Decline in executive function in patients with white matter hyperintensities from the static and dynamic perspectives of amplitude of low‐frequency fluctuations

Author(s):  
Shanshan Cao ◽  
Jun Zhang ◽  
Chen Chen ◽  
Xiaojing Wang ◽  
Yang Ji ◽  
...  
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.


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.


2018 ◽  
Vol 4 (1) ◽  
pp. 85-89 ◽  
Author(s):  
Esther MC van Leijsen ◽  
Mayra I Bergkamp ◽  
Ingeborg WM van Uden ◽  
Sjacky Cooijmans ◽  
Mohsen Ghafoorian ◽  
...  

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.


2012 ◽  
Vol 6 (3) ◽  
pp. 145-151 ◽  
Author(s):  
Felipe Kenji Sudo ◽  
Carlos Eduardo Oliveira Alves ◽  
Gilberto Sousa Alves ◽  
Letice Ericeira-Valente ◽  
Chan Tiel ◽  
...  

ABSTRACT Objective: Non-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI) may represent preclinical Vascular Dementia (VaD). The aim of this study was to summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and to assess its patterns of progression to dementia. Methods: Searches were made in the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms "mild cognitive impairment" and "executive function". Altogether, 944 articles were retrieved. Results: VaMCI cases had poorer performances on fronto-executive tasks, a higher prevalence of stroke, presence of periventricular and profound white matter hyperintensities on MRI images, as well as more extrapyramidal signs and behavioral symptoms. Executive dysfunction might be associated with disconnection of fronto-parietal-subcortical circuits. Progression to dementia was associated with baseline deficits in executive function, in simple sustained attention and language, and large periventricular WMH. Discussion: VaMCI develops with impairment in non-memory domains and subcortical white matter changes on MRI images, which are consistent with clinical and neuroimaging findings in VaD.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012572
Author(s):  
Irene S Heger ◽  
Kay Deckers ◽  
Miranda T Schram ◽  
Coen DA Stehouwer ◽  
Pieter C Dagnelie ◽  
...  

Background and Objectives:Observational research has shown that a substantial proportion of all dementia cases worldwide is attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the LIfestyle for BRAin health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population.Methods:Cross-sectional data was used from the observational population-based cohort of The Maastricht Study.. The weighted compound score of LIBRA (including twelve dementia risk and protective factors, e.g. hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, grey matter, CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in three domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SD below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modelling were used, adjusted for age, sex, education, intracranial volume and type-2 diabetes.Results:Participants (n=4,164; mean age 59y; 49.7% men) with higher LIBRA scores (mean=1.19, range=-2.7 to +9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β=0.051, p=.002), and lower scores on information processing speed (β=-0.067, p=.001) and executive function and attention (β=-0.065, p=.004). Only in men, associations between LIBRA and volumes of grey matter (β=-0.093, p<.001), CSF (β=0.104, p<.001) and memory (β=-0.054, p=.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA and cognition.Discussion:Higher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored.Classification of Evidence:This study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores on some cognitive domains and a higher risk of cognitive impairment.


2019 ◽  
Vol 61 (4) ◽  
pp. 496-507 ◽  
Author(s):  
Yi Cheng ◽  
Xin Huang ◽  
Yu-Xiang Hu ◽  
Mu-Hua Huang ◽  
Bo Yang ◽  
...  

Background Previous neuroimaging studies demonstrated that individuals with high myopia are associated with abnormalities in anatomy of the brain. Purpose The purpose of this study was to explore alterations in the intrinsic brain activity by studying the amplitude of low-frequency fluctuations. Material and Methods A total of 64 myopia individuals (41 with high myopia with a refractive error <–600 diopter [D], 23 with low/moderate myopia with a refractive error between –100 and –600 D, and similarly 59 healthy controls with emmetropia closely matched for age) were recruited. The amplitude of low-frequency fluctuations method was conducted to investigate the difference of intrinsic brain activity across three groups. Results Compared with the healthy controls, individuals with low/moderate myopia showed significantly decreased amplitude of low-frequency fluctuation values in the bilateral rectal gyrus, right cerebellum anterior lobe/calcarine, and bilateral thalamus and showed significantly increased amplitude of low-frequency fluctuation values in left white matter (optic radiation), right prefrontal cortex, and left primary motor cortex (M1)/primary somatosensory cortex (S1). In addition, individuals with high myopia showed significantly decreased amplitude of low-frequency fluctuation values in the right cerebellum anterior lobe/calcarine/bilateral parahippocampal gyrus, bilateral posterior cingulate cortex, and bilateral middle cingulate cortex and significantly increased amplitude of low-frequency fluctuation values in left white matter (optic radiation), bilateral frontal parietal cortex, and left M1/S1. Moreover, we found that the amplitude of low-frequency fluctuation values of the different brain areas was closely related to the clinical features in the high myopia group. Conclusion Our results demonstrated that individuals with low/moderate myopia and high myopia had abnormal intrinsic brain activities in various brain regions related to the limbic system, default mode network, and thalamo-occipital pathway.


2021 ◽  
Vol 18 ◽  
Author(s):  
Bibek Gyanwali ◽  
Benedict Lui ◽  
Chuen Seng Tang ◽  
Eddie Jun Yi Chong ◽  
Henri Vrooman ◽  
...  

Background: Cerebral small vessel disease (SVD); lacunes, cerebral microbleeds (CMBs), and white matter hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hyper- tensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive de- cline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. Methods: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuro- psychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Results: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed simi- lar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cogni- tion, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Conclusion: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.


2017 ◽  
Vol 13 (7) ◽  
pp. P225
Author(s):  
Kathryn P. Sparks ◽  
Jonathan D. Jackson ◽  
Rachel F. Buckley ◽  
Dorene M. Rentz ◽  
Reisa A. Sperling ◽  
...  

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.


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