Abstract Details

Title Contribution of Genetic Risk Factors in Progression from Cognitive Impairment to Alzheimer Disease in 2 Large Canadian Cohorts

Topic Aging and Dementia

Presentation(s) S34 - (-)

Poster/Presentation
Number 001

Objective

Background Recent GWAS identified novel genetic risk factors for late-onset AD. However, their utility in predicting outcome of patients with cognitive impairment has not been examined in depth. Here, we used 2 Canadian cohorts to study the role of these genes in predicting the outcome of participants with cognitive impairment. The Canadian Study on Health and Aging (CSHA) is a population-based study of the elderly with 10 years follow-up. The Canadian Cohort study on Cognitive impairment and Related Dementias (ACCORD) is a longitudinal cohort from 8 specialized dementia clinics with up to 7 years follow-up.

Design/Methods Single nucleotide polymorphisms genotypes in CR1, PICALM, TOMM40, BIN1, CD33, CLU, CD2AP, MS4A4A, EPHA1, and ABCA7 were obtained in subjects diagnosed as cognitively impaired no dementia (CIND). Chi-squared was used to analyze genotype, and odds ratios were calculated by logistic regression with covariates including age, sex, education, and APOE ?4-status.

Results In this combined cohort, 152 participants with CIND at baseline progressed to AD during follow-up (progressors), while 202 participants were diagnosed as CIND at baseline but remained stable during the period of follow-up or death (stables). We found that BIN1 (rs7561528) (p=0.033) and TOMM40 (rs2075650) (p=0.034) were associated with increased risk of progression to AD. Further logistic regression modeling confirmed BIN1 (O.R. 0.61; 95%C.I. 0.39-0.95) and TOMM40 (O.R. 1.79; 95%C.I. 1.15-2.80) to be significant genetic predictors of CIND progression to AD, after adjustment for the covariates. Additionally, in APOE ?4-carriers, CLU (rs1136000) T-allele was associated with reduced risk of CIND progression to AD (p=0.04; O.R. 0.43; 95%C.I. 0.19-0.98).

Conclusions Addition of BIN1, CLU, and TOMM40 to APOE genotype may assist with predicting the risk of progression to AD in CIND subjects.

Authors/Disclosures
Ardeshir Omoumi, MD, PhD (University of British Columbia Hospital) PRESENTER	No disclosure on file
	No disclosure on file
Howard Feldman, MD, FAAN (University of California San Diego)	The institution of Dr. Feldman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead Pharmaceuticals. The institution of Dr. Feldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. The institution of Dr. Feldman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen Research & Development LLC. The institution of Dr. Feldman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Banner/API. The institution of Dr. Feldman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tau Consortium. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from Vivoryon Therapeutics. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from LuMind Foundation. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from Biohaven Pharmaceuticals. The institution of Dr. Feldman has received research support from UC San Diego School of Medicine Brain Health Support Program & Sanford Institute for Empathy and Compassion. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. The institution of Dr. Feldman has received research support from US National Institute of Health NIH/NIA. Dr. Feldman has received intellectual property interests from a discovery or technology relating to health care. Dr. Feldman has a non-compensated relationship as a Medical Advisory Council with Association for Frontotemporal Degeneration (AFTD) that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a International Scientific Advisory Board with Translating Research in Elder Care (TREC) that is relevant to AAN interests or activities.
Dessa Sadovnick, PhD (VCHA-UBC Hospital)	No disclosure on file
Ging-Yuek R. Hsiung, MD, FAAN (University of British Columbia)	Dr. Hsiung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Hsiung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Hsiung has received research support from CIHR. The institution of Dr. Hsiung has received research support from NIH. The institution of Dr. Hsiung has received research support from Eli Lilly. The institution of Dr. Hsiung has received research support from Biogen.
Cinzia Cordioli, MD (Centro Sclerosi Multipla Spedali Civili di Br)	Dr. Cordioli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Almirall. Dr. Cordioli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Cordioli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.

��ɫ��

��ɫ��