CHARACTERIZATION OF COGNITIVE PERFORMANCE, GRAY MATTER VOLUME AND WHITE MATTER MICROSTRUCTURE IN COGNITIVELY UNIMPAIRED ADULTS WITH INSOMNIA SYMPTOMS

Abstract Background Mounting evidence links poor sleep quality with a higher risk of late-life dementia. However, the structural and cognitive correlates of insomnia are still not well understood. The study aims were to characterize the cognitive performance and brain structural pattern of cognitively unimpaired adults at increased risk for Alzheimer’s disease (AD) with insomnia. Methods This cross-sectional study included 1683 cognitively unimpaired middle/late-middle-aged adults from the ALFA (ALzheimer and FAmilies) study who underwent neuropsychological assessment, T1-weighted structural imaging (n = 366), and diffusion-weighted imaging (n = 334). The World Health Organization’s World Mental Health Survey Initiative version of the Composite International Diagnostic Interview was used to define the presence or absence of insomnia. Multivariable regression models were used to evaluate differences in cognitive performance between individuals with and without insomnia, as well as potential interactions between insomnia and the APOE genotype. Voxel-based morphometry and tract-based spatial statistics were used to assess between-group differences and potential interactions between insomnia and the APOE genotype in gray matter volume and white matter diffusion metrics. Results Insomnia was reported by 615 out of 1683 participants (36.5%), including 137 out of 366 (37.4%) with T1-weighted structural imaging available and 119 out of 334 (35.6%) with diffusion-weighted imaging. Individuals with insomnia (n = 615) performed worse in executive function tests than non-insomniacs and displayed lower gray matter volume in left orbitofrontal and right middle temporal cortex, bilateral precuneus, posterior cingulate cortex and thalamus, higher gray matter volume in the left caudate nucleus, and widespread reduction of mean and axial diffusivity in right hemisphere white matter tracts. Insomnia interacted with the APOE genotype, with APOE-ε4 carriers displaying lower gray matter volumes when insomnia was present, but higher volumes when insomnia was not present, in several gray matter regions, including the left angular gyrus, the bilateral superior frontal gyri, the thalami, and the right hippocampus. Conclusions Insomnia in cognitively unimpaired adults at increased risk for AD is associated to poorer performance in some executive functions and volume changes in cortical and subcortical gray matter, including key areas involved in Alzheimer’s disease, as well as decreased white matter diffusivity.

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Changes in Gray Matter Volume and White Matter Microstructure in Adolescents with Obsessive-Compulsive Disorder

Biological Psychiatry ◽

10.1016/j.biopsych.2011.06.032 ◽

2011 ◽

Vol 70 (11) ◽

pp. 1083-1090 ◽

Cited By ~ 107

Author(s):

Mojtaba Zarei ◽

David Mataix-Cols ◽

Isobel Heyman ◽

Morgan Hough ◽

Joanne Doherty ◽

...

Keyword(s):

White Matter ◽

Obsessive Compulsive Disorder ◽

Gray Matter ◽

Gray Matter Volume ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Matter Volume ◽

White Matter Microstructure

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Subspecialization within default mode nodes characterized in 10,000 UK Biobank participants

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804876115 ◽

2018 ◽

Vol 115 (48) ◽

pp. 12295-12300 ◽

Cited By ~ 51

Author(s):

Julius M. Kernbach ◽

B. T. Thomas Yeo ◽

Jonathan Smallwood ◽

Daniel S. Margulies ◽

Michel Thiebaut de Schotten ◽

...

Keyword(s):

White Matter ◽

Gray Matter ◽

Gray Matter Volume ◽

Intrinsic Activity ◽

Functional Coupling ◽

Pattern Learning ◽

Uk Biobank ◽

Default Mode ◽

Matter Volume ◽

White Matter Microstructure

The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places.

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Sleep duration over 28 years, cognition, gray matter volume, and white matter microstructure: a prospective cohort study

SLEEP ◽

10.1093/sleep/zsz290 ◽

2020 ◽

Vol 43 (5) ◽

Cited By ~ 4

Author(s):

Jennifer Zitser ◽

Melis Anatürk ◽

Enikő Zsoldos ◽

Abda Mahmood ◽

Nicola Filippini ◽

...

Keyword(s):

White Matter ◽

Sleep Duration ◽

Gray Matter ◽

Latent Class ◽

Gray Matter Volume ◽

Latent Class Growth Analysis ◽

Matter Volume ◽

White Matter Microstructure ◽

Gray Matter Volumes ◽

Latent Class Growth

Abstract Study Objectives To examine the association between sleep duration trajectories over 28 years and measures of cognition, gray matter volume, and white matter microstructure. We hypothesize that consistently meeting sleep guidelines that recommend at least 7 hours of sleep per night will be associated with better cognition, greater gray matter volumes, higher fractional anisotropy, and lower radial diffusivity values. Methods We studied 613 participants (age 42.3 ± 5.03 years at baseline) who self-reported sleep duration at five time points between 1985 and 2013, and who had cognitive testing and magnetic resonance imaging administered at a single timepoint between 2012 and 2016. We applied latent class growth analysis to estimate membership into trajectory groups based on self-reported sleep duration over time. Analysis of gray matter volumes was carried out using FSL Voxel-Based-Morphometry and white matter microstructure using Tract Based Spatial Statistics. We assessed group differences in cognitive and MRI outcomes using nonparametric permutation testing. Results Latent class growth analysis identified four trajectory groups, with an average sleep duration of 5.4 ± 0.2 hours (5%, N = 29), 6.2 ± 0.3 hours (37%, N = 228), 7.0 ± 0.2 hours (45%, N = 278), and 7.9 ± 0.3 hours (13%, N = 78). No differences in cognition, gray matter, and white matter measures were detected between groups. Conclusions Our null findings suggest that current sleep guidelines that recommend at least 7 hours of sleep per night may not be supported in relation to an association between sleep patterns and cognitive function or brain structure.

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

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00759-3 ◽

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.

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Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Neurology ◽

10.1212/wnl.0000000000012869 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012869

Author(s):

Raffaello Bonacchi ◽

Alessandro Meani ◽

Elisabetta Pagani ◽

Olga Marchesi ◽

Andrea Falini ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Linear Models ◽

Gray Matter Volume ◽

Age At Onset ◽

Healthy Controls ◽

Compensatory Mechanisms ◽

Cross Sectional ◽

Matter Volume

Objective:To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients, given its influence on clinical phenotype and disease course.Method:In this hypothesis-driven cross-sectional study, we enrolled 67 pediatric-onset MS (POMS) patients and 143 sex- and disease duration (DD)-matched randomly-selected adult-onset MS (AOMS) patients, together with 208 healthy controls. All subjects underwent neurological evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in POMS and AOMS patients were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach.Results:At DD=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS patients. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS patients was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS patients, median DD was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 18 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.36).Conclusions:Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.

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A Correlational Study between Microstructural White Matter Properties and Macrostructural Gray Matter Volume Across Normal Ageing: Conjoint DTI and VBM Analysis

Magnetic Resonance Insights ◽

10.1177/1178623x18799926 ◽

2018 ◽

Vol 11 ◽

pp. 1178623X1879992 ◽

Cited By ~ 4

Author(s):

Vikas Pareek ◽

VP Subramanyam Rallabandi ◽

Prasun K Roy

Keyword(s):

White Matter ◽

Life Span ◽

Fractional Anisotropy ◽

Gray Matter ◽

Healthy Aging ◽

Gray Matter Volume ◽

Mean Diffusivity ◽

Radial Diffusivity ◽

Axial Diffusivity ◽

Matter Volume

We investigate the relationship between Gray matter’s volume vis-a-vis White matter’s integrity indices, such Axial diffusivity, Radial diffusivity, Mean diffusivity, and Fractional anisotropy, in individuals undergoing healthy aging. We investigated MRI scans of 177 adults across 20 to 85 years. We used Voxel-based morphometry, and FDT-FSL analysis for estimation of Gray matter volume and White matter’s diffusion indices respectively. Across the life span, we observed an inter-relationship between the Gray matter and White matter, namely that both Axial diffusivity and Mean Diffusivity show strong correlation with Gray matter volume, along the aging process. Furthermore, across all ages the Fractional anisotropy and Mean diffusivity are found to be significantly reduced in females when compared to males, but there are no significant gender differences in Axial Diffusivity and Radial diffusivity. We conclude that for both genders across all ages, the Gray matter’s Volume is strongly correlated with White matter’s Axial Diffusivity and Mean Diffusivity, while being weakly correlated with Fractional Anisotropy. Our study clarifies the multi-scale relationship in brain tissue, by elucidating how the White matter’s micro-structural parameters influences the Gray matter’s macro-structural characteristics, during healthy aging across the life-span.

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Multimodal Magnetic Resonance Imaging reveals alterations of sensorimotor circuits in restless legs syndrome

SLEEP ◽

10.1093/sleep/zsz171 ◽

2019 ◽

Vol 42 (12) ◽

Cited By ~ 3

Author(s):

Ambra Stefani ◽

Thomas Mitterling ◽

Anna Heidbreder ◽

Ruth Steiger ◽

Christian Kremser ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Gray Matter ◽

Disease Duration ◽

Gray Matter Volume ◽

Resonance Imaging ◽

Iron Storage ◽

Matter Volume ◽

The Right

Abstract Study Objectives Integrated information on brain microstructural integrity and iron storage and its impact on the morphometric profile is not available in restless legs syndrome (RLS). We applied multimodal magnetic resonance imaging (MRI) including diffusion tensor imaging, the transverse relaxation rate (R2*), a marker for iron storage, as well as gray and white matter volume measures to characterize RLS-related MRI signal distribution patterns and to analyze their associations with clinical parameters. Methods Eighty-seven patients with RLS (mean age 51, range 20–72 years; disease duration, mean 13 years, range 1–46 years, of those untreated n = 30) and 87 healthy control subjects, individually matched for age and gender, were investigated with multimodal 3T MRI. Results Volume of the white matter compartment adjacent to the post- and precentral cortex and fractional anisotropy (FA) of the frontopontine tract were both significantly reduced in RLS compared to healthy controls, and these alterations were associated with disease duration (r = 0.25, p = 0.025 and r = 0.23, p = 0.037, respectively). Corresponding gray matter volume increases of the right primary motor cortex in RLS (p < 0.001) were negatively correlated with the right FA signal of the frontopontine tract (r = −0.22; p < 0.05). Iron content evaluated with R2* was reduced in the putamen as well as in temporal and occipital compartments of the RLS cohort compared to the control group (p < 0.01). Conclusions Multimodal MRI identified progressing white matter decline of key somatosensory circuits that may underlie the perception of sensory leg discomfort. Increases of gray matter volume of the premotor cortex are likely to be a consequence of functional neuronal reorganization.

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