Sex and Cardiovascular Function in Relation to Vascular Brain Injury in Patients with Cognitive Complaints

Article type: Research Article

Authors: Kuipers, Sanne^{a; *} | Biessels, Geert Jan^a | Greving, Jacoba P.^b | Amier, Raquel P.^c | de Bresser, Jeroen^d | Bron, Esther E.^e | van der Flier, Wiesje M.^{f; g} | van der Geest, Rob J.^d | Hooghiemstra, Astrid M.^f | van Oostenbrugge, Robert J.^h | van Osch, Matthias J.P.^d | Kappelle, L. Jaap^a | Exalto, Lieza G.^a | Heart-Brain Connection Consortium

Affiliations: [a] Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands | [b] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands | [c] Department of Cardiology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Science, Amsterdam, the Netherlands | [d] Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands | [e] Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands | [f] Alzheimer Center Amsterdam & Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands | [g] Department of Epidemiology, VU University Medical Center, Amsterdam, the Netherlands | [h] Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands

Correspondence: [*] Correspondence to: Sanne Kuipers, MD, Department of Neurology G03.232, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 88 7573738; Fax: +31 30 2542100; E-mail: s.kuipers-2@umcutrecht.nl.

Abstract: Background:Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function. Objective:To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function. Methods:160 outpatient clinic patients (68.8±8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker). Results:Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction terms > 0.05). Conclusion:Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns.

Keywords: Cardiovascular function, cerebrovascular disorders, cognitive dysfunction, female, male, sex, vascular brain injury

DOI: 10.3233/JAD-210360

Journal: Journal of Alzheimer's Disease, vol. 84, no. 1, pp. 261-271, 2021