Age dependent white matter lesions and brain volume changes in healthy volunteers

The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males and females. Our results suggest that with aging central atrophy increases more (relatively) than cortical atrophy. No correlation was found between the decreasing volume of the cerebral hemispheres and the increasing number and size of WMHL, nor between the increasing volume of the lateral ventricles and the increasing number and size of WMHL.

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Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects

Neurology ◽

10.1212/01.wnl.0000144280.59178.78 ◽

2004 ◽

Vol 63 (10) ◽

pp. 1892-1897 ◽

Cited By ~ 80

Author(s):

R. M. Wiseman ◽

B. K. Saxby ◽

E. J. Burton ◽

R. Barber ◽

G. A. Ford ◽

...

Keyword(s):

White Matter ◽

Brain Volume ◽

White Matter Lesions ◽

Hippocampal Atrophy ◽

Whole Brain

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Genetic Risk Factors for Longitudinal Changes in Structural MRI in Former Organolead Workers

Journal of Aging Research ◽

10.4061/2011/362189 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Bryan D. James ◽

Brian Caffo ◽

Walter F. Stewart ◽

David Yousem ◽

Christos Davatzikos ◽

...

Keyword(s):

Risk Factors ◽

White Matter ◽

Brain Volume ◽

Density Lipoprotein ◽

White Matter Lesions ◽

Structural Mri ◽

Population Based ◽

Effect Modification ◽

Longitudinal Change ◽

Brain Volumes

This study examined associations between polymorphisms in three genes, apolipoprotein E (APOE), angiotensin converting enzyme (ACE), and vitamin D receptor (VDR), and longitudinal change in brain volumes and white matter lesions (WML) as well as effect modification by cardiovascular factors and tibia lead concentrations. Two MRIs, an average of 5 years apart, were obtained for 317 former organolead workers and 45 population-based controls. Both regions-of-interest and voxel-wise analyses were conducted.APOEε3/ε4andε4/ε4genotypes were associated with less decline in white matter volumes. There was some evidence of interaction between genetic polymorphisms and cardiovascular risk factors (ACEand high-density lipoprotein;VDRand diabetes) on brain volume decline. TheVDR FokIff genotype was associated with an increase in WML (no association forAPOEorACE). This study expands our understanding of how genetic precursors of dementia and cardiovascular diseases are related to changes in brain structure.

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Cardiovascular risk and white matter lesions after endocrine control of Cushing's syndrome

Acta Endocrinologica ◽

10.1530/eje-15-0600 ◽

2015 ◽

Vol 173 (6) ◽

pp. 765-775 ◽

Cited By ~ 22

Author(s):

Alicia Santos ◽

Eugenia Resmini ◽

Beatriz Gómez-Ansón ◽

Iris Crespo ◽

Esther Granell ◽

...

Keyword(s):

Cardiovascular Risk ◽

White Matter ◽

Cushing’S Syndrome ◽

Grey Matter ◽

Brain Volume ◽

White Matter Lesions ◽

Cushing's Syndrome ◽

Vascular Age ◽

Patient Groups ◽

Active Patients

ObjectiveCushing's syndrome (CS) is associated with high cardiovascular risk. White matter lesions (WML) are common on brain magnetic resonance imaging (MRI) in patients with increased cardiovascular risk.AimTo investigate the relationship between cardiovascular risk, WML, neuropsychological performance and brain volume in CS.Design/methodsThirty-eight patients with CS (23 in remission, 15 active) and 38 controls sex-, age- and education-level matched underwent a neuropsychological and clinical evaluation, blood and urine tests and 3Tesla brain MRI. WML were analysed with the Scheltens scale. Ten-year cardiovascular risk (10CVR) and vascular age (VA) were calculated according to an algorithm based on the Framingham heart study.ResultsPatients in remission had a higher degree of WML than controls and active patients (P<0.001 andP=0.008 respectively), which did not correlate with cognitive performance in any group. WML severity positively correlated with diastolic blood pressure (r=0.659,P=0.001) and duration of hypertension (r=0.478,P=0.021) in patients in remission. Both patient groups (active and in remission) had higher 10CVR (P=0.030,P=0.041) and VA than controls (P=0.013,P=0.039). Neither the 10CVR nor the VA correlated with WML, although both negatively correlated with cognitive function and brain volume in patients in remission (P<0.05). Total brain volume and grey matter volume in both CS patient groups were reduced compared to controls (total volume: activeP=0.006, in remissionP=0.012; grey matter: activeP=0.001, in remissionP=0.003), with no differences in white matter volume between groups.ConclusionsPatients in remission of Cushing's syndrome (but not active patients) have more severe white matter lesions than controls, positively correlated with diastolic pressure and duration of hypertension. Ten-year cardiovascular risk and vascular age appear to be negatively correlated with the cognitive function and brain volume in patients in remission of Cushing's syndrome.

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Neither retinal nor brain atrophy can be shown in patients with isolated unilateral optic neuritis at the time of presentation

Multiple Sclerosis Journal ◽

10.1177/1352458510382017 ◽

2010 ◽

Vol 17 (1) ◽

pp. 89-95 ◽

Cited By ~ 11

Author(s):

Klaus Kallenbach ◽

Birgit Sander ◽

Anna Tsakiri ◽

Benedikte Wanscher ◽

Dan Fuglø ◽

...

Keyword(s):

White Matter ◽

Optic Neuritis ◽

Healthy Volunteers ◽

Brain Atrophy ◽

White Matter Lesions ◽

Clinical Event ◽

Brain Volumes ◽

Structural Measures ◽

The Brain ◽

Fellow Eyes

Background:Acute monosymptomatic optic neuritis (ON) may be the earliest manifestation of multiple sclerosis (MS). Atrophy has been shown to be a prominent feature of MS with great impact on disability. Objectives:The objectives of this study were to evaluate retinal and brain atrophy and possible associations at the earliest possible stages of MS. Methods:In a prospective observational cohort study we included 60 untreated patients with monosymptomatic ON and 19 healthy volunteers. Unaffected fellow eyes were examined with optical coherence tomography (OCT) and normalized brain volumes were calculated based on MRI. Additionally, visual evoked potentials (VEPs) were recorded. Results:Neither OCT measurements nor brain volume measures revealed signs of localized or generalized atrophy in patients compared with healthy volunteers. Stratification of patients into high risk based on the presence of white matter lesions did not reveal differences. The association between OCT measures and brain volumes previously found could not be confirmed at the time of the first clinical event. VEP latency was significantly prolonged in patients with white matter lesions compared to those without lesions. A trend towards a relationship between VEP amplitude of fellow eyes and brain volumes was noted. Conclusions:In this cohort we were not able to show atrophic features in the retina or the brain, and the association between structural measures of the retina and the brain as indicated in the later stages of MS could not be reproduced. These findings suggest that atrophy does require time to evolve and indicate the complexity of the relationship between local and general structural measures.

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Brain Atrophy and White Matter Damage Linked to Peripheral Bioenergetic Deficits in the Neurodegenerative Disease FXTAS

International Journal of Molecular Sciences ◽

10.3390/ijms22179171 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9171

Author(s):

Junyi Wang ◽

Eleonora Napoli ◽

Kyoungmi Kim ◽

Yingratana A. McLennan ◽

Randi J. Hagerman ◽

...

Keyword(s):

White Matter ◽

Brain Volume ◽

Neurodegenerative Disorder ◽

Fragile X ◽

Mitochondrial Bioenergetics ◽

Mri Findings ◽

Mitochondrial Mass ◽

Atp Production ◽

Age Dependent ◽

Ataxia Syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting subjects (premutation carriers) with a 55-200 CGG-trinucleotide expansion in the 5′UTR of the fragile X mental retardation 1 gene (FMR1) typically after age 50. As both the presence of white matter hyperintensities (WMHs) and atrophied gray matter on magnetic resonance imaging (MRI) are linked to age-dependent decline in cognition, here we tested whether MRI outcomes (WMH volume (WMHV) and brain volume) were correlated with mitochondrial bioenergetics from peripheral blood monocytic cells in 87 carriers with and without FXTAS. As a parameter assessing cumulative damage, WMHV was correlated to both FXTAS stages and age, and brain volume discriminated between carriers and non-carriers. Similarly, mitochondrial mass and ATP production showed an age-dependent decline across all participants, but in contrast to WMHV, only FADH2-linked ATP production was significantly reduced in carriers vs. non-carriers. In carriers, WMHV negatively correlated with ATP production sustained by glucose-glutamine and FADH2-linked substrates, whereas brain volume was positively associated with the latter and mitochondrial mass. The observed correlations between peripheral mitochondrial bioenergetics and MRI findings—and the lack of correlations with FXTAS diagnosis/stages—may stem from early brain bioenergetic deficits even before overt FXTAS symptoms and/or imaging findings.

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Total Cerebral Blood Flow, White Matter Lesions and Brain Atrophy: The SMART-MR Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9600563 ◽

2007 ◽

Vol 28 (3) ◽

pp. 633-639 ◽

Cited By ~ 53

Author(s):

Auke PA Appelman ◽

Yolanda van der Graaf ◽

Koen L Vincken ◽

Audrey M Tiehuis ◽

Theo D Witkamp ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Magnetic Resonance ◽

Brain Atrophy ◽

Brain Volume ◽

White Matter Lesions ◽

Arterial Disease ◽

Subcortical Brain ◽

Mr Study

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58±10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0±10.2 mL/min per 100 mL, mean BPF was 79.2±2.9%, and mean VF was 2.03±0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.

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Evaluating and reducing the impact of white matter lesions on brain volume measurements

Human Brain Mapping ◽

10.1002/hbm.21344 ◽

2011 ◽

Vol 33 (9) ◽

pp. 2062-2071 ◽

Cited By ~ 161

Author(s):

Marco Battaglini ◽

Mark Jenkinson ◽

Nicola De Stefano

Keyword(s):

White Matter ◽

Brain Volume ◽

White Matter Lesions ◽

Volume Measurements ◽

The Impact

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Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes

Multiple Sclerosis Journal ◽

10.1177/1352458512473190 ◽

2013 ◽

Vol 19 (9) ◽

pp. 1175-1181 ◽

Cited By ~ 55

Author(s):

Angela Vidal-Jordana ◽

Jaume Sastre-Garriga ◽

Francisco Pérez-Miralles ◽

Carmen Tur ◽

Mar Tintoré ◽

...

Keyword(s):

White Matter ◽

Brain Volume ◽

Corticosteroid Treatment ◽

First Year ◽

Volume Loss ◽

White Matter Volume ◽

Volume Changes ◽

Brain Volumes ◽

Matter Volume ◽

Brain Volume Loss

Background: Investigation of atrophy data from a pivotal natalizumab trial has demonstrated an increased rate of volume loss, compared to placebo, after the first year of therapy. It was considered to be probably due to a pseudoatrophy effect. Objective: To assess grey and white matter volume changes and their relation to global brain volume changes and to baseline inflammation, for patients under natalizumab therapy. Methods: We selected 45 patients on natalizumab therapy for at least 24 months, with magnetic resonance imaging (MRI) scans at baseline, 12 and 24 months. We calculated the percentage brain volume change (PBVC) for the first and second year, using SIENA software. Grey and white matter fractions (GMF and WMF, respectively) for the first year were calculated with SPM5, using lesion masks. After quality checks, six patients were excluded. We studied the predictive variables of change in brain volumes. Results: The PBVC decrease was faster during the first year (−1.10% ± 1.43%), as compared to the second (−0.51% ± 0.96%) ( p = 0.037). These differences were more marked in patients with baseline gadolinium-enhancing lesions ( p = 0.005). Mean GMF and WMF changes during the first year of treatment were +1.15% (n.s.) and −1.72% ( p = 0.017), respectively. The presence of active lesions at baseline MRI predicted PBVC ( p = 0.022) and WMF change ( p = 0.026) during the first year of treatment, after adjusting for age and corticosteroid treatment. No predictors were found for GMF volume changes. Conclusion: Early brain volume loss during natalizumab therapy is mainly due to WMF volume loss and it is related to the inflammatory activity present at the onset of therapy. We found that the pseudoatrophy effect is mostly due to white matter volume changes.

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