Abstract P366: High Burden of Tract-Specific White Matter Hyperintensities Relates to Impaired Microstructural Integrity of Distal White Matter Tracts in Community-Dwelling Elders

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
YANPENG LIU ◽  
YIWEI XIA ◽  
XIAOXIAO WANG ◽  
YI WANG ◽  
LUMENG YANG ◽  
...  

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.

Neurology ◽  
2018 ◽  
Vol 90 (15) ◽  
pp. e1291-e1297 ◽  
Author(s):  
So Young Moon ◽  
Philipe de Souto Barreto ◽  
Yves Rolland ◽  
Marie Chupin ◽  
Ali Bouyahia ◽  
...  

ObjectiveTo evaluate the relationship of white matter hyperintensities (WMH) with decline in lower extremity function (LEF) over approximately 3 years in dementia-free older adults with memory complaints.MethodsWe obtained brain MRI data from 458 community-dwelling adults, aged 70 years or over, at baseline, and from 358 adults over an average follow-up of 963 days. We evaluated LEF using the Short Physical Performance Battery (SPPB). We related baseline WMH volumes and progression to SPPB scores over time, using mixed-effect linear regressions. For the secondary analyses, we categorized baseline WMH volume into quartiles, and dichotomized the WMH progression to compare fast and slow progression.ResultsBaseline WMH volume (β = −0.017, 95% confidence interval [CI] −0.025 to −0.009), as well as WMH progression (β = −0.002, 95% CI −0.003 to −0.001), significantly associated with a decline in SPPB performance in adjusted analyses. Compared with the lowest quartile of baseline WMH volume, the highest quartile associated with a decline in SPPB performance (β = −0.301, 95% CI −0.558 to −0.044). Fast progression also associated with a decline in SPPB performance. We found clinically meaningful differences in the SPPB, with higher scores in participants with slow progression of WMH, at both 24 and 36 months.ConclusionsBaseline level and WMH progression associated with longitudinal decline in SPPB performance among older adults. We detected clinically meaningful differences in SPPB performance on comparing fast with slow progression of WMH, suggesting that speed of WMH progression is an important determinant of LEF during aging.


2017 ◽  
Vol 39 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Leonie Lampe ◽  
Shahrzad Kharabian-Masouleh ◽  
Jana Kynast ◽  
Katrin Arelin ◽  
Christopher J Steele ◽  
...  

White matter hyperintensities (WMH) are associated with cognitive decline. We aimed to identify the spatial specificity of WMH impact on cognition in non-demented, healthy elderly. We quantified WMH volume among healthy participants of a community dwelling cohort ( n = 702, age range 60 – 82 years, mean age = 69.5 years, 46% female) and investigated the effects of WMH on cognition and behavior, specifically for executive function, memory, and motor speed performance. Lesion location influenced their effect on cognition and behavior: Frontal WMH in the proximity of the frontal ventricles mainly affected executive function and parieto-temporal WMH in the proximity of the posterior horns deteriorated memory, while WMH in the upper deep white matter—including the corticospinal tract—compromised motor speed performance. This study exposes the subtle and subclinical yet detrimental effects of WMH on cognition in healthy elderly, and strongly suggests a causal influence of WMH on cognition by demonstrating the spatial specificity of these effects.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S586-S586
Author(s):  
C Elizabeth Shaaban ◽  
Andrea Metti ◽  
Cindy Barha ◽  
Kristine Yaffe ◽  
Caterina Rosano

Abstract Brain-derived neurotrophic factor (BDNF) may protect against cerebral gray and white matter impairments in older age. The val66met genetic polymorphism of BDNF is recently emerging as an early marker of brain structural integrity. However, evidence is sparse, cross-sectional, and mostly in men. In a longitudinal cohort study of community-dwelling older adults (N=139, mean age=81.6, 58% female, 58% white, mean follow-up=3.4 years), we estimated the overall and sex-stratified effects of BDNF val66met polymorphism on changes in cognition and gray and white matter macro- and micro-structure. Annualized percent change was computed for volume of white matter (WM) hyperintensities and gray matter (GM), fractional anisotropy of normal appearing WM, and mean diffusivity (MD) of GM in whole brain and memory and executive control function networks. Significant associations were adjusted for variables differing by genotype (race, APOE4, diabetes, triglycerides, smoking). Compared to met carriers, val homozygotes had slower annual whole brain WMH accrual (median (IQR) 31.4% (61.7) vs. 60.7% (92.4)), stronger in women. Met carriers had slower annual accrual of hippocampal MD (median (IQR) 1.26% (0.92) vs. 1.85% (1.09) for right hippocampus, stronger for women, and 1.45% (1.06) vs. 1.97% (1.22) for left hippocampus, stronger for men) compared to val homozygotes. Associations were robust to covariates’ adjustment. BDNF polymorphism was not associated with cognitive changes. BDNF polymorphism may help in early identification of those more likely to resist accrual of WMH and loss of hippocampal microstructural integrity, with effects varying by sex.


SLEEP ◽  
2016 ◽  
Vol 39 (4) ◽  
pp. 785-791 ◽  
Author(s):  
Sara K. Rostanski ◽  
Molly E. Zimmerman ◽  
Nicole Schupf ◽  
Jennifer J. Manly ◽  
Andrew J. Westwood ◽  
...  

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Maria D Valdes-Hernandez ◽  
Paul A Armitage ◽  
Eleni Sakka ◽  
Susana Munoz Maniega ◽  
Natalie A Royle ◽  
...  

Background: Volume measures of normal brain tissue and white matter hyperintensities (WMH) between two time points gives limited information about the complex dynamics of tissue change. We evaluated two quantitative parameters that characterise the microstructure of normal-appearing white matter (NAWM), deep grey matter (DGM) and WMH on brain images obtained at presentation with minor stroke and at 1 year to investigate the microstructural changes. Methods: From 182 brain MRI datasets of patients with minor stroke obtained at baseline and 1 year, we extracted the WMH, DGM and NAWM, and separated WMH into less-intense and intense WMH, using validated semi-automatic methods and validated criteria. We registered the binary structural masks to diffusion space and performed a voxel-wise subtraction of the combined masks at both time points. Then we measured fractional anisotropy (FA) and mean diffusivity (MD)(valuex10 -9 m 2 /s) in each tissue mask at baseline and 1 year. Results: WMH volume median increase was 1.4ml (IQR 6.98) mainly due to changes in less-intense WMH: 0.94ml (7.13). WMH that were visible at both time points, ie damage that remained after a year, had the lowest FA= 0.21(0.06) and highest MD=1.05(0.12) at baseline, and were mainly intense WMH at baseline (FA=0.12(0.03), MD=1.55(0.27)). WMH seen only at follow-up, ie that were NAWM at baseline, had the highest FA=0.30(0.06) and lowest MD=0.85 (0.06) at baseline. WMH that were observed only at baseline had intermediate FA=0.26(0.08) and MD=0.90(0.10). NAWM FA=0.26(0.03), MD=0.78(0.04) and DGM FA=0.23(0.03), MD=0.79(0.06) did not change between time points. Conclusions: WMH at baseline can partially evolve to normal-appearing tissues, remain or precede tissue loss. Differentiation between severe and subtle damage and spatial analysis are necessary to characterise the dynamic of WMH evolution.


2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.


2020 ◽  
Author(s):  
Michele Veldsman ◽  
Emilio Werden ◽  
Natalia Egorova ◽  
Mohamed Salah Khlif ◽  
Amy Brodtmann

ABSTRACTObjectiveExecutive dysfunction affects 40% of stroke patients and is associated with poor quality of life. Stroke severity and lesion volume rarely predict whether a patient will have executive dysfunction. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We investigated whether measures of white matter microstructural integrity and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity.MethodsWe used structural equation modelling to examine multivariate relationships between cerebrovascular risk, white matter microstructural integrity (fractional anisotropy and mean diffusivity), stroke characteristics and executive dysfunction in 126 stroke patients (mean age 68.4 years), three months post-stroke, and compared to 40 age- and sex-matched control participants. Executive function was measured using the Trail Making Tests, Clock Drawing task and Rey Complex Figure copy task. Microstructural integrity was estimated using a standard pipeline to process diffusion weighted images.ResultsExecutive function was below what would be expected for age and education level in stroke patients (t-test compared to controls t(79)=5.75, p<0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk. Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity, than executive dysfunction and stroke severity. Mediation analysis showed the relationship between executive function and white matter integrity is mediated by cerebrovascular burden.InterpretationWhite matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity.


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