Brain Volume Changes Research Articles

The Diagnostic Challenges of Late-onset Neuropsychiatric Symptoms and Early-onset Dementia: A Clinical and Neuropathological Case Study

The emergence of new-onset neuropsychiatric symptoms in middle age presents a diagnostic challenge, particularly when differentiating between a primary psychiatric disorder and an early neurodegenerative disease. The discrepancy between bedside clinical diagnosis and subsequent neuropathological findings in such cases further highlights the difficulty of accurately predicting pathology, especially when there are no evident focal lesions or changes in brain volume. Here we present the case of a 59-year-old woman with inconclusive neuroimaging who exhibited pronounced neuropsychiatric and behavioral symptoms initially suggestive of a mood disorder, then of behavioral variant frontotemporal dementia. However, upon autopsy, we identified coexisting Lewy body disease pathology and tau-related changes, including argyrophilic grain disease and primary age–related tauopathy. This case illustrates the challenges encountered when diagnosing late-onset neuropsychiatric symptoms, emphasizes the link between such symptoms and early-onset dementia and argyrophilic grain disease, and contributes to our understanding of the impact of mixed neuropathology in this population. Accurate diagnosis is essential for the development of molecular-specific therapies and, as well as for accurate prognosis and enrollment in clinical trials.

Brain volume loss after cranial irradiation: a controlled comparison study between photon vs proton radiotherapy for WHO grade 2-3 gliomas.

Radiation therapy (RT) is an integral treatment component in patients with glioma but associated with neurotoxicity. Proton RT (PRT), as compared with photon RT (XRT), reduces excess radiation to nontarget tissue. We used a retrospective method to evaluate brain imaging metrics of neurotoxicity after treatment with PRT and XRT for glioma. We analyzed brain volume change in thirty-four patients with WHO grade 2-3 gliomas treated with either PRT (n = 17) or XRT (n = 17). Both groups were carefully matched by demographic/clinical criteria and assessed longitudinally for two years post-radiotherapy. Brain volume change was measured as ventricular volume expansion in the tumor free hemisphere (contralateral to RT target) as a proxy indicator of brain volume loss. We further assessed the impact of volumetric changes on cognition in PRT patients, who completed neuropsychological testing as part of an outcome study. We found significant ventricular volume increases in the contralesional hemisphere in both groups at two years post-RT (F(1, 31) = 18.45, p < 0.000, partial η2 = 0.373), with greater volume change observed in XRT (26.55%) vs. PRT (12.03%) (M = 12.03%, SD = 16.26; F(1,31) = 4.26, p = 0.048, partial η2 = 0.121). Although, there was no group-level change on any cognitive test in PRT treated patients, individual changes on cognitive screening, working memory, processing speed and visual memory tasks correlated with contralesional brain volume loss. This study suggests progressive brain volume loss following cranial irradiation, with greater severity after XRT vs. PRT. Radiation-induced brain volume loss appears to be associated with measurable cognitive changes on an individual level. Prospective studies are warranted to validate these findings and their impacts on long-term cognitive function and quality of life. An improved understanding of the structural and functional consequences of cranial radiation is essential to develop neuroprotective strategies.

Slowly expanding lesions are associated with disease activity and gray matter loss in relapse-onset multiple sclerosis.

Slowly expanding lesions (SELs) have been proposed as novel MRI markers of chronic active lesions in multiple sclerosis (MS). However, the mechanism through which SELs affect brain volume loss in patients with MS remains unknown. Additionally, the prevalence and significance of SELs in Asian patients with MS remain unclear. This study aimed to investigate the association between SELs and no evidence of disease activity (NEDA)-3 status as well as brain volume loss in Japanese patients. A total of 99 patients with relapse-onset MS were retrospectively evaluated. SELs were identified on brain MRI based on local deformation when consecutive scans were registered longitudinally. We developed a logistic regression model and generalized linear mixed models (GLMMs) to evaluate the association between the number of SELs and disease activity and changes in brain volume. During the observation period (2.0±0.22years), 35 patients developed at least one SEL. Multivariable logistic regression analysis showed that ≥2 SELs were associated with 0.2 times the risk of achieving a NEDA-3 status. GLMMs revealed that the number of SELs was negatively associated with volume changes in the cortex (p=.00169) and subcortical gray matter (p=.00964) after correction for multiple comparisons. SELs were identified in Japanese patients with MS during the 2-year observation period. The number of SELs is associated with disease activity and brain volume loss, suggesting that the number of SELs could be a biomarker of disease activity in MS.

Decoding Brain Development and Aging

Abstract The aging process induces a variety of changes in the brain detectable by magnetic resonance imaging (MRI). These changes include alterations in brain volume, fluid-attenuated inversion recovery (FLAIR) white matter hyperintense lesions, and variations in tissue properties such as relaxivity, myelin, iron content, neurite density, and other microstructures. Each MRI technique offers unique insights into the structural and compositional changes occurring in the brain due to normal aging or neurodegenerative diseases. Age-related brain volume changes encompass a decrease in gray matter and an increase in ventricular volume, associated with cognitive decline. White matter hyperintensities, detected by FLAIR, are common and linked to cognitive impairments and increased risk of stroke and dementia. Tissue relaxometry reveals age-related changes in relaxivity, aiding the distinction between normal aging and pathological conditions. Myelin content, measurable by MRI, changes with age and is associated with cognitive and motor function alterations. Iron accumulation, detected by susceptibility-sensitive MRI, increases in certain brain regions with age, potentially contributing to neurodegenerative processes. Diffusion MRI provides detailed insights into microstructural changes such as neurite density and orientation. Neurofluid imaging, using techniques like gadolinium-based contrast agents and diffusion MRI, reveals age-related changes in cerebrospinal and interstitial fluid dynamics, crucial for brain health and waste clearance. This review offers a comprehensive overview of age-related brain changes revealed by various MRI techniques. Understanding these changes helps differentiate between normal aging and pathological conditions, aiding the development of interventions to mitigate age-related cognitive decline and other symptoms. Recent advances in machine learning and artificial intelligence have enabled novel methods for estimating brain age, offering also potential biomarkers for neurological and psychiatric disorders.

Impact of Clinical Progression on Brain Volume Changes in Patients with Anti-NMDAR Autoimmune Encephalitis

Impact of Clinical Progression on Brain Volume Changes in Patients with Anti-NMDAR Autoimmune Encephalitis

9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis

BackgroundMultiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage. ObjectivesTo investigate the potential association between plasma-derived LMs and MRI-quantified WM damage using fractional anisotropy (FA) and grey matter (GM) atrophy in dimethyl fumarate-treated relapsing remitting MS (RRMS) patients. MethodsSeverity of FA-based WM damage and GM atrophy was determined in RRMS patients (n=28) compared to age- and sex-matched controls (n=31) at treatment initiation (baseline) and after 6 months. Plasma LMs were assessed using HPLC-MS/MS and baseline LMs were correlated to changes in FA and brain volumes. ResultsWe observed significant WM damage in RRMS patients (mean age 41.4 [SD 9.1]) at baseline and follow-up (z-score=-0.33 and 0.31, respectively) compared to controls (mean age 41.9 [SD 9.5]; p<0.001 for both comparisons). Patients with severe WM damage showed a decline of thalamic volume (p=0.02), and this decline correlated (r=0.51, p<0.001) with lower baseline levels of 9-HODE. This LM also predicted FA worsening (beta=0.14, p<0.001) over time at 6 months. ConclusionDespite the relatively small sample size, lower baseline levels of the LM 9-HODE correlated with more thalamic atrophy and predicted subsequent worsening of WM damage in RRMS patients.

Correlating stroke risk with non-invasive cerebrovascular perfusion dynamics using a portable speckle contrast optical spectroscopy laser device.

Stroke poses a significant global health threat, with millions affected annually, leading to substantial morbidity and mortality. Current stroke risk assessment for the general population relies on markers such as demographics, blood tests, and comorbidities. A minimally invasive, clinically scalable, and cost-effective way to directly measure cerebral blood flow presents an opportunity. This opportunity has the potential to positively impact effective stroke risk assessment prevention and intervention. Physiological changes in the cerebrovascular system, particularly in response to hypercapnia and hypoxia during voluntary breath-holding can offer insights into stroke risk assessment. However, existing methods for measuring cerebral perfusion reserves, such as blood flow and blood volume changes, are limited by either invasiveness or impracticality. Herein we propose a non-invasive transcranial approach using speckle contrast optical spectroscopy (SCOS) to non-invasively monitor regional changes in brain blood flow and volume during breath-holding. Our study, conducted on 50 individuals classified into two groups (low-risk and higher-risk for stroke), shows significant differences in blood dynamic changes during breath-holding between the two groups, providing physiological insights for stroke risk assessment using a non-invasive quantification paradigm. Given its cost-effectiveness, scalability, portability, and simplicity, this laser-centric tool has significant potential for early diagnosis and treatment of stroke in the general population.

Impact of social isolation on change in brain volume in community-dwelling older Japanese people: The NEIGE Study

BackgroundSeveral studies have shown that social isolation is a risk factor for cognitive decline and dementia; however, its neurological mechanisms are not fully understood. Using longitudinal data, this study examined the effects of social isolation on hippocampal and total gray matter volumes in community-dwelling older Japanese individuals. MethodsData were obtained from the Neuron to Environmental Impact Across Generations (NEIGE) Study conducted in Tokamachi City (Niigata Prefecture, Japan), including 279 community-dwelling persons aged 65–84 years who underwent brain magnetic resonance imaging in 2017 and 2021 (male: 47.6 %; mean age: 73.0 years). We investigated two dimensions of social isolation: poor social networks and solitary living. ResultsMultiple regression analysis with inverse probability weighting showed that individuals with a social contact frequency of <1 time/week had a greater decrease in hippocampal volume than those with a contact frequency of more than or equal to 4 times/week, whereas those who lived alone tended to have a smaller decrease in hippocampal volume than those who lived with others. We found no association between the frequency of social contact, living alone, and total gray matter volume. Furthermore, there was no interaction between sex and age for any of the outcomes. ConclusionOur longitudinal analysis suggested that the relationship between social isolation and dementia onset may be mediated by hippocampal atrophy; however, the direction of the influence depends on the isolation type. These findings are expected to contribute to the elucidation of the social mechanisms underlying dementia onset.

Circadian Rhythms Tied to Changes in Brain Morphology in a Densely Sampled Male.

Circadian, infradian, and seasonal changes in steroid hormone secretion have been tied to changes in brain volume in several mammalian species. However, the relationship between circadian changes in steroid hormone production and rhythmic changes in brain morphology in humans is largely unknown. Here, we examined the relationship between diurnal fluctuations in steroid hormones and multiscale brain morphology in a precision imaging study of a male who completed 40 MRI and serological assessments at 7 A.M. and 8 P.M. over the course of a month, targeting hormone concentrations at their peak and nadir. Diurnal fluctuations in steroid hormones were tied to pronounced changes in global and regional brain morphology. From morning to evening, total brain volume, gray matter volume, and cortical thickness decreased, coincident with decreases in steroid hormone concentrations (testosterone, estradiol, and cortisol). In parallel, cerebrospinal fluid and ventricle size increased from A.M. to P.M. Global changes were driven by decreases within the occipital and parietal cortices. These findings highlight natural rhythms in brain morphology that keep time with the diurnal ebb and flow of steroid hormones.

Early Life Neuroimaging: The Generalizability of Cortical Area Parcellations Across Development.

The cerebral cortex comprises discrete cortical areas that form during development. Accurate area parcellation in neuroimaging studies enhances statistical power and comparability across studies. The formation of cortical areas is influenced by intrinsic embryonic patterning as well as extrinsic inputs, particularly through postnatal exposure. Given the substantial changes in brain volume, microstructure, and functional connectivity during the first years of life, we hypothesized that cortical areas in 1-to-3-year-olds would exhibit major differences from those in neonates and progressively resemble adults as development progresses. Here, we parcellated the cerebral cortex into putative areas using local functional connectivity gradients in 92 toddlers at 2 years old. We demonstrated high reproducibility of these cortical regions across 1-to-3-year-olds in two independent datasets. The area boundaries in 1-to-3-year-olds were more similar to adults than neonates. While the age-specific group parcellation fitted better to the underlying functional connectivity in individuals during the first 3 years, adult area parcellations might still have some utility in developmental studies, especially in children older than 6 years. Additionally, we provided connectivity-based community assignments of the parcels, showing fragmented anterior and posterior components based on the strongest connectivity, yet alignment with adult systems when weaker connectivity was included.

Association of open skill exercise and long-chain polyunsaturated fatty acid intake with brain volume changes among older community-dwelling Japanese individuals

Considering that a multifactorial lifestyle approach may prove more effective than a single factor approach to improve or maintain brain health, we evaluated the association of exercise (open skill exercise [OSE] or closed skill exercise [CSE]) combined with long-chain polyunsaturated fatty acid (LCPUFAs) (docosahexaenoic acid [C22:6n-3, DHA], eicosapentaenoic acid [C20:5n-3, EPA], and arachidonic acid [C20:4n-6, ARA]) intake with brain atrophy among older Japanese individuals (n = 795, aged 60–88 years) without a self-reported history of dementia based on the datasets of a two-year longitudinal study. Brain volumes were measured using three-dimensional T1-weighted brain magnetic resonance imaging for follow-up periods of two years. The associations between multivariate-adjusted changes in brain volumes and OSE or CSE frequency (≥ once/month and < once/month) along with LCPUFA intake (≥ median and < median) at the baseline were assessed using a general linear model. Subgroup analysis was performed by restricting DHA and EPA intakes (n = 263; median, 323 mg/d), which represented levels similar to those in countries with low fish consumption. Higher OSE frequencies, ARA intakes, and their combination were inversely associated with decreases in total gray matter and frontal cortex volumes. In subgroup analysis, a combination of higher OSE frequencies and DHA intakes was also associated with a smaller decrease in total gray matter volume. Overall, our findings suggest that regular OSE engagement and appropriate LCPUFA intake may contribute to preventing brain volume decreases in older individuals.

Hyperhomocysteinemia and its effect on ageing and language functions – HEAL study

Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke’s Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [β (95% CI) − 1.354 (− 2.655, − 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [β (95% CI) − 5617.182 (− 11062.762, − 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function.

Predicting brain atrophy and cognitive aging trajectories with baseline subjective cognitive concerns in cognitively normal older adults

Subjective cognitive concerns (SCC) are common even in cognitively normal older adults who lack objectively-detectable deficits on standard neuropsychological evaluation. The clinical relevance of these concerns, particularly considering the nature of concerns (e.g., memory versus non-memory), remains unclear. Thus, we examined whether baseline memory and non-memory SCC relate to longitudinal change in brain volume and neuropsychological test performance in 476 functionally-intact, objectively unimpaired older adults (Mage = 72y, 56 % female, follow-up time = 1 – 9 years). Mixed-effects models revealed that both higher baseline memory and non-memory SCC predicted greater atrophy in total gray matter and dorsolateral prefrontal cortex atrophy over time, while only memory SCC predicted steeper medial temporal lobe atrophy. Regarding neuropsychological performance, higher non-memory SCC predicted decline in processing speed performance, while memory SCC did not predict neuropsychological trajectories. SCC are a risk factor for more adverse brain and cognitive aging trajectories, even in functionally-intact, seemingly cognitively normal older adults.

A Comparison of Pre- and Post-Treatment Cranial MRI Characteristics in Patients with Pediatric Epilepsy Receiving Levetiracetam.

Background and Objectives: This study was performed for the purpose of assessing whether antiepileptic levetiracetam treatment produces a change in brain volumes in children with epilepsy. To that end, we compared the volumes of the basal ganglia (caudate nucleus, putamen, globus, hip-pocampus, and thalamus) at magnetic resonance imaging (MRI) before and after treatment (months 18-24) in pediatric epilepsy patients using levetiracetam. Materials and Methods: This retrospective study involved a volumetric comparison of patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic between 01.08.2019 and 01.11.2023 and diagnosed with epilepsy, and who underwent cranial MRI before and 18-24 months after treatment at the radiology department. The demographic and clinical characteristics (age, sex, family history of epilepsy, type of epilepsy, and EEG features (normal, abnormal, epileptiform)) of the patients included in the study were recorded. Results: The comparison of basal ganglia volumes at cranial MRI before and at months 18-24 of treatment revealed significant differences in the left caudate nucleus, right putamen, left putamen, left globus pallidus, right thalamus, left thalamus, and right hippocampal regions. Conclusions: In conclusion, differing findings are encountered at cranial imaging in patients with epilepsy, depending on the seizure frequency, activity, and the type of antiepileptic drugs used. This study compared basal ganglia volumes on cranial MRIs taken before and 18-24 months after treatment in pediatric epilepsy patients using levetiracetam. A significant increase was observed in the volumes of basal ganglia (caudate nucleus, putamen, globus pallidus, hippocampus, and thalamus) on the MRIs of pediatric epilepsy patients using levetiracetam.

Efficacy and safety of peginterferon beta-1a compared to interferon beta-1a in relapsing remitting multiple sclerosis patients: A phase 3, randomized, non-inferiority clinical trial (PEGINTEGRITY)

BackgroundMultiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients. MethodsThis study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments. ResultsA total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes. ConclusionThe results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS.This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133).

Brain volume and microglial density changes are correlated in a juvenile mouse model of cranial radiation and CSF1R inhibitor treatment.

Microglia have been shown to proliferate and become activated following cranial radiotherapy (CRT), resulting in a chronic inflammatory response. We investigated the role of microglia in contributing to widespread volume losses observed in the brain following CRT in juvenile mice. To manipulate microglia, we used low-dose treatment with a highly selective CSF1R inhibitor called PLX5622 (PLX). We hypothesized that alteration of the post-CRT microglia population would lead to changes in brain development outcomes, as evaluated by structural MRI. Wild-type C57BL/6J mice were provided with daily intraperitoneal injections of PLX (25 mg/kg) or vehicle from postnatal day (P)14 to P19. Mice also received whole-brain irradiation (7 Gy) or sham irradiation (0 Gy) at 16 days of age. In one cohort of mice, immunohistochemical assessment in tissue sections was conducted to assess the impact of the selected PLX and CRT doses as well as their combination. In a separate cohort, mice were imaged using MRI at P14 (pretreatment), P19, P23, P42 and P63 in order to assess induced volume changes, which were measured based on structures from a predefined atlas. We observed that PLX and radiation treatments led to sex-specific changes in the microglial cell population. Across treatment groups, MRI-detected anatomical volumes at P19 and P63 were associated with microglia and proliferating microglia densities, respectively. Overall, our study demonstrates that low-dose PLX treatment produces a sex-dependent response in juvenile mice, that manipulation of microglia alters CRT-induced volume changes and that microglia density and MRI-derived volume changes are correlated in this model.

Cognitive performance and brain volume among survivors of pediatric hematological malignancies: a case-control study.

Cognitive dysfunction may be one of the hazardous late effects among survivors of pediatric hematological malignancies. Our study aimed to explore cognitive performance and assess the global and regional brain volume changes in survivors of hematological malignancies. This case-control study was conducted on 68 survivors of hematological malignancies, with a median follow-up period of 2years (ranging from 1 to 6.2years). Stanford-Binet Testwas used for cognitive assessment. A quantitative volumetric assessment of the brain was done using the NeuroQuant Brain Magnetic Resonance. Age and sex-matched 68 children were selected as a comparison group. Cancer survivors showed significantly lower levels of IQ and their subtests than the control group. Global brain atrophy was observed in the majority of the survivors. Many risk factors significantly affected different IQ subtests, such as radiotherapy (RTH), high cumulative doses of methotrexate (MTX), and prednisone. At the same time, low white matter volume (WMV) was observed with higher cumulative doses of MTX and anthracyclines. Hematological malignancies have a negative impact on cognition. Neurocognitive impairment and related brain changes were evident in those who received RTH, HDMTX, or high cumulative doses of steroids.

Poor sleep and decreased cortical thickness in veterans with mild traumatic brain injury and post-traumatic stress disorder

BackgroundPoor sleep quality has been associated with changes in brain volume among veterans, particularly those who have experienced mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). This study sought to investigate (1) whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans, and (2) whether these associations differ topographically depending on the presence or absence of mTBI and PTSD.MethodsA sample of 440 post-9/11 era U.S. veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston, MA from 2010 to 2022 was included in the study. We examined the relationship between sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and cortical thickness in veterans with mTBI (n = 57), PTSD (n = 110), comorbid mTBI and PTSD (n = 129), and neither PTSD nor mTBI (n = 144). To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group, we employed a General Linear Model (GLM) at each vertex on the cortical mantle. The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients.ResultsThere were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI (n = 144) or in the PTSD-only group (n = 110). In the mTBI-only group (n = 57), lower sleep quality was significantly associated with reduced thickness bilaterally in frontal, cingulate, and precuneus regions, as well as in the right parietal and temporal regions (β = −0.0137, P < 0.0005). In the comorbid mTBI and PTSD group (n = 129), significant associations were observed bilaterally in frontal, precentral, and precuneus regions, in the left cingulate and the right parietal regions (β = −0.0094, P < 0.0005). Interaction analysis revealed that there was a stronger relationship between poor sleep quality and decreased cortical thickness in individuals with mTBI (n = 186) compared to those without mTBI (n = 254) specifically in the frontal and cingulate regions (β = −0.0077, P < 0.0005).ConclusionsThis study demonstrates a significant relationship between poor sleep quality and lower cortical thickness primarily within frontal regions among individuals with both isolated mTBI or comorbid diagnoses of mTBI and PTSD. Thus, if directionality is established in longitudinal and interventional studies, it may be crucial to consider addressing sleep in the treatment of veterans who have sustained mTBI.

Cortical atrophy patterns in myelin oligodendrocyte glycoprotein antibody-associated disease.

Global brain volume changes in patients with myelin oligodendrocyte glycoprotein antibody-associated disease compared with healthy controls (HC) could be revealed by magnetic resonance imaging, but specific atrophy patterns of cortical structures and relation to cognitive impairment are not yet comprehensively known. Thus, we aimed to investigate cortical thickness differences in patients with myelin oligodendrocyte glycoprotein antibody-associated disease compared with HC. 3-Tesla brain magnetic resonance imaging was performed in 23 patients with myelin oligodendrocyte glycoprotein antibody-associated disease and 49 HC for voxel-wise group comparisons and neuropsychological testing in patients. Surface-based morphometry with region of interest-based surface analysis and region of interest-based extraction of cortical thickness was performed in patients compared with HC and in patient subgroups with and without cognitive impairment. Comparing patients with myelin oligodendrocyte glycoprotein antibody-associated disease with HC, exploratory surface-based morphometry demonstrated cortical volume reduction in pericalcarine and lingual cortical regions. Region of interest-based surface analysis specified reduced cortical thickness in the adjacent pericalcarine and orbitofrontal regions in myelin oligodendrocyte glycoprotein antibody-associated disease, as well as reduced temporal cortical thickness in patients with cognitive impairment (n = 10). Patients without cognitive impairment (n = 13) showed only circumscribed cortical brain volume loss compared with HC in the pericalcarine region. In conclusion, cortical atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease was characterized by cortical thickness reduction in the adjacent pericalcarine and orbitofrontal regions, with a tendency of temporal thickness reduction in cognitively impaired patients.

Teriflunomide, cognition and MRI: A longitudinal study

BackgroundAs cognitive impairment in multiple sclerosis (MS) is a frequent and disabling symptom, it is particularly important to identify treatments that have proven efficacy in this aspect of the disease. Several disease-modifying therapies for MS have been evaluated and shown to have a potential effect on cognition and its neurobiological correlates, but to date there is very little data on Teriflunomide (TRF). The aim of this study is to explore the influence of TRF on comprehensive cognitive function and its MRI correlations (global and focal brain volume) in relapsing-remitting multiple sclerosis (RRMS) after two years of therapy. MethodsTwenty-four patients with RRMS were evaluated at baseline and after two years of treatment with BCcogSEP, a French translation of the Brief Repeatable Battery (BRB-N) including 3 additional tests. We explored the performance evolution for each test and correlation with MRI data for all patients. We also differentiated MS patients with and without cognitive impairment. ResultsAfter two years of treatment, an improvement is observed at the Selective Reminding Test for mean number of words (p = 0.044), learning (p = 0.018), and delayed recall (p = 0.002) and at GoNoGo task (p = 0.022). At MRI, the corpus callosum volume variation correlates positively with SRT total recall test (p = 0,047). Intergoup analysis shows that the evolution of group performance differs only for the SRT total recall test. The comparison of patients with or without cognitive impairment showed a clear difference in white matter substance volume (p = 0,003) and in the Percentage Brain Volume Change (p = 0,016). ConclusionResults suggest that TRF treatment in RRMS has a positive effect in cognitive function, and specifically on long term verbal memory and inhibition. Neuroimaging data suggest a link between cognition and global and focal white matter volume, particularly in the corpus callosum which is involved in anatomical disconnection syndrome and therefore brain plasticity capacities.