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Abstract Details

Epigenetic Age and Brain Health Events: Findings from the Health and Retirement Study
Aging, Dementia, and Behavioral Neurology
P2 - Poster Session 2 (11:45 AM-12:45 PM)
9-004
We hypothesize that brain health events (BHE) lead to epigenetic age acceleration and that, conversely, accelerated epigenetic age leads to higher risk of BHE.
It is increasingly recognized that chronological age provides an incomplete assessment of true biological age. Epigenetic clocks use DNA methylation data to estimate biological age more accurately. 

We conducted a 3-stage epigenetic study within the Health and Retirement Study (Figure). In 2016, participants provided blood samples and methylation and genomic data was generated. Epigenetic age was calculated as the average of thirteen epigenetic clocks that used different combinations of methylation data. BHE was a composite of stroke, dementia and late-life depression. Stage 1 entailed testing for association between BHE prior to 2016 (exposure) and epigenetic age (outcome). Stage 2 entailed testing for association between epigenetic age (exposure) and BHE occurring after 2016 (outcome). All models were adjusted for age, sex, race/ethnicity and cardiovascular risk factors. Stage 3 entailed testing for causal associations using Mendelian Randomization (MR).
Out of 4,018 participants with epigenomic data, 2,221 (55%) had a history of a BHE before 2016. A history of BHE was associated with an older epigenetic age (beta 0.05, SE 0.01; p<0.01). Of the 3,047 study participants with available follow-up data, 1,018 (33%) developed a BHE over a mean follow up of 4 years. Epigenetic age acceleration was associated with higher odds of BHE (OR 1.57, [1.22-2.01]). Causal associations estimated via MR analyses confirmed both results.
A history of BHE was associated with epigenetic age acceleration and, conversely, epigenetic age acceleration was linked to a higher risk of brain health events. MR analyses suggest that these associations are causal. These results indicate that more nuanced strategies for ascertaining biological age are needed in neurological research and point to epigenetic clocks as a promising tool for this purpose. 
Authors/Disclosures
Cyprien Rivier, MD (Yale University)
PRESENTER 		Dr. Rivier has nothing to disclose.
Natalia Szejko, MD, PhD Dr. Szejko has nothing to disclose.
Daniela B. Renedo, MD (Yale University) Dr. Renedo has nothing to disclose.
Adam De Havenon, MD, FAAN (Yale University) Dr. De Havenon has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Dr. De Havenon has or had stock in Certus.Dr. De Havenon has or had stock in TitinKM. The institution of Dr. De Havenon has received research support from NIH/NINDS. Dr. De Havenon has received publishing royalties from a publication relating to health care.
Kevin N. Sheth, MD, FAAN (Yale UniversityDivision of Neuro and Critical Care) Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care.
Thomas Gill Thomas Gill has nothing to disclose.
Guido J. Falcone, MD (Yale School of Medicine) The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.