White Matter Hyperintensity Distribution Differences in Aging and Neurodegenerative Disease Cohorts

Introduction: White matter hyperintensities (WMHs) are common magnetic resonance imaging (MRI) findings in the aging population in general, as well as in patients with neurodegenerative diseases. They are known to exacerbate the cognitive deficits and worsen the clinical outcomes in the patients. However, it is not well-understood whether there are disease-specific differences in prevalence and distribution of WMHs in different neurodegenerative disorders. Methods: Data included 976 participants with cross-sectional T1-weighted and fluid attenuated inversion recovery (FLAIR) MRIs from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort of the Canadian Consortium on Neurodegeneration in Aging (CCNA) with eleven distinct diagnostic groups: cognitively intact elderly (CIE), subjective cognitive impairment (SCI), mild cognitive impairment (MCI), vascular MCI (V-MCI), Alzheimers dementia (AD), vascular AD (V-AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), cognitively intact elderly with Parkinsons disease (PD-CIE), cognitively impaired Parkinsons disease (PD-CI), and mixed dementias. WMHs were segmented using a previously validated automated technique. WMH volumes in each lobe and hemisphere were compared against matched CIE individuals, as well as each other, and between men and women. Results: All cognitively impaired diagnostic groups had significantly greater overall WMH volumes than the CIE group. Vascular groups (i.e. V-MCI, V-AD, and mixed dementia) had significantly greater WMH volumes than all other groups, except for FTD, which also had significantly greater WMH volumes than all non-vascular groups. Women tended to have lower WMH burden than men in most groups and regions, controlling for age. The left frontal lobe tended to have a lower WMH burden than the right in all groups. In contrast, the right occipital lobe tended to have greater WMH loads than the left. Conclusions: There were distinct differences in WMH prevalence and distribution across diagnostic groups, sexes, and in terms of asymmetry. WMH burden was significantly greater in all neurodegenerative dementia groups, likely encompassing areas exclusively impacted by neurodegeneration as well as areas related to cerebrovascular disease pathology.

Download Full-text

Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer’s disease

Brain ◽

10.1093/brain/awaa342 ◽

2020 ◽

Cited By ~ 1

Author(s):

Andréa L Benedet ◽

Antoine Leuzy ◽

Tharick A Pascoal ◽

Nicholas J Ashton ◽

Sulantha Mathotaarachchi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

White Matter ◽

Imaging Biomarkers ◽

Cognitively Impaired ◽

Cross Sectional ◽

Neurofilament Light ◽

Tau Pet ◽

Alzheimer’S Disease Dementia

Abstract Neurofilament light (NfL) is a marker of neuroaxonal injury, a prominent feature of Alzheimer’s disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer’s disease continuum. The aim of this study was to investigate how plasma NfL relates to amyloid and tau PET and MRI measures of brain atrophy in participants with and without cognitive impairment. We retrospectively examined the association between plasma NfL and MRI measures of grey/white matter volumes in the Alzheimer’s Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n = 420, Alzheimer’s disease dementia n = 347)]. Longitudinal plasma NfL was measured using single molecule array (Simoa) technology. Cross-sectional associations between plasma NfL and PET amyloid and tau measures were independently assessed in two cohorts: ADNI [n = 198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n = 67, Alzheimer’s disease dementia n = 21), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n = 116; 74 cognitively unimpaired, 42 cognitively impaired (MCI n = 16, Alzheimer’s disease dementia n = 26), data obtained November 2017 to January 2019]. Associations between plasma NfL and imaging-derived measures were examined voxel-wise using linear regression (cross-sectional) and linear mixed effect models (longitudinal). Cross-sectional analyses in both cohorts showed that plasma NfL was associated with PET findings in brain regions typically affected by Alzheimer’s disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P < 0.05). Longitudinal analyses showed that NfL levels were associated with grey/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE ε4 carriers (P < 0.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer’s disease, but is related to tau-mediated neurodegeneration in symptomatic patients. As such, plasma NfL may a useful measure to monitor effects in disease-modifying drug trials.

Download Full-text

Mapping the contribution and strategic distribution patterns of neuroimaging features of small vessel disease in poststroke cognitive impairment

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-317817 ◽

2018 ◽

Vol 89 (9) ◽

pp. 918-926 ◽

Cited By ~ 6

Author(s):

Lin Shi ◽

Lei Zhao ◽

Fu Ki Yeung ◽

Shun Yiu Wong ◽

Ronald K T Chan ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Small Vessel Disease ◽

Distribution Patterns ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Support Vector ◽

Imaging Features ◽

Cross Sectional ◽

Vessel Disease

ObjectivesIndividual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment.MethodsWe studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation.ResultsThe combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains.ConclusionsMultiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.

Download Full-text

Early Microstructure Changes of White Matter Fiber Bundles in Patients with Amnestic Mild Cognitive Impairment Predicts Progression of Mild Cognitive Impairment to Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210495 ◽

2021 ◽

pp. 1-14

Author(s):

Fangmei He ◽

Yuchen Zhang ◽

Xiaofeng Wu ◽

Youjun Li ◽

Jie Zhao ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Brain Regions ◽

Amnestic Mild Cognitive Impairment ◽

Microstructure Changes ◽

Disease Trajectory ◽

Development Trajectory ◽

The Right

Background: Amnestic mild cognitive impairment (aMCI) is the transitional stage between normal aging and Alzheimer’s disease (AD). Some aMCI patients will progress into AD eventually, whereas others will not. If the trajectory of aMCI can be predicted, it would enable early diagnosis and early therapy of AD. Objective: To explore the development trajectory of aMCI patients, we used diffusion tensor imaging to analyze the white matter microstructure changes of patients with different trajectories of aMCI. Methods: We included three groups of subjects:1) aMCI patients who convert to AD (MCI-P); 2) aMCI patients who remain in MCI status (MCI-S); 3) normal controls (NC). We analyzed the fractional anisotropy and mean diffusion rate of brain regions, and we adopted logistic binomial regression model to predicate the development trajectory of aMCI. Results: The fraction anisotropy value is significantly reduced, the mean diffusivity value is significantly increased in the two aMCI patient groups, and the MCI-P patients presented greater changes. Significant changes are mainly located in the cingulum, fornix, hippocampus, and uncinate fasciculus. These changed brain regions significantly correlated with the patient’s Mini-Mental State Examination scores. Conclusion: The study predicted the disease trajectory of different types of aMCI patients based on the characteristic values of the above-mentioned brain regions. The prediction accuracy rate can reach 90.2%, and the microstructure characteristics of the right cingulate band and the right hippocampus may have potential clinical application value to predict the disease trajectory.

Download Full-text

Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment

Stroke ◽

10.1161/str.46.suppl_1.44 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Jonathan Graff-Radford ◽

Rosebud Roberts ◽

Malini Madhavan ◽

Alejandro Rabinstein ◽

Ruth Cha ◽

...

Keyword(s):

Atrial Fibrillation ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

White Matter ◽

Cerebrovascular Disease ◽

Regression Models ◽

Grey Matter ◽

White Matter Hyperintensity ◽

Carrier Status

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.

Download Full-text

Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment

Journal of Alzheimer s Disease ◽

10.3233/jad-180280 ◽

2018 ◽

Vol 66 (2) ◽

pp. 533-549 ◽

Cited By ~ 5

Author(s):

Ashwati Vipin ◽

Heidi Jing Ling Foo ◽

Joseph Kai Wei Lim ◽

Russell Jude Chander ◽

Ting Ting Yong ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Grey Matter ◽

White Matter Hyperintensity ◽

Grey Matter Atrophy

Download Full-text

Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽

10.1136/bmjopen-2020-040466 ◽

2020 ◽

Vol 10 (10) ◽

pp. e040466

Author(s):

Aravind Ganesh ◽

Philip Barber ◽

Sandra E Black ◽

Dale Corbett ◽

Thalia S Field ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Vascular Cognitive Impairment ◽

White Matter Injury ◽

White Matter Hyperintensity ◽

Limb Ischaemia ◽

Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

Download Full-text

The Effects of Longitudinal White Matter Hyperintensity Change on Cognitive Decline and Cortical Thinning over Three Years

Journal of Clinical Medicine ◽

10.3390/jcm9082663 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2663

Author(s):

Seung Joo Kim ◽

Dong Kyun Lee ◽

Young Kyoung Jang ◽

Hyemin Jang ◽

Si Eun Kim ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Cognitive Decline ◽

Dynamic Change ◽

Surrogate Marker ◽

Brain Magnetic Resonance Imaging ◽

Longitudinal Change ◽

White Matter Hyperintensity ◽

Cortical Thinning ◽

Automated Method

White matter hyperintensity (WMH) has been recognised as a surrogate marker of small vessel disease and is associated with cognitive impairment. We investigated the dynamic change in WMH in patients with severe WMH at baseline, and the effects of longitudinal change of WMH volume on cognitive decline and cortical thinning. Eighty-seven patients with subcortical vascular mild cognitive impairment were prospectively recruited from a single referral centre. All of the patients were followed up with annual neuropsychological tests and 3T brain magnetic resonance imaging. The WMH volume was quantified using an automated method and the cortical thickness was measured using surface-based methods. Participants were classified into WMH progression and WMH regression groups based on the delta WMH volume between the baseline and the last follow-up. To investigate the effects of longitudinal change in WMH volume on cognitive decline and cortical thinning, a linear mixed effects model was used. Seventy patients showed WMH progression and 17 showed WMH regression over a three-year period. The WMH progression group showed more rapid cortical thinning in widespread regions compared with the WMH regression group. However, the rate of cognitive decline in language, visuospatial function, memory and executive function, and general cognitive function was not different between the two groups. The results of this study indicated that WMH volume changes are dynamic and WMH progression is associated with more rapid cortical thinning.

Download Full-text

Changes in mild cognitive impairment and its subtypes as seen on diffusion tensor imaging

International Psychogeriatrics ◽

10.1017/s1041610212000270 ◽

2012 ◽

Vol 24 (9) ◽

pp. 1483-1493 ◽

Cited By ~ 12

Author(s):

Senthil Thillainadesan ◽

Wei Wen ◽

Lin Zhuang ◽

John Crawford ◽

Nicole Kochan ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Multiple Testing ◽

Diffusion Tensor ◽

Internal Capsule ◽

Anterior Cingulate ◽

Corona Radiata ◽

Amnestic Mci ◽

Subcortical Regions ◽

The Right

ABSTRACTBackground: Previous studies using diffusion tensor imaging (DTI) have observed microstructural abnormalities in white matter regions in both Alzheimer's disease and mild cognitive impairment (MCI). The aim of this work was to examine the abnormalities in white matter and subcortical regions of MCI and its subtypes in a large, community-dwelling older aged cohortMethods: A community-based sample of 396 individuals without dementia underwent medical assessment, neuropsychiatric testing, and neuroimaging. Of these, 158 subjects were classified as MCI and 238 as cognitively normal (controls) based on international MCI consensus criteria. Regional fractional anisotropy (FA) and mean diffusivity (MD) measures were calculated from the DTI and compared between groups. The false discovery rate correction was applied for multiple testing.Results: Subjects with MCI did not have significant differences in FA compared with controls after correction for multiple testing, but had increased MD in the right putamen, right anterior limb of the internal capsule, genu and splenium of the corpus callosum, right posterior cingulate gyrus, left superior frontal gyrus, and right and left corona radiata. When compared with controls, changes in left anterior cingulate, left superior frontal gyrus, and right corona radiata were associated with amnestic MCI (aMCI), whereas changes in the right putamen, right anterior limb of the internal capsule, and the right corona radiata were associated with non-amnestic MCI (naMCI). On logistic regression, the FA values in the left superior gyrus and MD values in the anterior cingulate distinguished aMCI from naMCI.Conclusions: MCI is associated with changes in white matter and subcortical regions as seen on DTI. Changes in some anterior brain regions distinguish aMCI from naMCI.

Download Full-text