Total White Matter Volume Research Articles

Maternal polyunsaturated fatty acids during pregnancy and offspring brain development in childhood

Emerging evidence suggests an association of maternal PUFA concentrations during pregnancy with child cognitive and neuropsychiatric outcomes such as intelligence and autistic traits. However, little is known about prenatal maternal PUFAs in relation to child brain development, which may underlie these associations. We aimed to investigate the association of maternal PUFA status during pregnancy with child brain morphology, including volumetric and white matter microstructure measures. This study was embedded in a prospective population-based study. In total, 1553 mother-child dyads of Dutch origin were included. Maternal plasma glycerophospholipid PUFAs were assessed in midpregnancy. Child brain morphologic outcomes, including total gray and white matter volumes, as well as white matter microstructure quantified by global fractional anisotropy and mean diffusivity, were measured using MRI (including diffusion tensor imaging) at age 9-11 y. Maternal ω-3 (n-3) long-chain PUFA (LC-PUFA) concentrations during pregnancy had an inverted U-shaped relation with child total gray volume (linear term: β: 16.7; 95% CI: 2.0, 31.5; quadratic term: β: -1.1; 95% CI: -2.1, -0.07) and total white matter volume (linear term: β: 15.7; 95% CI: 3.6, 27.8; quadratic term: β: -1.0; 95% CI: -1.8, -0.16). Maternal gestational ω-6 LC-PUFA concentrations did not predict brain volumetric differences in children, albeit the linolenic acid concentration was inversely associated with child total white matter volume. Maternal PUFA status during pregnancy was not related to child white matter microstructure. Sufficient maternal ω-3 PUFAs during pregnancy may be related to more optimal child brain development in the long term. In particular, exposure to lower ω-3 PUFA concentrations in fetal life was associated with less brain volume in childhood. Maternal ω-6 LC-PUFAs were not related to child brain morphology.

The role of lateralisation and sex on insular cortex: 3D volumetric analysis

Background/aim The insula has attracted the attention of many neuroimaging studies because of its key role between brain structures. However, the number of studies investigating the effect of sex and laterality on insular volume is insufficient. The aim of this study was to investigate the differences in insular volume between sexes and hemispheres.Materials and methodsA total of 47 healthy participants [24 males (20.08 ± 1.44 years) and 23 females (19.57 ± 0.90 years)] underwent magnetic resonance imaging (MRI). Imaging was performed using the 3T MRI scanner. The insular volume was measured using the Individual Brain Atlases using Statistical Parametric Mapping (IBASPM); total intracranial, cerebral, grey and white matter volumes were measured using volBrain. Results The right insular volume was significantly higher than the left insular volume in the participants, and the left cerebral volume was significantly higher than the right cerebral volume (p < 0.05). The total brain, total cerebral, left and right insular, and cerebral volumes were significantly larger in males than in females (p < 0.001). Also, the ratios of the insular volume to total brain and cerebral volume were significantly higher in males than in females (p < 0.05). Conclusion This study shows that insular volume differs with laterality and sex. This outcome may be explained by the anatomical relationship between the insula and behavioural functions and emotional reactions and the fact that the right side of the brain is best at expressive and creative tasks.

High coffee consumption, brain volume and risk of dementia and stroke

ABSTRACT Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. Objectives We examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke. Methods We conducted prospective analyses of habitual coffee consumption on 398,646 UK Biobank participants (age 37–73 years), including 17,702 participants with MRI information. We examined the associations with brain volume using covariate adjusted linear regression, and with odds of dementia (4,333 incident cases) and stroke (6,181 incident cases) using logistic regression. Results There were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup −1.42, 95% CI −1.89, −0.94), grey matter (β −0.91, 95% CI −1.20, −0.62), white matter (β −0.51, 95% CI −0.83, −0.19) and hippocampal volumes (β −0.01, 95% CI −0.02, −0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β −0.01, 95% CI −0.07, 0.05). The association between coffee consumption and dementia was non-linear (P non-linearity = 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1–2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). Conclusion High coffee consumption was associated with smaller total brain volumes and increased odds of dementia.

Brain white matter extracellular free-water increases are related to reduced neurocognitive function in systemic lupus erythematosus.

Brain white matter (WM) microstructural changes evaluated by diffusion MRI are well documented in patients with SLE. Yet, the conventional diffusion tensor imaging technique fails to differentiate WM changes that originate from tissue alterations from those due to increased extracellular free water (FW) related to neuroinflammation, microvascular disruption, atrophy, or other extracellular processes. Here, we sought to delineate changes in WM tissue microstructure and extracellular FW volume and examine their relationships with neurocognitive function in SLE patients. Twenty SLE patients [16 females, aged 36.0 (10.6)] without clinically overt neuropsychiatric manifestation and 61 healthy controls (HCs) [29 females, aged 29.2 (9.4)] underwent diffusion MRI and computerized neuropsychological assessments cross-sectionally. The FW imaging method was applied to compare microstructural tissue changes and extracellular FW volume of the brain WM between SLE patients and HCs. Association between extracellular FW changes and neurocognitive performance was studied. SLE patients had higher WM extracellular FW compared with HCs (family-wise-error-corrected P < 0.05), while no group difference was found in FW-corrected tissue compartment and structural connectivity metrics. Extracellular FW increases in SLE patients were associated with poorer neurocognitive performance that probed sustained attention (P = 0.022) and higher cumulative glucocorticoid dose (P = 0.0041). Such findings remained robust after controlling for age, gender, intelligence quotient, and total WM volume. The association between WM extracellular FW increases and reduced neurocognitive performance suggest possible microvascular degradation and/or neuroinflammation in SLE patients with clinically inactive disease. The mechanistic impact of cumulative glucocorticoids on WM FW deserves further evaluation.

Chinese Classical Dancers Have Improved Spontaneous Activity in Visual Brain Areas

Abstract. Resting-state functional magnetic resonance imaging (fMRI) studies demonstrate that long-term exercise or dance training may cause changes in brain structure and function. However, the changes of neurofunction in the long-term practitioners of Chinese classical dance are still unclear. The purpose of the study is to explore the neurofunctional alterations associated with long-term Chinese classical dance training. Thirty female college students were selected, 15 students majoring in Chinese classical dance (average training years = 9.73 ± 1.75 years) and 15 education-matched non-dancer students with no previous experience of regular dance training. In this cross-sectional design, the resting-state fMRI data were acquired only once to observe the structural and functional changes of the brain. Compared with non-dancers, professional dancers had no significant difference in the total volume of whole brain, gray matter, white matter, and cerebrospinal fluid. While in professional dancers, we found increased amplitude of low-frequency fluctuation (ALFF) in the left superior occipital gyrus, right Cuneus, and left calcarine fissure and surrounding cortex (Calcarine); increased fractional ALFF and regional homogeneity in the right Calcarine, indicating the increase of spontaneous brain activity in these brain areas. Since these brain areas are related to visual cognitive function, the results suggest that long-term Chinese classical dance training is associated with increased spontaneous regional brain activity in the visual areas. This may be closely related to the specific characteristics of Chinese classical dance and long-term professional training.

Abstract MP25: Brain Atrophy And White Matter Injury In Relation To Cardiovascular Risk Factors And Race/ethnicity: The Multi-ethnic Study Of Atherosclerosis

Introduction: Cardiovascular risk factors are associated with cognitive decline and dementia. Brain magnetic resonance imaging (MRI) provides sensitive measurement of cerebral atrophy and small vessel disease, reflecting multiple pathologies leading to dementia. However, large brain MRI studies include primarily white participants. We investigated associations in the diverse Multi-Ethnic Study of Atherosclerosis (MESA). Hypothesis: Cardiovascular and sociodemographic risk factors are associated with brain morphology and white matter injury in a racially and ethnically diverse population. Methods: In MESA, brain MRI was performed in 2018-2019 with automated measurement of total brain volume, gray and white matter (GM, WM) volume, and measures of WM injury including WM lesion volume, WM fractional anisotropy, and WM apparent diffusion coefficient. In cross-sectional analyses, we assessed the association of race/ethnicity with MRI measures, with and without adjustment for cardiovascular risk factors, education, and socioeconomic status. In a multivariable model, we assessed the association of cardiovascular risk factors with brain MRI measures. All analyses of volumes, including WM lesion volume, were adjusted for total intracranial volume. Results: MRI data were complete in 1,051 participants; 40% were white, 15% Chinese-American, 25% African-American, and 20% Hispanic. Mean (standard deviation, SD) age was 73 (8) years and 53% of participants were women. Adjusted for age and sex, African-American participants had slightly greater total brain and WM volume than white participants. Adjusted for age and sex, African-American participants had on average more WM injury than whites as measured by higher WM lesion volume (46.7% higher, 95% CI: 19.9, 79.4%) and lower fractional anisotropy (-0.20 SD, 95% CI: -0.34, -0.05); these associations were attenuated after additional adjustment for cardiovascular risk factors and socioeconomic status (24.3% higher WM lesion volume, 95% CI: 0.0, 54.3; -0.06 SD fractional anisotropy, 95% CI: -0.22, 0.09). Conversely, all non-white race/ethnic groups had slightly less WM injury than white participants as estimated by apparent diffusion coefficient. Overall, greater age, diabetes, current smoking, high systolic blood pressure, and treated hypertension were strongly associated with more WM injury; in addition, age and diabetes were strongly associated with lower brain volumes. Conclusions: We found little evidence of differences in measures of brain atrophy and WM injury by race/ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. Findings of differences by race/ethnicity in apparent diffusion coefficient are intriguing and need further investigation. Consistent with previous studies, age, diabetes, current smoking and hypertension were strongly and consistently associated with WM injury.

Gait and balance impairments in patients with subcortical vascular cognitive impairment

BackgroundSubcortical vascular cognitive impairment (SVCI) is a subtype of vascular cognitive impairment associated with extensive cerebral small vessel diseases (CSVDs) imaging biomarkers. The objectives of this work were to study the existence and patterns of gait and balance impairments in patients with SVCI due to CSVDs.MethodsThe study was conducted on 28 newly diagnosed SVCI patients and 22 healthy control subjects (HCS) submitted to the advanced activity of daily living scale (AADLs), Berg balance test (BBT), Montreal Cognitive Assessment Scale (MoCA), computerized dynamic posturography (CDP), vision-based 3-D skeletal data gait analysis, and brain MRI volumetric assessment.ResultsSVCI patients showed a significant decrease in AADLs as well as total cerebral white matter volume, total cerebral cortical volume, and mean cortical thickness which were proportional to the degree of cognitive impairment as measured by the MoCA score. Regarding CDP analysis, patients with SVCI revealed prolongation of cancelation time and spectral power for mid- and high frequencies in dynamic positions. In respect to gait analysis, there were significant decreases in mean stride length and mean cadence as well as increases in mean step width and left to right step length difference in the SVCI group compared to HCS while doing a single task. These variables get highly significant during the dual-task performance with a p value < 0.001 for each one.ConclusionPatients with SVCI suffer from gait and balance impairments that are proportional to the severity of their cognitive decline and greatly impair their ADLs.

Different phenotypes of neuropsychiatric systemic lupus erythematosus are related to a distinct pattern of structural changes on brain MRI

ObjectivesThe underlying structural brain correlates of neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) remain unclear, thus hindering correct diagnosis.We compared brain tissue volumes between a clinically well-defined cohort of patients with NPSLE and SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE). Within the NPSLE patients, we also examined differences between patients with two distinct disease phenotypes: ischemic and inflammatory.MethodsIn this prospective (May 2007 to April 2015) cohort study, we included 38 NPSLE patients (26 inflammatory and 12 ischemic) and 117 non-NPSLE patients. All patients underwent a 3-T brain MRI scan that was used to automatically determine white matter, grey matter, white matter hyperintensities (WMH) and total brain volumes. Group differences in brain tissue volumes were studied with linear regression analyses corrected for age, gender, and total intracranial volume and expressed as B values and 95% confidence intervals.ResultsNPSLE patients showed higher WMH volume compared to non-NPSLE patients (p = 0.004). NPSLE inflammatory patients showed lower total brain (p = 0.014) and white matter volumes (p = 0.020), and higher WMH volume (p = 0.002) compared to non-NPSLE patients. Additionally, NPSLE inflammatory patients showed lower white matter (p = 0.020) and total brain volumes (p = 0.038) compared to NPSLE ischemic patients.ConclusionWe showed that different phenotypes of NPSLE were related to distinct patterns of underlying structural brain MRI changes. Especially the inflammatory phenotype of NPSLE was associated with the most pronounced brain volume changes, which might facilitate the diagnostic process in SLE patients with neuropsychiatric symptoms.Key Points• Neuropsychiatric systemic lupus erythematosus (NPSLE) patients showed a higher WMH volume compared to SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE).• NPSLE patients with inflammatory phenotype showed a lower total brain and white matter volume, and a higher volume of white matter hyperintensities, compared to non-NPSLE patients.• NPSLE patients with inflammatory phenotype showed lower white matter and total brain volumes compared to NPSLE patients with ischemic phenotype.

Aberrant Structural and Functional Developmental Trajectories in Children With Intellectual Disability

Intellectual disability (ID) is associated with aberrant structural and functional development of the brain, yet how the dynamical developmental changes of the structure and function of ID from childhood to around puberty remains unknown. To explore the abnormal developmental trajectories of structure and function, 40 children with ID aged 6–13 years and 30 sex-, age-, and educational level-matched healthy controls (HC) with age range from 6 to 13 were recruited. The automatic voxel-based morphometry (VBM) and resting-state functional connectivity (FC) analyses were adopted to delineate the structural and functional differences. Significantly decreased total gray matter volume (GMV) and white matter volume (WMV) in children with ID were found, and the developmental trajectories of GMV and WMV in children with ID showed an opposite direction as compared with HC. The voxel-wise VMB analysis further revealed significantly increased GMV in the dorsal medial prefrontal cortex (dmPFC), bilateral orbital part of the inferior frontal gyrus (orb_IFG.L, orb_IFG.R), right cuneus (cuneus.R), and bilateral middle frontal gyrus (MFG.L, MFG.R) in children with ID. The following seed-based whole-brain functional connectivity analyses of the brain areas with changed GMV found decreased FCs between the cuneus.R and left intraparietal sulcus (IPS.L) and between the MFG.R and anterior cingulate cortex (ACC) in children with ID. Moreover, negative correlations between GMV values in the dmPFC, orb_IFG.L, cuneus.R, and intelligence quotient (IQ) scores and positive correlations between the FCs of the cuneus.R with IPS.L and MFG.R with ACC and IQ scores were found in children with ID and HC. Our findings provide evidence for the abnormal structural and functional development in children with ID and highlight the important role of frontoparietal network in the typical development. The abnormal development of GMV and functional couplings found in this study may be the neuropathological bases of children with ID.

Design-based stereological study of the guinea-pig (Cavia porcellus) cerebellum.

Guinea pigs have proved useful as experimental animal models in studying cerebellar anatomical and structural alterations in human neurological disease; however, they are also currently acquiring increasing veterinary interest as companion animals. The morphometric features of the normal cerebellum in guinea pigs have not been previously investigated using stereology. The objective of the present work was to establish normal volumetric and quantitative stereological parameters for cerebellar tissues in guinea pigs, by means of unbiased design-based stereology. Cerebellar total volume, gray and white matter volume fractions, molecular and granular layers volume fractions, cerebellar surface area, Purkinje cellular and nuclear volumes, and the Purkinje cell total count were stereologically estimated. For this purpose, cerebellar hemispheres from six adult male guinea pigs were employed. Isotropic, uniform random sections were obtained by applying the orientator method, and subsequently processed for light microscopy. The cerebellar total volume, the white and grey matter volume fractions, and the molecular and granular layer volumes were estimated using the Cavalieri's principle and the point counting system. The cerebellar surface area was estimated through the use of test lines; Purkinje cellular and nuclear volumes were analysed using the nucleator technique, whereas the Purkinje cell total count was obtained by means of the optical disector technique. The mean±standard deviation total volume of a guinea-pig cerebellar hemisphere was 0.11±0.01cm3 . The mean volumetric proportions occupied by the gray and white matters were, respectively, 78.0±2.6% and 22.0±2.6%, whereas their mean absolute volumes were found to be 0.21±0.02cm3 and 0.059±0.006cm3 . The volumes of the molecular and granular layers were estimated at 112.4±20.6mm3 and 104.4±7.3mm3 , whereas their mean thicknesses were calculated to be 0.184±0.020mm and 0.17±0.02mm. The molecular and granular layers accounted for 40.7±3.9% and 37.4±1.8% of total cerebellar volume respectively. The surface area of the cerebellum measured 611.4±96.8mm2 . Purkinje cells with a cellular volume of 3210.1µm3 and with a nuclear volume of 470.9µm3 had a higher incidence of occurrence. The mean total number of Purkinje cells for a cerebellar hemisphere was calculated to be 253,090±34,754. The morphometric data emerging from the present study provide a set of reference data which might prove valuable as basic anatomical contribution for practical applications in veterinary neurology.

Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study.

Cross-sectional studies, including one from our NOVICE cohort [Neurological Visual and Cognitive performance in children with treated perinatally acquired HIV (PHIV) compared with matched HIV-negative controls], have revealed that the brains of children with PHIV have lower white matter and grey matter volumes, more white matter hyperintensities (WMH) and poorer white matter integrity. This longitudinal study investigates whether these differences change over time. We approached all NOVICE participants to repeat MRI after 4.6 ± 0.3 years, measuring total white matter and grey matter volume, WMH volume and white matter integrity, obtained by T1-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI), respectively. We compared rates of change between groups using multivariable linear mixed effects models, adjusted for sex and age at enrolment. We investigated determinants of developmental deviation, and explored associations with cognitive development. Twenty out of 31 (65%) PHIV-positive, and 20 out of 37 (54%) HIV-negative participants underwent follow-up MRI. Groups did not significantly differ in terms of age and sex. Over time, we found no statistically different changes between groups for white matter and WMH volumes, and for white matter integrity (P > 0.1). Total grey matter volume decreased significantly less in PHIV [group∗time 10 ml, 95% confidence interval -1 to 20, P = 0.078], but this difference in rate of change lost statistical significance after additional adjustment for height (group∗time 9 ml, 95% confidence interval -2 to 20, P = 0.112). We found no HIV-associated determinants for potential reduced grey matter pruning, nor associations with cognitive development. While using long-term antiretroviral treatment, structural brain development of adolescents growing up with perinatally acquired HIV appears largely normal.

Apolipoprotein E ε4 Allele-Based Differences in Brain Volumes Are Largely Uniform Across Late Middle Aged and Older Hispanic/Latino- and Non-Hispanic/Latino Whites Without Dementia.

Hispanics/Latinos are at an equal or a greater risk for Alzheimer's disease (AD), yet risk factors remain more poorly characterized as compared to non-Hispanic/Latino Whites. Among non-Hispanic/Latino White cohorts, the apolipoprotein E (APOE) ε4 allele is one of the strongest risk factors for AD with subtle declines in episodic memory and brain volumes detectable in the preclinical stages. We examined whether the APOE ε4 status had a differential impact on cognition and brain volumes among cognitively healthy and mild cognitively impaired Hispanics/Latinos (n = 86; ε4 n = 23) compared to a well-matched group of non-Hispanic/Latino Whites (n = 92; ε4 n = 29). Neither the APOE ε4 status nor the interaction between the ε4 status and ethnicity was associated with cognitive performance. The APOE ε4 status was associated with white matter and not with gray matter volumes. APOE ε4 carriers had a significantly smaller total brain white matter volumes, as well as smaller right middle temporal and left superior temporal volumes. The Hispanics/Latinos had significantly smaller left middle frontal gray matter volumes, yet marginally larger overall white matter volumes, than the non-Hispanic/Latino Whites. Exploratory analysis within the Hispanic/Latino sample found that those people whose primary language was Spanish had larger total brain white matter volumes compared primarily to the English speakers. Importantly, primary language differences only held for Hispanic/Latino ε4 carriers and did not differentiate Hispanic/Latino non-carriers, underscoring the need for further investigation into the impacts of language and acculturation on cognitive aging among the fastest growing ethnic minority group in the United States.

Association between Toxoplasma gondii seropositivity and serointensity and brain volume in adults: A cross-sectional study.

The intracellular protozoal parasite Toxoplasma gondii has been associated with worsened cognitive function in animal models and in humans. Despite these associations, the mechanisms by which Toxoplasma gondii might affect cognitive function remain unknown, although Toxoplasma gondii does produce physiologically active intraneuronal cysts and appears to affect dopamine synthesis. Using data from the UK Biobank, we sought to determine whether Toxoplasma gondii is associated with decreased prefrontal, hippocampal, and thalamic gray-matter volumes and with decreased total gray-matter and total white-matter volumes in an adult community-based sample. The results from adjusted multivariable regression modelling showed no associations between Toxoplasma gondii and prefrontal, hippocampal, and thalamic brain gray-matter volumes. In contrast, natural-log transformed antibody levels against the Toxoplasma gondii p22 (b = -3960, 95-percent confidence interval, -6536 to -1383, p < .01) and sag1 (b = -4863, 95-percent confidence interval, -8301 to -1425, p < .01) antigens were associated with smaller total gray-matter volume, as was the mean of natural-log transformed p22 and sag1 titers (b = -6141, 95-percent confidence interval, -9886 to -2397, p < .01). There were no associations between any of the measures of Toxoplasma gondii and total white-matter volume. These findings suggest that Toxoplasma gondii might be associated with decreased total gray-matter in middle-aged and older middle-aged adults in a community-based sample from the United Kingdom.

Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort.

Background and purposeCurrent methods to diagnose neurodegenerative diseases are costly and invasive. Retinal neuroanatomy may be a biomarker for more neurodegenerative processes and can be quantified in vivo using optical coherence tomography (OCT), which is inexpensive and noninvasive. We examined the association of neuroretinal morphology with brain MRI image‐derived phenotypes (IDPs) in a large cohort of healthy older people.MethodsUK Biobank participants aged 40 to 69 years old underwent comprehensive examinations including ophthalmic and brain imaging assessments. Macular retinal nerve fibre layer (mRNFL), macular ganglion cell‐inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and total macular thicknesses were obtained from OCT. Magnetic resonance imaging (MRI) IDPs assessed included total brain, grey matter, white matter and hippocampal volume. Multivariable linear regression models were used to evaluate associations between retinal layers thickness and brain MRI IDPs, adjusting for demographic factors and vascular risk factors.ResultsA total of 2131 participants (mean age 55 years; 51% women) with both gradable OCT images and brain imaging assessments were included. In multivariable regression analysis, thinner mGCIPL, mGCC and total macular thickness were all significantly associated with smaller total brain (p < 0.001), grey matter and white matter volume (p < 0.01), and grey matter volume in the occipital pole (p < 0.05). Thinner mGCC and total macular thicknesses were associated with smaller hippocampal volume (p < 0.02). No association was found between mRNFL and the MRI IDPs.ConclusionsMarkers of retinal neurodegeneration are associated with smaller brain volumes. Our findings suggest that retinal structure may be a biomarker providing information about important brain structure in healthy older adults.

Brain-derived neurotrophic factor Val66Met variant on brain volumes in infants.

The brain-derived neurotrophic factor (BDNF) has many important roles in neurogenesis and neuronal health. BDNF is also involved in learning and memory. Individuals with BDNF-Val66Met variant (Met +) are at higher risk for neuropsychiatric disorders and have smaller hippocampi and amgydalae compared to those without this variant (Met-). Whether these smaller brain volumes are already present at birth is unknown and were evaluated. 66 newborn infants were genotyped for BDNF-rs6265 and had brain MRI scans. The T1-weighted images were automatically parcellated for hippocampus and amygdala, as well as the intracranial volume (ICV), total brain volume, total gray and white matter, using a multi-atlas label fusion method implemented in the MRICloud ( https://braingps.anatomyworks.org ). The segmented brain volumes were normalized to the ICV for group comparisons. The two infant groups were not different in their demographics and birth characteristics. However, compared to Met- infants, the Met + infants had smaller hippocampi (p = 0.013), smaller amygdalae (p = 0.041), and less steep age-related declines in total brain volume and % white matter volume. The smaller relative hippocampal and amygdala volumes in Met + infants suggest that the Met + genotype affected prenatal developmental processes. In addition, the slower age-dependent declines in the relative total brain and white matter volumes of the Met + group in this cross-sectional dataset suggest the BDNF-Val66Met variant might have an ongoing negative influence on the postnatal developmental processes.

Quantitative MRI phenotypes capture biological heterogeneity in multiple sclerosis patients

Magnetization transfer ratio (MTR) and brain volumetric imaging are (semi-)quantitative MRI markers capturing demyelination, axonal degeneration and/or inflammation. However, factors shaping variation in these traits are largely unknown. In this study, we collected a longitudinal cohort of 33 multiple sclerosis (MS) patients and extended it cross-sectionally to 213. We measured MTR in lesions, normal-appearing white matter (NAWM), normal-appearing grey matter (NAGM) and total brain, grey matter, white matter and lesion volume. We also calculated the polygenic MS risk score. Longitudinally, inter-patient differences at inclusion and intra-patient changes during follow-up together explained > 70% of variance in MRI, with inter-patient differences at inclusion being the predominant source of variance. Cross-sectionally, we observed a moderate correlation of MTR between NAGM and NAWM and, less pronounced, with lesions. Age and gender explained about 30% of variance in total brain and grey matter volume. However, they contributed less than 10% to variance in MTR measures. There were no significant associations between MRI traits and the genetic risk score. In conclusion, (semi-)quantitative MRI traits change with ongoing disease activity but this change is modest in comparison to pre-existing inter-patient differences. These traits reflect individual variation in biological processes, which appear different from those involved in genetic MS susceptibility.

Associations between left ventricular function, vascular function and measures of cerebral small vessel disease: a cross-sectional magnetic resonance imaging study of the UK Biobank.

Impaired cardiovascular function has been associated with cognitive deterioration; however, to what extent cardiovascular dysfunction plays a role in structural cerebral changes remains unclear. We studied whether vascular and left ventricular (LV) functions are associated with measures of cerebral small vessel disease (cSVD) in the middle-aged general population. In this cross-sectional analysis of the UK Biobank, 4366 participants (54% female, mean age 61 years) underwent magnetic resonance imaging to assess LV function (ejection fraction [EF] and cardiac index [CI]) and cSVD measures (total brain volume, grey and white matter volumes, hippocampal volume and white matter hyperintensities [WMH]). Augmentation index (AIx) was used as a measure of arterial stiffness. Linear and non-linear associations were evaluated using cardiovascular function measures as determinants and cSVD measures as outcomes. EF was non-linearly associated with total brain volume and grey matter volume, with the largest brain volume for an EF between 55 and 60% (both p < 0.001). EF showed a negative linear association with WMH (- 0.23% [- 0.44; - 0.02], p = 0.03), yet no associations were found with white matter or hippocampal volume. CI showed a positive linear association with white matter (β 3194 mm3 [760; 5627], p = 0.01) and hippocampal volume (β 72.5 mm3 [23.0; 122.0], p = 0.004). No associations were found for CI with total brain volume, grey matter volume or WMH. No significant associations were found between AIx and cSVD measures. This study provides novel insights into the complex associations between the heart and the brain, which could potentially guide early interventions aimed at improving cardiovascular function and the prevention of cSVD. • Ejection fraction is non-linearly and cardiac index is linearly associated with MRI-derived measures of cerebral small vessel disease. • No associations were found for arterial stiffness with cSVD measures.

Effects of cerebral hypoperfusion on the cerebral white matter: a meta‑analysis.

Decreased cerebral blood flow (CBF) in aging is known to induce aging‑related cerebral deteriorations, such as neuronal degeneration, white matter (WM) alterations, and vascular deformations. However, the effects of cerebral hypoperfusion on WM alterations remain unclear. This study investigates the relationship between cerebral hypoperfusion and WM total volume changes by assessing the trends in CBF and WM changes by meta‑analysis. In this meta‑analysis, the differences in CBF were compared according to cerebral hypoperfusion type and the effect of cerebral hypoperfusion on the total volume of WM changes in rodents. Using subgroup analysis, 13 studies were evaluated for comparing CBF according to the type of cerebral hypoperfusion; 12 studies were evaluated for comparing the effects of cerebral hypoperfusion on the total volume of WM changes. Our meta‑analysis shows that the total volume of WM decreases with a decrease in CBF. However, the reduction in\r\nthe total volume of WM was greater in normal aging mice than in the cerebral hypoperfusion model mice. These results suggest that the reduction of cerebral WM volume during the aging process is affected by other factors in addition to a decrease in CBF.

The relationship between white matter microstructure and self-perceived cognitive decline

Subjective cognitive decline (SCD) is a perceived cognitive change prior to objective cognitive deficits, and although it is associated with Alzheimer’s disease (AD) pathology, it likely results from multiple underlying pathologies. We investigated the association of white matter microstructure to SCD as a sensitive and early marker of cognitive decline and quantified the contribution of white matter microstructure separate from amyloidosis. Vanderbilt Memory & Aging Project participants with diffusion MRI data and a 45-item measure of SCD were included [n = 236, 137 cognitively unimpaired (CU), 99 with mild cognitive impairment (MCI), 73 ± 7 years, 37% female]. A subset of participants (64 CU, 40 MCI) underwent a fasting lumbar puncture for quantification of cerebrospinal fluid (CSF) amyloid-β(CSF Aβ42), total tau (CSF t-tau), and phosphorylated tau (CSF p-tau). Diffusion MRI data was post-processed using the free-water (FW) elimination technique, which allowed quantification of extracellular (FW) and intracellular compartment (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) microstructure. Microstructural values were quantified within 11 cognitive-related white matter tracts, including medial temporal lobe, frontal transcallosal, and fronto-parietal tracts using a region of interest approach. General linear modeling related each tract to SCD scores adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile scores, APOE ε4 carrier status, diagnosis, Geriatric Depression Scale scores, hippocampal volume, and total white matter volume. Competitive models were analyzed to determine if white matter microstructural values have a unique role in SCD scores separate from CSF Aβ42. FW-corrected radial diffusivity (RDT) was related to SCD scores in 8 tracts: cingulum bundle, inferior longitudinal fasciculus, as well as inferior frontal gyrus (IFG) pars opercularis, IFG orbitalis, IFG pars triangularis, tapetum, medial frontal gyrus, and middle frontal gyrus transcallosal tracts. While CSF Aβ42 was related to SCD scores in our cohort (Radj2 = 39.03%; β = −0.231; p = 0.020), competitive models revealed that fornix and IFG pars triangularis transcallosal tract RDT contributed unique variance to SCD scores beyond CSF Aβ42 (Radj2 = 44.35% and Radj2 = 43.09%, respectively), with several other tract measures demonstrating nominal significance. All tracts which demonstrated nominal significance (in addition to covariates) were input into a backwards stepwise regression analysis. ILF RDT, fornix RDT, and UF FW were best associated with SCD scores (Radj2 = 46.69%; p = 6.37 × 10-12). Ultimately, we found that medial temporal lobe and frontal transcallosal tract microstructure is an important driver of SCD scores independent of early amyloid deposition. Our results highlight the potential importance of abnormal white matter diffusivity as an early contributor to cognitive decline. These results also highlight the value of incorporating multiple biomarkers to help disentangle the mechanistic heterogeneity of SCD as an early stage of cognitive decline.

Cingulate white matter volume and associated cognitive and behavioral impulsivity in Veterans with a history of suicide behavior

BackgroundSuicide is one of the leading causes of death for military personnel and Veterans. Neuroimaging studies have revealed abnormalities in white matter tracts and brain connectivity in suicide behavior (SB); however, reports of alterations in white matter volume and its association with related behaviors are limited. The current study examined the relationship between cingulate white matter volume (WMV), impulsivity, and SB in Veterans. MethodsFifty-two Veterans, ages 18 to 65, underwent magnetic resonance imaging on a 3T Siemens Verio scanner. Morphometric analysis of brain images was performed to evaluate differences in WMV in cingulate regions of interest. Participants completed the Columbia Suicide Severity Rating Scale to assess lifetime suicide behavior and the Barratt Impulsivity Scale (BIS) and the Continuous Performance Test (CPT) to assess impulsivity. ResultsTwenty-nine Veterans had a history of suicidal ideation (SI) and 23 had a history of suicide attempts (SA). Controlling for age, sex, handedness and total white matter volume, reduced WMV was observed in the left rostral anterior cingulate cortex (rACC) in Veterans with SA relative to Veterans with SI, p = .008. Additionally, non-planning on the BIS was negatively correlated with left rACC WMV for Veterans with a history of SA, p = .04. Other subregions of the ACC WMV were negatively correlated with planning and attention impulsivity (BIS) and omission and commission errors (CPT) for attempters. ConclusionsReduction in rACC WMV in Veterans with SA was negatively correlated with nonplanning measures. These findings are consistent with ACC involvement in inhibitory processes and build on evidence that SB is associated with neurobiological abnormalities and suggest that white matter changes may be related to actual attempts.