Association between white matter lesions and cerebral Aβ burden.
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ABSTRACT: Introduction
White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment in older adults. The purpose of this study was to evaluate the association between WMLs and cerebral amyloid-β (Aβ) burden in patients with cognitive impairment.Methods
A total of 83 patients with cognitive impairment, who underwent brain MRI and F-18 florbetaben PET, were included prospectively: 19 patients were cognitively unimpaired, 30 exhibited mild cognitive impairment (MCI), and 34 exhibited dementia. The Fazekas scale was used to quantify WMLs on T2-weighted brain MR images. Cerebral Aβ burden was quantitatively estimated using volume-of-interest analysis. Differences in cerebral Aβ burden were evaluated between low-WML (Fazekas scale ≤1) and high-WML (Fazekas scale ≥2) groups. The relationship between the Fazekas rating and cerebral Aβ burden was evaluated using linear regression analysis after adjusting for age and sex.Results
In the overall cohort, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.011) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.299, P = 0.006). In patients with MCI, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.019) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.517, P = 0.003).Conclusion
The presence of WMLs was associated with cerebral Aβ burden in patients with MCI. Our findings suggest that small vessel disease in the brain is related to Alzheimer's disease pathology.
SUBMITTER: Yi HA
PROVIDER: S-EPMC6152974 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND At present, the association between blood pressure, regional cerebral blood flow, and white matter lesions is not well understood. MATERIAL AND METHODS A total of 147 subjects aged from 40 to 80 years were assessed by the Fazekas score for white matter lesions, CT perfusion imaging for regional cerebral blood flow, and 24-h ambulatory blood pressure monitoring for blood pressure level and rhythm. Logistic regression analysis was used to obtain the odds ratio and 95% confidence interval between Fazekas scores and relevant factors. The relationship between blood pressure index and regional cerebral blood flow was analyzed through cubic curve estimation. RESULTS Fazekas score was negatively correlated with regional cerebral blood flow (r=-0.801; r=-0.831, P<0.001). For subcortical lesion, the regional cerebral blood flow of Fazekas grade 0 was 1.976 times that of Fazekas grade 3 (OR=1.976, 95% CI=1.576-2.477), and for periventricular lesion, the regional cerebral blood flow of Fazekas grade 0 was 2.034 times that of Fazekas grade 3 (OR=2.034, 95% CI=1.602-2.583). Increased nighttime systolic blood pressure may be more dangerous (OR=1.112, 95% CI=1.059-1.169). The day-night systolic blood pressure ratio (OR=0.801, 95% CI 0.711-0.902) and the day-night diastolic blood pressure ratio (OR=0.876, 95% CI 0.807-0.950) were significantly correlated with Fazekas score. CONCLUSIONS The decrease of white matter regional cerebral blood flow caused by hypertension is probably one of the important causes of white matter lesions. Patients with white matter lesions should also pay attention to the rhythm of blood pressure when controlling hypertension, especially if their blood pressure is too high or too low at night.
| S-EPMC8230251 | biostudies-literature
Project description:ImportanceThe effect of intensive blood pressure lowering on brain health remains uncertain.ObjectiveTo evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes.Design, setting, and participantsA substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016.InterventionsParticipants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315).Main outcomes and measuresThe primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.ResultsAmong 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]).Conclusions and relevanceAmong hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.Trial registrationClinicalTrials.gov Identifier: NCT01206062.
| S-EPMC6692679 | biostudies-literature
Project description:White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified.We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts.We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 × 10(-9) ; p(replication) = 1.3 × 10(-7) ; p(combined) = 4.0 × 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9) ), rs11869977 (p = 5.7 × 10(-9) ), rs936393 (p = 6.8 × 10(-9) ), rs3744017 (p = 7.3 × 10(-9) ), and rs1055129 (p = 4.1 × 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample).This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH.
| S-EPMC3122147 | biostudies-literature
Project description:Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of ?-amyloid (A?) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of A? in cerebrospinal fluid (CSF) and cortical A? in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of A?38 and A?40 were consistently associated with increased WML in all subgroups, while lower levels of CSF A?42 were associated with WML mainly in AD. CSF A?38 and A?40 were associated with regional WML in all regions, while CSF A?42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with A? isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of A? species, particularly of A?38 and A?40. However, in AD cases, A?42 pathology might be associated with WML, especially in the temporal lobe.
| S-EPMC4746584 | biostudies-literature
Project description:ObjectiveCerebral white matter hyperintensity (WMH) with magnetic resonance imaging (MRI) has a potential for predicting cognitive impairment. Serum polyunsaturated fatty acid (PUFA) levels are important for evaluating the extent of atherosclerosis. We investigated whether abnormal PUFA levels affected WMH grading and cognitive function in patients without significant cognitive impairment.MethodsAtherosclerotic risk factors, the internal carotid artery (ICA) plaque, and serum ratios of eicosapentaenoic to arachidonic acids (EPA/AA) and docosahexaenoic to arachidonic acids (DHA/AA) were assessed in 286 patients. The relationship among these risk factors, WMH, and cognitive function was evaluated using WMH grading and the Mini-Mental State Examination (MMSE).ResultsThe development of WMH was associated with aging, hypertension, ICA plaques, and a low serum EPA/AA ratio (<0.38, obtained as the median value) but was not related to dyslipidemia, diabetes, smoking, and a low serum DHA/AA ratio (<0.84, obtained as the median value). In addition, the MMSE score deteriorated slightly with the progression of WMH (29.7 ± 1.0 compared to 28.4 ± 2.1, P < 0.0001).ConclusionsThe progression of WMH was associated with a low serum EPA/AA ratio and accompanied minimal deterioration in cognitive function. Sufficient omega-3 PUFA intake may be effective in preventing the development of cognitive impairment.
| S-EPMC4637015 | biostudies-literature
Project description:Background and objectiveWhite matter lesions (WMLs) are imaging changes in MRI of cerebral small vessel disease associated with vascular risk factors, increasing the risk of dementia, depression, and stroke. Aldosterone (ALD) or activation of mineralocorticoid receptor (MR) causes cerebrovascular injury in a mouse model. We aimed to analyze the relationship between ALD and WMLs in a population with hypertension.MethodsWe conducted a retrospective review of all patients screened for causes of secondary hypertension. We enrolled 547 patients with WMLs and matched these to controls without WMLs at a 1:1 ratio. White matter lesion load was assessed by using a modified Scheltens' scale.ResultsAmong the analytic sample (N = 1,094) with ages ranging from 30 to 64 years, 62.2% were male. We divided plasma ALD concentration (PAC), plasma renin activity (PRA), and ALD-renin ratio (ARR) into the third tertile (Q3), second tertile (Q2), and first tertile (Q1). We also analyzed them simultaneously as continuous variables. Multivariate logistic regression analysis showed that participants in Q3 (>17.26 ng/dl) of PAC (OR 1.59, 95% CI 1.15, 2.19), Q3 (<0.80 ng/dl) of PRA (OR 2.50, 95% CI 1.81, 3.44), and Q3 (>18.59 ng/dl per ng/ml*h) of ARR (OR 2.90, 95% CI 2.10, 4.01) had a significantly higher risk of WMLs than those in Q1 (<12.48) of PAC, Q1 (>2.19) of PRA, and Q1 (<6.96) of ARR. In linear regression analysis, we separately analyzed the correlation between the modified Scheltens' scale score and log(PAC) (β = 2.36; 95% CI 1.30, 3.41; p < 0.001), log(PRA) (β = -1.76; 95% CI -2.09, -1.43; p < 0.001), and log(ARR) (β = 1.86; 95% CI 1.55, 2.17; p < 0.001), which were all significantly correlated with white matter lesion load, after adjusting for confounding factors. Simple mediation analyses showed that systolic blood pressure (SBP) or diastolic blood pressure (DBP) mediated -3.83% or -2.66% of the association between PAC and white matter lesion load, respectively. In stratified analyses, there was no evidence of subgroup heterogeneity concerning the change in the risk of WMLs (p > 0.05 for interaction for all).ConclusionHigher PAC, especially in PAC >17.26 ng/dl, increased the risk of WMLs. PAC was positively associated with white matter lesion load independent of SBP or DBP.
| S-EPMC8637536 | biostudies-literature
Project description:Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer's disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.
| S-EPMC8172636 | biostudies-literature
Project description:White matter lesions (WMLs) are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer's disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity (FC) of three resting-state networks (RSNs) related to the changed cognitive domains: the default mode network (DMN) and the bilateral fronto-parietal network (FPN). We also performed voxel-based morphometry analysis to compare whole-brain gray matter (GM) volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between FC and structural connectivity. We observed FC alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant GM atrophy difference was found. Furthermore, the right precuneus FC in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance.
| S-EPMC4757671 | biostudies-literature
Project description:Background and purposeCerebral white matter signal abnormalities (WMSAs) are a significant radiological marker associated with brain and vascular aging. However, understanding their clinical impact is limited because of their pathobiological heterogeneity. We determined whether use of robust reliable automated procedures can distinguish WMSA classes with different clinical consequences.MethodsData from generally healthy participants aged >50 years with moderate or greater WMSA were selected from the Human Connectome Project-Aging (n=130). WMSAs were segmented on T1 imaging. Features extracted from WMSA included total and regional volume, number of discontinuous clusters, size of noncontiguous lesion, contrast of lesion intensity relative to surrounding normal appearing tissue using a fully automated procedure. Hierarchical clustering was used to classify individuals into distinct classes of WMSA. Radiological and clinical variability was evaluated across the individual WMSA classes.ResultsClass I was characterized by multiple, small, lower-contrast lesions predominantly in the deep WM; class II by large, confluent lesions in the periventricular WM; and class III by higher-contrast lesions restricted to the juxtaventricular WM. Class II was associated with lower myelin content than the other 2 classes. Class II was more prevalent in older subjects and was associated with a higher prevalence of hypertension and lower physical activity levels. Poor sleep quality was associated with a greater risk of class I.ConclusionsWe classified heterogeneous subsets of cerebral white matter lesions into distinct classes that have different clinical risk factors. This new method for identifying classes of WMSA will be important in understanding the underlying pathophysiology and in determining the impact on clinical outcomes.
| S-EPMC9477514 | biostudies-literature
Project description:Gray matter (GM) atrophy and white matter (WM) lesions may contribute to cognitive decline in patients with delayed neurological sequelae (DNS) after carbon monoxide (CO) poisoning. However, there is currently a lack of evidence supporting this relationship. This study aimed to investigate the volume of GM, cortical thickness, and burden of WM lesions in 33 DNS patients with dementia, 24 DNS patients with mild cognitive impairment, and 51 healthy controls. Various methods, including voxel-based, deformation-based, surface-based, and atlas-based analyses, were used to examine GM structures. Furthermore, we explored the connection between GM volume changes, WM lesions burden, and cognitive decline. Compared to the healthy controls, both patient groups exhibited widespread GM atrophy in the cerebral cortices (for volume and cortical thickness), subcortical nuclei (for volume), and cerebellum (for volume) (p < .05 corrected for false discovery rate [FDR]). The total volume of GM atrophy in 31 subregions, which included the default mode network (DMN), visual network (VN), and cerebellar network (CN) (p < .05, FDR-corrected), independently contributed to the severity of cognitive impairment (p < .05). Additionally, WM lesions impacted cognitive decline through both direct and indirect effects, with the latter mediated by volume reduction in 16 subregions of cognitive networks (p < .05). These preliminary findings suggested that both GM atrophy and WM lesions were involved in cognitive decline in DNS patients following CO poisoning. Moreover, the reduction in the volume of DMN, VN, and posterior CN nodes mediated the WM lesions-induced cognitive decline.
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