Columbia University)	No disclosure on file
	No disclosure on file
Deborah Raymond (Beth Isreal Medical Center)	The institution of Ms. Raymond has received research support from NIH.
Ernerst Roos	Ernerst Roos has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Ziv Gan-Or, MD, PhD (McGill University)	Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Gan-Or has received personal compensation in the range of $0-$499 for serving as a Consultant for Lighthouse. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Therapeutics. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Gan-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Handl Therapeutics. Dr. Gan-Or has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial Biotech.
	No disclosure on file
	No disclosure on file
Laurie J. Ozelius, PhD	The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care.
Lorraine N. Clark, PhD (Columbia University)	No disclosure on file
Nir Giladi, MD, FAAN (Tel-Aviv Medical Center)	Dr. Giladi has received personal compensation in the range of $0-$499 for serving as a Consultant for Sionara. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pharma2B. Dr. Giladi has stock in Vibrant. Dr. Giladi has stock in Lysosomal Therapeutics . The institution of Dr. Giladi has received research support from The Michael J Fox Foundation. The institution of Dr. Giladi has received research support from The National Parkinson Foundation. The institution of Dr. Giladi has received research support from The European Union . The institution of Dr. Giladi has received research support from The Israel Science Foundation. The institution of Dr. Giladi has received research support from Biogen . The institution of Dr. Giladi has received research support from Ionis. The institution of Dr. Giladi has received research support from Sieratzki Family Foundation . The institution of Dr. Giladi has received research support from The Aufzien Academic Center in Tel-Aviv University.
Susan B. Bressman, MD, FAAN (Mount Sinai Health System)	The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH .
Karen S. Marder, MD, MPH, FAAN (Columbia University)	Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Marder has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson's Foundation . Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CHDI. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC therapeutics. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer LTD. The institution of Dr. Marder has received research support from Vaccinex. The institution of Dr. Marder has received research support from Genentech. The institution of Dr. Marder has received research support from Triplet Therapeutics. The institution of Dr. Marder has received research support from Prilenia.

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