scholarly journals Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

2021 ◽  
Author(s):  
Wenhao Zhu ◽  
◽  
Hao Huang ◽  
Shiqi Yang ◽  
Xiang Luo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cognitive Decline ◽  
Grey Matter ◽  
White Matter Hyperintensities ◽  
Grey Matter Volume ◽  
Independent Dataset ◽  
The Relationship ◽  
Robust Evidence ◽  
Bilateral Thalamus

AbstractGrey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

scholarly journals White Matter Hyperintensity Load Drives Differential Grey Matter Changes in Mild Cognitive Impairment

2020 ◽  
Author(s):  
Ashwati Vipin ◽  
Benjamin Yi Xin Wong ◽  
Dilip Kumar ◽  
Audrey Low ◽  
Kok Pin Ng ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Executive Control ◽  
Grey Matter ◽  
White Matter Hyperintensities ◽  
White Matter Hyperintensity ◽  
Grey Matter Volume ◽  
Executive Control Network ◽  
Matter Volume

Abstract Background: Small-vessel cerebrovascular disease often represented as white matter hyperintensities on magnetic resonance imaging, is considered an important risk factor for progression to dementia. Grey matter volume alterations in Alzheimer’s disease-specific regions comprising the default mode network and executive control network are also key features of early Alzheimer’s disease. However, the relationship between increasing white matter hyperintensity load and grey matter volume needs further examination in the cognitively normal and mild cognitive impairment. Here, we examined the load-dependent influence of white matter hyperintensities on grey matter volume and cognition in the cognitively normal and mild cognitive impairment stages.Methods: Magnetic resonance imaging data from 93 mild cognitive impairment and 90 cognitively normal subjects were studied and white matter hyperintensity load was categorized into low, medium and high terciles. We examined how differing loads of white matter hyperintensities related to whole-brain voxel-wise and regional grey matter volume in the default mode network and executive control network. We further investigated how regional grey matter volume moderated the relationship between white matter hyperintensities and cognition at differing white matter hyperintensity loads.Results: We found differential load-dependent effects of white matter hyperintensity burden on voxel-wise and regional grey matter atrophy in only mild cognitive impairment subjects. At low load, white matter hyperintensity load was positively related to grey matter volume in the executive control network but at high load, white matter hyperintensity load was negatively related to grey matter volume across both the executive control and default mode networks and no relationship was observed at medium white matter hyperintensity load. Additionally, negative associations between white matter hyperintensities and domains of memory and executive function were moderated by regional grey matter volume. Conclusions: Our results demonstrate dynamic relationships between white matter hyperintensity load, grey matter volume and cognition in the mild cognitive impairment stage. Interventions to slow the progression of white matter hyperintensities, instituted when white matter hyperintensity load is low could potentially prevent further cognitive decline.

Abstract TP181: Serum Eiocosapentaenoic Acids Is Protective Against White Matter Lesions

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Daiki Takano ◽  
Takashi Yamazaki ◽  
Tetsuya Maeda ◽  
Yuichi Satoh ◽  
Yasuko Ikeda ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
White Matter Hyperintensity ◽  
Partial Regression Coefficient ◽  
The Relationship ◽  
Total Pufa ◽  
Periventricular Hyperintensity

[Introduction] White matter hyperintensities (WMH) are considered manifestation of arteriosclerotic small vessel disease and WMH burden increases risk of ischemic stroke and cognitive decline. There are only a few evidences concerning the relationship between polyunsaturated fatty acids (PUFA) and WMH. The present study was designed to elucidate the association between WMH and PUFA profile including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in patients with Alzheimer’s disease (AD). [Methods] The present study was based on 119 patients who were diagnosed as having a probable AD according to the NINCDS-ADRDA criteria. Their mean age was 78.3 years old. All subjects underwent neuropsychological evaluation including mini mental state exam (MMSE) and 1.5-Tesla MRI. Fasting blood samples were also collected for the PUFA measurements. We measured the ratio of serum EPA, DHA and AA concentration to the total PUFA concentration. The WMH were evaluated on T2-weight images and classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The severity of WMH was graded 5 categories. We investigated the relationship between WMH and PUFA profiles. [Results] The EPA ratio correlated negatively with both PVH (rs=-0.2036, p=0.0264) and DWMH grade (rs=-0.3155, p=0.0005). It remained still significant after adjustment for age, sex, statins use, antithrombotics use, mean blood pressure and presence of hypertension (standardized partial regression coefficient(β)=-0.2516, p=0.0122 for PVH, β=-0.3598, p=0.0001 for DWMH). Neither DHA nor AA ratio correlated with DWMH or PVH grade. The EPA ratio but not DHA or AA ratio correlated positively with total MMSE score (rs=0.2310, p=0.0115). [Conclusions] Our data revealed that the serum EPA was protective against WMH as well as cognitive decline in AD patients. Pathophysiology underlying WMH is complex and the possible mechanisms involved in the pathogenesis of WMH encompass incomplete brain ischemia, increased permeability of blood-brain barrier, and inflammation responses. The relationship between serum EPA and WMH can be partly explained by those anti-ischemic and anti-arteriosclerotic effects of EPA.

scholarly journals Associations of the Lifestyle for Brain Health Index With Structural Brain Changes and Cognition: Results From the Maastricht Study

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012572
Author(s):  
Irene S Heger ◽  
Kay Deckers ◽  
Miranda T Schram ◽  
Coen DA Stehouwer ◽  
Pieter C Dagnelie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Information Processing ◽  
Executive Function ◽  
White Matter ◽  
Processing Speed ◽  
Grey Matter ◽  
White Matter Hyperintensities ◽  
Information Processing Speed ◽  
Brain Health ◽  
Dementia Risk

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.

scholarly journals Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment

2019 ◽  
Vol 75 (7) ◽  
pp. 1382-1392 ◽  
Author(s):  
Marie Caillaud ◽  
Carol Hudon ◽  
Benjamin Boller ◽  
Simona Brambati ◽  
Simon Duchesne ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Hippocampal Volume ◽  
Subjective Cognitive Decline

Abstract Objective The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer’s disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. Method We included 126 participants from the Consortium for the Early Identification of Alzheimer’s disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). Results Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. Discussion As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD’s hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

The relationship of white matter hyperintensities to depression and apathy in mild cognitive impairment

2010 ◽  
Vol 6 (4) ◽  
pp. S296
Author(s):  
Melissa J. Slavin ◽  
Brian Draper ◽  
Wei Wen ◽  
Henry Brodaty ◽  
Nicole A. Kochan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Relationship Of ◽  
The Relationship

scholarly journals Network Efficiency Mediates the Relationship Between Vascular Burden and Cognitive Impairment

Stroke ◽  
2020 ◽  
Vol 51 (6) ◽  
pp. 1682-1689 ◽  
Author(s):  
Jun Shen ◽  
Daniel J. Tozer ◽  
Hugh S. Markus ◽  
Jonathan Tay
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Network Efficiency ◽  
Global Efficiency ◽  
Vascular Burden ◽  
The Relationship

Background and Purpose— Cerebrovascular disease contributes to age-related cognitive decline, but the mechanisms underlying this phenomenon remain incompletely understood. We hypothesized that vascular risk factors would lead to cognitive impairment through the disruption of brain white matter network efficiency. Methods— Participants were 19 346 neurologically healthy individuals from UK Biobank that underwent diffusion MRI and cognitive testing (mean age=62.6). Global efficiency, a measure of network integration, was calculated from white matter networks constructed using deterministic diffusion tractography. First, we determined whether demographics (age, sex, ethnicity, socioeconomic status, and education), vascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, smoking, body mass index), and white matter hyperintensities were related to global efficiency using multivariate linear regression. Next, we used structural equation modeling to model a multiple regression. The dependent variable was a latent cognition variable using all cognitive data, while independent variables were a latent factor including all vascular risk factors (vascular burden), demographic variables, white matter hyperintensities, and global efficiency. Finally, we used mediation analysis to determine whether global efficiency explained the relationship between vascular burden and cognition. Results— Hypertension and diabetes mellitus were consistently associated with reduced global efficiency even after controlling for white matter hyperintensities. Structural equation models revealed that vascular burden was associated with cognition ( P =0.023), but not after adding global efficiency to the model ( P =0.09), suggesting a mediation effect. Mediation analysis revealed a significant indirect effect of global efficiency on cognition through vascular burden ( P <0.001), suggesting a partial mediation effect. Conclusions— Vascular burden is associated with reduced global efficiency and cognitive impairment in the general population. Network efficiency partially mediates the relationship between vascular burden and cognition. This suggests that treating specific risk factors may prevent reductions in brain network efficiency and preserve cognitive functioning in the aging population.

scholarly journals Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Man Li ◽  
Yue Li ◽  
Long Zuo ◽  
Wenli Hu ◽  
Tao Jiang
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Grey Matter ◽  
Leakage Rate ◽  
White Matter Hyperintensity ◽  
Normal Appearing White Matter ◽  
Cortical Grey Matter ◽  
Deep Grey Matter ◽  
The Relationship

Abstract Background Blood-brain barrier (BBB) breakdown, as an early biomarker for vascular mild cognitive impairment (vMCI), has only been validated by a few studies. The aim of this study was to investigate whether compromised BBB integrity is involved in vMCI patients, and detect the relationship between BBB breakdown and cognitive function. BBB leakage in vMCI was explored, and the relationship between BBB leakage and cognitive function was discussed in this study. Methods This is a cross-sectional study involving 26 vMCI patients and 21 sex- and age-matched healthy controls. Dynamic contrast-enhanced-magnetic resonance imaging was performed for all participants, to determine BBB leakage. Leakage volume, leakage rate, and fractional blood plasma volume (Vp) in the grey and white matter were evaluated. Neuropsychological tests were used to determine cognitive function. Leakage rate, leakage volume, and Vp in different brain locations, including deep grey matter, cortical grey matter, white matter hyperintensity, and normal-appearing white matter were compared between the two groups. Results Multivariable linear regression analyses revealed that in all regions of interest, the leakage rate was significantly higher in vMCI patients relative to controls. Leakage volume in normal-appearing white matter and white matter hyperintensity were significantly higher, while Vp in normal-appearing white matter, deep grey matter, and cortical grey matter were significantly lower in vMCI patients. Moreover, Montreal Cognitive Assessment scores decreased with the increase of leakage rate in white matter hyperintensity. Conclusion Increased BBB permeability was detected in vMCI patients and was related to cognitive decline, which suggested that BBB breakdown might be involved in cognitive dysfunction pathogenesis.

scholarly journals White Matter Hyperintensities, Grey Matter Atrophy, and Cognitive Decline in Neurodegenerative Diseases

2021 ◽  
Author(s):  
Mahsa Dadar ◽  
Ana Manera ◽  
D. Louis Collins
Keyword(s):  
White Matter ◽  
Neurodegenerative Diseases ◽  
Cognitive Decline ◽  
Grey Matter ◽  
White Matter Hyperintensities ◽  
Normal Aging ◽  
Jacobian Determinant ◽  
Additional Contribution ◽  
Significant Difference ◽  
Normal Controls

Introduction: White matter hyperintensities (WMHs) as seen on T2w and FLAIR scans represent small-vessel disease related changes in the brain. WMHs are associated with cognitive decline in the normal aging population in general and more specifically in patients with neurodegenerative diseases. In this study, we assessed the different spatial patterns and relationships between WMHs and grey matter (GM) atrophy in normal aging, individuals with mild cognitive impairment (MCI), Alzheimers dementia (AD), fronto-temporal dementia (FTD), and de novo Parkinsons disease (PD). Methods: Imaging and clinical data were obtained from 3 large multi-center databases: The Alzheimers Disease Neuroimaging Initiative (ADNI), the frontotemporal lobar degeneration neuroimaging initiative (NIFD), and the Parkinsons Progression Markers Initiative (PPMI). WMHs and GM atrophy maps were measured in normal controls (N= 571), MCI (N= 577), AD (N= 222), FTD (N= 144), and PD (N= 363). WMHs were segmented using T1w and T2w/PD or FLAIR images and mapped onto 45 white matter tracts using the Yeh WM atlas. GM volume was estimated from the Jacobian determinant of the nonlinear deformation field required to map the subject MRI to a standard template. The CerebrA atlas was used to obtain volume estimates in 84 GM regions. Mixed effects models were used to compare WMH in different WM tracts and volume of multiple GM structures between patients and controls, assess the relationship between regional WMHs and GM loss for each disease, and investigate their impact on cognition. Results: MCI, AD, and FTD patients had significantly higher WMH loads than the matched controls. There was no significant difference in WMHs between PD and controls. For each cohort, significant interactions between WMH load and GM atrophy were found for several regions and tracts, reflecting additional contribution of WMH burden to GM atrophy. While these associations were more relevant for insular and parieto-occipital regions in MCI and AD cohorts, WMH burden in FTD subjects had greater impact on frontal and basal ganglia atrophy. Finally, we found additional contribution of WMH burden to cognitive deficits in AD and FTD subjects compared with matched controls, whereas their impact on cognitive performance in MCI and PD were not significantly different from controls. Conclusions: WMHs occur more extensively in MCI, AD, and FTD patients than age-matched normal controls. WMH burden on WM tracts also correlates with regional GM atrophy in regions anatomically and functionally related to those tracts, suggesting a potential involvement of WMHs in the neurodegenerative process.

scholarly journals Obesity impairs cognitive function via metabolic syndrome and cerebrovascular disease: an SEM analysis in 15,000 adults from the UK Biobank

2020 ◽  
Author(s):  
Filip Morys ◽  
Mahsa Dadar ◽  
Alain Dagher
Keyword(s):  
Metabolic Syndrome ◽  
Cognitive Impairment ◽  
White Matter ◽  
Cerebrovascular Disease ◽  
Cortical Thickness ◽  
White Matter Hyperintensities ◽  
Uk Biobank ◽  
Central Nervous System Damage ◽  
The Uk ◽  
The Relationship

AbstractChronic obesity is associated with several complications, including cognitive impairment and dementia. However, we have piecemeal knowledge of the mechanisms linking obesity to central nervous system damage. Adiposity leads to the metabolic syndrome, consisting of inflammation, hypertension, dyslipidemia and insulin resistance. In turn, these metabolic abnormalities cause cerebrovascular dysfunction, which may cause white and grey matter tissue loss and consequent cognitive impairment. While there have been several neuroimaging studies linking adiposity to changes in brain morphometry, a comprehensive investigation of the relationship has so far not been done. Here we use structural equation modelling applied to over 15,000 individuals from the UK Biobank to identify the causal chain that links adiposity to cognitive dysfunction. We found that body mass index and waist-to-hip ratio were positively related to higher plasma C-reactive protein, dyslipidemia, occurrence of hypertension and diabetes, all of which were in turn related to cerebrovascular disease as measured by volume of white matter hyperintensities on magnetic resonance imaging. White mater hyperintensities were associated with lower cortical thickness and volume and higher subcortical volumes, which were associated with cognitive deficits on tests of visuospatial memory, fluid intelligence, and working memory among others. In follow-up analyses we found that inflammation, hypertension and diabetes mediated 20% of the relationship between obesity and cerebrovascular disease and that cerebrovascular disease mediated a significant proportion of the relationship between obesity and cortical thickness and volume. We also showed that volume of white matter hyperintensities was related to decreased fractional anisotropy and increased mean diffusivity in the majority of white matter tracts, pointing to white matter dysconnectivity as a major cause of impaired cognition. Our results have clinical implications, supporting a role for the management of adiposity in the prevention of late-life dementia and cognitive decline.

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