Smaller Brain Volumes Research Articles

COMPARISON OF PLYOMETRICS AND AEROBIC EXERCISES ON THE MEMORY

ABSTRACT
 Background: Problems of a person's desire to exercise is still a major highlight in the realm of health, both in Indonesia and in the world. Lack of exercise affects brain work, which is a smaller brain volume in people who are not actively exercising, so doing plyometrics and aerobic exercises can be a solution to these problems because exercise can be easily done for health and increased cognitive abilities.
 Aim: To understand which exercises are more effective at improving one's short-term memory.
 Methods: This study is a quasi-experimental study with 54 subjects, all of whom are students of the Faculty of Medicine Diponegoro University, aged between 15-25 years. Subjects were divided into three groups, namely the plyometrics group, the aerobic group and the control group. Subjects were selected by purposive sampling method and participated in the measurement of short-term memory at the time before exercise and after exercise for 6 weeks. Statistical analysis in this study using paired t-test and independent t-test.
 Results: There was a significant difference in the short-term memory measurement results between the treatment and control groups, but a higher increase was found in the plyometrics group, with p value <0.001.
 Conclusion: Plyometrics and aerobic exercises improve short-term memory in students of the Faculty of Medicine Diponegoro University. A more significant improvement was found in the plyometrics group.
 Keywords: plyometrics exercise, aerobic exercise, short term memory.

Proteobacteria abundance during nursing predicts physical growth and brain volume at one year of age in young rhesus monkeys.

Over the last decade, multiple studies have highlighted the essential role of gut microbiota in normal infant development. However, the sensitive periods during which gut bacteria are established and become associated with physical growth and maturation of the brain are still poorly defined. This study tracked the assembly of the intestinal microbiota during the initial nursing period, and changes in community structure after transitioning to solid food in infant rhesus monkeys (Macaca mulatta). Anthropometric measures and rectal swabs were obtained at 2-month intervals across the first year of life and bacterial taxa identified by 16S rRNA gene sequencing. At 12months of age, total brain and cortical regions volumes were quantified through structural magnetic resonance imaging. The bacterial community structure was dynamic and characterized by discrete maturational phases, reflecting an early influence of breast milk and the later transition to solid foods. Commensal microbial taxa varied with diet similar to findings in other animals and human infants; however, monkeys differ in the relative abundances of Lactobacilli and Bifidobacteria, two taxa predominant in breastfed human infants. Higher abundances of taxa in the phylum Proteobacteria during nursing were predictive of slower growth trajectories and smaller brain volumes at one year of age. Our findings define discrete phases of microbial succession in infant monkeys and suggest there may be a critical period during nursing when endogenous differences in certain taxa can shift the community structure and influence the pace of physical growth and the maturational trajectory of the brain.

Abstract P121: Twenty-two-year Cognitive Decline Was Significantly Associated With Vascular And Neurodegenerative Brain Changes In The Aric Neurocognitive Study

Introduction: Studies have found that smaller brain volumes, cerebral infarcts, and white matter abnormalities are associated with dementia and mild cognitive impairment. However, these studies have been limited by short follow-up precluding a strong establishment of temporality. Therefore, it is unknown whether brain imaging findings are preceded by long-term changes in cognition. We sought to address this gap by examining brain imaging and two decades of cognitive changes in and a large, representative population-based cohort of older adults of black and white race. Hypothesis: We hypothesized that 22-year declines in global cognitive factor scores (GCFS) would be associated with a pattern of smaller total brain and temporal lobe meta region of interest (likely to be affected by Alzheimer’s disease) volumes, larger white matter hyperintensity volumes, and greater odds of ≥1 lacunar infarct and elevated brain β-amyloid deposition. Methods: ARIC participants with brain imaging data, complete cognitive factor score, and not missing key covariates were included. GCFS were collected at three visits across 22 years (1990-2013), and brain MRI and florbetapir PET imaging were collected in 2011-13; PET in subset of n=327. Mixed effects models with random intercepts and slopes predicted individual change in GCFS. Outcomes of interest were total brain volume (cc), temporal lobe meta region volume, log 2 (white matter hyperintensity volume), ≥1 lacunar infarct, and elevated brain β-amyloid deposition (SUVR >1.2). Multivariable linear and logistic regression was used to relate outcomes to GCFS slopes after adjusting for confounders, including vascular risk factors. As appropriate, models were also adjusted for total intracranial volume. Results: Among 1957 with complete brain MRI imaging, 1830 were included in the study, 60% (n=1096) women and 26% (n=480) black. At the first visit, the mean (SD) baseline age was 55 (5.2) yrs. The mean (SD) observed GCFS at the three visits were 0.16 (0.79), 0.05 (0.75), and -0.78 (0.86). After adjustment, a 1-SD larger decline in GCFS was significantly associated with a smaller brain volume by 1.6% [95%CI: 1.3, 1.8] relative to mean brain volume, a smaller temporal lobe meta region volume by 2.4% [2.1, 2.8] relative to the mean volume, a 15% [11, 19] larger volume of white matter hyperintensities, 1.3-fold [1.2, 1.4] higher odds of having ≥1 lacune, and 1.8-fold [1.4, 2.4] higher odds of elevated brain β-amyloid deposition. Associations remained significant after further adjustment for first or last GCFS. Conclusions: Greater declines in long-term cognitive functioning were significantly associated with smaller brain volumes and dementia-related brain characteristics and were independent of last visit GCFS. This suggests long-term changes in cognition may precede late-life brain morphology and outperform cross-sectional cognitive measures.

Abstract P123: Prospective Association Between Periodontal Disease And Brain Imaging Markers Of Cerebrovascular And Neurodegenerative Disease: The Atherosclerosis Risk In Communities Study

Background: Periodontal disease (PD) is associated positively with neurocognitive outcomes. Few studies have investigated the relationship between PD and indicators of brain aging and vascular changes. Hypothesis: PD is associated with greater cerebral small vessel disease, lower total and regional brain volumes and elevated β-amyloid (Aβ) deposition. Methods: We included 6,793 participants who received full-mouth periodontal examinations and tooth counts at Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities Study. We used a modified 3-level version of the Periodontal Profile Class to categorize PD based on severity and extent of gingival inflammation and tissue loss. Among participants who attended Visit 5 (2011-2013), n=1,306 received a brain MRI and n=248 received a PET scan. Total brain volume, Alzheimer’s disease signature volume, and presence of microhemorrhages and cerebral infarctions were ascertained via 3T MRI; Aβ deposition was assessed from PET. We regressed brain volumes on baseline PD status using weighted multivariable linear regression. Presence of cerebrovascular microhemorrhages, infarctions, or elevated Aβ (standardized uptake value ratio>1.2) were regressed on PD category using logistic models. We examined the interaction between Apolipoprotein E ε4 ( APOE ) allele possession and PD categories on the Aβ outcome. Results: Prevalence of baseline periodontal disease was 73% (959/1306) and 87% (206/248) among the MRI and PET subgroups, respectively. PD was not associated with volumetric brain measures nor microhemorrhages. PD was inversely associated with the odds of subcortical and lacunar infarctions. PD and Aβ were not associated in main effect or interaction analyses, although there was a notably stronger association among carriers of APOE . Conclusion: PD was not associated with altered brain structure, cerebral microhemorrhages or elevated Aβ deposition. Counter to the hypothesis, PD and complete tooth loss were inversely associated with cerebral infarctions.

Seizure burden in preterm infants and smaller brain volume at term-equivalent age.

Background:Seizures are underrecognized in preterm infants, and little is known about their impact on brain growth. We aimed to define the association between early seizures and subsequent brain growth.Methods:Infants <30 weeks’ gestation underwent 72h of prospective aEEG monitoring, term-equivalent age (TEA) MRI, and 2y neurodevelopmental testing.Seizures were defined as trains of sharp waves >10 seconds, evolving in frequency/amplitude/morphology, and identified using automated algorithms with manual review.Using T2-weighted images, cortical surface area (CSA) and gyrification index (GI) were calculated and volumes were segmented into five tissue classes: CSF, gray matter, white matter (WM), deep nuclear gray matter, and cerebellum. Correlations between total seizure burden and tissue-specific volumes were evaluated, controlling for clinical variables of interest.Results:Ninety-nine infants underwent aEEG/MRI assessments (mean GA=26.3 weeks, birthweight=899g). Seizure incidence was 55% with a median of two events; median length=66s and mean burden=285s.Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (R2=−0.603, p<.01), even after controlling for confounders. There was no association with GI.Conclusion:Seizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors.

The effect of low-dose radiation spillage during stereotactic radiosurgery for brain metastases on the development of de novo metastases

Purpose/Objective(s)Stereotactic radiosurgery (SRS) for metastatic disease to the brain is associated with higher in-brain failures compared to whole brain radiation therapy (WBRT). Here we investigated the relationship between low-dose fall off during SRS and location of new brain lesions. Materials and MethodsOne hundred sixty-seven patients treated with single fraction or fractionated SRS for intact or resected brain metastases at our institution from January 2016 to June 2018 were reviewed. Patients with imaging findings of new brain metastases after the initial SRS were included. Patients with WBRT before SRS were excluded. MRI scans for repeat treatments were fused with initial SRS plan. New lesions were outlined on the initial SRS planning CT. The mean dose that the site of new lesions received from initial SRS was tabulated. ResultsThirty-eight patients met inclusion criteria. 165 new lesions were evaluated. There was a lower propensity to develop new brain lesions with increasing dose received by the regions from prior SRS, with 66%, 34%, 19%, 13%, 6%, 5%, 2% and 1% of new lesions appearing in regions that received less than 1 Gy, greater than or equal to 1, 2, 3, 4, 5, 6, and 7 Gy, respectively. Higher doses are received by smaller brain volumes during SRS. After accounting for volume, 14, 14, 11, 7, 2, 2, 1 and 1 new lesions appeared per 100 cm3 of brain in regions that received doses of less than 1 Gy, greater than or equal to 1, 2, 3, 4, 5, 6, and 7 Gy, respectively, from prior SRS. ConclusionsWe identified low dose spillage during SRS to be associated with lower incidence of new brain metastases. Validation in larger dataset or prospective study of the combination of SRS with low dose WBRT would be crucial in order to establish causality of these findings.

A population-based study of head injury, cognitive function and pathological markers.

ObjectiveTo assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later‐life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia‐free individuals.MethodsParticipants (n = 502, age = 69–71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18F‐florbetapir Aβ‐PET and MR imaging. Measures include Aβ‐PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer’s disease (AD)‐related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15 years prior to the scan (ii) anytime up to age 71.ResultsCompared to those with no evidence of an LOC HI, only those reporting an LOC HI>15 years prior (16%, n = 80) performed worse on cognitive tests at age 69–71, taking into account premorbid cognition, particularly on the digit‐symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD‐related cortical thickness or NFL (all p > 0.01).InterpretationHaving a LOC HI aged 50’s and younger was linked with lower later‐life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).

Clinical Relevance of Cortical Cerebral Microinfarcts on 1.5T Magnetic Resonance Imaging in the Late-Adult Population.

Cortical cerebral microinfarcts (CMIs) have been linked with dementia and impaired cognition in cross-sectional studies. However, the clinical relevance of CMIs in a large population-based setting is lacking. We examine the association of cortical CMIs detected on 1.5T magnetic resonance imaging with cardiovascular risk factors, cerebrovascular disease, and brain tissue volumes. We further explore the association between cortical CMIs with cognitive decline and risk of stroke, dementia, and mortality in the general population. Two thousand one hundred fifty-six participants (age: 75.7±5.9 years, women: 55.6%) with clinical history and baseline magnetic resonance imaging (January 2009-December 2013) were included from the Rotterdam Study. Cortical CMIs were graded based on a previously validated method. Markers of cerebrovascular disease and brain tissue volumes were assessed on magnetic resonance imaging. Cognition was assessed using a detailed neuropsychological test at baseline and at 5 years of follow-up. Data on incident stroke, dementia, and mortality were included until January 2016. Two hundred twenty-seven individuals (10.5%) had ≥1 cortical CMIs. The major risk factors of cortical CMIs were male sex, current smoking, history of heart disease, and stroke. Furthermore, presence of cortical CMIs was associated with infarcts and smaller brain volume. Persons with cortical CMIs showed cognitive decline in Stroop tests (color-naming and interference subtasks; β for color-naming, 0.18 [95% CI, 0.04-0.33], P interaction ≤0.001 and β for interference subtask, 1.74, [95% CI, 0.66-2.82], P interaction ≤0.001). During a mean follow-up of 5.2 years, 73 (4.3%) individuals developed incident stroke, 95 (5.1%) incident dementia, and 399 (19.2%) died. People with cortical CMIs were at an increased risk of stroke (hazard ratio, 1.18 [95% CI, 1.09-1.28]) and mortality (hazard ratio, 1.09 [95% CI, 1.00-1.19]). Cortical CMIs are highly prevalent in a population-based setting and are associated with cardiovascular disease, cognitive decline, and increased risk of stroke and mortality. Future investigations will have to show whether cortical CMIs are a useful biomarker to intervene upon to reduce the burden of stroke.

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.

Relationship of hearing impairment with MRI brain volumes and cognitive decline in the Atherosclerosis Risk in Communities study

AbstractBackgroundHearing impairment is associated with cognitive decline but whether it is a cause or marker is unknown. We investigated the association of hearing impairment with brain volumes and 8‐year cognitive decline. Because the superior temporal gyrus (STG) is the location of the primary auditory cortex, we stratified results by STG volume to investigate if the association of hearing and cognition differed among participants with and without evidence of possible hearing‐related brain atrophy.MethodWe used data from 1195 community‐dwelling adults (72‐94 years, 61% female, 36% black) from the Atherosclerosis Risk in Communities Study. A composite cognitive score was created from 10 neuropsychological tests administered at 3 study visits spanning 8 years (2011‐13 to 2018‐19). Brain volumes were calculated from structural magnetic resonance imaging scans for 6 regions of interest. Pure tone air conduction hearing thresholds (frequencies 0.5‐4 kHz) were obtained in 2016‐17 and averaged, with better‐ear hearing impairment defined as an average &gt;25 dB. Multivariable‐adjusted linear regression was used to estimate cross‐sectional differences in standardized brain volumes, adjusting for intracranial volume, demographic and clinical covariates. We estimated differences in annual rates of cognitive change by hearing impairment status adjusting for demographic and clinical covariates using linear mixed models; results were stratified by intracranial volume‐adjusted STG volume (below vs. equal to or greater than the median value).ResultThe mean STG volume difference comparing hearing impairment to normal hearing was ‐0.121 standard deviations (SD) (95% CI: ‐0.213, ‐0.028). Overall, the difference in the rate of cognitive decline associated with hearing impairment was ‐0.014 SD (‐0.023, ‐0.005). Hearing was more strongly associated with cognitive decline among participants with smaller STG volumes; rate difference, ‐0.014 SD (‐0.027, ‐0.002) compared to ‐0.008 (‐0.022, 0.006) for participants with larger STG volumes.ConclusionHearing impairment was associated with smaller brain volumes in the primary auditory region, but not with other regions. Our stratified analysis suggests that hearing treatment might be an important possible strategy to delay cognitive decline, even among participants with hearing‐related brain atrophy. Furthermore, the adverse cognitive effects of hearing impairment could potentially be mitigated if early hearing treatment can prevent STG atrophy.

Effects of anticholinergic medication use on brain integrity in persons living with HIV and persons without HIV.

This study examined relationships between anticholinergic medication burden and brain integrity in people living with HIV (PLWH) and people without HIV (HIV-). Neuropsychological performance z-scores (learning, retention, executive function, motor/psychomotor speed, language domains, and global cognition), and neuroimaging measures (brain volumetrics and white matter fractional anisotropy) were analyzed in PLWH (n = 209) and HIV- (n = 95) grouped according to the Anticholinergic Cognitive Burden (ACB) scale (0 = no burden, 1-3 = low burden, >3 = high burden). Neuropsychological performance and neuroimaging outcomes were compared between HIV- and PLWH with high anticholinergic burden. Within a cohort of PLWH (n = 90), longitudinal change in ACB score over ∼2 years was correlated to the rate of change per month of study interval in neuropsychological performance and neuroimaging measures. A higher number of anticholinergic medications and ACB was observed in PLWH compared with HIV- (P < 0.05). A higher ACB was associated with worse motor/psychomotor performance, smaller occipital lobe, putamen, subcortical gray matter and total gray matter volumes in HIV-; and poorer executive function, retention and global cognition, smaller brain volumes (frontal, parietal and temporal lobes, hippocampus, amygdala, cortex, subcortical gray matter and total gray matter), and reduced fractional anisotropy (posterior corpus callosum, perforant pathway) in PLWH. PLWH with high anticholinergic burden performed worse on tests of learning and executive function compared with HIV- with high anticholinergic burden. Longitudinally, PLWH who reduced their ACB over time had better neuropsychological performance and neuroimaging measures. Anticholinergic medications were associated with worse neuropsychological performance and reduced structural brain integrity, and these effects were more widespread in PLWH. Use of anticholinergic medications should be carefully monitored in older adults with deprescription considered whenever possible.

Neurocognitive Dysfunction and Smaller Brain Volumes in Adolescents and Adults With a Fontan Circulation.

Neurocognitive outcomes beyond childhood in people with a Fontan circulation are not well defined. This study aimed to investigate neurocognitive functioning in adolescents and adults with a Fontan circulation and associations with structural brain injury, brain volumetry, and postnatal clinical factors. In a binational study, participants with a Fontan circulation without a preexisting major neurological disability were prospectively recruited from the Australia and New Zealand Fontan Registry. Neurocognitive function was assessed by using Cogstate software in 107 participants with a Fontan circulation and compared with control groups with transposition of the great arteries (n=50) and a normal circulation (n=41). Brain MRI with volumetric analysis was performed in the participants with a Fontan circulation and compared with healthy control data from the ABIDE I and II (Autism Brain Imaging Data Exchange) and PING (Pediatric Imaging, Neurocognition, and Genetics) data repositories. Clinical data were retrospectively collected. Of the participants with a Fontan circulation who had a neurocognitive assessment, 55% were male and the mean age was 22.6 years (SD 7.8). Participants with a Fontan circulation performed worse in several areas of neurocognitive function compared with those with transposition of the great arteries and healthy controls (P<0.05). Clinical factors associated with worse neurocognitive outcomes included more inpatient days during childhood, younger age at Fontan surgery, and longer time since Fontan procedure (P<0.05). Adults with a Fontan circulation had more marked neurocognitive dysfunction than adolescents with a Fontan circulation in 2 domains (psychomotor function, P=0.01 and working memory, P=0.02). Structural brain injury was present in the entire Fontan cohort; the presence of white matter injury was associated with worse paired associate learning (P<0.001), but neither the presence nor severity of infarct, subcortical gray matter injury, and microhemorrhage was associated with neurocognitive outcomes. Compared with healthy controls, people with a Fontan circulation had smaller global brain volumes (P<0.001 in all regions) and smaller regional brain volumes in most cerebral cortical regions (P<0.05). Smaller global brain volumes were associated with worse neurocognitive functioning in several domains (P<0.05). A significant positive association was also identified between global brain volumes and resting oxygen saturations (P≤0.04). Neurocognitive impairment is common in adolescents and adults with a Fontan circulation and is associated with smaller gray and white matter brain volume. Understanding modifiable factors that contribute to brain injury to optimize neurocognitive function is paramount.

Prenatal opioid exposure is associated with smaller brain volumes in multiple regions.

Background:The impact of prenatal opioid exposure on brain development remains poorly understood.Methods:We conducted a prospective study of term-born infants with and without prenatal opioid exposure. Structural brain MRI was performed between 40–48 weeks postmenstrual age. T2-weighted images were processed using the Developing Human Connectome Project structural pipeline. We compared 63 relative regional brain volumes between groups.Results:Twenty-nine infants with prenatal opioid exposure and 42 unexposed controls were included. The groups had similar demographics, except exposed infants had lower birth weights, more maternal smoking and maternal Hepatitis C, fewer mothers with a college degree, and were more likely non-Hispanic White. After controlling for sex, postmenstrual age at scan, birth weight, and maternal education, exposed infants had significantly smaller relative volumes of the deep gray matter, bilateral thalamic ventrolateral nuclei, bilateral insular white matter, bilateral subthalamic nuclei, brainstem, and cerebrospinal fluid. Exposed infants had larger relative volumes of the right cingulate gyrus white matter and left occipital lobe white matter.Conclusion:Infants with prenatal opioid exposure had smaller brain volumes in multiple regions compared to controls, with two regions larger in the opioid-exposed group. Further research should focus on the relative contributions of maternal opioids and other exposures.

Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease.

Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery. Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157.

Higher Body-Mass Index and Lower Gray Matter Volumes in First Episode of Psychosis.

BackgroundNeurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP.MethodWe analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses.ResultsIn primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations.ConclusionsThis study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our findings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP.

Diffusion Tensor Imaging-Based Analysis of Baseline Neurocognitive Function and Posttreatment White Matter Changes in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Therapy

To determine the preirradiation baseline association of white matter integrity with neurocognitive function and to assess posttreatment changes in pediatric patients with craniopharyngioma treated with proton therapy. Ninety children and adolescents (2-20 years old) with craniopharyngioma were treated with proton therapy (54 Gy[RBE]) in a prospective therapeutic trial. Neurocognitive performance at the postoperative baseline before proton therapy and diffusion tensor imaging (DTI) data acquired at baseline and at annual follow-up were analyzed. Tract-based spatial statistics and structural connectomics were used to derive global and local white matter features from DTI. Baseline DTI features were compared for patients with average and below-average neurocognitive performance. Longitudinal DTI data were analyzed to determine the proton dose effect on white matter structures in relation to the irradiated brain volume and baseline age. Before proton therapy, patients with below-average working memory, processing speed, verbal fluency, verbal learning, or fine motor dexterity exhibited more globally degraded white matter structures compared with their counterparts with average performance, as indicated by lower mean fractional anisotropy, decreased global efficiency, or higher modularity. Surgery, obstructive hydrocephalus, and preoperative hypothalamic involvement appeared to be related to this degradation. In local analyses, tract-based spatial statistics revealed left-lateralized associations with verbal and motor functions, which supported surgical approaches to midline tumors via the right hemisphere. The mean fractional anisotropy of the brain and the global efficiency derived from DTI increased over the 5 years after proton therapy. The rate of increase was lower with larger irradiated brain volumes and in older children. Below-average baseline neurocognitive performance in patients with craniopharyngioma before proton therapy appeared to be related to structural degradation of white matter tracts. Posttherapy longitudinal DTI showed improving trends in global integrity and efficiency measures, particularly in children in whom a smaller brain volume was irradiated.

Association of mid-life serum lipid levels with late-life brain volumes: The atherosclerosis risk in communities neurocognitive study (ARIC[sbnd]NCS)

BackgroundLimited information exists regarding the association between midlife lipid levels and late-life total and regional brain volumes. MethodsWe studied 1872 participants in the longitudinal community-based Atherosclerosis Risk in Communities Neurocognitive Study. Serum lipid levels were measured in 1987–1989 (mean age, 53 ± 5 years). Participants underwent 3T brain MRI scans in 2011–2013. Brain volumes were measured using FreeSurfer image analysis software. Linear regression models were used to assess the associations between serum lipids and brain volumes modeled in standard deviation (SD) units, adjusting for potential confounders. ResultsIn adjusted analyses, one SD higher low-density lipoprotein cholesterol (LDL) levels were associated with larger total brain volumes (β 0.033, 95% CI 0.006–0.060) as well as larger volumes of the temporal (β 0.038, 95% CI 0.003–0.074) and parietal lobes (β 0.044, 95% CI 0.009–0.07) and Alzheimer disease-related region (β 0.048, 95% CI 0.048–0.085). Higher triglyceride levels were associated with smaller total brain volumes (β -0.033, 95% CI -0.060, -0.007). The associations between LDL levels and brain volumes were modified by age (P for interaction <0.001), with higher LDL levels associated with larger total and regional brain volumes only among adults >53 years at baseline, and were attenuated after application of weights to account for informative attrition, although associations with the parietal and Alzheimer's disease-related region remained significant. High-density lipoprotein cholesterol was not associated with brain volumes. ConclusionHigher LDL levels in late midlife were associated with larger brain volumes later in life, while higher triglyceride levels were associated with smaller brain volumes. These associations were driven by adults >53 years at baseline.

Association between brain morphology and electrophysiological features in Congenital Zika Virus Syndrome: A cross-sectional, observational study.

BackgroundIntrauterine infection with the Zika virus (ZIKV) has been connected to severe brain malformations, microcephaly, and abnormal electrophysiological activity.MethodsWe describe the interictal electroencephalographic (EEG) recordings of 47 children born with ZIKV-derived microcephaly. EEGs were recorded in the first year of life and correlated with brain morphology. In 31 subjects, we tested the association between computed tomography (CT) findings and interictal epileptiform discharges (IED). In eighteen, CTs were used for correlating volumetric measurements of the brainstem, cerebellum, and prosencephalon with the rate of IED.FindingsTwenty-nine out of 47 (62%) subjects were diagnosed as having epilepsy. Those subjects presented epileptiform discharges, including unilateral interictal spikes (26/29, 90%), bilateral synchronous and asynchronous interictal spikes (21/29, 72%), and hypsarrhythmia (12/29, 41%). Interestingly, 58% of subjects with clinical epilepsy were born with rhombencephalon malformations, while none of the subjects without epilepsy showed macroscopic abnormalities in this region. The presence of rhombencephalon malformation was associated with epilepsy (odds ratio of 34; 95% CI: 2 - 654). Also, the presence of IED was associated with smaller brain volumes. Age-corrected total brain volume was inversely correlated with the rate of IED during sleep. Finally, 11 of 44 (25%) subjects presented sleep spindles. We observed an odds ratio of 0·25 (95% CI: 0·06 - 1·04) for having sleep spindles given the IED presence.InterpretationThe findings suggest that certain CT imaging features are associated with an increased likelihood of developing epilepsy, including higher rates of IED and impaired development of sleep spindles, in the first year of life of CZVS subjects.FundingThis work was supported by the Brazilian Federal Government through a postdoctoral fellowship for EBS (Talented Youth, Science without Borders), an undergraduate scholarship for AJR (Institutional Program of Science Initiation Scholarships, Federal University of Rio Grande do Norte, Brazil), by International Centre for Genetic Engineering and Biotechnology (CRP/BRA18–05_EC) and by CAPES (Grant number 440893/2016-0), and CNPq (Grant number 88881.130729/2016-01).

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer's Disease patients analyzed by MRI: a retrospective study.

ObjectivesAlzheimer’s disease (AD), impaired fasting glucose (IFG), and Type 2 diabetes mellitus (T2DM) were reported associated with smaller brain volumes. Nevertheless, the association of hyperglycemia with brain volume changes in AD patients remains unclear. To investigate this issue, structural magnetic resonance imaging was used to compare brain volumes among AD patients with different fasting glucose levels.MethodsEighty-five AD patients were divided into three groups based on their fasting glucose level as suggested by the American Diabetes Association: normal fasting glucose group (AD_NFG, n = 45), AD_IFG group (n = 15), and AD_T2DM group (n = 25). Sagittal 3D T1-weighted images were obtained to calculate the brain volume. Brain parenchyma and 33 brain structures were automatically segmented. Each regional volume was analyzed among groups. For regions with statistical significance, partial correlation analysis was used to evaluate their relationships with fasting glucose level, corrected for Mini-Mental State Examination score, age, education level, cholesterol, triglyceride, and blood pressure.ResultsCompared with the AD_IFG and AD_NFG groups, the volume of pons in AD_T2DM group was significantly smaller. Fasting glucose was negatively correlated with pontine volume.ConclusionsT2DM may exacerbate pontine atrophy in AD patients, and fasting glucose level is associated with pontine volume.