Impact of 25-Hydroxy Vitamin D on White Matter Hyperintensity in Elderly Patients: A Systematic Review and Meta-Analysis.
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ABSTRACT:
SUBMITTER: Zhao Y
PROVIDER: S-EPMC8794798 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Automated segmentation of the aging brain raises significant challenges because of the prevalence, extent, and heterogeneity of white matter hyperintensities. White matter hyperintensities can be frequently identified in magnetic resonance imaging (MRI) scans of older individuals and among those who have Alzheimer's disease. We propose OASIS-AD, a method for automatic segmentation of white matter hyperintensities in older adults using structural brain MRIs. OASIS-AD is an approach evolved from OASIS, which was developed for automatic lesion segmentation in multiple sclerosis. OASIS-AD is a major refinement of OASIS that takes into account the specific challenges raised by white matter hyperintensities in Alzheimer's disease. In particular, OASIS-AD combines three processing steps: 1) using an eroding procedure on the skull stripped mask; 2) adding a nearest neighbor feature construction approach; and 3) applying a Gaussian filter to refine segmentation results, creating a novel process for WMH detection in aging population. We show that OASIS-AD performs better than existing automatic white matter hyperintensity segmentation approaches.
| S-EPMC6957792 | biostudies-literature
Project description:White matter hyperintensities (WMHs) are associated with progressive age-related cognitive decline and cardiovascular risk factors, but their biological relevance as indicators of generalized white matter injury is unclear. Diffusion tensor imaging provides more sensitive indications of subtle white matter disruption and can therefore clarify whether WMHs represent foci of generalized white matter damage that extends over a broader neighborhood.Two hundred eight participants from the University of California, Davis Alzheimer's Disease Center received a comprehensive clinical evaluation and brain MRI including fluid-attenuated inversion recovery and diffusion tensor imaging sequences. Voxelwise maps of WMHs were produced from fluid-attenuated inversion recovery using a standardized WMH detection protocol. Fractional anisotropy maps were calculated from diffusion tensor imaging. All WMH and fractional anisotropy maps were coregistered to a standardized space. For each normal-appearing white matter voxel in each subject fluid-attenuated inversion recovery scan, a neighborhood white matter injury score was calculated that increased with increasing number and proximity of WMH in the vicinity of the normal-appearing white matter voxel. Fractional anisotropy was related to neighborhood white matter injury using a nonlinear mixed effect model controlling for relevant confounding factors.Fractional anisotropy was found to decrease as neighborhood white matter injury increased (? = -0.0017/%, P < 0.0001) with an accelerated rate (P < 0.0001) for neighborhood white matter injury >0.4. An increase of 1% in neighborhood white matter injury score was associated with a decrease in mean fractional anisotropy of 0.012 (P < 0.001).WMH may represent foci of more widespread and subtle white matter changes rather than distinct, sharply delineated anatomic abnormalities. We use the term white matter hyperintensities penumbra to explain this phenomenon.
| S-EPMC3125449 | biostudies-literature
Project description:Background White matter hyperintensity (WMH), characterized by hyperintensities on T2-weighted fluid-attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS. Methods and Results We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson r=0.24, P=0.03; >50 years, Pearson r=0.62, P<0.0001; juxtacortical WMH: ≤50 years, Pearson r=0.09, P=0.40; >50 years, Pearson r=0.55, P<0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient -0.17, P=0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow-up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05-1.92; P=0.03). Conclusions Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.
| S-EPMC8751863 | biostudies-literature
Project description:BackgroundWhite matter hyperintensity has been correlated with cognitive disorders and its genetic predictors remain unclear. Here we conducted a genome-wide association study to identify novel genetic determinants that were correlated with white matter hyperintensity volume (WMHV) among non-demented elders.MethodsThree hundred and fifty non-Hispanic Caucasian subjects aged 55-80 years were included from the Alzheimer's Disease Neuroimaging Initiative cohort. Associations of WMHV with genetic polymorphisms were explored using multiple linear regression under an additive genetic model. Further studies were conducted to explore the influence of genetic variants on cognition-related phenotypes.ResultsRs7220676 near HS3ST3A1 and MIR548H3 genes was associated with WMHV levels at genome-wide significance (P = 2.96 × 10-8). Single nucleotide polymorphisms comprising rs9675262 (near HS3ST3A1 and MIR548H3 genes, P = 1.15 × 10-7), rs9820240 (in DCLK3 gene, P = 2.23 × 10-7), rs10916409 (near ISCA1P2 gene, P = 4.55 × 10-6), and rs540422 (in PICALM gene, P = 9.68 × 10-6) were identified as suggestive loci linked to WMHV levels. The minor allele of rs7220676 (C) showed association with lower log (WMHV) in a dose-dependent manner. Besides, rs7220676 was correlated with rates of cognitive decline assessed by Mini-mental State Examination and memory scores.ConclusionsA novel locus near HS3ST3A1 and MIR548H3 genes was associated with WMHV levels and it may be involved in neurodegenerative diseases.
| S-EPMC7021640 | biostudies-literature
Project description:The detrimental outcomes of white matter hyperintensity (WMH) are known to be proportional to WMH volume. This study aimed to evaluate the association between kidney dysfunction and white matter hyperintensity (WMH) volume. A total of 2,203 subjects who underwent brain magnetic resonance imaging (MRI) as part of a screening health check-up was included in this study. WMH was defined as hyperintensity signals without cavity formation in the white matter on fluid-attenuated inversion recovery images. WMH volume was measured quantitatively, and data were normalized by square root transformation prior to analysis. Mean age of the subjects was 56.9 years and mean WMH volume was 2.7 cm3. Mean estimated glomerular filtration rate (eGFR) level was 78.0 ml/min/1.73 m2, and 172 subjects (7.8%) were diagnosed with moderate-to-severe kidney dysfunction (eGFR < 60). Mean Urine albumin-to-creatinine ratio (UACR) was 0.02, and 166 subjects showed significant albuminuria (UACR ≥ 0.03). Multivariate analyses showed that each of UACR, significant albuminuria, and moderate-to-severe kidney dysfunction was significantly associated with increased WMH volume (all p < 0.05). When we considered significant albuminuria and moderate-to-severe kidney dysfunction simultaneously, subjects with both significant albuminuria and moderate-to-severe kidney dysfunction had more than twice the WMH volume as did those in the other groups (all p < 0.05). Kidney dysfunction, defined by albuminuria and eGFR, was independently associated with WMH volume. Risk factors related to WMH and its detrimental outcomes should be strictly modified in subjects with kidney dysfunction, especially in those with both albuminuria and a reduced eGFR.
| S-EPMC6565737 | biostudies-literature
Project description:White matter hyperintensity (WMH) is associated with vascular hemodynamic alterations and reflects white matter injury. To date, the sex difference of tract-specific WMH and the relationship between high blood pressure (BP) and tract-specific WMH remain unclear. We recruited 515 subjects from the Shanghai Changfeng study (range 53-89 years, mean age 67.33 years). Systolic and diastolic blood pressure (SBP and DBP) were collected and used to calculate pulse pressure (PP). Magnetic resonance T1 and T2 FLAIR images were acquired to measure WMH and calculate WMH index. The ANCOVA test was performed to test the difference between sexes, and the linear regression model was used to examine the associations between BP and WMH index. Men showed higher WMH index than women in all white matter tracts (p < .001, respectively) except for the bilateral superior longitudinal fasciculus (SLF) and its left temporal part (tSLF). High SBP and PP was associated with a lower WMH index on the left corticospinal tract (CST), SLF, tSLF and right cingulum in hippocampus (p ≤ .001, respectively) in women, while high DBP was associated with a higher WMH index on the bilateral CST (left p < .001; right p = .001), left inferior longitudinal fasciculus (p < .001) and inferior fronto-occipital fasciculus (p = .002) in men. Men tend to have more WMH compared to women. A high SBP/PP relates to a lower WMH burden in women. This suggests that women could benefit from higher blood pressure in older age.
| S-EPMC9980881 | biostudies-literature
Project description:Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N?=?51), dichotomized according to pathological or normal levels of amyloid-? peptide (A?42) in cerebrospinal fluid (CSF). Thirty-one subjects with low CSF A?42 (A?+) and 20 subjects with normal CSF A?42 (A?-) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in A?+ relative to A?-; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.
| S-EPMC5363752 | biostudies-literature
Project description:ObjectiveTo assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study.MethodsWe recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression.ResultsAmong 190 participants (mean age 65.3 years, range 34.3-96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (β = 0.0053, 95% confidence interval [CI] 0.00099-0.0097 fewer WMH per 1-mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (β = 0.075, 95% CI 0.0025-0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, β = 0.27, 95% CI 0.047-0.50 more WMH per event, p = 0.018).ConclusionsSome WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets.
| S-EPMC5589793 | biostudies-literature
Project description:Hypertension is an important cause of cerebral small vessel disease, especially of white matter hyperintensity (WMH). The ability of intensive blood pressure (BP) control in preventing this pathological progression remains unclear. The authors systematically searched PubMed, EMBASE, SCOPUS, and Cochrane library for publications until July 20, 2020. Studies included were clinical trials with random allocation to an antihypertensive medication against placebo, or different treatment targets. The primary outcome was intergroup differences in the change of WMH volume. A random-effect model was applied for pooling effect measures. Subgroup analysis and meta-regression were conducted to explore heterogeneity. Seven studies with 2693 patients were identified. Compared with the control group, patients in the intensive BP control group had a slower progression of WMH, with a pooled intergroup standard mean difference (SMD) for WMH change of -0.22 (95% CI: -0.35 ~ -0.09, I2 = 63%). For studies comparing intensive and standard BP target, the pooled SMD is -0.37 (95% CI:-0.50~-0.24, I2 = 0%), while the pooled SMD of studies comparing active antihypertensive medication and placebo was only -0.08 (95% CI: -0.17 ~ 0.01, I2 = 0%). Meta-regression analysis showed that the reduction in WMH progression is proportional to the magnitude of intensive BP control (β = -0.028, P < .001). In conclusion, intensive BP control prevents WMH progression, and its effect is associated with the magnitude of intensive BP control.
| S-EPMC8029786 | biostudies-literature
Project description:Gait speed is associated with multiple adverse outcomes of aging. White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been associated with gait speed, though few studies have examined changes in gait speed over time in population-based studies comprising participants from diverse cultural backgrounds. The purpose of this study was to examine the association between a decline in gait speed and total and regional WMH volumes in a community-based study of aging. Participants (n = 701) underwent gait-speed measurement via a 4-m walk test at the time of initial enrollment and MRI at a second time interval (mean 4.7 [SD = 0.5] years apart). Logistic regression was used to examine the association between large WMH volume and regional WMH volume with gait speed <0.5 m/s (abnormal speed), and a transition to abnormal gait speed. Analyses were adjusted for demographic and clinical factors. Large WMH volume was associated with abnormal gait speed and a transition to abnormal gait speed between the two visits, but not after adjustment for modifiable vascular disease risk factors. Increased frontal lobe WMH volume was associated with abnormal gait speed and transition to abnormal gait speed, but not in adjusted models. WMH are associated with slowing of gait over time. Prevention of WMH presents a potential strategy for the prevention of gait speed decline.
| S-EPMC3594567 | biostudies-literature