scholarly journals Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Malo Gaubert ◽  
Catharina Lange ◽  
Antoine Garnier-Crussard ◽  
Theresa Köbe ◽  
Salma Bougacha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Glucose Metabolism ◽  
Corpus Callosum ◽  
Gray Matter ◽  
Fdg Pet ◽  
White Matter Hyperintensities ◽  
Gray Matter Volume ◽  
Matter Volume

Abstract Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

scholarly journals Cortisol associated with hypometabolism across the Alzheimer’s disease spectrum

2019 ◽  
Author(s):  
Miranka Wirth ◽  
Catharina Lange ◽  
Willem Huijbers ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Gray Matter ◽  
Plasma Cortisol ◽  
Gray Matter Volume ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
Matter Volume ◽  
Neuroimaging Biomarkers

AbstractObjectiveHypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer’s disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum.MethodsCognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer’s Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses.ResultsAcross the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients.InterpretationHigh plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.

scholarly journals Plasma pTau181 predicts cortical brain atrophy in aging and Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Cécile Tissot ◽  
◽  
Andréa L. Benedet ◽  
Joseph Therriault ◽  
Tharick A. Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Gray Matter Volume ◽  
Cognitively Impaired ◽  
White Matter Volume ◽  
Mixed Effect ◽  
Matter Volume

Abstract Background To investigate the association of plasma pTau181, assessed with a new immunoassay, with neurodegeneration of white matter and gray matter cross-sectionally and longitudinally, in aging and Alzheimer’s disease. Methods Observational data was obtained from the Alzheimer’s Disease Neuroimaging Initiative, in which participants underwent plasma assessment and magnetic resonance imaging. Based on their clinical diagnosis, participants were classified as cognitively unimpaired and cognitively impaired. Linear regressions and linear mixed-effect models were used to test the cross-sectional and longitudinal associations between baseline plasma pTau181 and neurodegeneration using voxel-based morphometry. Results We observed a negative correlation at baseline between plasma pTau181 and gray matter volume in cognitively unimpaired individuals. In cognitively impaired individuals, we observed a negative association between plasma pTau181 and both gray and white matter volume. In longitudinal analyses conducted in the cognitively unimpaired group, plasma pTau181 was negatively correlated with gray matter volume, starting 36 months after baseline assessments. Finally, in cognitively impaired individuals, plasma pTau181 concentrations were negatively correlated with both gray and white matter volume as early as 12 months after baseline, and neurodegeneration increased in an incremental manner until 48 months. Conclusions Higher levels of plasma pTau181 correlate with neurodegeneration and predict further brain atrophy in aging and Alzheimer’s disease. Plasma pTau181 may be useful in predicting AD-related neurodegeneration, comparable to positron emission tomography or cerebrospinal fluid assessment with high specificity for AD neurodegeneration.

Reproducibility of Brain Volume Changes in Longitudinal Voxel-Based Morphometry Between Non-Accelerated and Accelerated Magnetic Resonance Imaging

2021 ◽  
pp. 1-10
Author(s):  
Hidemasa Takao ◽  
Shiori Amemiya ◽  
Osamu Abe ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Resonance ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
Elderly Subjects ◽  
Voxel Based Morphometry ◽  
Volume Changes ◽  
Matter Volume ◽  
Healthy Elderly

Background: Scan acceleration techniques, such as parallel imaging, can reduce scan times, but reliability is essential to implement these techniques in neuroimaging. Objective: To evaluate the reproducibility of the longitudinal changes in brain morphology determined by longitudinal voxel-based morphometry (VBM) between non-accelerated and accelerated magnetic resonance images (MRI) in normal aging, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 database, comprising subjects who underwent non-accelerated and accelerated structural T1-weighted MRI at screening and at a 2-year follow-up on 3.0 T Philips scanners, we examined the reproducibility of longitudinal gray matter volume changes determined by longitudinal VBM processing between non-accelerated and accelerated imaging in 50 healthy elderly subjects, 54 MCI patients, and eight AD patients. Results: The intraclass correlation coefficient (ICC) maps differed among the three groups. The mean ICC was 0.72 overall (healthy elderly, 0.63; MCI, 0.75; AD, 0.63), and the ICC was good to excellent (0.6–1.0) for 81.4%of voxels (healthy elderly, 64.8%; MCI, 85.0%; AD, 65.0%). The differences in image quality (head motion) were not significant (Kruskal–Wallis test, p = 0.18) and the within-subject standard deviations of longitudinal gray matter volume changes were similar among the groups. Conclusion: The results indicate that the reproducibility of longitudinal gray matter volume changes determined by VBM between non-accelerated and accelerated MRI is good to excellent for many regions but may vary between diseases and regions.

scholarly journals Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function

2018 ◽  
Vol 7 (11) ◽  
pp. 413 ◽  
Author(s):  
Jiyeon Lee ◽  
Jihyeon Kim ◽  
Seong Shin ◽  
Soowon Park ◽  
Dong Yoon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Gray Matter ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Volume Loss ◽  
Matter Volume

Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss.

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