Precision Neurology for Dementia (P2-6.002)

Abstract

<h3>Objective:</h3> To establish a precision medicine workflow for Alzheimer’s disease and related dementias (AD/ADRDs) and assess its impact. <h3>Background:</h3> AD/ADRDs are clinically, pathologically, and genetically heterogeneous. Precision medicine promises individualized, etiologic diagnosis and ultimately, targeted therapies. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 <i>APOE</i>; two participants carried the <i>lipoprotein(a)</i> 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. <h3>Conclusions:</h3> Overall, our experience and emerging results establish feasibility and will inform implementation of precision neurology for dementia. <b>Disclosure:</b> The institution of Dr. Shulman has received research support from National Institutes of Health. Dr. Shulman has received personal compensation in the range of $10,000-$49,999 for serving as a Advisory Council member with Helis Medical Foundation. The institution of Dr. Vanegas-Arroyave has received research support from National Institutes of Health. Jamie Fong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Sarah Elsea has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dicerna. Sarah Elsea has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers. The institution of Sarah Elsea has received research support from NIH. The institution of Sarah Elsea has received research support from Speragen. The institution of Sarah Elsea has received research support from PTC Therapeutics. The institution of Sarah Elsea has received research support from PRISMS, Inc. The institution of Sarah Elsea has received research support from Smith-Magenis Syndrome Research Foundation. The institution of Sarah Elsea has received research support from Jerome Lejeune Foundation. 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. Hiba Saade has nothing to disclose. Miss Chavez has nothing to disclose. Ms. Walker has stock in Thermo Fisher Scientific. The institution of Ms. Walker has received research support from NIH - All of Us Program. Bo Yuan has nothing to disclose. Dr. Venner has stock in Codified Genomics. Dr. Hu has nothing to disclose. Mr. Levchenko has nothing to disclose. Dr. Smith has nothing to disclose. Ms. Robinson has nothing to disclose. The institution of Prof. Pascual has received research support from NIH. The institution of Prof. Pascual has received research support from NIH. The institution of Donna Muzny has received research support from NIH. Richard Gibbs has nothing to disclose. Dr. McGuire has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Danaher Life Sciences. Dr. McGuire has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Greenwall Foundation. Dr. McGuire has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for King and Spalding. Dr. McGuire has stock in Facebook. The institution of Dr. McGuire has received research support from NIH. The institution of Dr. McGuire has received research support from Greenwall Foundation. Dr. Masdeu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Moody Foundation. The institution of Dr. Masdeu has received research support from Biogen. The institution of Dr. Masdeu has received research support from Eli Lilly. The institution of Dr. Masdeu has received research support from Eisai. The institution of Dr. Masdeu has received research support from Novartis. 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.