Abstract Details

Title Progression of Motor Dysfunction in Elderly LRRK2 Carriers, Including Prior to Phenoconversion to PD

Topic Movement Disorders

Presentation(s) IN2 - (-)

Poster/Presentation
Number 005

Objective

Background Understanding the pre-diagnosis motor course in LRRK2 mutation carriers will inform clinical trials of LRRK2 inhibitors in unaffected carriers. We previously reported the course in six elderly carriers and now report an additional three years follow-up of motor ratings.

Design/Methods Subjects had yearly neurological examinations (including UPDRS) and digitized spiral analysis at the Einstein Aging Study. Six individuals carried the LRRK2 G2019S mutation and were matched 1:5 to controls on gender, age at study entry, and number of follow-up visits. The difference in UPDRS slopes between cases and matched controls was evaluated using a Wilcoxon matched-pairs signed ranks test.

Results Mutation carriers averaged 7.8 ± 1.3 (mean ± sd) visits (range: 6-9) with controls averaging 7.9 ± 2.4 (range: 4-12). Carriers had an average age of 89 ± 6.3 years at last visit (range: 79.6-96.8) with controls averaging 87.3 ± 4.1 (range: 79.7-96). Two G2019S carriers phenoconverted to PD, including one newly reported man who developed PD, characterized by asymmetric rigidity and bradykinesia at the ninth visit (age 87). UPDRS score increased in cases with an overall median slope of 1.97 points per year (IQR: 4.4) vs. 0.53 in controls (IQR: 0.93); however, this did not reach statistical significance (0.063).

Conclusions The trend toward overall worse slopes in motor decline in UPDRS supports the hypothesis that elderly LRRK2 carriers remain at high risk of phenoconversion to PD. Further, the trajectories of UPDRS in the cases who developed PD suggests that there may be slow development of motor decline that precedes phenoconversion by several years. However, larger samples are necessary to perform change-point models and assess inflection points to determine when a shift in slopes occur.

Authors/Disclosures
PRESENTER	No disclosure on file
Andres F. Deik Acosta Madiedo, MD, FAAN (University of Pennsylvania)	Dr. Deik Acosta Madiedo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. Deik Acosta Madiedo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Supernus Therapeutics. Dr. Deik Acosta Madiedo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Deik Acosta Madiedo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amneal. The institution of Dr. Deik Acosta Madiedo has received research support from Teva Pharmaceuticals. The institution of Dr. Deik Acosta Madiedo has received research support from Cerevel Therapeutics. The institution of Dr. Deik Acosta Madiedo has received research support from Prevail Therapeutics. The institution of Dr. Deik Acosta Madiedo has received research support from Lundbeck Therapeutics. The institution of Dr. Deik Acosta Madiedo has received research support from AskBio. The institution of Dr. Deik Acosta Madiedo has received research support from Annovis Bio. The institution of Dr. Deik Acosta Madiedo has received research support from Ono pharmaceuticals. The institution of Dr. Deik Acosta Madiedo has received research support from Amylyx therapeutics. Dr. Deik Acosta Madiedo has received publishing royalties from a publication relating to health care. Dr. Deik Acosta Madiedo has received publishing royalties from a publication relating to health care.
James P. Battista, MD (Optum/Caremount Medical)	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.
Richard B. Lipton, MD, FAAN (Albert Einstein College of Medicine)	Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Pfizer. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axon. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cool Tech. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BDSI. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Linpharma. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axsome. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clexio. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shiratronics. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. Dr. Lipton has stock in Axon. Dr. Lipton has stock in CoolTech. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from Veterans Administration. Dr. Lipton has received publishing royalties from a publication relating to health care.
Marta San Luciano, MD, FAAN (University of California San Francisco)	Dr. San Luciano has received research support from NIH (NINDS).
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.
	No disclosure on file

��ɫ��

��ɫ��