Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study

AbstractBackgroundAtrial fibrillation (AF) and brain volume loss are prevalent in older individuals. Further study investigating the causal effect of AF on brain volume is warranted.MethodsThis study was a Mendelian randomization (MR) analysis. The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis and included 537,409 individuals of European ancestry. The outcome summary statistics for quantile-normalized white or grey matter volume measured by magnetic resonance imaging were provided by the previous GWAS of 8426 white British UK Biobank participants. The main MR method was the inverse variance weighted method, supported by sensitivity MR analysis including MR-Egger regression and the weighted median method. The causal estimates from AF to white or grey matter volume were further adjusted for effects of any stroke or ischemic stroke by multivariable MR analysis.ResultsA higher genetic predisposition for AF (one standard deviation increase) was significantly associated with lower white matter volume [beta −0.128 (−0.208, −0.048)] but not grey matter volume [beta −0.041 (−0.101, 0.018)], supported by all utilized sensitivity MR analyses. The multivariable MR analysis indicated that AF is causally linked to lower white matter volume independent of the stroke effect.ConclusionsAF is a causative factor for white matter volume loss. The effect of AF on grey matter volume was inapparent in this study. A future trial is necessary to confirm whether appropriate AF management can be helpful in preventing cerebral white matter volume loss or related brain disorders in AF patients.

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Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

BMC Medicine ◽

10.1186/s12916-021-02152-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Sehoon Park ◽

Soojin Lee ◽

Yaerim Kim ◽

Semin Cho ◽

Kwangsoo Kim ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Gray Matter ◽

Grey Matter ◽

Brain Volume ◽

Gray Matter Volume ◽

European Ancestry ◽

Grey Matter Volume ◽

White Matter Volume ◽

Matter Volume

Abstract Background Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis. Methods The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR. Results A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome. Conclusions This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.

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Hemoglobin Level and Platelet Size Predicts Grey and White Matter Volume Loss Measured By Tensor Based Morphology in Sickle Cell Disease

Blood ◽

10.1182/blood.v128.22.2481.2481 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2481-2481

Author(s):

Soyoung Choi ◽

Adam M Bush ◽

Matt Borzage ◽

Anand Joshi ◽

Thomas D. Coates ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Brain Volume ◽

Laboratory Data ◽

Volume Loss ◽

White Matter Volume ◽

Cell Disease ◽

Chronic Anemia ◽

Brain Morphometry ◽

Matter Volume

Abstract Background: Sickle cell disease (SCD) is a life-threatening genetic disease whose patients suffer from chronic anemia, hemolysis, vascular damage, and impaired cerebral blood flow that lead to early and cumulative neurological insults. Adverse effects associated with chronic anemia and hemolysis in SCD include progressive large vessel vasculopathy, stroke, silent cerebral infarctions, and ultimately, early mortality. Few studies have attempted to characterize the effects of this disease on brain morphometry and most have been limited to school age children, despite the progressive nature of the cerebrovascular disease. Thus, this study aims to quantify the hematological effects of SCD on brain morphometry in adolescents and young adults. Methods: 3D T1-weighted images (TE =3.8ms TR =8.3ms; resolution = 1mm3) were acquired on 25 clinically asymptomatic SCD patients (age=20.8 ± 6.7; F=13, M=12) and 26 ethnically matched control subjects (age=26.4 ± 7.7; F=17, M=9). MRI data were acquired on a 3T Philips Achieva (v.3.2.1) using an 8-channel head coil. All patients were recruited with informed consent or assent; the study was approved by the Institutional Review Board at Children's Hospital Los Angeles (CCI#11-00083). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. T1-weighted images were processed using BrainSuite (brainsuite.org) in a semi-automated fashion to calculate whole brain gray matter volume (GMV), and white matter volume (WMV). Stepwise multivariate regression analysis was run on GMV and WMV against laboratory data and vital signs to find predictors of total brain volume. Laboratory data probed including complete blood counts and indices, quantitative hemoglobin electrophoresis, and markers of hemolysis (LDH, reticulocyte count, cell free hemoglobin). After correcting for age and sex, the remaining predictors of grey and white matter volume were used to probe for regional changes in brain volume through tensor based morphometry (Brain Suite Statistics Toolbox). Results: White matter, but not grey matter, was diffusely smaller in SCD patients. Sex, age (log transformed) and mean platelet volume (MPV) were the parameters retained in the multivariate model to predict GMV (r2=0.65; F ratio=28.9) where MPV had a positive correlation to GMV. Hemoglobin, sex, and MPV were found as predictors of WMV (r2=0.43; F ratio = 11.8) where both hemoglobin and MPV had a positive correlation to WMV. Using tensor based morphometry (TBM), both hemoglobin and MPV were positively associated with brain volume changes diffusely in the frontal, parietal, and temporal cortices (Figure 1). Hemoglobin had a strong localized effect on the subcortex (white matter and basal ganglia) (Figure 1) suggesting that anemia was associated with volume loss in these areas. MPV overall was found to have a strong effect on cortical morphology diffusely. Conclusion: Hemoglobin's relationship to brain volume and morphology suggests global white matter shrinkage due to anemia. The association is strongest in the phylogenetically younger portions of the brain and co-localizes with brain regions impacted by silent stroke. MPV was an unexpectedly strong predictor of cortical volumes in both SCD and control subjects. MPV is an indicator of platelet activation and is associated with ischemic stroke, hypertension, obstructive sleep apnea, and coronary artery syndromes in the general population, similar to C-reactive protein. However, the broad association of MPV and grey matter volumes in both SCD patients and controls, independently, suggests a developmental interplay between brain maturation and inflammatory signaling that requires further study. Disclosures Wood: Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy; AMAG: Consultancy; Apopharma: Consultancy; Apopharma: Consultancy; Biomed Informatics: Consultancy; Biomed Informatics: Consultancy; AMAG: Consultancy; Celgene: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; World Care Clinical: Consultancy; Vifor: Consultancy; World Care Clinical: Consultancy.

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Age-specific adult rat brain MRI templates and tissue probability maps

10.31219/osf.io/htgqn ◽

2021 ◽

Cited By ~ 1

Author(s):

Eilidh MacNicol ◽

Paul Wright ◽

Eugene Kim ◽

Irene Brusini ◽

Oscar Esteban ◽

...

Keyword(s):

White Matter ◽

Rat Brain ◽

Grey Matter ◽

Brain Volume ◽

Grey Matter Volume ◽

Total Brain Volume ◽

Adult Rat ◽

Matter Volume ◽

Probability Maps ◽

Total Brain

Age-specific resources mitigate biases in human MRI processing arising from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue’s relative contribution to total brain volume would change with age in the adult rat. However, the currently available tissue probability maps, which provide a priori information for tissue volume estimation, provide inaccurate grey matter probabilities in subcortical structures, particularly the thalamus. Consequently, age-specific templates and tissue probability maps were generated from a longitudinal study that scanned a cohort of rats at 3, 5, 11, and 17 months old. Mixed-effects models assessed the effect of age on brain, grey matter, white matter, and CSF volumes, and the relative tissue proportions. Grey and white matter volume increased with age, and the tissue proportions relative to total brain volume varied throughout adulthood. Furthermore, we present evidence of a systematic underestimation of thalamic grey matter volume with existing resources, which is mitigated with the use of age-specific tissue probability maps since the derived estimates better matched histological evidence. To reduce age-related biases in image pre-processing, a set of rat brain resources from across the adult lifespan is consequently released to expand the preclinical MRI community’s fundamental resources.

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Brain volume reductions in medication-naive patients with schizophrenia in relation to intelligence quotient

Psychological Medicine ◽

10.1017/s0033291712000098 ◽

2012 ◽

Vol 42 (9) ◽

pp. 1847-1856 ◽

Cited By ~ 20

Author(s):

M. Rais ◽

W. Cahn ◽

H. G. Schnack ◽

H. E. Hulshoff Pol ◽

R. S. Kahn ◽

...

Keyword(s):

White Matter ◽

Healthy Subjects ◽

Intelligence Quotient ◽

Brain Volume ◽

First Episode ◽

Volume Loss ◽

White Matter Volume ◽

Matter Volume ◽

Brain Volume Loss ◽

First Episode Schizophrenia

BackgroundGlobal brain abnormalities such as brain volume loss and grey- and white-matter deficits are consistently reported in first-episode schizophrenia patients and may already be detectable in the very early stages of the illness. Whether these changes are dependent on medication use or related to intelligence quotient (IQ) is still debated.MethodMagnetic resonance imaging scans were obtained for 20 medication-naive patients with first-episode schizophrenia and 26 matched healthy subjects. Volume measures of total brain grey and white matter, third and lateral ventricles and cortical thickness/surface were obtained. Differences between the groups were investigated, taking into account the effect of intelligence.ResultsMedication-naive patients showed statistically significant reductions in whole-brain volume and cerebral grey- and white-matter volume together with lateral ventricle enlargement compared to healthy subjects. IQ was significantly lower in patients compared to controls and was positively associated with brain and white-matter volume in the whole group. No significant differences in cortical thickness were found between the groups but medication-naive patients had a significantly smaller surface in the left superior temporal pole, Heschl's gyrus and insula compared to controls.ConclusionsOur findings suggest that brain volume loss is present at illness onset, and can be explained by the reduced surface of the temporal and insular cortex. These abnormalities are not related to medication, but IQ.

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Late chronotype is linked to greater cortical thickness in the left fusiform and entorhinal gyri

10.21203/rs.3.rs-588446/v1 ◽

2021 ◽

Author(s):

Michal Rafal Zareba ◽

Magdalena Fafrowicz ◽

Tadeusz Marek ◽

Ewa Beldzik ◽

Halszka Oginska ◽

...

Keyword(s):

White Matter ◽

Cortical Thickness ◽

Grey Matter ◽

Brain Regions ◽

Affective Processing ◽

Grey Matter Volume ◽

Imaging Data ◽

White Matter Volume ◽

Matter Volume ◽

Anatomical Basis

Abstract Humans can be classified as early, intermediate and late chronotypes based on the preferred sleep and wakefulness patterns. The anatomical basis of these distinctions remains largely unexplored. Using magnetic resonance imaging data from 113 healthy young adults (71 females), we aimed to replicate cortical thickness and grey matter volume chronotype differences reported earlier in the literature using a greater sample size, as well as to explore the volumetric white matter variation linked to contrasting circadian phenotypes. Instead of comparing the chronotypes, we correlated the individual chronotype scores with their morphometric brain measures. The results revealed one cluster in the left fusiform and entorhinal gyri showing increased cortical thickness with increasing preference for eveningness, potentially providing an anatomical substrate for chronotype-sensitive affective processing. No significant results were found for grey and white matter volume. We failed to replicate cortical thickness and volumetric grey matter distinctions in the brain regions reported in the literature. Furthermore, we found no association between white matter volume and chronotype. Thus, while this study confirms that circadian preference is associated with specific structural substrates, it adds to the growing concerns that reliable and replicable neuroimaging research requires datasets much larger than those commonly used.

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Magnetic resonance imaging (MRI) volumetry in children with nonlesional epilepsy, does it help?

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00409-0 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Ehab Ali Abdelgawad ◽

Samir M. Mounir ◽

Marah M. Abdelhay ◽

Mohammed A. Ameen

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Grey Matter ◽

Normal Group ◽

Grey Matter Volume ◽

White Matter Volume ◽

Resonance Imaging ◽

Matter Volume ◽

The Right

Abstract Background Epilepsy is a chronic condition characterized by repeated spontaneous seizures. It affects up to 1% of the population worldwide. Children with magnetic resonance imaging (MRI) negative (or “nonlesional”) focal epilepsy constitute the most challenging pharmacoresistant group undergoing pre-neurosurgical evaluation. Volumetric magnetic resonance imaging (VMRI) is a non-invasive brain imaging technique done to measure the volume and structure of specific regions of the brain. It is useful for many things, but primarily for discovering atrophy (wasting away of body tissue) and measuring its progression. The aim of this study is to assess role of volumetric magnetic resonance imaging in evaluation of nonlesional childhood epilepsy in which no specific findings detected in conventional MRI. Results There were 20 children with normal MRI brain volumetry (33.3%) and 40 children (66.6%) with abnormal MRI brain volumetry. Grey matter volume in the abnormal group was significantly higher (P value was 0.001*) than the normal group (mean ± S.D 934.04 ± 118.12 versus 788.57 ± 57.71 respectively). White matter volume in the abnormal group was significantly smaller (P value was < 0.0001*) than in the normal group (mean ± S.D 217.79 ± 65.22 versus 418.07 ± 103.76 respectively). Right hippocampus CA4-DG volume in the abnormal volume group was found to be significantly smaller (P value < 0.0001*) than that of the normal group volume (mean ± S.D 0.095 ± 0.04 versus 0.32 ± 0.36 respectively). Right hippocampus subiculum volume in the abnormal volume group were found to be significantly smaller (P value was < 0.0001*) than that of the normal group volume (mean ± S.D 0.42 ± 0.11 versus 0.84 ± 0.09 respectively). Thalamus volume in the abnormal group was significantly smaller (P value 0.048*) than in the normal group (mean ± S.D 10.235 ± 3.22 versus 11.82 ± 0.75 respectively). Right thalamus was significantly smaller (P value was 0.028*) than in the normal group (mean ± S.D 5.01 ± 1.62 versus 5.91 ± 0.39 respectively). The sensitivity of the right hippocampus subiculum volume and right hippocampus CA4-DG was 100%. The sensitivity of white matter volume and grey matter volume and thalamus was 85% and 75% and 55% respectively. The specificity of the right hippocampus subiculum volume and right hippocampus CA4-DG was 90% and 90% respectively. The specificity of the right hippocampus subiculum volume and right hippocampus CA4-DG and grey matter volume and white matter volume and total hippocampus and thalamus was 100%. The specificity of brain volume was 60%. The accuracy of the right hippocampus subiculum volume and right hippocampus CA4-DG was 100%. The specificity of white matter volume, grey matter volume, thalamus, total hippocampus, and brain volume was 97%, 87%, 65%, 61%, and 57% respectively. Conclusion Volumetric magnetic resonance imaging is a promising imaging technique that can provide assistance in evaluation of nonlesional pharmacoresistant childhood epilepsy.

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Late chronotype is linked to greater cortical thickness in the left fusiform and entorhinal gyri

10.21203/rs.3.rs-588446/v2 ◽

2021 ◽

Author(s):

Michal Rafal Zareba ◽

Magdalena Fafrowicz ◽

Tadeusz Marek ◽

Ewa Beldzik ◽

Halszka Oginska ◽

...

Keyword(s):

White Matter ◽

Cortical Thickness ◽

Grey Matter ◽

Brain Regions ◽

Affective Processing ◽

Grey Matter Volume ◽

Imaging Data ◽

White Matter Volume ◽

Matter Volume ◽

Anatomical Basis

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Cognitive impairment in paediatric multiple sclerosis patients is not related to cortical lesions

Multiple Sclerosis Journal ◽

10.1177/1352458514557303 ◽

2014 ◽

Vol 21 (7) ◽

pp. 956-959 ◽

Cited By ~ 12

Author(s):

Maria A Rocca ◽

Ermelinda De Meo ◽

Maria P Amato ◽

Massimiliano Copetti ◽

Lucia Moiola ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Grey Matter ◽

Cognitively Impaired ◽

Grey Matter Volume ◽

Cortical Lesions ◽

White Matter Volume ◽

White Matter Damage ◽

Matter Volume ◽

Multiple Sclerosis Patients

We investigated the contribution of cortical lesions to cognitive impairment in 41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion volumes did not differ between cognitively impaired and cognitively preserved MS patients. Cortical lesions number, cortical lesions volume and grey matter volume did not differ between cognitively impaired and cognitively preserved patients, whereas white matter volume was significantly lower in cognitively impaired versus cognitively preserved MS patients ( p=0.01). Contrary to adult MS, cortical lesions do not seem to contribute to cognitive impairment in paediatric MS patients, which is likely driven by white matter damage.

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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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Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability

Multiple Sclerosis Journal ◽

10.1177/1352458511404916 ◽

2011 ◽

Vol 17 (9) ◽

pp. 1098-1106 ◽

Cited By ~ 111

Author(s):

Stefan D Roosendaal ◽

Kerstin Bendfeldt ◽

Hugo Vrenken ◽

Chris H Polman ◽

Stefan Borgwardt ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Physical Disability ◽

Grey Matter ◽

Grey Matter Volume ◽

Lesion Volume ◽

White Matter Volume ◽

Matter Volume ◽

Secondary Progressive ◽

Relapsing Remitting

Background: Although grey matter damage in multiple sclerosis is currently recognized, determinants of grey matter volume and its relationship with disability are not yet clear. Objectives: The objectives of the study were to measure grey and white matter volumes across different disease phenotypes; identify MRI parameters associated with grey matter volume; and study grey and white matter volume as explanatory variables for clinical impairment. Methods: This is a cross-sectional study in which MRI data of 95 clinically isolated syndrome, 657 relapsing–remitting, 125 secondary-progressive and 50 primary-progressive multiple sclerosis patients from three centres were acquired. Grey and white matter volumes were determined, together with T2 and T1 lesion volumes. Physical disability was assessed with the Expanded Disability Status Scale, cognitive impairment with the Paced Auditory Serial Addition Task. Data were analysed using multiple regression. Results: Grey matter volume was lower in relapsing–remitting patients (mean [SD]: 0.80 [0.05] L) than in clinically isolated syndrome patients (0.82 [0.05] L), and even greater relative atrophy was found in secondary-progressive patients (0.77 [0.05] L). In contrast, white matter volume in secondary-progressive patients was comparable to that in relapsing–remitting patients. Grey matter volume was the strongest independent predictor of physical disability and cognitive impairment, and was associated with both T2 and T1 lesion volume. Conclusions: Our findings show that grey matter volume is lower in secondary-progressive than in relapsing–remitting disease. Grey matter volume explained physical and cognitive impairment better than white matter volume, and is itself associated with T2 and T1 lesion volume.

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