Dataset Information

Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

ABSTRACT: We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46-76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness (p = 0.009) after controlling for covariates. This association was found for periventricular WMH (p = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.

SUBMITTER: Mayer C

PROVIDER: S-EPMC8221767 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

Mayer Carola C Frey Benedikt M BM Schlemm Eckhard E Petersen Marvin M Engelke Kristin K Hanning Uta U Jagodzinski Annika A Borof Katrin K Fiehler Jens J Gerloff Christian C Thomalla Götz G Cheng Bastian B

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20201201 7

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tracto ...[more]

PMID: 33259747

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Project description:BackgroundThe underlying mechanisms of incident lacunes regarding their spatial distribution remain largely unknown. We investigated the spatial distribution pattern and MRI predictors of incident lacunes in relation to white matter hyperintensity (WMH) over 14 years follow-up in sporadic small vessel disease.MethodsFive hundred three participants from the ongoing prospective single-center Radboud University Nijmegen Diffusion Tensor and Magnetic resonance Cohort (RUN DMC) were recruited with baseline assessment in 2006 and follow ups in 2011, 2015, and 2020. Three hundred eighty-two participants who underwent at least 2 available brain MRI scans were included. Incident lacunes were systematically identified, and the spatial relationship between incident lacunes located in subcortical white matter and WMH were determined using a visual rating scale. Adjusted multiple logistic regression and linear mixed-effect regression models were used to assess the association between baseline small vessel disease markers, WMH progression, and incident lacunes. Participants with atrial fibrillation were excluded in multivariable analysis.ResultsEighty incident lacunes were identified in 43 patients (mean age 66.5±8.2 years, 37.2% women) during a mean follow-up time of 11.2±3.3 years (incidence rate 10.0/1000 person-year). Sixty percent of incident lacunes were in the white matter, of which 48.9% showed no contact with preexisting WMH. Baseline WMH volume (odds ratio=2.5 [95% CI, 1.6-4.2]) predicted incident lacunes after adjustment for age, sex, and vascular risk factors. WMH progression was associated with incident lacunes independent of age, sex, baseline WMH volume, and vascular risk factors (odds ratio, 3.2 [95% CI, 1.5-6.9]). Baseline WMH volume and progression rate were higher in participants with incident lacunes in contact with preexisting WMH. No difference in vascular risk factors was observed regarding location or relation with preexisting WMH.ConclusionsThe 2 different distribution patterns of lacunes regarding their relation to WMH may suggest distinct underlying mechanisms, one of which may be more closely linked to a similar pathophysiology as that of WMH. The longitudinal relation between WMH and lacunes further supports plausible shared mechanisms between the 2 key markers.

Project description:Objectives: To assess the ability of 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis to discriminate between multiple sclerosis lesions (MSL) and white matter hyperintensities of presumed vascular origin (WMH) and to compare APTw signal intensity of healthy white matter (healthy WM) with APTw signal intensity of MSL and WHM. Materials and Methods: A total of 27 patients (16 female, 11 males, mean age 39.6 years) with multiple sclerosis, 35 patients (17 females, 18 males, mean age 66.6 years) with small vessel disease (SVD) and 20 healthy young volunteers (9 females, 11 males, mean age 29 years) were included in the MSL, the WMH, and the healthy WM group. MSL and WMH were segmented on fluid attenuated inversion recovery (FLAIR) images underlaid onto APTw images. Histogram parameters (mean, median, 10th, 25th, 75th, 90th percentile) were calculated. Mean APTw signal intensity values in healthy WM were defined by "Region of interest" (ROI) measurements. Wilcoxon rank sum tests and receiver operating characteristics (ROC) curve analyses of clustered data were applied. Results: All histogram parameters except the 75 and 90th percentile were significantly different between MSL and WMH (p = 0.018-p = 0.034). MSL presented with higher median values in all parameters. The histogram parameters offered only low diagnostic performance in discriminating between MSL and WMH. The 10th percentile yielded the highest diagnostic performance with an AUC of 0.6245 (95% CI: [0.532, 0.717]). Mean APTw signal intensity values of MSL were significantly higher than mean values of healthy WM (p = 0.005). The mean values of WMH did not differ significantly from the values of healthy WM (p = 0.345). Conclusions: We found significant differences in APTw signal intensity, based on straightforward magnetization transfer analysis, between MSL and WMH and between MSL and healthy WM. Low AUC values from ROC analyses, however, suggest that it may be challenging to determine type of lesion with APTw imaging. More advanced analysis of the APT CEST signal may be helpful for further differentiation of MSL and WMH.

Project description:White matter hyperintensities (WMHs) have a heterogeneous aetiology, associated with both vascular risk factors and amyloidosis due to Alzheimer's disease. While spatial distribution of both amyloid and WM lesions carry important information for the underlying pathogenic mechanisms, the regional relationship between these two pathologies and their joint contribution to early cognitive deterioration remains largely unexplored. We included 662 non-demented participants from three Amyloid Imaging to Prevent Alzheimer's disease (AMYPAD)-affiliated cohorts: EPAD-LCS (N = 176), ALFA+ (N = 310), and EMIF-AD PreclinAD Twin60++ (N = 176). Using PET imaging, cortical amyloid burden was assessed regionally within early accumulating regions (medial orbitofrontal, precuneus, and cuneus) and globally, using the Centiloid method. Regional WMH volume was computed using Bayesian Model Selection. Global associations between WMH, amyloid, and cardiovascular risk scores (Framingham and CAIDE) were assessed using linear models. Partial least square (PLS) regression was used to identify regional associations. Models were adjusted for age, sex, and APOE-e4 status. Individual PLS scores were then related to cognitive performance in 4 domains (attention, memory, executive functioning, and language). While no significant global association was found, the PLS model yielded two components of interest. In the first PLS component, a fronto-parietal WMH pattern was associated with medial orbitofrontal-precuneal amyloid, vascular risk, and age. Component 2 showed a posterior WMH pattern associated with precuneus-cuneus amyloid, less related to age or vascular risk. Component 1 was associated with lower performance in all cognitive domains, while component 2 only with worse memory. In a large pre-dementia population, we observed two distinct patterns of regional associations between WMH and amyloid burden, and demonstrated their joint influence on cognitive processes. These two components could reflect the existence of vascular-dependent and -independent manifestations of WMH-amyloid regional association that might be related to distinct primary pathophysiology.

Dataset Information

Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

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Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

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