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Franz Fazekas - One of the best experts on this subject based on the ideXlab platform.
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genome wide association studies of cerebral White Matter Lesion burden the charge consortium
Annals of Neurology, 2011Co-Authors: Myriam Fornage, Arfan M Ikram, Sigurdur Sigurdsson, Helena Schmidt, Joshua C Bis, Carole Dufouil, Stephanie Debette, Thomas Lumley, Anita L Destefano, Franz FazekasAbstract:textabstractObjective: White Matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (pdiscovery= 4.0 × 10-9; preplication= 1.3 × 10-7; pcombined= 4.0 × 10-15). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10-9), rs11869977 (p = 5.7 × 10-9), rs936393 (p = 6.8 × 10-9), rs3744017 (p = 7.3 × 10-9), and rs1055129 (p = 4.1 × 10-8). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH.
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White Matter Lesion progression brain atrophy and cognitive decline the austrian stroke prevention study
Annals of Neurology, 2005Co-Authors: Reinhold Schmidt, Stefan Ropele, Christian Enzinger, K Petrovic, Stephen M Smith, Helena Schmidt, Paul M Matthews, Franz FazekasAbstract:White Matter Lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in White Matter Lesion and brain parenchymal volumes. After 6 years, the median increase in White Matter Lesion load was 0.2 cm3 (interquartile range [IQR], 0.0-0.80 cm3) with a maximum of 31.4 cm3. The median loss of brain volume was 2.3% (IQR, 1.13-3.58%). Increasing White Matter Lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in White Matter Lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of Lesion burden.
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White Matter Lesion progression brain atrophy and cognitive decline the austrian stroke prevention study
Annals of Neurology, 2005Co-Authors: Reinhold Schmidt, Katja Petrovic, Stefan Ropele, Christian Enzinger, Stephen M Smith, Helena Schmidt, Paul M Matthews, Franz FazekasAbstract:White Matter Lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in White Matter Lesion and brain parenchymal volumes. After 6 years, the median increase in White Matter Lesion load was 0.2cm3 (interquartile range [IQR], 0.0–0.80cm3) with a maximum of 31.4cm3. The median loss of brain volume was 2.3% (IQR, 1.13–3.58%). Increasing White Matter Lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in White Matter Lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of Lesion burden. Ann Neurol 2005;58:610–616
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White Matter Lesion progression a surrogate endpoint for trials in cerebral small vessel disease
Neurology, 2004Co-Authors: Reinhard Edwin Schmidt, Frederik Barkhof, Ph Scheltens, Timo Erkinjuntti, Leonardo Pantoni, Hugh S Markus, Anders Wallin, Franz FazekasAbstract:There is neuropathologic evidence that confluent MRI White Matter Lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of White Matter Lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent White Matter Lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in Lesion volume was 5.2 cm 3 after 3 years. Based on these data in a clinical trial, 195 subjects with confluent Lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in White Matter Lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it Matters to the patient in terms of function.
Reinhold Schmidt - One of the best experts on this subject based on the ideXlab platform.
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White Matter Lesion Progression in LADIS: Frequency, Clinical Effects, and Sample Size Calculations
Stroke, 2012Co-Authors: Reinhold Schmidt, Sofia Madureira, Wiesje M. Van Der Flier, Andrea Berghold, Katja Petrovic, Philip Scheltens, Hanna Jokinen, Frederik Barkhof, Alida A. Gouw, Ana VerdelhoAbstract:Background and Purpose—White Matter Lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between Lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. Methods—Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. Results—WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent Lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on Lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. Conclusions—WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure. (Stroke. 2012;43:2643-2647.)
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cortical and frontal atrophy are associated with cognitive impairment in age related confluent White Matter Lesion
Journal of Neurology Neurosurgery and Psychiatry, 2011Co-Authors: Vincent Mok, Reinhold Schmidt, Kelvin K Wong, Yunyun Xiong, Adrian Wong, Winnie C W Chu, Eric Y L Leung, Sirong Chen, Yangkun Chen, W K TangAbstract:Objective Although age-related confluent White-Matter Lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML. Methods Among 100 patients with ischaemic stroke with confluent WML on MRI, the authors assessed executive function and global cognition by the Mattis Dementia Rating Scale—Initiation/Perseveration Subscale (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric measures were corrected for intracranial volume. The authors investigated the association between basic demography, vascular risk factors, APOE status, WML volume, infarct measures (volume, number, location), microbleed number, atrophy measures (global, central, regional) and cognitive performance. The authors also performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired patients with stroke. Results WML was no longer related to cognitive performance after adding atrophy into regression equations. Multivariate regression models showed that cortical grey Matter volume independently accounted for performance on both the MDRS I/P (β=0.241, p=0.045) and MMSE (β=0.243, p=0.032). Models examining frontal subregions revealed that volumes of both left (β=0.424, p Conclusions Cognitive impairment in patients with confluent WML is mediated by global and frontal cortical atrophy.
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White Matter Lesion progression brain atrophy and cognitive decline the austrian stroke prevention study
Annals of Neurology, 2005Co-Authors: Reinhold Schmidt, Stefan Ropele, Christian Enzinger, K Petrovic, Stephen M Smith, Helena Schmidt, Paul M Matthews, Franz FazekasAbstract:White Matter Lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in White Matter Lesion and brain parenchymal volumes. After 6 years, the median increase in White Matter Lesion load was 0.2 cm3 (interquartile range [IQR], 0.0-0.80 cm3) with a maximum of 31.4 cm3. The median loss of brain volume was 2.3% (IQR, 1.13-3.58%). Increasing White Matter Lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in White Matter Lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of Lesion burden.
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White Matter Lesion progression brain atrophy and cognitive decline the austrian stroke prevention study
Annals of Neurology, 2005Co-Authors: Reinhold Schmidt, Katja Petrovic, Stefan Ropele, Christian Enzinger, Stephen M Smith, Helena Schmidt, Paul M Matthews, Franz FazekasAbstract:White Matter Lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in White Matter Lesion and brain parenchymal volumes. After 6 years, the median increase in White Matter Lesion load was 0.2cm3 (interquartile range [IQR], 0.0–0.80cm3) with a maximum of 31.4cm3. The median loss of brain volume was 2.3% (IQR, 1.13–3.58%). Increasing White Matter Lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in White Matter Lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of Lesion burden. Ann Neurol 2005;58:610–616
Meike W Vernooij - One of the best experts on this subject based on the ideXlab platform.
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apnea hypopnea index nocturnal arousals oxygen desaturation and structural brain changes a population based study
Neurobiology of Sleep and Circadian Rhythms, 2016Co-Authors: Lisette A Zuurbier, Meike W Vernooij, Annemarie I Luik, Desana Kocevska, Harry Whitmore, Arfan M Ikram, Albert Hofman, Henning TiemeierAbstract:Abstract Sleep apnea has been related to brain changes such as atrophy. However, which component of sleep apnea, the apnea-hypopnea index (AHI), nocturnal oxygen desaturation or arousals, can explain this association is unclear. In this large population-based study ( n =681, mean age 62.1 years), we investigated the associations of AHI, nocturnal oxygen desaturation and arousals with global and regional gray Matter and White Matter volumes and with White Matter Lesion volumes. All participants underwent one night of polysomnography and MRI scanning of their brain. Gray Matter, White Matter and White Matter Lesion volumes adjusted for intracranial volume were studied as markers of brain atrophy. Nocturnal oxygen desaturation was related to whole brain White Matter atrophy independent of covariates (multivariable adjusted B =−8.3, 95% CI=−16.7; −0.02). This association was most prominently reflected in the association between more oxygen desaturation and a smaller White Matter parietal volume ( B =−3.95 ml, 95% CI=−6.02; −1.88). Furthermore, oxygen desaturation was related to a smaller hippocampus ( B =−0.22 ml, 95% CI=−0.42; −0.01). Although a higher AHI was related to smaller parietal gray ( B =−0.05, 95% CI=−0.09; −0.004) and White Matter ( B =−0.06, 95% CI=−0.12; −0.10) volumes, these associations disappeared when adding oxygen desaturation to the model. We did not find a relation between arousals and gray and White Matter brain atrophy and White Matter Lesion volumes. This suggests that oxygen desaturation mainly explains the association between sleep apnea and brain damage.
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cerebral small vessel disease is related to disturbed 24 h activity rhythms a population based study
European Journal of Neurology, 2015Co-Authors: Lisette A Zuurbier, M. Arfan Ikram, Eus J.w. Van Someren, Meike W Vernooij, Annemarie I Luik, Albert Hofman, Henning TiemeierAbstract:Background and purpose: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. Methods: This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as White Matter Lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White Matter Lesions, instability, fragmentation and sleep quality were standardized for analyses. Results: Higher White Matter Lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. Conclusions: White Matter Lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.
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high blood pressure and cerebral White Matter Lesion progression in the general population
Hypertension, 2013Co-Authors: Benjamin F.j. Verhaaren, Meike W Vernooij, Albert Hofman, Aad Van Der Lugt, Renske De Boer, Wiro J. Niessen, Arfan M IkramAbstract:High blood pressure is considered an important risk factor for cerebral White Matter Lesions (WMLs) in the aging population. In a longitudinal population-based study of 665 nondemented persons, we investigated the longitudinal relationship of systolic blood pressure, diastolic blood pressure, and pulse pressure with annual progression of WMLs. Means of blood pressure were calculated over a 5-year period before longitudinal MRI scanning. WML progression was subsequently measured on 2 scans 3.5 years apart. We performed analyses with linear regression models and evaluated adjustments for age, sex, cardiovascular risk factors, and baseline WML volume. In addition, we evaluated whether treatment of hypertension is related to less WML progression. Both systolic and diastolic blood pressures were significantly associated with annual WML progression (regression coefficient [95% confidence interval], 0.08 [0.03; 0.14] mL/y and 0.09 [0.03; 0.15] mL/y per SD increase in systolic and diastolic blood pressure, respectively). Pulse pressure was also significantly associated with WML progression, but not independent from hypertension. After adjustment for baseline WML volume, only systolic blood pressure remained significantly associated: 0.05 (0.00; 0.09) mL/y per SD increase. People with uncontrolled untreated hypertension had significantly more WML progression than people with uncontrolled treated hypertension (difference [95% confidence interval], 0.12 [0.00; 0.23] mL/y). The present study further establishes high blood pressure to precede WMLs and implies that hypertension treatment could reduce WML progression in the general population.
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Automated measurement of local White Matter Lesion volume
NeuroImage, 2011Co-Authors: Fedde Van Der Lijn, M. Arfan Ikram, Henri A. Vrooman, Meike W Vernooij, Benjamin F.j. Verhaaren, Stefan Klein, Marleen De Bruijne, Alexander Hammers, Daniel Rueckert, Aad Van Der LugtAbstract:It has been hypothesized that White Matter Lesions at different locations may have different etiology and clinical consequences. Several approaches for the quantification of local White Matter Lesion load have been proposed in the literature, most of which rely on a distinction between Lesions in a periventricular region close to the ventricles and a subcortical zone further away. In this work we present a novel automated method for local White Matter Lesion volume quantification in magnetic resonance images. The method segments and measures the White Matter Lesion volume in 43 regions defined by orientation and distance to the ventricles, which allows a more spatially detailed study of Lesion load. The potential of the method was demonstrated by analyzing the effect of blood pressure on the regional White Matter Lesion volume in 490 elderly subjects taken from a longitudinal population study. The method was also compared to two commonly used techniques to assess the periventricular and subcortical Lesion load. The main finding was that high blood pressure was primarily associated with Lesion load in the vascular watershed area that forms the border between the periventricular and subcortical regions. It explains the associations found for both the periventricular and subcortical load computed for the same data, and that were reported in the literature. But the proposed method can localize the region of association with greater precision than techniques that distinguish between periventricular and subcortical Lesions only.
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Replication Study of Chr17q25 With Cerebral White Matter Lesion Volume
Stroke, 2011Co-Authors: Benjamin F.j. Verhaaren, Meike W Vernooij, Albert Hofman, Aad Van Der Lugt, Renske De Boer, Fernando Rivadeneira, André G. Uitterlinden, Gabriel P. Krestin, Wiro J. Niessen, Monique M B BretelerAbstract:Background and Purpose—Recently, the first genomewide association study on cerebral White Matter Lesion burden identified chr17q25 to be significantly associated with White Matter Lesions. We report on the first independent replication study of this genetic association. Methods—In a population-based cohort study, we investigated the association between the 6 genomewide significant single nucleotide polymorphisms at that locus and cerebral White Matter Lesion volume on MRI, measured quantitatively, adjusted for age, sex, and intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk factors were evaluated separately. Finally, we performed a meta-analysis of all published data for the single most significant single nucleotide polymorphism, rs3744028. Results—The risk alleles of all the 6 single nucleotide polymorphisms were significantly associated with White Matter Lesion volume with P=1.1*10−3 for rs3744028, adjusted for age, sex, and intracranial volume. Additional adjustments only ha...
Clinton B Wright - One of the best experts on this subject based on the ideXlab platform.
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diastolic blood pressure is associated with regional White Matter Lesion load the northern manhattan study
Stroke, 2020Co-Authors: Michelle R Caunca, Mitchell S V Elkind, Ralph L Sacco, Ying Kuen Cheung, Tatjana Rundek, Marialaura Simonetto, Noam Alperin, Sang H Lee, Clinton B WrightAbstract:Background and Purpose— Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using ...
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blood pressure control in aging predicts cerebral atrophy related to small vessel White Matter Lesions
Frontiers in Aging Neuroscience, 2017Co-Authors: Kyle C Kern, Clinton B Wright, Kaitlin L Bergfield, Megan C Fitzhugh, Kewei Chen, James R Moeller, Nooshin Nabizadeh, Mitchell S V Elkind, Ralph L Sacco, Yaakov SternAbstract:Cerebral small-vessel damage manifests as White Matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of White Matter Lesion load on regional gray Matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray Matter voxel-based morphometry with the scaled subprofile model to 1) identify regional covariance patterns of gray Matter volume differences associated with White Matter Lesion load, 2) compare this relationship across blood pressure groups, and 3) relate it to cognitive performance. In this group of participants aged 60 to 86 years, we identified a pattern of reduced gray Matter volume associated with White Matter Lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, White Matter Lesions from small-vessel disease are associated with a regional pattern of gray Matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.
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cognitive correlates of White Matter Lesion load and brain atrophy the northern manhattan study
Neurology, 2015Co-Authors: Chuanhui Dong, Nooshin Nabizadeh, Mitchell S V Elkind, Ralph L Sacco, Yaakov Stern, Michelle R Caunca, Ying Kuen Cheung, Tatjana Rundek, Charles Decarli, Clinton B WrightAbstract:Objective: We investigated White Matter Lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified White Matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray Matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% White). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE e4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, White Matter Lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance.
Paul M Matthews - One of the best experts on this subject based on the ideXlab platform.
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White Matter Lesion progression brain atrophy and cognitive decline the austrian stroke prevention study
Annals of Neurology, 2005Co-Authors: Reinhold Schmidt, Stefan Ropele, Christian Enzinger, K Petrovic, Stephen M Smith, Helena Schmidt, Paul M Matthews, Franz FazekasAbstract:White Matter Lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in White Matter Lesion and brain parenchymal volumes. After 6 years, the median increase in White Matter Lesion load was 0.2 cm3 (interquartile range [IQR], 0.0-0.80 cm3) with a maximum of 31.4 cm3. The median loss of brain volume was 2.3% (IQR, 1.13-3.58%). Increasing White Matter Lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in White Matter Lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of Lesion burden.
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White Matter Lesion progression brain atrophy and cognitive decline the austrian stroke prevention study
Annals of Neurology, 2005Co-Authors: Reinhold Schmidt, Katja Petrovic, Stefan Ropele, Christian Enzinger, Stephen M Smith, Helena Schmidt, Paul M Matthews, Franz FazekasAbstract:White Matter Lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in White Matter Lesion and brain parenchymal volumes. After 6 years, the median increase in White Matter Lesion load was 0.2cm3 (interquartile range [IQR], 0.0–0.80cm3) with a maximum of 31.4cm3. The median loss of brain volume was 2.3% (IQR, 1.13–3.58%). Increasing White Matter Lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in White Matter Lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of Lesion burden. Ann Neurol 2005;58:610–616
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regional axonal loss in the corpus callosum correlates with cerebral White Matter Lesion volume and distribution in multiple sclerosis
Brain, 2000Co-Authors: Nikos Evangelou, Stephen M Smith, D Konz, M M Esiri, J Palace, Paul M MatthewsAbstract:Previous imaging studies have suggested that there is substantial axonal loss in the normal-appearing White Matter (NAWM) of brains from multiple sclerosis patients and that this axonal loss may be an important determinant of disability. Recently, substantial axonal loss in the NAWM has been confirmed directly in post-mortem tissue. Whether the NAWM changes occur as a consequence of damage to axons traversing Lesions or to a more diffuse injury process is uncertain. Using formalin-fixed brains of eight multiple sclerosis patients and eight age-matched controls, we examined the relationship between demyelinating Lesion load in three volumes of the cerebral White Matter and the loss of axons in NAWM of the corresponding three projection regions (anterior, middle, posterior) in the corpus callosum (CC). There was a significant loss of calculated total number of axons crossing the CC in each of the three regions relative to the non-multiple sclerosis controls. Strong correlations were found between the regional Lesion load and both the axonal density ( r = –0.673, P = 0.001) and the total estimated number of axons crossing the corresponding projection area in the CC ( r = –0.656, P = 0.001) for the patients. This suggests that Wallerian degeneration of axons transected in the demyelinating Lesions makes a major contribution to the substantial, diffuse loss of axons in the NAWM in multiple sclerosis. These findings emphasize the need to consider the consequences of multiple sclerosis Lesions in terms of both local and distant effects in functionally connected regions of the brain.
