Dataset Information

Periventricular rather than deep white matter hyperintensities mediate effects of hypertension on cognitive performance in the population-based 1000BRAINS study.

ABSTRACT:

Objectives

White matter hyperintensities (WMH) of presumed vascular origin are frequent in cerebral MRI of older people. They represent a sign of small vessel disease, are promoted by arterial hypertension, and relate to cognitive deficits. The interdependence of blood pressure and its treatment, WMH, and cognitive performance has not systematically been studied in population-based studies.

Methods

Consequently, we analysed the interdependence of SBP, DBP, and antihypertensive medications, as well as BP/treatment category, with WMH and cognitive performance in 560 participants of the population-based 1000BRAINS study.

Results

BP, its treatment, and BP/treatment category were moderately associated with cognitive performance (e.g. unadjusted β = -0.10, 95%CI = -0.19 to -0.02 for the association of SBP (per standard deviation of 17.2 mmHg) with global cognition (per standard deviation of 0.5 z score)]. The harmful effect of BP on cognition was strongly mediated by periventricular hyperintensities (PVH), which were significantly associated with both SBP [ β = 0.24, 95% CI = 0.14-0.34 (per 1-point-increase in Fazekas score)] and global cognition ( β = -0.22, 95%CI = -0.32 to -0.13). Thus, PVH mediated as much as 52% of the effects of SBP on cognitive performance. Mediation was less strong for deep white matter hyperintensities (DWMH, 16%), which showed less association with SBP ( β = 0.14, 95% CI = 0.05-0.24) and global cognition ( β = -0.12, 95%CI = -0.21 to -0.03). Regarding different cognitive domains, PVH most strongly mediated effects of SBP on nonverbal memory (94%) and executive function (81%).

Conclusion

Our results indicate that PVH may predispose to cognitive impairment associated with hypertension, especially in the domains of nonverbal memory and executive function.

SUBMITTER: Gronewold J

PROVIDER: S-EPMC9640292 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Periventricular rather than deep white matter hyperintensities mediate effects of hypertension on cognitive performance in the population-based 1000BRAINS study.

Gronewold Janine J Jokisch Martha M Schramm Sara S Himpfen Heiko H Ginster Theresa T Tenhagen Isabell I Doeppner Thorsten R TR Jockwitz Christiane C Miller Tatiana T Lehmann Nils N Moebus Susanne S Jöckel Karl-Heinz KH Erbel Raimund R Caspers Svenja S Hermann Dirk M DM

Journal of hypertension 20220818 12

<h4>Objectives</h4>White matter hyperintensities (WMH) of presumed vascular origin are frequent in cerebral MRI of older people. They represent a sign of small vessel disease, are promoted by arterial hypertension, and relate to cognitive deficits. The interdependence of blood pressure and its treatment, WMH, and cognitive performance has not systematically been studied in population-based studies.<h4>Methods</h4>Consequently, we analysed the interdependence of SBP, DBP, and antihypertensive med ...[more]

PMID: 35983864

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Project description:Background and purposePeriventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.MethodsParticipants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.ResultsIn the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype.ConclusionsOur study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

Dataset Information

Periventricular rather than deep white matter hyperintensities mediate effects of hypertension on cognitive performance in the population-based 1000BRAINS study.

Objectives

Methods

Results

Conclusion

Publications

Periventricular rather than deep white matter hyperintensities mediate effects of hypertension on cognitive performance in the population-based 1000BRAINS study.

Similar Datasets

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