Abstract Details

Title Precision Neurology for Dementia

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 7-002

Objective

To establish a precision medicine workflow for Alzheimer’s disease and related dementias (AD/ADRDs) and assess its impact.

Background

AD/ADRDs are clinically, pathologically, and genetically heterogeneous. Precision medicine promises individualized, etiologic diagnosis and ultimately, targeted therapies.

Design/Methods

27 participants have been enrolled from the Houston community (n=13) or neurology outpatient clinics (n=14) at Baylor College of Medicine or Houston Methodist Hospital, including individuals with established AD/ADRD, mild cognitive impairment (MCI), or no known cognitive impairment (NCI). Participants received (i) comprehensive neurologic and neuropsychological assessments (NACC Uniform Data Set), (ii) brain MRI and amyloid PET, and (iii) CAP-CLIA whole genome sequencing. Genome data was filtered using a virtual gene panel specifically developed for this project, including 219 causes of AD/ADRD, cardiovascular diseases, or other medically-actionable conditions unrelated to dementia, along with 3 ADRD/cardiovascular risk genes. All subjects were consented for comprehensive disclosure of dementia risk.

Results

Participants had a mean age=70, were 41% female, and reported mixed race/ancestry (white=66%, Hispanic/Latino=18%, African American=7%, Asian=7%). Following baseline assessments and prior to neuroimaging biomarkers, participants had clinical diagnoses of AD (n=7), Lewy body dementia (n=1), MCI (n=8), and NCI (n=11). All participants were negative for known monogenic causes of dementia. 15 individuals (56%) had increased dementia risk due to APOE; two participants carried the lipoprotein(a) cardiovascular risk allele; and three individuals had medically actionable, ACMG-reportable secondary findings. Neuroimaging studies are currently being reviewed, and results will be integrated for etiologic diagnosis using the 2018 NIA-AA research (A/T/N) framework. In disclosure visits, all participants will receive precision diagnostic results and a personalized genomic risk report. Surveys will assess perspectives including perceptions of the experience, psychological impact, self-efficacy, quality of life, advance planning, and health behaviors.

Conclusions

Overall, our experience and emerging results establish feasibility and will inform implementation of precision neurology for dementia.

Authors/Disclosures
Joshua M. Shulman, MD, PhD, FAAN (Duncan Neurological Research Institute) PRESENTER	Dr. Shulman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Helis Medical Foudation. The institution of Dr. Shulman has received research support from National Institutes of Health.
Nora Vanegas-Arroyave, MD (Baylor College of Medicine)	The institution of Dr. Vanegas-Arroyave has received research support from National Institutes of Health. The institution of Dr. Vanegas-Arroyave has received research support from MJFF.
	No disclosure on file
Sarah Elsea	The institution of Sarah Elsea has received research support from NIH. The institution of Sarah Elsea has received research support from Speragen, Inc. The institution of Sarah Elsea has received research support from PTC Therapeutics, Inc. The institution of Sarah Elsea has received research support from PRISMS, Inc. The institution of Sarah Elsea has received research support from Warren Alpert Foundation. Sarah Elsea has received personal compensation in the range of $0-$499 for serving as a Grant Reviewer with NIH. Sarah Elsea has received personal compensation in the range of $0-$499 for serving as a Reviewer with CDMRP-DOD.
Chi-Ying (Roy) Lin, MD, FAAN (Baylor College of Medicine)	Dr. Lin has received research support from Texas Alzheimer's Research and Care Consortium (TARCC). Dr. Lin has received research support from CurePSP. Dr. Lin has received research support from Mike Hogg Fund. Dr. Lin has received research support from The Michael J. Fox Foundation Parkinson's Progression Markers Initiative (PPMI). Dr. Lin has a non-compensated relationship as a Secretary with Broadway for Ataxia Foundation (a 501 (c) (3) non-profit organization) that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Belen Pascual, PhD (Houston Methodist Hospital)	The institution of Prof. Pascual has received research support from NIH. The institution of Prof. Pascual has received research support from NIH.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Joseph C. Masdeu, MD, PhD, FAAN (Houston Methodist Neurological Institute)	Dr. Masdeu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lilly . The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Houston Methodist Foundation. The institution of Dr. Masdeu has received research support from Alector. The institution of Dr. Masdeu has received research support from Aviado-Bio. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received personal compensation in the range of $100,000-$499,999 for serving as a Director, Nantz Nal Alzheimer Center with HOUSTON METHODIST NEUROLOGICAL INSTITUTE.

��ɫ��

��ɫ��