Abstract Details

Title Polygenic susceptibility to hypertension is associated with worse cognitive function

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) Behavioral and Cognitive Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 026

Objective To provide further evidence for a causal role of hypertension in the development of cognitive decline and dementia, weinvestigated whether polygenic susceptibility to hypertension leads to worse cognitive performance in a large cohort of middle-aged persons.

Background While observational studies indicate that hypertension is associated with higher risk of cognitive decline and dementia, clinical trials have failed to demonstrate that aggressive blood pressure control is effective as a prevention strategy.

Design/Methods

We conducted a nested genetic study within the UK Biobank. For this study, we restricted our analyses to study participants of European ancestry. To model polygenic susceptibility to hypertension, we constructing polygenic risk scores (PRS) using 249 and 228 independent genetic variants known to increase systolic and diastolic blood pleasure (BP), respectively. Cognitive function was evaluated via five cognitive functioning tests listed in the result section.

Results Out of a total of 502,536 study participants enrolled in the UK Biobank, 409,629 were from European ancestry. Of these, the following completed cognitive testing: prospective memory n= 208,412, visual memory n= 498,751, verbal-numerical reasoning n= 201,839, reaction time n= 496,850, numeric memory n= 77,471, respective. The systolic BP PRS was significantly associated with the worse performance in the verbal numeric reasoning test (β = -0.002, SE= 0.001, p= 0.05, per each additional standard deviation of the score), while the diastolic BP PRS was significantly associated with worse performance in reaction time test (β = 0.40, SE= 0.17, p= 0.02). A total 20,346 participants completed follow-up cognitive assessments after ~5.1 year. The diastolic (β =-1.49, SE=0.62, p=0.02) BP PRSs were associated with worsened reaction time.

Conclusions

These findings provide evidence for a causal link between SBP and DBP and worse cognitive functioning.

Authors/Disclosures
Natalia Szejko, MD, PhD PRESENTER	Dr. Szejko has nothing to disclose.
	No disclosure on file
Rommell Noche	Mr. Noche has nothing to disclose.
	No disclosure on file
Victor M. Torres-Lopez, MA (Yale University)	Mr. Torres-Lopez has nothing to disclose.
Audrey Leasure	Ms. Leasure has nothing to disclose.
Stacy C. Brown, MD (The Queen's Medical Center, Neuroscience Institute)	Dr. Brown has nothing to disclose.
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.

��ɫ��

��ɫ��