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It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance ( p  < .01) and lower hippocampal volumes ( p  < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.

Background: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS., Methods: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n = 80) and ASD children (n = 29). ANOVAs were conducted to compare groups on cognitive and adaptive assessments. ANCOVAs (covarying for age, sex, and total cerebral volume; TCV) compared cortical brain volumes between groups. Correlations between behavioral metrics and cortical and cerebellar volumes (separately for gray (GM) and white matter (WM)) were conducted separately by group., Results: As expected, children with DS had significantly lower cognitive skills compared to ASD and TD children. Daily Living adaptive skills were comparable between ASD children and children with DS, and both groups scored lower than TD children. Children with DS exhibited a smaller TCV compared to ASD and TD children. Additionally, when controlling for TCV, age, and sex, children with DS had significantly smaller total GM and tissue volumes. Cerebellum volumes were significantly correlated with Daily Living adaptive behaviors in the DS group only., Conclusions: Despite children with DS exhibiting lower cognitive skills and smaller brain volume overall than children with ASD, their deficits in Socialization and Daily Living adaptive skills are comparable. Differences in lobar volumes (e.g., Right Frontal GM/WM, Left Frontal WM, and Left and Right Temporal WM) were observed above and beyond overall differences in total volume. The correlation between cerebellum volumes and Daily Living adaptive behaviors in the DS group provides a novel area to explore in future research., Competing Interests: Declarations. Ethics approval and consent to participate: The research described in this work was approved by the local Institutional Review Board. Consent for publication: All authors have reviewed the manuscript and approved it for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Diet quality during pregnancy may affect offspring's neurobiology and cognitive performance in childhood. However, little is known about underlying mechanisms and potential long-term effects., Objectives: To examine associations of diet quality during pregnancy with offspring pre- and early-adolescent brain morphology and to investigate whether brain morphology mediates associations of diet quality during pregnancy with full-scale intelligence quotient (IQ) in early adolescence., Methods: We studied 2223 and 1582 mother-child dyads with brain scans collected using magnetic resonance imaging at ages 10 and 14 y in the population-based Generation R Study in The Netherlands. We assessed dietary intake during pregnancy with 293-item food-frequency questionnaires and calculated predefined diet quality scores (total score 0-15), reflecting adherence to dietary guidelines. Cognitive performance was assessed using Wechsler Intelligence Scale for Children-V at age 14 y. We examined associations using multiple regression models, corrected for multiple testing., Results: After adjustment for child age, sex, socioeconomic factors, maternal age, smoking, and psychopathological symptoms during pregnancy, we found that higher diet quality during pregnancy was associated with a larger total brain (B: 4.54, 95% confidence interval [CI]: 1.80, 7.28), cerebral white matter (1.83, 95% CI: 0.56, 3.10), cerebral gray matter (1.99, 95% CI: 0.63, 3.35), and subcortical volumes (0.16, 95% CI: 0.04, 0.28) of children at age 10 y. Similar results were found for age 14 y. Widespread differences in cortical thickness, gyrification, and surface area in both hemispheres were also observed. Better diet quality during pregnancy was associated with higher full-scale IQ scores of adolescents, particularly on verbal comprehension and matrix reasoning. The associations between diet quality during pregnancy and full-scale IQ in early adolescence were partially mediated by brain volumetric markers in pre-adolescence., Conclusions: Diet quality during pregnancy was associated with structural brain alterations in the offspring, which partly explained the relation between prenatal dietary patterns and cognitive outcomes in children., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to elucidate the comprehensive effects of metabolic syndrome (MetS) on the structural integrity of subcortical brain regions and associated structures through high-resolution magnetic resonance imaging (MRI) volumetric analysis, thereby contributing to a deeper understanding of the neuroanatomical dimensions of MetS and its potential implications for cognitive functions and overall brain health. Methods: A cross-sectional design was implemented, involving 25 individuals diagnosed with MetS for at least one year and a healthy control group of 15 individuals at a tertiary hospital's family medicine clinic in Eastern Turkey. Participants underwent a high-resolution MRI scan using a 1.5T Siemens Aera scanner. The MRICloud platform was employed for comprehensive segmentation and quantitative analysis of various brain structures. Results: The study revealed significant volumetric reductions in all measured subcortical brain regions among individuals with MetS compared to the control group (all P < 0.05). Notable differences were observed in key structures such as the substantia nigra, corpus callosum, and thalamus. In subcortical structures, the largest volumetric differences were noted in the basal ganglia L (1322.4 mm³), while the most significant percentage differences were seen in the substantia nigra R (25.24%) and caudate nucleus L (21.02%). Conclusion: The findings from this study underscore the significant neuroanatomical changes associated with MetS, manifesting as volumetric reductions in critical subcortical brain areas. These alterations underscore the necessity for further research into the comprehensive influence of MetS on cognitive processes and the potential for early therapeutic interventions.

Background: Low skeletal muscle volume may increase dementia risk through mechanisms affecting brain structure. However, it is unclear whether this relationship exists outside of sarcopenia and/or varies by other factors. We aimed to study the interplay between skeletal muscle volume and factors, such as age, sex, and body mass index (BMI), in explaining brain structure at midlife in a cohort without sarcopenia., Methods: We used abdominal and brain magnetic resonance imaging (MRI) data from a population-based cohort enrolled in the UK Biobank. The following measures were derived: thigh fat-free muscle volume (FFMV), total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), total hippocampal volume (THV), and white matter hyperintensity volume (WMHV). Participants below sex-based grip strength thresholds suggesting probable sarcopenia were excluded. Linear regression analysis was used to study the interaction or mediation effects of age, sex, and BMI on the associations between FFMV and brain volumes., Results: Data were available for 20,353 participants (median age 64 years, 53% female). We found interactions between thigh FFMV, BMI, and age (all p < 0.05). Greater thigh FFMV was associated with better brain volumes in those aged <64 years with normal (TBV: β = 2.0 ml/L, p = 0.004; GMV: β = 0.8 ml/L, p = 0.04; WMV: β = 1.1 ml/L, p = 0.006; WMHV: β = -0.2 ml/L, p = 3.7 × 10 -5 ) or low BMI (TBV: β = 21.2 ml/L, p = 0.003; WMV: β = 13.3 ml/L, p = 0.002, WMHV: β = -1.1 ml/L, p = 0.04)., Conclusion: Greater thigh muscle volume correlates with better brain volumes at midlife in people without sarcopenia, but this relationship weakens with greater age and BMI. Further study is required to investigate the underlying mechanisms to understand which components of body composition are potentially modifiable risk factors for dementia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Than, Beare, La Hood, Collyer, Srikanth and Moran.)

Background: Consistent evidence shows that magnesium (Mg) intake is associated with lower blood pressure (BP), and that lower BP is associated with improved cerebral health. However, recent findings indicate that the positive effect of dietary Mg intake on cerebral health is not mediated by a decrease in BP. As Mg's anti-inflammatory action is a plausible alternative mechanism, the objective of this study was to investigate the associations between Mg intake and inflammation to determine whether it mediates any neuroprotective effect., Methods: Participants from the UK Biobank (n = 5775, aged 40-73 years, 54.7% female) were assessed for dietary magnesium using an online food questionnaire, brain and white matter lesion (WML) volumes were segmented with FreeSurfer software, and inflammation markers including high-sensitivity C-reactive protein (hs-CRP), leukocyte, erythrocyte count, and Glycoprotein acetylation (GlycA) were measured using specific laboratory techniques such as immunoturbidimetry, automated cell counting, and nuclear magnetic resonance. Hierarchical linear regression models were performed to investigate the association between dietary Mg, and inflammatory markers and between dietary Mg, brain and WMLs volumes. Mediation analysis was performed to test a possible mediation role of inflammation on the association between dietary Mg and brain and WMLs volumes., Results: Higher dietary Mg intake was associated with lower inflammation: hs-CRP level (- 0.0497%; 95% confidence interval [CI] - 0.0497%,  - 0.0199%) leukocytes count (- 0.0015%; 95%CI - 0.00151%,  - 0.0011%), and GlycA (- 0.0519%; 95%CI - 0.1298%,  - 0.0129%). Moreover, higher dietary Mg intake was associated with larger grey matter volume (0.010%; 95%CI 0.004%, 0.017%), white matter volume (0.012%; 95%CI 0.003,  0.022) and right hippocampal volume (0.002%; 95%CI 0.0007, -0.0025%). Lower hs-CRP levels mediated the positive association between higher dietary Mg intake and larger grey matter volume., Conclusions: The anti-inflammatory effects of dietary Mg intake in the general population, appears to mediate its neuroprotective effect., (© 2024. The Author(s).)

Background: HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood., Methods: We assessed markers of T cell activation (HLA-DR + CD38+), immunosenescence (CD57 + CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models., Results: Of N = 51 participants, 84.3% were male, 86.3% had undetectable HIV RNA < 50 copies/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells/uL. Higher CD4 T cells expressing PD-1 + and/or TIM-3 + were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1 + and/or TIM-3 + were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1 + and TIM-3 + expressing CD4 and CD8 T-cells correlated with higher CD16 + monocyte numbers., Conclusions: This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16 + monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals., Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex., Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes., Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stickel, Tarraf, Gonzalez, Paredes, Zeng, Cai, Isasi, Kaplan, Lipton, Daviglus, Testai, Lamar, Gallo, Talavera, Gellman, Ramos, Ivanovic, Seiler, González and DeCarli.)

Neuromyelitis optica spectrum disorder (NMOSD) is a severe form of inflammation of the central nervous system (CNS) including acute myelitis, optic neuritis and brain syndrome. Currently, the classification of NMOSD relies on serologic testing, distinguishing between seropositive or seronegative anti-aquaporin-4 antibody (AQP4) status. However, the situation has recently grown more intricate with the identification of patients exhibiting the NMOSD phenotype and myelin oligodendrocyte glycoprotein antibodies (MOGAD). NMOSD is primarily recognized as a relapsing disorder; MOGAD can manifest with either a monophasic or relapsing course. Significant symptomatic inflammatory CNS injuries with stability in clinical findings outside the acute phase are reported in both diseases. Nevertheless, recent studies have proposed the existence of a subclinical pathological process, revealing longitudinal changes in brain and spinal cord atrophy. Within this context, we summarise key studies investigating brain and spinal cord measurements in adult NMOSD and MOGAD. We also explore their relationship with clinical aspects, highlight differences from multiple sclerosis (MS), and address future challenges. This exploration is crucial for determining the presence of chronic damage processes, enabling the customization of therapeutic interventions irrespective of the acute phase of the disease., Competing Interests: Declaration of competing interest Lorefice L and Cortese R. have nothing to disclose for this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Magnetic resonance imaging (MRI) studies have identified brain changes associated with anxiety disorders (ADs), but the results remain mixed, particularly at a younger age. One key predictor of ADs is behavioral inhibition (BI), a childhood tendency for high avoidance of novel stimuli. This study aimed to evaluate the relationships between candidate brain regions, BI, and ADs among children using baseline data from the Adolescent Brain Cognitive Development (ABCD) study., Methods: We analyzed global and regional brain volumes of 9,353 children (9-10 years old) in relation to BI and current ADs, using linear mixed models accounting for family clustering and important demographic and socioeconomic covariates. We further investigated whether and how past anxiety was related to brain volumes., Results: Among included participants, 249 (2.66%) had a current AD. Larger total white matter (Beta = -0.152; 95% CI [-0.281, -0.023]), thalamus (Beta = -0.168; 95% CI [-0.291, -0.044]), and smaller hippocampus volumes (Beta = 0.094; 95% CI [-0.008, 0.196]) were associated with lower BI scores. Amygdala volume was not related to BI. Larger total cortical (OR = 0.751; 95% CI [0.580;0.970]), amygdala (OR = 0.798; 95%CI [0.666;0.956]), and precentral gyrus (OR = 0.802; 95% CI [0.661;0.973]) volumes were associated with lower odds of currently having ADs. Children with past ADs had smaller total white matter and amygdala volumes., Conclusions: The results show associations between brain volumes and both BI and ADs at an early age. Importantly, results suggest that ADs and BI have different neurobiological correlates and that earlier occurrences of ADs may influence brain structures related to BI and ADs, motivating research that can better delineate the similarities and divergence in the neurobiological underpinnings and building blocks of BI and ADs across their development in early life., (© 2024. The Author(s).)

Mild cognitive impairment (MCI) has been frequently interpreted as a transitional phase between healthy cognitive aging and dementia, particularly of the Alzheimer's disease (AD) type. Of note, few studies explored that transition from a multifactorial perspective, taking into consideration the effect of basic factors such as biological sex. In the present study 96 subjects with MCI (37 males and 59 females) were followed-up and divided into two subgroups according to their clinical outcome: "progressive" MCI (pMCI = 41), if they fulfilled the diagnostic criteria for AD at the end of follow-up; and "stable" MCI (sMCI = 55), if they remained with the initial diagnosis. Different markers were combined to characterize sex differences between groups, including magnetoencephalography recordings, cognitive performance, and brain volumes derived from magnetic resonance imaging. Results indicated that the pMCI group exhibited higher low-frequency activity, lower scores in neuropsychological tests and reduced brain volumes than the sMCI group, being these measures significantly correlated. When sex was considered, results revealed that this pattern was mainly due to the influence of the females' sample. Overall, females exhibited lower cognitive scores and reduced brain volumes. More interestingly, females in the pMCI group showed an increased theta activity that correlated with a more abrupt reduction of cognitive and volumetric scores as compared with females in the sMCI group and with males in the pMCI group. These findings suggest that females' brains might be more vulnerable to the effects of AD pathology, since regardless of age, they showed signs of more pronounced deterioration than males., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

Background: Discontinuation of the deep medullary veins (DMVs) may be an early imaging marker for identifying cognitive impairment caused by cerebral small vessel disease (CSVD). However, this method lacks mechanistic exploration. We aimed to investigate whether the DMV score is related to CSVD imaging markers and cognitive impairment in patients with CSVD., Methods: This retrospective study included patients with CSVD who completed DMV score and cognition (e.g., MMSE, MoCA) assessments, and underwent MRI scanning (T2-FLAIR for white matter hyperintensities (WMH) volume, T1-weighted MRI for brain parenchymal fractions (BPF) analysis, and SWI for assessment of DMV score). The CSVD imaging markers were quantitatively assessed using the AccuBrain® system. We assessed the diagnostic value of neuroimaging biomarkers for detecting CSVD-related cognitive impairment. In addition, we explored the relationship between the DMV score, CSVD imaging markers, and cognition using mediation analysis., Results: Ninety-four patients with CSVD were divided into a cognitive impairment group (n = 39) and a non-cognitive impairment group (n = 55). Higher DMV scores, larger WMH volumes, and smaller BPF were observed in the cognitive impairment group than those in the non-cognitive impairment group. Receiver operating characteristics (ROC) analysis revealed that the discovery value of the integration of patient age, BPF, whole WMH volume, and DMV score for cognitive impairment was 0.742, with a sensitivity and specificity of 79.5 % and 61.5 %, respectively. Mediation analysis showed mediation by WMH and BPF in the relationship between DMV score and cognitive impairment (all P < 0.05)., Limitations: This study did not evaluate the DMV score in subregions according to DMV anatomy., Conclusions: The DMV score is significantly associated with cognitive impairment in patients with CSVD, and this association is mediated through WMH and BPF., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain volumes in pediatric opsoclonus-myoclonus ataxia syndrome patients compared with age- and sex-matched healthy children., Patients and Methods: This longitudinal case-control study included brain magnetic resonance imaging (MRI) scans from consecutive pediatric opsoclonus-myoclonus ataxia syndrome patients (2009-2020) and age- and sex-matched healthy control children. FreeSurfer analysis provided automatic volumetry of the brain. Paired t tests were performed on the curvature of growth trajectories, with Bonferroni correction., Results: A total of 14 opsoclonus-myoclonus ataxia syndrome patients (12 female) and 474 healthy control children (406 female) were included. Curvature of the growth trajectories of the cerebral white and gray matter, cerebellar white and gray matter, and brainstem differed significantly between opsoclonus-myoclonus ataxia syndrome patients and healthy control children (cerebral white matter, P  = .01; cerebral gray matter, P  = .01; cerebellar white matter, P  < .001; cerebellar gray matter, P  = .049; brainstem, P  < .01)., Discussion/conclusion: We found abnormal brain maturation in the supratentorial brain, brainstem, and cerebellum in children with opsoclonus-myoclonus ataxia syndrome., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EAY has received research funding from National Multiple Sclerosis Society (NMSS), Consortium of Multiple Sclerosis Centers (CMSC), Canadian Institues of Health Research (CIHR), National Institutes of Health (NIH), Ontario Institute for Regenerative Medicine (OIRM), Stem Cell Network (SCN), The Garry Hurvitz Centre for Brain & Mental Health (GH-CBMH) Chase an Idea, SickKids Foundation, Rare Diseases Foundation, MS Scientific Foundation, McLaughlin Centre, Leong Center, and Peterson Foundation; investigator-initiated research funding from Biogen; and is on the scientific advisory board of Hoffman-LaRoche. She receives support as a member of the data safety monitoring board of a clinical trial from TG Therapeutics; speaker honoraria from Biogen, Johns Hopkins University (JHU), Saudi Epilepsy Society, New York University (NYU), MS-ATL (MS-At the Limits), Catamount Education, PRIME Education, and Canadian Neuropathology Society. The remaining authors report no disclosures relevant to the manuscript.

Background: Abstinence following treatment for alcohol use disorder (AUD) is associated with significant improvements in psychiatric and physical health, however, recent studies suggest resumption of low risk levels of alcohol use can also be beneficial. The present study assessed whether post-treatment levels of alcohol use were associated with cortical brain volumedifferences at treatment entry., Methods: Individuals seeking treatment for AUD (n=75) and light/non-drinking controls (LN, n=51) underwent 1.5T magnetic resonance imaging. The volumes of 34 bilateral cortical regions of interest (ROIs) were quantitated via FreeSurfer. Individuals with AUD were classified according to post-treatment alcohol consumption using the WHO risk drinking levels (abstainers: AB; low risk: RL; or higher risk: RH). Regional volumes for AB, RL and RH, at treatment entry, were compared to LN., Results: Relative to LN, AB demonstrated smaller volumes in 18/68 (26%), RL in 24/68 (35%) and RH in 34/68 (50%) ROIs with the largest magnitude volume differences observed between RH and LN. RH and RL reported a higher frequency of depressive disorders than AB. Among RH and RL, level of depressive and anxiety symptomatology were associated with daily number of drinks consumed after treatment., Conclusions: Volumetric differences, at treatment entry, in brain regions implicated in executive function and salience networks corresponded with post-treatment alcohol consumption levels suggesting that pre-existing differences in neural integrity may contribute to treatment outcomes. Depressive and anxiety symptomatology was also associated with brain morphometrics and alcohol use patterns, highlighting the importance of effectively targeting these conditions during AUD treatment., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke., Objective: We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations., Methods: Lung function was measured at participants' midlife in 1990-1992 (mean age = 56±5 years) and later-life in 2011-2013 (mean age = 76±5 years), and brain MRI was performed in 2011-2013. Linear regression models were used to examine the associations of lung function with brain and white matter hyperintensity (WMH) volumes, and logistic regression models were used for cerebral infarcts and microbleeds, adjusting for potential confounders., Results: In cross-sectional analysis (i.e., examining later-life lung function and MRI markers, n = 1,223), higher forced-expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with larger brain and lower WMH volumes [e.g., 8.62 (95% CI:2.54-14.71) cm3 greater total brain volume per one-liter higher FEV1]. No association was seen with microbleeds in the overall sample, but higher FVC was associated with lower odds of microbleeds in never-smokers and higher odds in ever-smokers. In the cross-temporal analysis (i.e., associations with midlife lung function, n = 1,787), higher FVC levels were significantly associated with lower later-life brain volumes., Conclusions: Our results support modest associations of better lung function with less neurodegenerative and cerebrovascular pathology, although findings for microbleeds were unexpected in ever-smokers.

Background: The potential neuroprotective effects of regular physical activity on brain structure are unclear, despite links between activity and reduced dementia risk., Objective: To investigate the relationships between regular moderate to vigorous physical activity and quantified brain volumes on magnetic resonance neuroimaging., Methods: A total of 10,125 healthy participants underwent whole-body MRI scans, with brain sequences including isotropic MP-RAGE. Three deep learning models analyzed axial, sagittal, and coronal views from the scans. Moderate to vigorous physical activity, defined by activities increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes via partial correlations. Analyses adjusted for age, sex, and total intracranial volume, and a 5% Benjamini-Hochberg False Discovery Rate addressed multiple comparisons., Results: Participant average age was 52.98±13.04 years (range 18-97) and 52.3% were biologically male. Of these, 7,606 (75.1%) reported engaging in moderate or vigorous physical activity approximately 4.05±3.43 days per week. Those with vigorous activity were slightly younger (p < 0.00001), and fewer women compared to men engaged in such activities (p = 3.76e-15). Adjusting for age, sex, body mass index, and multiple comparisons, increased days of moderate to vigorous activity correlated with larger normalized brain volumes in multiple regions including: total gray matter (Partial R = 0.05, p = 1.22e-7), white matter (Partial R = 0.06, p = 9.34e-11), hippocampus (Partial R = 0.05, p = 5.96e-7), and frontal, parietal, and occipital lobes (Partial R = 0.04, p≤1.06e-5)., Conclusions: Exercise-related physical activity is associated with increased brain volumes, indicating potential neuroprotective effects.

Background: Electroconvulsive therapy (ECT) remains the one of the most effective of biological antidepressant interventions. However, the exact neurobiological mechanisms underlying the efficacy of ECT remain unclear. A gap in the literature is the lack of multimodal research that attempts to integrate findings at different biological levels of analysis METHODS: We searched the PubMed database for relevant studies. We review biological studies of ECT in depression on a micro- (molecular), meso- (structural) and macro- (network) level., Results: ECT impacts both peripheral and central inflammatory processes, triggers neuroplastic mechanisms and modulates large scale neural network connectivity., Conclusions: Integrating this vast body of existing evidence, we are tempted to speculate that ECT may have neuroplastic effects resulting in the modulation of connectivity between and among specific large-scale networks that are altered in depression. These effects could be mediated by the immunomodulatory properties of the treatment. A better understanding of the complex interactions between the micro-, meso- and macro- level might further specify the mechanisms of action of ECT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Excessive C4A-gene expression may result in increased microglia-mediated synaptic pruning. As C4A overexpression is observed in schizophrenia spectrum disorders (SSD), this mechanism may account for the altered brain morphology (i.e. reduced volume and cortical thickness) and cognitive symptoms that characterize SSD. Therefore, this study investigates the association of C4A serum protein levels with brain morphology and cognition, and in particular whether this association differs between recent-onset SSD (n = 69) and HC (n = 40)., Methods: Serum C4A protein levels were compared between groups. Main outcomes included total gray matter volume, mean cortical thickness and cognitive performance. Regression analysis on these outcomes included C4A level, group (SSD vs. HC), and C4A*Group interactions. All statistical tests were corrected for age, sex, BMI, and antipsychotic medication dose. Follow-up analyses were performed on separate brain regions and scores on cognitive sub-tasks., Results: The group difference in C4A levels was not statistically significant (p = 0.86). The main outcomes did not show a significant interaction effect (p > 0.13) or a C4A main effect (p > 0.27). Follow-up analyses revealed significant interaction effects for the left medial orbitofrontal and left frontal pole volumes (p < 0.001): C4A was negatively related to these volumes in SSD, but positively in HC., Conclusion: This study demonstrated that C4A was negatively related to - specifically - frontal brain volumes in SSD, but this relation was inverse for HC. The results support the hypothesis of complement-mediated brain volume reduction in SSD. The results also suggest that C4A has a differential association with brain morphology in SSD compared to HC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the extent to which the regional brain volumes associated with slow gait speed can inform subsequent cognitive decline in older adults from the Rush Memory and Aging Project., Approach: We utilized deformation-based morphometry (DBM) in a whole-brain exploratory approach to identify the regional brain volumes associated with gait speed assessed over a short distance during an in-home assessment. We created deformation scores to summarize the gait-associated regions and entered the scores into a series of longitudinal mixed effects models to determine the extent to which deformation predicted change in cognition over time, controlling for associations between gait and cognition., Results: In 438 older adults (81 ± 7; 76% female), DBM revealed that slower gait speed was associated with smaller volumes across frontal white matter, temporal grey matter, and subcortical areas and larger volumes in the ventricles during the same testing cycle. When a subset was followed over multiple (5 ± 2) years, slower gait speed was also associated with annual declines in global cognition, executive functioning, and memory abilities. Several of the gait-related brain structures were associated with these declines in cognition; however, larger ventricles and smaller medial temporal lobe volumes proved most robust and attenuated the association between slow gait and cognitive decline., Conclusion: Regional brain volumes in the ventricles and temporal lobe associated with both slow gait speed and faster cognitive decline have potential to improve risk stratification for cognitive decline in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Poole, Oveisgharan, Yu, Dawe, Leurgans, Zhang, Arfanakis, Buchman and Bennett.)

Background: Cardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association., Methods: Using data from 38,803 adults (aged 40-70 years) and followed-up for 5-15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life's Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer's Disease polygenic risk score for all outcomes, among potential confounders., Results: In fully adjusted models, hospital-treated infections were inversely related to GM (β ± SE: -1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Log e transformed) (β ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (β ± SE:-0.0011 ± 0.0003, p < 0.001, P LE8×IB  < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections., Conclusions: Hospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Fort Belvoir Community Hospital, the Defense Health Agency, Department of Defense, or U.S. Government. Reference to any commercial products within this publication does not create or imply any endorsement by Fort Belvoir Community Hospital, the Defense Health Agency, Department of Defense, or U.S. Government., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v 1 (2004-2009) and v 2 (2009-2013) plasma NfL exposure and ancillary sMRI data at v scan (2011-2015, n = 179, mean v 1 to v scan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL (v1) was associated with larger WMLV (both Log e transformed), after 5-6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv 2 was linked to a 125 mm 3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfL bayes ). Among African American adults, NfL v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cigarette smoking is believed to accelerate age-related neurodegeneration. Despite significant sex differences in both smoking behaviors and brain structures, the active literature is equivocal in parsing out a sex difference in smoking-associated brain structural changes., Objective: The current study examined subcortical and lateral ventricle gray matter (GM) volume differences among smokers, active, past, and never-smokers, stratified by sex., Methods: The current study data included 1959 Dallas Heart Study (DHS) participants with valid brain imaging data. Stratified by gender, multiple-group comparisons of three cigarette-smoking groups were conducted to test whether there is any cigarette-smoking group differences in GM volumes of the selected regions of interest (ROIs)., Results: The largest subcortical GM volumetric loss and enlargement of the lateral ventricle were observed among past smokers for both females and males. However, these observed group differences in GM volumetric changes were statistically significant only among males after adjusting for age and intracranial volumes., Conclusions: The study findings suggest a sex difference in lifetime-smoking-associated GM volumetric changes, even after controlling for aging and intracranial volumes.

Background Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. Methods and Results A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. Z- scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of Z -score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate P <0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate P =0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate P =0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate P <0.027). Conclusions Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short- and long-term hypoxic injury.

This study explores the relationship of life-course intergenerational social mobility with cognitive function and brain structure in older adults using Diagonal Reference Models. Data from the Irish Longitudinal Study on Ageing, a population-based cohort of adults aged 50 years and older (N = 4 620 participants; mean age: 66.1; standard deviation: 9.1; 55% female) was used for analysis. Brain magnetic resonance imaging data were available for 464 participants. Social mobility was characterized as the difference between childhood socioeconomic position (SEP; ie, father's occupation) and adulthood SEP (ie, own occupation). The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), cortical thickness, and total gray matter volume (GMV) served as global cognitive and brain measures. Exploratory analyses included the volumes of the ventromedial prefrontal cortex (vmPFC), anterior cingulate (AC), hippocampus, and amygdala. A social gradient in cognitive function was observed among the intergenerationally stable; brain structure was not as clearly socially patterned. Adulthood SEP was significantly associated with MoCA (weight = 0.76; p < .001), MMSE (weight = 0.91; p < .001), GMV (weight = 0.77; p = .002), and AC volume (weight = 0.76; p < .001), whereas childhood SEP was associated with vmPFC volume (weight = 1.00; p = .003). There was no independent association of social mobility with any of the outcomes. Together our results suggest that both childhood and adulthood SEP are important in shaping later-life brain health, but that adulthood SEP predominates in terms of its influence. This is potentially an important insight as it suggests that brain health may be modifiable if socioeconomic circumstances change., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Hispanic/Latino adults are a growing segment of the older U.S. population yet are underrepresented in brain aging research. We aimed to characterize brain aging among diverse Hispanic/Latino individuals. Hispanic/Latino individuals (unweighted n = 2273 ages 35-85 years; 56% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) population-based study underwent magnetic resonance imaging (MRI) as part of the SOL- Investigation of Neurocognitive Aging MRI (SOL-INCA-MRI) ancillary study (2018-2022). We performed linear regressions to calculate age associations with brain volumes for each outcome (total (global) brain, hippocampal, lateral ventricle, total white matter hyperintensity (WMH), individual cortical lobar, and total cortical gray matter) and tested modification by sex. Older age was associated with smaller gray matter volumes and larger lateral ventricle and WMH volumes. Age-related differences in global brain volumes and gray matter volumes in specific regions (i.e., the hippocampus and temporal and occipital lobes) were less pronounced among women. Our findings warrant further investigation into sex-specific mechanisms of brain aging using longitudinal studies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Brain growth in early childhood is reflected in the evolution of proportional cerebrospinal fluid volumes (pCSF), grey matter (pGM), and white matter (pWM). We study brain development as reflected in the relative fractions of these three tissues for a cohort of 388 children that were longitudinally followed between the ages of 18 and 96 months. We introduce statistical methodology (Riemannian Principal Analysis through Conditional Expectation, RPACE) that addresses major challenges that are of general interest for the analysis of longitudinal neuroimaging data, including the sparsity of the longitudinal observations over time and the compositional structure of the relative brain volumes. Applying the RPACE methodology, we find that longitudinal growth as reflected by tissue composition differs significantly for children of mothers with higher and lower maternal education levels., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Race is commonly used as a proxy for multiple features including socioeconomic status. It is critical to dissociate these factors, to identify mechanisms that affect infant outcomes, such as birth weight, gestational age, and brain development, and to direct appropriate interventions and shape public policy., Methods: Demographic, socioeconomic, and clinical variables were used to model infant outcomes. There were 351 participants included in the analysis for birth weight and gestational age. For the analysis using brain volumes, 280 participants were included after removing participants with missing magnetic resonance imaging scans and those matching our exclusion criteria. We modeled these three different infant outcomes, including infant brain, birth weight, and gestational age, with both linear and nonlinear models., Results: Nonlinear models were better predictors of infant birth weight than linear models ( R 2  = 0.172 vs. R  = .005). In contrast to linear models, nonlinear models ranked income, neighborhood disadvantage, and experiences of discrimination higher in importance than race while modeling birth weight. Race was not an important predictor for either gestational age or structural brain volumes.2  = 0.145, p  = .005). In contrast to linear models, nonlinear models ranked income, neighborhood disadvantage, and experiences of discrimination higher in importance than race while modeling birth weight. Race was not an important predictor for either gestational age or structural brain volumes., Conclusions: Consistent with the extant social science literature, the findings related to birth weight suggest that race is a linear proxy for nonlinear factors related to structural racism. Methods that can disentangle factors often correlated with race are important for policy in that they may better identify and rank the modifiable factors that influence outcomes., (© 2023 The Authors.)

There is a strong link between irritable bowel syndrome and brain volumes, yet, to date, research examining the mediators of this association has been little. Based on the phenotypic data of 15 248 participants from the UK Biobank, a two-stage mediation analysis was performed to assess the association among brain volumes, anxiety, and irritable bowel syndrome. In the first stage, we identified the candidate mediating role of anxiety for irritable bowel syndrome associated with brain volumes using regression models. Then, we quantified the magnitude of the mediation effects by evaluating the average causal-mediated effect and proportion of mediation through performing mediation analyses in the R package in the second stage. In the first stage, we identified the partly mediating role of anxiety in the association between irritable bowel syndrome and the volume of thalamus ( P left = 1.16 × 10 -4 , P right = 2.41 × 10 -4 ), and grey matter ( P left = 3.22 × 10 -2 , P right = 1.18 × 10 -2 ) in the VIIIa cerebellum. In the second stage, we observed that the proportion of the total effect of irritable bowel syndrome on volume of thalamus mediated by anxiety was 14.3% for the left region ( β Average causal-mediated effect = -0.008, P Average causal-mediated effect x= 0.018) of the total effect of irritable bowel syndrome on the volume of grey matter in the VIIIa cerebellum. Our study revealed the indirect mediating role of anxiety in the association between irritable bowel syndrome and brain volumes, promoting our understanding of the functional mechanisms of irritable bowel syndrome and its related psychosocial factors.β Average causal-mediated effect = -0.007, P Average causal-mediated effect = 0.006). Anxiety mediated 30.8% for the left region ( β Average causal-mediated effect = -0.013, P Average causal-mediated effect = 0.002) and 21.6% for the right region ( β Average causal-mediated effect = -0.010, P Average causal-mediated effect x= 0.018) of the total effect of irritable bowel syndrome on the volume of grey matter in the VIIIa cerebellum. Our study revealed the indirect mediating role of anxiety in the association between irritable bowel syndrome and brain volumes, promoting our understanding of the functional mechanisms of irritable bowel syndrome and its related psychosocial factors., Competing Interests: The authors declare that the publication of this paper has no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Metacognitive knowledge has been little investigated in aMCI patients. The aim of this study is to examine whether there are specific deficits in knowledge of self, task and strategies in mathematical cognition, due its importance for everyday functioning, mainly due to its importance for financial capacity in old age. A total of 24 patients with a diagnosis of aMCI and one-to-one 24 matched individuals (similar age, education and gender) were examined at three time points in a year with a number of neuropsychological tests and a slightly modified version of the Metacognitive Knowledge in Mathematics Questionnaire (MKMQ). We analyzed longitudinal MRI data regarding various brain areas for the aMCI patients. Results indicated that the aMCI group differed in all MKMQ subscale scores at the three time points compared to healthy controls. Correlations were found only for metacognitive avoidance strategies and left and right amygdala volumes at baseline, while after twelve months correlations were found for avoidance and right and left parahippocampal volumes. These preliminary results highlight the role of specific brain regions that could be used as indices in clinical practice for the detection of metacognitive knowledge deficits that are found in aMCI.

Purpose: Following a case-control design, as a primary objective, this study aimed to explore the relationship between quality of life (QoL) scores and gray matter (GM) volumes in patients with Huntington's disease (HD). As a secondary objective, we assessed the relationship between QoL scores and other important behavioral, clinical and demographical variables in patients with HD and HD patients' caregivers., Methods: We recruited 75 participants (25 HD patients, 25 caregivers, and 25 controls) and assessed their QoL using the World Health Organization Quality of Life scale-Brief Version (WHOQOL-BREF). Participants were also assessed with general cognitive functioning tests and clinical scales. In addition, we acquired MRI scans from all participants., Results: Our results showed that patients exhibited significantly lower scores in all four QoL domains (physical health, psychological wellbeing, social relationships, and relationship with the environment) compared to caregivers and controls. Caregivers showed lower scores than controls in the physical health and the environmental domains. In HD patients, lower scores in QoL domains were associated with lower GM volumes, mainly in the precuneus and the cerebellum. Moreover, in HD patients, physical disability and GM volume reduction were significant predictors of QoL decrease in all domains. For caregivers, years of formal education was the most important predictor of QoL., Conclusions: HD patients exhibit greater GM volume loss as well as lower QoL scores compared to caregivers and controls. However, caregivers displayed lower scores in QoL scores than controls, with years of education being a significant predictor. Our results reflect a first attempt to investigate the relationships among QoL, GM volumes, and other important factors in an HD and HD caregiver sample., (© 2022. The Author(s).)

Background: Strength and mobility are essential for activities of daily living. With aging, weaker handgrip strength, mobility, and asymmetry predict poorer cognition. We therefore sought to quantify the relationship between handgrip metrics and volumes quantified on brain magnetic resonance imaging (MRI)., Objective: To model the relationships between handgrip strength, mobility, and MRI volumetry., Methods: We selected 38 participants with Alzheimer's disease dementia: biomarker evidence of amyloidosis and impaired cognition. Handgrip strength on dominant and non-dominant hands was measured with a hand dynamometer. Handgrip asymmetry was calculated. Two-minute walk test (2MWT) mobility evaluation was combined with handgrip strength to identify non-frail versus frail persons. Brain MRI volumes were quantified with Neuroreader. Multiple regression adjusting for age, sex, education, handedness, body mass index, and head size modeled handgrip strength, asymmetry and 2MWT with brain volumes. We modeled non-frail versus frail status relationships with brain structures by analysis of covariance., Results: Higher non-dominant handgrip strength was associated with larger volumes in the hippocampus (p = 0.02). Dominant handgrip strength was related to higher frontal lobe volumes (p = 0.02). Higher 2MWT scores were associated with larger hippocampal (p = 0.04), frontal (p = 0.01), temporal (p = 0.03), parietal (p = 0.009), and occipital lobe (p = 0.005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes., Conclusion: Greater handgrip strength and mobility were related to larger hippocampal and lobar brain volumes. Interventions focused on improving handgrip strength and mobility may seek to include quantified brain volumes on MR imaging as endpoints.

The purpose of the study is to quantify volumetric variations of cortical and subcortical brain structures after Vim ablation using MRgFUS, and correlate them with the patients’ clinical features and treatment outcomes. For this pilot retrospective study we enrolled 31 patients with a mean age of 70.86 years who were eligible for unilateral Vim thalamotomy. Clinical evaluation included tremor severity assessment using the FTM scale and cognitive assessment using the MoCA score. MRI data were acquired with a 3T scanner, using a dedicated 32-channel coil and acquiring a volumetric sequence of T1 3D IR FSPGR (BRAVO), before treatment and one year after MRgFUS thalamotomy. Image processing and volume data extraction were conducted with dedicated software. A volumetric analysis showed a significant reduction (p < 0.05) of the left thalamus 1 year after the treatment in patients with ET. Other significant results were found on the same side in the other nuclei of the basal ganglia and in the cerebellar cortex. In confronting the two groups (ET, PD), no significant differences were found in terms of age, FTM, MoCA scores, or brain volumes. Similarly, no significant correlations were found between the FTM and MoCA scores and the brain volumes before the treatment.

Point-of-care human milk analysis is now feasible in the neonatal intensive care unit (NICU) and allows accurate measurement of macronutrient delivery. Higher macronutrient intakes over this period may promote brain growth and development. In a prospective, observational study of 55 infants born at <32 weeks’ gestation, we used a mid-infrared spectroscopy-based human milk analyzer to measure the macronutrient content in repeated samples of human milk over the NICU hospitalization. We calculated daily nutrient intakes from unfortified milk and assigned infants to quintiles based on median intakes over the hospitalization. Infants underwent brain magnetic resonance imaging at term equivalent age to quantify total and regional brain volumes and fractional anisotropy of white matter tracts. Infants in the highest quintile of energy intake from milk, as compared with the lower four quintiles, had larger total brain volume (31 cc, 95% confidence interval [CI]: 5, 56), cortical gray matter (15 cc, 95%CI: 1, 30), and white matter volume (23 cc, 95%CI: 12, 33). Higher protein intake was associated with larger total brain (36 cc, 95%CI: 7, 65), cortical gray matter (22 cc, 95%CI: 6, 38) and deep gray matter (1 cc, 95%CI: 0.1, 3) volumes. These findings suggest innovative strategies to close nutrient delivery gaps in the NICU may promote brain growth for preterm infants.

Background: Compared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes., Methods: Objective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (<34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate., Results: Images were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found., Conclusions: Results reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Damiano, Pekar, Mori, Faria, Ye, Stashinko, Stanley, Alter, Hoon and Chin.)

Individual impacts of alcohol misuse and HIV on brain structure and function have been well demonstrated; however, the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use in HIV infection. We aimed to determine the effects of unhealthy alcohol use on brain morphometry and cognitive function amongst people with HIV (PWH). In 27 (50.9%) HIV-positive users of alcohol and 26 (49.1%) HIV-positive abstainers from alcohol, results revealed significant differences for left and right amygdala (p < 0.01), left and right hippocampus (p = 0.05), left and right posterior cingulate (p < 0.01), left and right precuneus (p < 0.01), left insula (p < 0.01), left and right caudate (p < 0.01), right thalamus (p < 0.01), and corpus callosum (p < 0.05). Mean volume of these regions was significantly smaller in HIV-positive alcohol users compared to HIV-positive abstainers. Homogeneity of slopes ANCOVA revealed significant associations between anterior cingulate cortex, precuneus, amygdala, hippocampus, and insula volumes and cognitive function in the domains of learning and delayed recall, motor function, speed of information processing, executive function, attention/working memory, and language. Among PWH, unhealthy alcohol use is associated with negative effects on brain structure and cognitive function., (© 2021. Journal of NeuroVirology, Inc.)

Background: Sleep disturbance is characteristic of schizophrenia and at-risk populations, suggesting a possible etiological role in psychosis. Biological mechanisms underlying associations between sleep and psychosis vulnerability are unclear, although reduced sleep-regulatory brain structure volumes are a proposed contributor. This study is the first to examine relationships between psychotic-like experiences (PLEs; subclinical symptoms reflecting psychosis vulnerability/risk), sleep, and brain volumes in youth., Methods: Brain volumes of five sleep-related structures were examined in relation to PLEs and difficulties initiating and maintaining sleep (DIMS) in 9260 9-11 year-olds participating in the Adolescent Brain Cognitive Development (ABCD) study. Analytic models examined relationships between DIMS, PLEs, and brain volumes, as well as DIMS as a mediator of brain volume-PLEs relationships. Although sleep regulation structures (i.e., thalamus, basal forebrain, hypothalamus) were of primary interest, other potentially-relevant structures to sleep-related functioning and psychosis (i.e., hippocampus, amygdala) were also examined., Results: PLEs were associated with increased DIMS as well as reduced volume in some, but not all, brain structures, including the thalamus and basal forebrain in children. DIMS was also associated with reduced left thalamus volume in youth. Increased DIMS partially, statistically mediated the relationship between left thalamic volume and PLEs, although the effect was relatively small., Conclusions: Results highlight left thalamic volume as a potential neural mechanism underlying sleep disturbances and PLEs in childhood. Future studies should assess causal relationships between sleep, PLEs, and brain structure across adolescent development, interactions with other psychosis risk factors, and the role of sleep interventions in prevention of psychosis and a range of psychiatric conditions across the lifespan., Competing Interests: CONFLICT OF INTERESTS The authors declare that they have no competing or potential conflicts of interest.

In their comprehensive review of sex differences in the brain, Eliot et al. (2021) conclude that (1) men and women significantly differ in global brain size, but this "mostly parallels the divergence of male/female body size during development" and that (2) "once we account for individual differences in brain size, there is almost no difference in the volume of specific cortical or subcortical structures between men and women". In sum, almost all brain differences would directly or indirectly follow from differences in body size. In a recent study that does not have the same limitations as most studies reviewed by Eliot et al., we find that sex differences in total brain volume are not accounted for by sex differences in height and weight, and that once global brain size is taken into account, there remain numerous regional sex differences in both directions (Williams et al., 2021)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Few neuroimaging studies are sufficiently large to adequately describe population-wide variations. This study's primary aim was to generate neuroanatomical norms and individual markers that consider age, sex, and brain size, from 629 cerebral measures in the UK Biobank (N = 40,028). The secondary aim was to examine the effects and interactions of sex, age, and brain allometry-the nonlinear scaling relationship between a region and brain size (e.g., total brain volume)-across cerebral measures. Allometry was a common property of brain volumes, thicknesses, and surface areas (83%) and was largely stable across age and sex. Sex differences occurred in 67% of cerebral measures (median |β| = .13): 37% of regions were larger in males and 30% in females. Brain measures (49%) generally decreased with age, although aging effects varied across regions and sexes. While models with an allometric or linear covariate adjustment for brain size yielded similar significant effects, omitting brain allometry influenced reported sex differences in variance. Finally, we contribute to the reproducibility of research on sex differences in the brain by replicating previous studies examining cerebral sex differences. This large-scale study advances our understanding of age, sex, and brain allometry's impact on brain structure and provides data for future UK Biobank studies to identify the cerebral regions that covary with specific phenotypes, independently of sex, age, and brain size., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Purpose: It is unknown whether frequently occurring mild brain lesions affect brain volumes in moderate (MP 2 ; 32 +0 -33 +6 weeks' gestation) and late (LP 3 ; 34 +0 -35 +6 weeks' gestation) preterm infants. Therefore, we aimed to investigate the effect of mild brain lesions on brain volumes in moderate-late preterm (MLPT 4 ) infants and to compare brain volumes between MP and LP infants., Methods: From August 2017 to November 2019, eligible MLPT infants born at Isala Women and Children's Hospital were enrolled in a prospective cohort study (Brain Imaging in Moderate-late Preterm infants 'BIMP-study'). MRI was performed around term equivalent age (TEA 5 ). MRI scans were assessed for (mild) brain lesions. T2-weighted images were used for automatic segmentation of eight brain structures. Linear regression analysis was performed to compare absolute and relative brain volumes between infants with and without mild brain lesions and between MP and LP infants., Results: 36 MP and 68 LP infants were included. In infants with mild brain lesions, intracranial volume (B = 27.4 cm 3 , p = 0.02), cerebrospinal fluid (B = 8.78 cm 3 , p = 0.01) and cerebellar volumes (B = 1.70 cm 3 , p = 0.03) were significantly larger compared to infants without mild brain lesions. After correction for weight and postmenstrual age at MRI, these volumes were no longer significantly different. LP infants had larger brain volumes than MP infants, but differences were not significant. Relative brain volumes showed no significant differences in both analyses., Conclusion: Neither having mild brain lesions, nor being born moderate prematurely affected brain volumes at TEA in MLPT infants., Competing Interests: Declarations of interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory., Methods: Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII., Results: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory., Conclusions: High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans., (© 2021 Research Society on Alcoholism.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood., (Copyright © 2021. Published by Elsevier Inc.)

Background : Increasing efforts have focused on the establishment of novel biomarkers for the early detection of Alzheimer's disease (AD) and prediction of Mild Cognitive Impairment (MCI)-to-AD conversion. Behavioral changes over the course of healthy ageing, at disease onset and during disease progression, have been recently put forward as promising markers for the detection of MCI and AD. The present study examines whether the temporal characteristics of speech in a collaborative referencing task are associated with cognitive function and the volumes of brain regions involved in speech production and known to be reduced in MCI and AD pathology. We then explore the discriminative ability of the temporal speech measures for the classification of MCI and AD. Method : Individuals with MCI, mild-to-moderate AD and healthy controls (HCs) underwent a structural MRI scan and a battery of neuropsychological tests. They also engaged in a collaborative referencing task with a caregiver. The associations between the conversational speech timing features, cognitive function (domain-specific) and regional brain volumes were examined by means of linear mixed-effect modeling. Genetic programming was used to explore the discriminative ability of the conversational speech features. Results : MCI and mild-to-moderate AD are characterized by a general slowness of speech, attributed to slower speech rate and slower turn-taking in conversational settings. The speech characteristics appear to be reflective of episodic, lexico-semantic, executive functioning and visuospatial deficits and underlying volume reductions in frontal, temporal and cerebellar areas. Conclusion : The implementation of conversational speech timing-based technologies in clinical and community settings may provide additional markers for the early detection of cognitive deficits and structural changes associated with MCI and AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 De Looze, Dehsarvi, Crosby, Vourdanou, Coen, Lawlor and Reilly.)

Moving from the central role of the thalamus in the integration of inner and external stimuli and in the implementation of a stress-related response, the objective of the present study was to investigate the presence of any MRI structural and volumetric changes of the thalamic structures in earthquake witnesses. Forty-one subjects were included, namely 18 university students belonging to the experimental earthquake-exposed group (8 males and 10 females, mean age 24.5 ± 1.8 years) and a control group of 23 students not living in any earthquake-affected areas at the time of the earthquake (14 males and 9 females, mean age 23.7 ± 2.0 years). Instrumental MRI evaluation was performed using a 3-Tesla scanner, by acquiring a three-dimensional fast spoiled gradient-echo (FSPGR) sequence for volumetric analysis and an EPI (echoplanar imaging) sequence to extract fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. As compared to the control one, the experimental group showed significantly lower gray matter volume in the mediodorsal nucleus of the left thalamus ( p < 0.001). The dominant hemisphere thalamus in the experimental group showed higher mean ADC values and lower mean FA values as compared to the control group.

Background: Anemia and red cell distribution width (RDW) have been linked to poor cognitive performance, pending studies of underlying mechanisms., Objective: We examined cross-sectional relationships of initial RDW status (v1), RDW change (δ), and anemia with brain structural magnetic resonance imaging (sMRI) markers, including global and cortical brain and hippocampal and white matter lesion (WML) volumes, 5-6 years later., Methods: Data were used from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study with complete v1 (2004-2009) and v2 (2009-2013) exposures and ancillary sMRI data at vscan (2011-2015, n = 213, mean v1 to vscan time: 5.7 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, by race, and within non-anemics, correcting for multiple testing with q-values., Results: In minimally adjusted models (socio-demographics and follow-up time), anemiav1 and RDWv1 were consistently associated with smaller bilateral hippocampal volumes overall, and among females (q < 0.05), without significant sex differences. RDWv1 was related to smaller select regional cortical brain gray and white matter volumes in hematological measure-adjusted models; anemiav1 was associated with larger WML volumes only among whites., Conclusion: In summary, baseline anemia and RDW were consistently associated with smaller bilateral hippocampal volumes, particularly among females, while anemia was linked to larger WML volume among Whites. In hematological measure-adjusted models, baseline RDW was linked to smaller regional gray and white matter volumes. Pending studies with sMRI repeats, randomized controlled trials are needed, demonstrating associations of anemia and elevated RDW with reduced brain volumes and cognitive dysfunction.

Markers of cerebral small vessel disease (CSVD) have previously been associated with age-related cognitive decline. Using longitudinal data of cognitively healthy, older adults (N = 216, mean age at baseline = 70.9 years), we investigated baseline status and change in white matter hyperintensities (WMH) (total, periventricular, deep), normal appearing white matter (NAWM), brain parenchyma volume (BPV) and processing speed over seven years as well as the impact of different covariates by applying latent growth curve (LGC) models. Generally, we revealed a complex pattern of associations between the different CSVD markers. More specifically, we observed that changes of deep WMH (dWMH), as compared to periventricular WMH (pWMH), were more strongly related to the changes of other CSVD markers and also to baseline processing speed performance. Further, the number of lacunes rather than their volume reflected the severity of CSVD. With respect to the studied covariates, we revealed that higher education had a protective effect on subsequent total WMH, pWMH, lacunar number, NAWM volume, and processing speed performance. The indication of antihypertensive drugs was associated with lower lacunar number and volume at baseline and the indication of antihypercholesterolemic drugs came along with higher processing speed performance at baseline. In summary, our results confirm previous findings, and extend them by providing information on true within-person changes, relationships between the different CSVD markers and brain-behavior associations. The moderate to strong associations between changes of the different CSVD markers indicate a common pathological relationship and, thus, support multidimensional treatment strategies., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI)., Objective: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China., Methods: This population-based study included 180 participants (aged≥65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014-2016. We defined aMCI following the Petersen's criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using general linear regression models., Results: Multi-adjusted β-coefficient (95% confidence interval) of brain volumes (cm3) associated with aMCI was -12.07 (-21.49, -2.64) for global grey matter (GM), -18.31 (-28.45, -8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p < 0.05)., Conclusion: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes.

Background: Ketamine is a novel fast-acting antidepressant. Acute ketamine treatment can reverse microstructure deficits and normalize functional alterations in the brain, but little is known about the impacts of ketamine on brain volumes in individuals with depression., Methods: We used 3 T magnetic resonance imaging (MRI) and tensorbased morphological methods to investigate the regional volume differences for 29 healthy control (HC) subjects and 21 subjects with major depressive disorder (MDD), including 10 subjects with comorbid post-traumatic stress disorder (PTSD). All the subjects participated in MRI scanning before and 24 h post intravenous ketamine infusion. The effects of acute ketamine administration on HC, MDD, and MDD/PTSD groups were examined separately by whole-brain voxel-wise t-tests., Results: Our data showed smaller volume of inferior frontal gyrus (IFG, opercular part) in MDD and MDD/PTSD subjects compared to HC, and a significant correlation between opercular IFG volume and depressive severity in MDD subjects only. Ketamine administration normalized the structural alterations of opercular IFG in both MDD and MDD/PTSD groups, and significantly improved depressive and PTSD symptoms. Twenty-four hours after a single ketamine infusion, there were two clusters of voxels with volume changes in MDD subjects, including significantly increased volumes of opercular IFG. No significant structural alterations were found in the MDD/PTSD or HC groups., Conclusion: These findings provide direct evidence that acute ketamine administration can normalize structural alterations associated with depression and highlight the importance of IFG in the guidance of future therapeutic targets., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.