Genetic analyses identify brain structures related to cognitive impairment associated with elevated blood pressure

Siedlinski, M. et al. (2023) Genetic analyses identify brain structures related to cognitive impairment associated with elevated blood pressure. European Heart Journal, 44(23), pp. 2114-2125. (doi: 10.1093/eurheartj/ehad101) (PMID:36972688) (PMCID:PMC10281555)

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Background and aims Observational studies have linked elevated blood pressure (BP) to impaired cognitive function. However, the functional and structural changes in the brain that mediate the relationship between BP elevation and cognitive impairment remain unknown. Using observational and genetic data from large consortia, this study aimed to identify brain structures potentially associated with BP values and cognitive function. Methods and results Data on BP were integrated with 3935 brain magnetic resonance imaging-derived phenotypes (IDPs) and cognitive function defined by fluid intelligence score. Observational analyses were performed in the UK Biobank and a prospective validation cohort. Mendelian randomisation (MR) analyses used genetic data derived from the UK Biobank, International Consortium for Blood Pressure, and COGENT consortium. Mendelian randomisation analysis identified a potentially adverse causal effect of higher systolic BP on cognitive function [−0.044 standard deviation (SD); 95% confidence interval (CI) −0.066, −0.021] with the MR estimate strengthening (−0.087 SD; 95% CI −0.132, −0.042), when further adjusted for diastolic BP. Mendelian randomisation analysis found 242, 168, and 68 IDPs showing significant (false discovery rate P < 0.05) association with systolic BP, diastolic BP, and pulse pressure, respectively. Most of these IDPs were inversely associated with cognitive function in observational analysis in the UK Biobank and showed concordant effects in the validation cohort. Mendelian randomisation analysis identified relationships between cognitive function and the nine of the systolic BP-associated IDPs, including the anterior thalamic radiation, anterior corona radiata, or external capsule. Conclusion Complementary MR and observational analyses identify brain structures associated with BP, which may be responsible for the adverse effects of hypertension on cognitive performance.

Item Type:Articles
Additional Information:This study was funded by the European Research Council [ERC and InflammaTENSION; ERC-CoG-726318; to T.J.G.], British Heart Foundation [FS/14/49/30838, RE/13/5/30177 and FS/4yPhD/F/20/34127A to T.J.G.], CVD ERA-CVD (PLAQUEFIGHT; 01KL1808 and ImmuneHyperCog to G.L. MoH Italy; and T.J.G.; NCBiR, Poland), and Italian MoH “Ricerca Corrente” and “RF-2018-12366235” to G.L. Dr Holmes works in a unit that receives funding from the UK Medical Research Council and is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/23/33512) and the National Institute for Health Research Oxford Biomedical Research Centre. MT and XX are supported by British Heart Foundation (PG/19/16/34270) and Kidney Research UK (RP_017_20180302 and RP_013_20190305). JW is supported by UK Dementia Research Institute funded by MRC, Alzheimer's Society and Alzheimer's Research UK. P.M. is supported by the British Heart Foundation grants (PG/19/84/34771, FS/19/56/34893A, PG/21/10541, PG/21/10634).
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale and Siedlinski, Mr Mateusz and Guzik, Professor Tomasz
Authors: Siedlinski, M., Carnevale, L., Xu, X., Carnevale, D., Evangelou, E., Caulfield, M., Maffia, P., Wardlaw, J., Samani, N. J., Tomaszewski, M., Lembo, G., Holmes, M. V., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN (Online):1522-9645
Published Online:27 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in European Heart Journal 44(23):2114-2125
Publisher Policy:Reproduced under a Creative Commons licence

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