Blood Pressure Determinants of Cerebral White Matter Hyperintensities and Microstructural Injury: UK Biobank Cohort Study.
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SUBMITTER: Wartolowska KA
PROVIDER: S-EPMC8260341 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsWhite matter hyperintensities (WMH) progress with age and hypertension, but the key period of exposure to elevated blood pressure (BP), and the relative role of systolic BP (SBP) vs. diastolic BP (DBP), remains unclear. This study aims to determine the relationship between WMH and concurrent vs. past BP.Methods and resultsUK Biobank is a prospective community-based cohort of 40-69-year olds from 22 centres, with magnetic resonance imaging in a subgroup of over 40 000 people at 4-12 years after baseline assessment. Standardized associations between WMH load (WMH volume normalized by total white matter volume and logit-transformed) and concurrent vs. past BP were determined using linear models, adjusted for age, sex, cardiovascular risk factors, BP source, assessment centre, and time since baseline. Associations adjusted for regression dilution bias were determined between median WMH and usual SBP or DBP, stratified by age and baseline BP.In 37 041 eligible participants with WMH data and BP measures, WMH were more strongly associated with concurrent SBP [DBP: β = 0.064, 95% confidence interval (CI) 0.050-0.078; SBP: β = 0.076, 95% CI 0.062-0.090], but the strongest association was for past DBP (DBP: β = 0.087, 95% CI 0.064-0.109; SBP: β = 0.045, 95% CI 0.022-0.069), particularly under the age of 50 (DBP: β = 0.103, 95% CI 0.055-0.152; SBP: β = 0.012, 95% CI -0.044 to 0.069). Due to the higher prevalence of elevated SBP, median WMH increased 1.126 (95% CI 1.107-1.146) per 10 mmHg usual SBP and 1.106 (95% CI 1.090-1.122) per 5 mmHg usual DBP, whilst the population attributable fraction of WMH in the top decile was greater for elevated SBP (19.1% for concurrent SBP; 24.4% for past SBP). Any increase in BP, even below 140 for SBP and below 90 mmHg for DBP, and especially if requiring antihypertensive medication, was associated with increased WMH.ConclusionsWMH were strongly associated with concurrent and past elevated BP with the population burden of severe WMH greatest for SBP. However, before the age of 50, DBP was more strongly associated with WMH. Long-term prevention of WMH may require control of even mildly elevated midlife DBP.
| S-EPMC7882359 | biostudies-literature
Project description:White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.
| S-EPMC7820685 | biostudies-literature
Project description:BackgroundTwo markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease.Aim and/or hypothesisTo test for independent associations between two Alzheimer's disease-susceptibility gene loci--APOE ? and the TOMM40 '523' poly-T repeat--and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults.MethodsParticipants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ? and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation?=?0·7; range?=?71-74).ResultsNo significant effects of APOE ? or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants.ConclusionsLack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature.
| S-EPMC4950052 | biostudies-literature
Project description:BackgroundHigh blood pressure variability (BPV) may be a risk factor for stroke and dementia in patients with ischemic stroke, but the underlying mechanism is unknown. We aimed to investigate whether high BPV is associated with presence and progression of white matter hyperintensities (WMH).MethodsWe performed a post-hoc analysis on the MRI substudy of the PRoFESS trial, including 771 patients with ischemic stroke who underwent MRI at baseline and after a median of 2.1 years. WMH were rated with a semi-quantitative scale. Visit-to-visit BPV was expressed as the coefficient of variation (interval 3-6 months, median number of visits 7). The association of BPV with WMH burden and progression was assessed with linear and logistic regression analyses adjusted for confounders.ResultsBPV was associated with burden of periventricular WMH (β 0.36 95%CI 0.19-0.53, per one SD increase in BPV) and subcortical (log-transformed) WMH (β 0.25, 95%CI 0.08-0.42). BPV was not associated with periventricular (OR 1.09, 95%CI 0.94-1.27) and subcortical WMH progression (OR 1.15, 95%CI 0.99-1.35). Associations were independent of mean BP.ConclusionHigh visit-to-visit BPV was associated with both subcortical and periventricular WMH burden in patients with ischemic stroke, but not with WMH progression in this study.
| S-EPMC10827490 | biostudies-literature
Project description:Background and Purpose: White matter hyperintensities (WMH) are commonly seen on structural MRI of older adults and are a manifestation of underlying and adjacent tissue damage. WMH may contribute to cortical disconnection and cognitive dysfunction, but it is unclear how WMH affect intersecting or nearby white matter tract integrity. This study investigated the effects of WMH on tract microstructure by determining the spatial distribution of water diffusion characteristics in white matter tract areas adjacent to both intersecting and nearby WMH. Methods: We used diffusion and structural MRI data from 52 representative participants from the Lothian Birth Cohort 1936 (72.2 ± 0.7 years) including a range of WMH burden. We segmented WMH, reconstructed 18 main white mater tracts using automated quantitative tractography and identified intersections between tracts and WMH. We measured mean diffusivity (MD) and fractional anisotropy (FA) in tract tissue at 2 mm incremental distances from tract-intersecting and non-intersecting (nearby) WMH. Results: We observed a spatial gradient of FA and MD abnormalities for most white matter tracts which diminished with a similar distance pattern for tract-intersecting and nearby WMH. Overall, FA was higher, while MD was lower around nearby WMH compared with tract-intersecting WMH. However, for some tracts, FA was lower in areas immediately surrounding nearby WMH, although with faster normalization than in FA values surrounding tract-intersecting WMH. Conclusion: WMH have similar effects on tract infrastructure, whether they be intersecting or nearby. However, the observed differences in tract water diffusion properties around WMH suggest that degenerative processes in small vessel disease may propagate further along the tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. Longitudinal studies should address differential effects of intersecting vs. nearby WMH progression and how they contribute to cognitive aging.
| S-EPMC6673707 | biostudies-literature
Project description:Importance:White matter hyperintense lesions (WMHs) are highly prevalent in patients with reversible cerebral vasoconstriction syndrome (RCVS); however, their characteristics and underlying pathophysiology are unclear. Objective:To investigate the spatiotemporal distribution and pathomechanisms of WMHs in patients with RCVS. Design, Setting, and Participants:We prospectively recruited patients with RCVS over a 3-year period from January 2010 through December 2012 from the headache center or emergency department of Taipei Veterans General Hospital, Taipei, Taiwan, a 2947-bed national medical center. In total, 85 patients with RCVS were approached, of whom 4 declined to participate, 5 declined follow-up scans, 6 were lost to follow-up, and 5 had suboptimal images. Patients received serial isotropic 3-dimension fluid-attenuated inversion recovery sequence imaging (1-mm slice thickness) with a 3-T magnetic resonance imaging machine as well as transcranial and extracranial color-coded sonography on registration and during follow-ups (at 1 and 2 months, with variations adapting to clinical condition). Data were analyzed from January 2015 to May 2017. Main Outcomes and Measures:The fluid-attenuated inversion recovery lesion segmentation toolbox was used to segment WMHs automatically. The WMHs were classified as periventricular or deep and were segmented into 13 anatomical locations. The neuroimaging scientists who executed the program were blinded to clinical information. Vascular parameters, including the Lindegaard index (vasoconstriction severity), pulsatility index, and resistance index of the internal carotid artery, were independently collected for comparison. Results:Sixty-five patients with RCVS completed the study and underwent a total of 162 magnetic resonance imaging examinations. Of the 65 included patients, 58 (89%) were women, and the mean (SD) age was 50.1 (8.9) years. The total mean (SD) WMH load peaked at 3.2 (4.4) cm3 in the third week postonset and fell to 0.8 (0.6) cm3 in the fourth week. White matter hyperintensities were predominantly frontal and periventricular. White matter hyperintensity load correlated strongly with Lindegaard index during the second week of the disease course (r?=?0.908; P?<?.001) and also correlated with the pulsatility index and resistance index of the internal carotid artery. Conclusions and Relevance:White matter hyperintensities in patients with RCVS have a dynamic temporal evolution that parallels disease severity. The finding of partially reversible WMHs deserves attention and should be known by clinicians taking care of patients with RCVS. White matter hyperintensities in RCVS may be attributed, at least partially, to regional hypoperfusion and impaired dampening capacity to central pulsatile flow.
| S-EPMC6143117 | biostudies-literature
Project description:BackgroundPsychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, particularly if associated with distress. As PLEs have been related to alterations in both white matter and cognition, we investigated whether cognition (g-factor and processing speed) mediates the relationship between white matter and PLEs.MethodsWe investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis. For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. For the smaller sample, variables whole-brain white matter network efficiency and microstructure were also derived from structural connectome data.ResultsThe mediation of cognition on the relationships between white matter properties and PLEs was non-significant. However, lower gFA was associated with having PLEs in combination with distress in the full available sample (standardized β = -0.053, p = 0.011). Additionally, lower gFA/higher gMD was associated with lower g-factor (standardized β = 0.049, p < 0.001; standardized β = -0.027, p = 0.003), and partially mediated by processing speed with a proportion mediated of 7% (p = < 0.001) for gFA and 11% (p < 0.001) for gMD.ConclusionsWe show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. Furthermore, we replicated that processing speed mediates the relationship between white matter microstructure and g-factor.
| S-EPMC10123836 | biostudies-literature
Project description:We examined the relationship among white matter (WM) tract integrity, WM hyperintensities (WMH), lobar gray matter (GM) volumes, and cognition in the cross-sectional Framingham Offspring Study. Six hundred eighty participants (71.7 ± 7.7 years) completed cognitive testing and magnetic resonance imaging. Diffusion tensor imaging probabilistic tractography was used to reconstruct major WM tracts. We computed tract-specific mean fractional anisotropy (FA) and tract-specific WMH ratio. Linear regressions identified relations between tracts and lobar GM volumes. Partial least squares regression examined associations between integrity of combined tracts, lobar GM volumes and cognition, including scores of memory and processing speed. Five tracts were particularly vulnerable to WMH, and tract-specific WMH volumes were inversely associated with tract-specific FA (p values < 0.05). Tract-specific FA related to lobar GM volumes. Memory was associated with lobar GM, while processing speed related to both tract integrity and lobar GM volumes. We conclude that subtle microstructural WM tract degeneration relates to specific lobar GM atrophy. The integrity of associated WM tracts and GM lobes differentially impacts memory and processing speed.
| S-EPMC6242702 | biostudies-literature
Project description:BACKGROUND:The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. METHODS AND RESULTS:We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). CONCLUSIONS:We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
| S-EPMC4427240 | biostudies-literature
Project description:Neuroticism is a major risk factor for neurodegenerative disorders, such as Alzheimer's disease and related dementias. This study investigates whether neuroticism is associated with white matter hyperintensities and whether this measure of brain integrity is a mediator between neuroticism and cognitive function. Middle-aged and older adults from the UK Biobank (N = 40,602; aged 45-82 years, M = 63.97, SD = 7.66) provided information on demographic and health covariates, completed measures of neuroticism and cognition, and underwent magnetic resonance imaging from which the volume of white matter hyperintensities was derived. Regression analyses that included age and sex as covariates found that participants who scored higher on neuroticism had more white matter hyperintensities (β = 0.024, 95% CI 0.015 to 0.032; p < .001), an association that was consistent across peri-ventricular and deep brain regions. The association was reduced by about 40% when accounting for vascular risk factors (smoking, obesity, diabetes, high blood pressure, heart attack, angina, and stroke). The association was not moderated by age, sex, college education, deprivation index, or APOE e4 genotype, and remained unchanged in sensitivity analyses that excluded individuals with dementia or those younger than 65. The mediation analysis revealed that white matter hyperintensities partly mediated the association between neuroticism and cognitive function. These findings identify white matter integrity as a potential neurobiological pathway that accounts for a small proportion of the association between neuroticism and cognitive health.
| S-EPMC10528519 | biostudies-literature