Decrease In Brain Volume Research Articles

Two-dimensional measurements with cut-off values are useful for assessing brain volume, physical disability, and processing speed in multiple sclerosis

BackgroundTwo-dimensional (2D) measures have been proposed as potential proxy measures for whole-brain volume in multiple sclerosis (MS); however, cut-off values that determine the degree of brain volume loss (BVL) have not been established. Since we had previously developed a system to categorize MS patients into clusters with significantly different degrees of BVL, we tried to identify cut-off values for 2D measurements that can discriminate MS patients on the basis of disease severity associated with brain atrophy. MethodsIn this cross-sectional analysis, ninety-one consecutive Japanese MS patients—clinically isolated syndrome (5%), relapsing-remitting MS (78%) and progressive MS (17%)—were categorized into two clusters (CL1 and CL2) with a significantly different degree of BVL using the method described in our previous study. MS patients were also evaluated for 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), bicaudate ratio (BCR), and corpus callosum index (CCI). Thereafter, we performed receiver operating characteristic analysis to determine the cut-off values of the 2D measurements for categorizing the MS patients into two clusters. ResultsWe identified optimal cut-off values for each 2D measure with high specificity and sensitivity. The cut-off values for LVW, BCR, and CCI divided the MS patients into two subgroups, in which whole-brain and grey matter volume, EDSS, and processing speed were significantly different. ConclusionLVW, BCR, and CCI with particular cut-off values are useful to discriminate MS patients with decreased brain volume, physical disability, and processing speed.

Contribution of white matter hyperintensities to ventricular enlargement in older adults

Lateral ventricles might increase due to generalized tissue loss related to brain atrophy. Alternatively, they may expand into areas of tissue loss related to white matter hyperintensities (WMH).We assessed longitudinal associations between lateral ventricle and WMH volumes, accounting for total brain volume, blood pressure, history of stroke, cardiovascular disease, diabetes and smoking at ages 73, 76 and 79, in participants from the Lothian Birth Cohort 1936, including MRI data from all available time points.Lateral ventricle volume increased steadily with age, WMH volume change was more variable. WMH volume decreased in 20% and increased in remaining subjects. Over 6 years, lateral ventricle volume increased by 3% per year of age, 0.1% per mm Hg increase in blood pressure, 3.2% per 1% decrease of total brain volume, and 4.5% per 1% increase of WMH volume. Over time, lateral ventricle volumes were 19% smaller in women than men.Ventricular and WMH volume changes are modestly associated and independent of general brain atrophy, suggesting that their underlying processes do not fully overlap.

Interaction of amyloid beta oligomers and α3-GABAA Rs in locus coeruleus neuronal excitability and Alzheimer's pathology.

Amyloid β oligomers (AβO) are potent modulators of Alzheimer's pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AβO impact the spontaneous excitability of LC neurons. This parameter determines brain-wide noradrenaline (NA) release, and thus NA-mediated brain functions, including cognition, emotion and immune function, which are all compromised in Alzheimer's. Therefore, the aim of this research was to determine the expression profile of AβO in the LC of Alzheimer's patients and to probe their potential impact on the molecular and functional correlates of LC excitability, using a mouse model of increased Aβ production (APP-PSEN1). Immunohistochemistry and confocal microscopy were used for correlative AβO expression analyses in samples from Alzheimer's patients and APP-PSEN1. Patch clamp electrophysiology was used to assess the impact of AβO on LC neuronal excitability and neurotransmitter receptor function. LC AβO immunoreactivity was located intraneuronally and extracellularly in both Alzheimer's and APP-PSEN1 samples. APP-PSEN1 LC neuronal hyperexcitability accompanied this AβO expression profile, arising from a diminished inhibitory effect of GABA, due to impaired expression and function of the GABA-A receptor (GABAA R) α3 subunit. This altered LC α3-GABAA R expression profile overlapped with AβO expression in samples from both APP-PSEN1 mice and Alzheimer's patients. Aged α3-GABAA R knockout mice in turn exhibited increased LC AβO expression, impaired recognition memory, neuroinflammation and decreased brain volume, suggesting a direct interaction between α3-GABAA R, AβO pathways and Alzheimer's-associated brain pathology. Finally, strychnine-sensitive glycine receptors remained resilient to Aβ-induced changes and their activation reversed LC hyperexcitability. The data suggest a close association between AβO and α3-GABAA Rs in the LC of Alzheimer's patients, and their potential to dysregulate LC activity, thereby contributing to the spectrum of pathology of the LC-NA system in this condition.

HIV‐associated neurocognitive disorder: An investigation using structural neuroimaging in a c‐ART treated Tanzanian cohort

AbstractBackgroundThere is a newly emergent ageing population of people living with HIV (PLWH) in Africa. However, there is little research into HIV‐associated neurocognitive disorder (HAND) in this population. Existing research suggests HAND is prevalent however the aetiology remains unclear. This study aims to determine whether HAND is truly prevalent and explore potential causes in PLWH on c‐ART using objective structural measures.MethodA systematic sample of PLWH aged ≥ 50 receiving combination antiretroviral treatment (cART) according to local guidelines were recruited from a HIV clinic in Kilimanjaro, Tanzania. Demographic data and comorbidities were self‐reported. HIV‐disease management data were obtained from detailed clinic data sheets. HIV viral load and CD4 count were measured. A detailed low‐literacy neurocognitive battery, informant history for functional impairment and neurological examination were conducted and HAND diagnosis made by consensus panel using AAN criteria. Cerebral atrophy (brain and ventricle volume) and WMH were measured using quantitative analysis of 1.5T MRI.ResultThis cohort (n=91, 100% on cART, 64.8% female) had well‐managed HIV (75.9% suppressed viral load, median CD4 507 cells/ul). However, 66.7% had gross atrophy on their MRI scan, and HAND had a prevalence of 63.7%. The significant independent predictor (IP) of decreased brain volume was older age at HIV diagnosis (p=.001), and of increased ventricle volume was increased age (p<.0001), male gender (p<.0001) and increased frailty (p<.0001). The significant IPs of increased WMH volume were increased age (p<.0001) and smoking (p=.021). Only memory impairment independently predicted all structural measures.ConclusionThis is the first MRI study of older c‐ART treated PLWH in Africa. Despite c‐ART and good disease management, HAND was objectively prevalent and unrelated to measures of HIV disease severity. Cerebral atrophy and WMH were associated with factors of neurodegeneration. Cerebral atrophy was associated with male gender and older age at diagnosis. Association with older age at diagnosis may be 'legacy effect' of early CNS effect of the HIV virus rather than current management.

Rapidly progressive brain atrophy in septic ICU patients: a retrospective descriptive study using semiautomatic CT volumetry

BackgroundSepsis is often associated with multiple organ failure; however, changes in brain volume with sepsis are not well understood. We assessed brain atrophy in the acute phase of sepsis using brain computed tomography (CT) scans, and their findings’ relationship to risk factors and outcomes.MethodsPatients with sepsis admitted to an intensive care unit (ICU) and who underwent at least two head CT scans during hospitalization were included (n = 48). The first brain CT scan was routinely performed on admission, and the second and further brain CT scans were obtained whenever prolonged disturbance of consciousness or abnormal neurological findings were observed. Brain volume was estimated using an automatic segmentation method and any changes in brain volume between the two scans were recorded. Patients with a brain volume change < 0% from the first CT scan to the second CT scan were defined as the “brain atrophy group (n = 42)”, and those with ≥ 0% were defined as the “no brain atrophy group (n = 6).” Use and duration of mechanical ventilation, length of ICU stay, length of hospital stay, and mortality were compared between the groups.ResultsAnalysis of all 42 cases in the brain atrophy group showed a significant decrease in brain volume (first CT scan: 1.041 ± 0.123 L vs. second CT scan: 1.002 ± 0.121 L, t (41) = 9.436, p < 0.001). The mean percentage change in brain volume between CT scans in the brain atrophy group was –3.7% over a median of 31 days, which is equivalent to a brain volume of 38.5 cm3. The proportion of cases on mechanical ventilation (95.2% vs. 66.7%; p = 0.02) and median time on mechanical ventilation (28 [IQR 15–57] days vs. 15 [IQR 0–25] days, p = 0.04) were significantly higher in the brain atrophy group than in the no brain atrophy group.ConclusionsMany ICU patients with severe sepsis who developed prolonged mental status changes and neurological sequelae showed signs of brain atrophy. Patients with rapidly progressive brain atrophy were more likely to have required mechanical ventilation.

Differences in Diffusion Tensor Imaging White Matter Integrity Related to Verbal Fluency Between Young and Old Adults.

Throughout adulthood, the brain undergoes an array of structural and functional changes during the typical aging process. These changes involve decreased brain volume, reduced synaptic density, and alterations in white matter (WM). Although there have been some previous neuroimaging studies that have measured the ability of adult language production and its correlations to brain function, structural gray matter volume, and functional differences between young and old adults, the structural role of WM in adult language production in individuals across the life span remains to be thoroughly elucidated. This study selected 38 young adults and 35 old adults for diffusion tensor imaging (DTI) and performed the Controlled Oral Word Association Test to assess verbal fluency (VF). Tract-Based Spatial Statistics were employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and local diffusion homogeneity (LDH) in 12 WM regions of interest associated with language production. To investigate group differences on each DTI metric, an analysis of covariance (ANCOVA) controlling for sex and education level was performed, and the statistical threshold was considered at p < 0.00083 (0.05/60 labels) after Bonferroni correction for multiple comparisons. Significant differences in DTI metrics identified in the ANCOVA were used to perform correlation analyses with VF scores. Compared to the old adults, the young adults had significantly (1) increased FA values on the bilateral anterior corona radiata (ACR); (2) decreased MD values on the right ACR, but increased MD on the left uncinate fasciculus (UF); and (3) decreased RD on the bilateral ACR. There were no significant differences between the groups for AD or LDH. Moreover, the old adults had only a significant correlation between the VF score and the MD on the left UF. There were no significant correlations between VF score and DTI metrics in the young adults. This study adds to the growing body of research that WM areas involved in language production are sensitive to aging.

DEMENTIA IN ONCOLOGICAL PATIENTS

Oncological diseases are one of the main causes of morbidity and mortality in the world. The problem is quite topical since the number of patients with cancer is a sensitive theme. At present, there are about 20 million people having the disease all over the world. Hence, the number of elderly people with the disease is about 10-15%. The purpose of our research was to study dementia in cancer patients. The study was conducted in the Batumi high-tech hospital (Batumi Oncological Center). 100 patients aged 25 to 75 participated in this study. Among them, the 60 patients were female and 40 were male. At the same time, only 45 patients were operated on. Of these, 16 patients were operated after chemotherapy, 4 patients after radiotherapy and 35 patients during combination therapy. 6 patients with lung cancer, 22 patients with breast cancer, 6 patients with skin cancer, 7 patients with gastric cancer, 4 patients with bladder cancer, 15 patients with ovarian cancer, 25 patients with uterine cancer were examined. In the study, three of them had the family history of dementia. We studied the patient's medical history, physiological data, assessed their mental and cognitive functions to determine the diagnosis of dementia. We studied the patient's medical history, physiological data, assessed their mental and cognitive functions, mini-mental state examination, and carried out a survey of family members as the patients often had difficulty precisely describing the symptoms to determine the diagnosis of dementia. Out of 100 patients, 20% of them had mild dementia, 44% - moderate dementia and 35 % - severe dementia. Among the patients examined, dementia was not observed in 1%. Computed tomography of the brain was performed on the examined patients. Cerebral atrophy, a decrease in brain mass and volume in 34%, cortical atrophy in 60% of patients and the expansion of the ventricle system of the brain in 35% were revealed in the pathomorphological picture. The atrophic process is strongly expressed in the pariental (17%), frontal and temporal lobes (76%). Therefore, dementia is quite common in cancer patients with severe and moderate depression, predominant in 79%. Dementia was not observed only in one case, which is very important. The researchers point out reversible dementia after chemotherapy, which is reversible after a while. Community involvement has great importance for the treatment and psychological adaptation to the new reality of cancer patients. It is necessary to develop educational programs aimed at providing assistance from the moment of diagnosis to the end of treatment.

#3029 HIV-associated neurocognitive disorder: an investigation using structural neuroimaging in a c-ART treated tanzanian cohort

BackgroundThere is a newly emergent ageing population of people living with HIV (PLWH) in Africa. However, there is little research into HIV-associated neurocognitive disorder (HAND) in this population. Existing research suggests HAND is prevalent however the aetiology remains unclear. This study aims to determine whether HAND is truly prevalent and explore potential causes in PLWH on c-ART using objective structural measures.AimsExplore whether substantial atrophy and/or white matter hyperintensities (WMH) is present on the clinical magnetic resonance imaging (MRI) reports and quantitative analysis of people with optimally managed HIV in Northern Tanzania.Explore the aetiology of HAND by assessing whether cerebral atrophy and/or WMH is associated with demographic risk factors, HIV–related factors and/or comorbidities.Investigate whether structural damage is related to objectively measured cognitive impairment, and whether this is a subcortical or cortical impairment.Explore which neurocognitive test is the best predictor of structural damage and therefore most valid diagnostic test for HAND.MethodsA systematic sample of PLWH aged ≥ 50 were recruited from a HIV clinic in Kilimanjaro, Tanzania. Demographic data and comorbidities were self-reported. HIV-disease management data were obtained. Viral load and CD4 count were measured. A neurocognitive battery and informant history of functional impairment identified HAND. Cerebral atrophy (brain and ventricle volume) and WMH were measured using quantitative analysis of 1.5T MRI.Preliminary resultsThis cohort (n=91) had well-managed HIV (75.9% suppressed viral load, median CD4 507 cells/ul). The significant independent predictor (IP) of decreased brain volume was older age at HIV diagnosis (p=.001), and of increased ventricle volume was increased age (p&lt;.0001), male gender (p&lt;.0001) and increased frailty (p&lt;.0001). The significant IPs of increased WMH volume were increased age (p&lt;.0001) and smoking (p=.021). Only memory impairment independently predicted all structural measures.ConclusionsThis is the first MRI study of older c-ART treated PLWH in Africa. Despite c-ART and good disease management, HAND was objectively prevalent and unrelated to measures of HIV. Cerebral atrophy and WMH were associated with factors of neurodegeneration. Cerebral atrophy was associated with male gender and age at diagnosis (legacy effect).

3D CNN based Alzheimer’s diseases classification using segmented Grey matter extracted from whole-brain MRI

A recent study from MRI has revealed that there is a minor increase in cerebral-spinal fluid (CSF) content in brain ventricles and sulci, along with a substantial decrease in grey matter (GM) content and brain volume among Alzheimer's disease (AD) patients. It has been discovered that the grey matter volume shrinkage may indicate the possible case of dementia and related diseases like AD. Clinicians and radiologists use imaging techniques like Magnetic Resonance Imaging (MRI), Computed Tomography (CT) scan, and Positron Emission Tomography (PET) to diagnose and visualize the tissue contents of the brain. Using the whole brain MRI as the feature is an on-going approach among machine learning researchers, however, we are interested only in grey matter content. First, we segment the MRI using the SPM (Statistical parameter mapping) tool and then apply the smoothing technique to get a 3D image of grey matter (later called as grey version) from each MRI. This image file is then fed into 3D convolutional neural network (CNN) with necessary pre-processing so that it can train the network, to produce a classifying model. Once trained, an untested MRI (i.e. its grey version) can be passed through the CNN to determine whether it is a healthy control (HC), or Mild Cognitive Impairment (MCI) due to AD (mAD) or AD dementia (ADD). Our validation and testing accuracy are reported here and compared with normal MRI and its grey version.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate β^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. β^T was compared to the corresponding regression coefficient estimate β^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis β T = β R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

Sensory and memory processing in old female and male Wistar rat brain, and its relationship with the cortical and hippocampal redox state.

The brain is one of the most sensitive organs damaged during aging due to its susceptibility to the aging-related oxidative stress. Hence, in this study, the sensory nerve pathway integrity and the memory were evaluated and related to the redox state, the antioxidant enzymes function, and the protein oxidative damage in the brain cortex (Cx) and the hippocampus (Hc) of young (4-month-old) and old (24-month-old) male and female Wistar rats. Evoked potentials (EP) were performed for the auditory, visual, and somatosensory pathways. In both males and females, the old rat groups' latencies were larger in almost all waves when compared to the young same-sex animals. The novel object test was performed to evaluate memory. The superoxide dismutase and catalase antioxidant activity, as well as the protein oxidative damage, and the redox state were evaluated. Magnetic resonance (MR) imaging was used to obtain the diffusion tensor imaging, and the brain volume, while MR spectroscopy was used to obtain the brain metabolite concentrations (glutamine, glutamate, Myo-inositol, N-acetyl-aspartate, creatine) in the Cx and the Hc of young and old females. Our data suggest that, although there are limited variations regarding memory and nerve conduction velocity by sex, the differences concerning the redox status might be important to explain the dissimilar reactions during brain aging between males and females. Moreover, the increment in Myo-inositol levels in the Hc of old rats and the brain volume decrease suggest that redox state alterations might be correlated to neuroinflammation during brain aging.

Brain Volume Analysis with T1-MRI Data in Autism Spectrum Disorder

Purpose: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by impaired social interactions. Early detection can prevent the progression of the disease. So far, much research has been done to better diagnose autism. Investigation of brain structure using Magnetic Resonance Imaging (MRI) provides valuable information on the evolution of the brain of patients with autism. Materials and Methods: In this study, we equally selected T1-MRI data from 20 control subjects and 20 patients, aged under 13 years (male and female, right hand and left hand). MRI research has shown that the brain of autistic children has grown locally and globally. In this paper, for the brain volumetric evaluation of autistic patients, the MRI data was segmented and then analyzed with a statistical method, which has been investigated more generally, in both the cortical and subcortical areas. Results: We extracted 110 cortical and subcortical brain areas. The statistical analysis show which areas are important in discriminant between ASD and healthy control groups. According to the results of MRI, an increase in overall growth is seen in the subcortical areas of the brain (amygdala and hippocampus) as well as the cerebellum, but in adults with autism, a decrease in brain volume is seen. Conclusion: In this study, we analyze the T1-MRI data of ASD subjects for early detection of Autism disorder. Our results were shown in the 6 brain areas that have P-values under 0.005. These areas are important in the early detestation and treatment of ASD.

Association of Intensive vs Standard Blood Pressure Control With Magnetic Resonance Imaging Biomarkers of Alzheimer Disease

Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control. To evaluate the association of intensive blood pressure control on AD-related brain biomarkers. This is a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT MIND), a multicenter randomized clinical trial that compared the efficacy of 2 different blood pressure-lowering strategies. Potential participants (n = 1267) 50 years or older with hypertension and without a history of diabetes or stroke were approached for a brain magnetic resonance imaging (MRI) study. Of these, 205 participants were deemed ineligible and 269 did not agree to participate; 673 and 454 participants completed brain MRI at baseline and at 4-year follow-up, respectively; the final follow-up date was July 1, 2016. Analysis began September 2019 and ended November 2020. Participants were randomized to either a systolic blood pressure goal of less than 120 mm Hg (intensive treatment: n = 356) or less than 140 mm Hg (standard treatment: n = 317). Changes in hippocampal volume, measures of AD regional atrophy, posterior cingulate cerebral blood flow, and mean fractional anisotropy in the cingulum bundle. Among 673 recruited patients who had baseline MRI (mean [SD] age, 67.3 [8.2] years; 271 women [40.3%]), 454 completed the follow-up MRI at a median (interquartile range) of 3.98 (3.7-4.1) years after randomization. In the intensive treatment group, mean hippocampal volume decreased from 7.45 cm3 to 7.39 cm3 (difference, -0.06 cm3; 95% CI, -0.08 to -0.04) vs a decrease from 7.48 cm3 to 7.46 cm3 (difference, -0.02 cm3; 95% CI, -0.05 to -0.003) in the standard treatment group (between-group difference in change, -0.033 cm3; 95% CI, -0.062 to -0.003; P = .03). There were no significant treatment group differences for measures of AD regional atrophy, cerebral blood flow, or mean fractional anisotropy. Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. However, intensive treatment was not associated with changes in any of the other MRI biomarkers of AD compared with standard treatment. ClinicalTrials.gov Identifier: NCT01206062.

Abstract P370: Early Brain Volume Change After Stroke: Subgroup Analysis From the Axis-2 Trial

Objective: The timing of brain atrophy after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. Methods: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size and white matter changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) were rated visually and the presence of lacunes was assessed. Results: We enrolled 173 patients with a mean age of 67±11 years, 44 % were female. There was a median 6 mL decrease in volume (25th percentile -1mL-75th percentile 21mL) over time, equivalent to a median 0.5% (IQR-0.07% - 1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 mL 95% CI 2 mL-8 mL). Baseline DWI lesion volume was not associated with greater volume loss (per 10 mL of lesion volume, change by 0 mL (95% CI -0.1 mL-0.1mL). Increasing Fazekas scores of deep white matter hyperintensity were associated with greater tissue loss (5 mL, 95% CI 1 mL-10 mL). Brain volume change was associated with ordinal change on the modified Rankin scale at 90 days (per 10 ml, OR 1.085, 95% CI 1.031-1.141) but the association was not present when adjusting for age, baseline diffusion lesion volume and NIHSS score (OR 1.044, 95% CI 0.990-1.010).Interpretation-Global brain volume loss occurs over 1 month after stroke and is associated with age and deep white matter disease. We did not find evidence that more severe strokes lead to increased early tissue loss.

Effects of carnosine and hypothermia combination therapy on hypoxic-ischemic brain injury in neonatal rats.

BackgroundCarnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown.PurposeHere we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats.MethodsPostnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27°C for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments.ResultsVehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only.ConclusionCarnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.

Experimental cerebral palsy causes microstructural brain damage in areas associated to motor deficits but no spatial memory impairments in the developing rat

IntroductionCerebral palsy (CP) is the major cause of motor and cognitive impairments during childhood. CP can result from direct or indirect structural injury to the developing brain. In this study, we aimed to describe brain damage and behavioural alterations during early adult life in a CP model using the combination of maternal inflammation, perinatal anoxia and postnatal sensorimotor restriction. MethodsPregnant Wistar rats were injected intraperitoneally with 200 µg/kg LPS at embryonic days E18 and E19. Between 3 and 6 h after birth (postnatal day 0 - PND0), pups of both sexes were exposed to anoxia for 20 min. From postnatal day 2 to 21, hindlimbs of animals were immobilized for 16 h daily during their active phase. From PND40, locomotor and cognitive tests were performed using Rota-Rod, Ladder Walking and Morris water Maze. Ex-vivo MRI Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) were used to assess macro and microstructural damage and brain volume alterations induced by the model. Myelination and expression of neuronal, astroglial and microglial markers, as well as apoptotic cell death were evaluated by immunofluorescence. ResultsCP animals showed decreased body weight, deficits in gross (rota-rod) and fine (ladder walking) motor tasks compared to Controls. No cognitive impairments were observed. Ex-vivo MRI showed decreased brain volumes and impaired microstructure in the cingulate gyrus and sensory cortex in CP brains. Histological analysis showed increased cell death, astrocytic reactivity and decreased thickness of the corpus callosum and altered myelination in CP animals. Hindlimb primary motor cortex analysis showed increased apoptosis in CP animals. Despite the increase in NeuN and GFAP, no differences between groups were observed as well as no co-localization with the apoptotic marker. However, an increase in Iba-1+ microglia with co-localization to cleaved caspase 3 was observed. ConclusionOur results suggest that experimental CP induces long-term brain microstructural alterations in myelinated structures, cell death in the hindlimb primary motor cortex and locomotor impairments. Such new evidence of brain damage could help to better understand CP pathophysiological mechanisms and guide further research for neuroprotective and neurorehabilitative strategies for CP patients.

Infants with congenital heart defects have reduced brain volumes

Children with congenital heart defects (CHDs) have increased risk of cognitive disabilities for reasons not fully understood. Previous studies have indicated signs of disrupted fetal brain growth from mid-gestation measured with ultrasound and magnetic resonance imaging (MRI) and infants with CHDs have decreased brain volumes at birth. We measured the total and regional brain volumes of infants with and without CHDs using MRI to investigate, if certain areas of the brain are at particular risk of disrupted growth. MRI brain volumetry analyses were performed on 20 infants; 10 with- (postmenstrual age 39–54 weeks, mean 44 weeks + 5 days) and 10 without CHDs (postmenstrual age 39–52 weeks, mean 43 weeks + 5 days). In six infants with- and eight infants without CHDs grey and white matter were also differentiated. Infants with CHDs had smaller brains (48 ml smaller; 95% CI, 6.1–90; p = 0.03), cerebrums (37.8 ml smaller; 95% CI, 0.8–74.8; p = 0.04), and cerebral grey matter (25.8 ml smaller; 95% CI, 3.5–48; p = 0.03) than infants without CHD. Brain volume differences observed within weeks after birth in children with CHDs confirm that the brain impact, which increase the risk of cognitive disabilities, may begin during pregnancy.

Social Health Is Associated With Structural Brain Changes in Older Adults: The Rotterdam Study

BackgroundSocial health markers have been linked to the development of dementia. We hypothesize that social health affects brain structure and consequently influences cognitive function. We aim to elucidate the cross-sectional and longitudinal associations between social health markers and structural brain changes in older adults in the general population. MethodsSocial health markers (loneliness, perceived social support, marital status) were assessed in the Rotterdam Study from 2002 to 2008. Magnetic resonance imaging of the brain was performed repeatedly between 2005 and 2015 for 3737 participants to obtain brain volumetrics, cerebral small vessel disease markers, and white matter microstructural integrity as measures of brain structure. Cross-sectional associations between social health and brain structure were studied using multivariable linear and logistic regression models. Longitudinal associations between baseline social health and changes in brain structure were examined using linear mixed models and generalized estimating equations. ResultsLoneliness was associated with smaller white matter volume at baseline (mean difference = −4.63 mL, 95% CI = −8.46 to −0.81). Better perceived social support was associated with larger total brain volume and gray matter volume at baseline and a less steep decrease in total brain volume over time. Better social support was associated with higher global fractional anisotropy and lower mean diffusivity at baseline. Participants who had never been married had a smaller total brain volume (mean difference = −8.27 mL, 95% CI = −13.16 to −3.39) at baseline than married peers. ConclusionsSocial health is associated with brain structure. Better perceived social support at baseline was associated with better brain structure over time.

Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis.

To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests. Cross-sectional study. 1Florida Alzheimer's Disease Research Center baseline study. Two-hundred and twelve participants with Mini-Mental State Examination (MMSE) score above 16 and a broad array of cognitive diagnoses ranging from cognitively normal (CN) to dementia, of whom 58% were female, mean age of 72.1 (SD 7.9). Participants underwent extensive clinical and neuropsychological evaluations, MR and amyloid Positron Emission Tomography/Computer/Computer Tomography (PET/CT) imaging, and analyses of APOE ϵ4 genotype. Confirmatory path analyses were conducted in the structural equation modeling framework that estimated multiple equations simultaneously while controlling for important covariates such as sex, education, language of evaluation, and global cognitive impairment. Both amyloid positivity and decreased brain volumes in AD-prone regions were directly related to LASSI-L Cued B1 and Cued B2 intrusions (sensitive to PSI and frPSI effects) even after controlling for covariates. APOE ϵ4 status did not evidence direct effects on these LASSI-L cognitive markers, but rather exerted their effects on amyloid positivity, which in turn related to PSI and frPSI. Similarly, age did not have a direct relationship with LASSI-L scores, but exerted its effects indirectly through amyloid positivity and volumes of AD-prone brain regions. Our study provides insight into the relationships among age, APOE ϵ4, amyloid, and brain volumetric reductions as it relates to semantic intrusion errors. The investigation expands our understanding of the underpinnings of PSI and frPSI intrusions in a large cohort.

Cobalamin in the complex treatment and prevention of cognitive impairment

Cognitive impairment (CI) develops not only in structural damage to the central nervous system, but also in encephalopathies of dysmetabolic and deficiency etiology. Recently, special attention is focused on the appearance of CI due to the deficiency of cobalamin (vitamin B12) and folic acid (FA), the change in the level of homocysteine (HC). To detect vitamin B12 deficiency is possible by examining key biomarkers in serum based on a decrease in the levels of vitamin B12 and holotranscobalamin, and levels of methylmalonic acid (MMA) and HC. The article presents an analysis of studies conducted in Norway, Korea, India, and other countries to assess the risks of CI in the presence of reduced levels of vitamin B12 in the elderly, which demonstrated a decrease in brain volume in the elderly (according to MRI data) in combination with altered test parameters that assess cognitive functions. In many studies, female patients with reduced levels of vitamin B12 predominated among the studied patients. Also, some studies have demonstrated the effectiveness of complex CI therapy with the inclusion of vitamin B12 (both for oral and intravenous administration). Oral vitamin B12 therapy at a dose of 1000 μg has been shown to be adequate for the treatment of vitamin B12 deficiency. Also, the administration of vitamin B12 for prophylactic purposes is recommended for patients with subnormal or borderline concentrations of vitamin B12 in the blood serum.