Brain Volume Changes Research Articles

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.

Evaluating age-and gender-related changes in brain volumes in normal adult using synthetic magnetic resonance imaging.

Normal aging is associated with brain volume change, and brain segmentation can be performed within an acceptable scan time using synthetic magnetic resonance imaging (MRI). This study aimed to investigate the brain volume changes in healthy adult according to age and gender, and provide age- and gender-specific reference values using synthetic MRI. A total of 300 healthy adults (141 males, median age 48; 159 females, median age 50) were underwent synthetic MRI on 3.0 T. Brain parenchymal volume (BPV), gray matter volume (GMV), white matter volume (WMV), myelin volume (MYV), and cerebrospinal fluid volume (CSFV) were calculated using synthetic MRI software. These volumes were normalized by intracranial volume to normalized GMV (nGMV), normalized WMV (nWMV), normalized MYV (nMYV), normalized BPV (nBPV), and normalized CSFV (nCSFV). The normalized brain volumes were plotted against age in both males and females, and a curve fitting model that best explained the age dependence of brain volume was identified. The normalized brain volumes were compared between different age and gender groups. The approximate curves of nGMV, nWMV, nCSFV, nBPV, and nMYV were best fitted by quadratic curves. The nBPV decreased monotonously through all ages in both males and females, while the changes of nCSFV showed the opposite trend. The nWMV and nMYV in both males and females increased gradually and then decrease with age. In early adulthood (20s), nWMV and nMYV in males were lower and peaked later than that in females (p<.005). The nGMV in both males and females decreased in the early adulthood until the 30s and then remains stable. A significant decline in nWMV, nBPV, and nMYV was noted in the 60s (Turkey test, p<.05). Our study provides age- and gender-specific reference values of brain volumes using synthetic MRI, which could be objective tools for discriminating brain disorders from healthy brains.

Evaluating the effect of dimethyl fumarate on subclinical biomarkers in a real-world patient cohort

ObjectiveEvaluate the real-world effect of dimethyl fumarate (DMF) on subclinical biomarkers in patients with relapsing-remitting multiple sclerosis (RRMS) and compare with results from clinical trials. MethodsMagnetic resonance imaging (MRI) data from 102 RRMS patients were retrospectively collected and processed using icobrain to assess brain atrophy and to assist semi-manual lesion count. ResultsMean (±SD) annualized percent brain volume change in the first 3 years after DMF-initiation were: −0.33 ± 0.68, −0.10 ± 0.60, and − 0.35 ± 0.71%/year, respectively. No new FLAIR lesions were detected in 73.7%, 77.3%, and 73.3% of the patients during years 1, 2, and 3. ConclusionsResults of this real-world study were consistent with previous DMF phase III clinical trials, supporting the generalizability of the effects observed in clinical trials to the real-world clinical setting.

PATHOPHYSIOLOGICAL, NEUROCHEMICAL AND BRAIN IMAGING ANALYSIS AS PARAMETERS FOR THE EARLY DIAGNOSIS OF BIPOLAR DISORDER

Introduction: Bipolar affective disorder is a complex psychiatric disorder. Its most striking feature is the alternation, sometimes sudden, of episodes of depression with those of euphoria (mania and hypomania) and asymptomatic periods in between. The crises can vary in intensity (mild, moderate and severe), frequency and duration. Objectives: The aim of this study was to identify the pathophysiology and neurochemistry of bipolar disorder, from diagnosis to treatment. Material and Methods: The methodology used was a literature review. The research was carried out through an electronic search for scientific articles published on the Scielo (Scientific Electronic Library Online) and Lilacs (Latin American Health Sciences Literature) and Pubmed websites. The health terminologies consulted in the Health Sciences descriptors (DeCS/BIREME) were used; the pathophysiology and neurochemistry of bipolar disorder, from diagnosis to treatment. Results: Structural neuroimaging studies have shown significant changes in brain volume, suggesting atrophy and/or neuronal loss, at least in a proportion of individuals with BD. Several studies have reported a significant decrease in gray matter in the prefrontal and temporal cortex, as well as an increase in the lateral ventricles. Bipolar patients tend to show reductions in gray matter in the frontal regions of the brain involved in self-control, while sensory and visual regions are normal. Conclusion: When struggling with a mental health disorder, the road to improvement usually begins with the long process of trying various treatments and approaches to find the one that best suits the patient.

Revolutionizing Neurology: The Role of Artificial Intelligence in Advancing Diagnosis and Treatment.

Artificial intelligence (AI) has emerged as a powerful tool in the field of neurology, significantly impacting the diagnosis and treatment of neurological disorders. Recent technological breakthroughs have given us access to a plethora of information relevant to many aspects of neurology. NeuroscienceandAIshare a long history of collaboration.Along with great potential, we encounter obstacles relating to data quality, ethics, and inherent difficulty in applying data science in healthcare. Neurological disorders pose intricate challenges due to their complex manifestations and variability.Automating image interpretation tasks, AI algorithms accurately identify brain structures and detect abnormalities. This accelerates diagnosis and reduces the workload on medical professionals. Treatment optimization benefits from AI simulations that model different scenarios and predict outcomes. These AI systems can currently perform many of the sophisticated perceptual and cognitive capacities of biological systems, such as object identification and decision making. Furthermore, AI is rapidly being used as a tool in neuroscience research, altering our understanding of brain functioning. It has the ability to revolutionize healthcare as we know it into a system in which humans and robots collaborate to deliver better care for our patients.Image analysis activities such as recognizing particular brain regions, calculating changes in brain volume over time, and detecting abnormalities in brain scans can be automated by AI systems. This lessens the strain on radiologists and neurologists while improving diagnostic accuracy and efficiency.It is now obvious that cutting-edge artificial intelligence models combined with high-quality clinical data will lead to enhanced prognostic and diagnostic models in neurological illness, permitting expert-level clinical decision aids across healthcare settings.In conclusion, AI's integration into neurology has revolutionized diagnosis, treatment, and research. As AI technologies advance, they promise to unravel the complexities of neurological disorders further, leading to improved patient care and quality of life. The symbiosis of AI and neurology offers a glimpse into a future where innovation and compassion converge to reshape neurological healthcare. This abstract provides a concise overview of the role of AI in neurology and its transformative potential.

Diffusion-Weighted Imaging in Minimal Hepatic Encephalopathy Using Mono-, Bi-, and Stretched Exponential Models

Background: Currently, there is no gold standard for diagnosing minimal hepatic encephalopathy (MHE). Diffusion-weighted imaging (DWI) can non-invasively evaluate changes in brain volume and damage to brain function. Objectives: The current study aims to evaluate changes in cerebral blood flow and brain function as predictors of MHE using DWI. Patients and Methods: Participants from October 2016 to October 2021 were scanned using a 3.0T superconductive MR machine (Discovery MR750, GE Medical Systems). Intravoxel incoherent motion DWI (IVIM-DWI) images of 30 patients with MHE and 30 controls were analyzed in a retrospective case-control study. The parameters of mono-, bi-, and stretched exponential models of the regions of interest, delineated from cerebral perfusion pseudo-color maps, were measured. The significance of the differences in parameter values between the groups was assessed using an independent t-test. Furthermore, the receiver operating characteristic curve was used to analyze the predictive efficiency of each parameter for MHE. Results: Compared to the control group, the distributed diffusion coefficient (DDC) of the bilateral frontal lobe, temporal lobe, occipital lobe, parietal lobe, cingulate gyrus, and thalamus in the MHE group was statistically different (P &lt; 0.05). The pseudo-diffusion coefficient (D*) and DDC demonstrated good diagnostic efficacy for MHE. D* had the highest area under the curve (AUC) in the bilateral parietal lobe, bilateral cingulate gyrus, and left occipital lobe. In contrast, DDC had the highest AUC in the right occipital and bilateral temporal lobes. Conclusion: Intravoxel incoherent motion DWI is an imaging method that can detect MHE. In addition, D* and DDC are better diagnostic parameters for screening MHE. Intravoxel incoherent motion DWI will be helpful in uncovering deeper intrinsic pathophysiological mechanisms and improving predictive efficiency.

The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI

BackgroundAnhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. MethodsThis is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. ResultsAs reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. LimitationsThis trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. ConclusionsIn this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

Complimentary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome.

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, neurobehavioral phenotypes including autism and attention deficit hyperactivity disorder (ADHD), and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function that will pave the way for future molecular studies into DESSH. These studies begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac, with advantages in each model.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (β=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

Five-Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub-Concussive Overpressures.

The Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5-year longitudinal trial was conducted in follow-up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure. To examine brain MRI findings in military personnel exposed to multiple repeated blast exposures. Five-year longitudinal prospective trial. Ninety-two males aged 23-42 with an average of 9.4 years of blast exposure. 3 T brain MRI/T1-weighted 3D with reconstruction in three planes, T2-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2-weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging. All MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form. Matching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers. A significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678-1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442-1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513-1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively. There were significant changes in brain volume, white matter lesions, and enlargement of VR spaces. 2 TECHNICAL EFFICACY: Stage 2.

ZOom Delivered Intervention Against Cognitive decline (ZODIAC) COVID-19 pandemic adaptations to the Post-Ischaemic Stroke Cardiovascular Exercise Study (PISCES): protocol for a randomised controlled trial of remotely delivered fitness training for brain health

BackgroundStroke increases subsequent dementia risk yet there are no specific post-stroke therapies to protect cognition. Cardiorespiratory exercise is recommended for secondary prevention of stroke and may be neuroprotective. The Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES) aims to reduce post-stroke secondary neurodegeneration and cognitive decline. During the pandemic, we pivoted to a ZOom Delivered Intervention Against Cognitive decline (ZODIAC) protocol, reducing pandemic-amplified barriers to exercise.MethodsWe present pandemic adaptions for a multicentre phase IIb assessor-blinded randomised controlled trial of ischaemic stroke survivors testing the efficacy and feasibility of an 8-week home-based exercise intervention delivered at 2 months post-stroke. We compare cardiorespiratory exercise (intervention arm) versus balance and stretching (active control arm). Participants are assessed with magnetic resonance imaging (MRI), fitness, blood, microbiome, and neuropsychological tests at three study visits: before and after the exercise intervention and at 12 months. Modifications to the original protocol include pre-exercise safety home visits, commercial delivery of exercise equipment to facilitate assessor blinding, and reconsideration of statistical plan to allow pooling of the studies. We have reduced in-person study visits from 27 to 3. Primary outcome remains between-group (intervention versus control) difference in brain volume change; secondary outcome is between-group difference in global cognitive ability to allow remote administration of a validated cognitive scale.DiscussionRemotely delivered exercise interventions reduce participant burden and may reduce barriers to recruitment. A decrease in the number of in-person study visits can be supported by greater information capture via self-reported questionnaires and phone surveys.Trial registrationProspectively ACTRN12616000942459. Registered on July 2016.

Long-term neuroprotective effects of natalizumab and fingolimod in multiple sclerosis: Evidence from real-world clinical data

BackgroundThe long-term effect of high efficacy disease modifying therapy (DMT) on neurodegeneration in people with multiple sclerosis (pwMS) is largely unknown. The aim of this study was to evaluate the long-term effect of natalizumab (NTZ) or fingolimod (FTY) therapy on the evolution of brain atrophy compared to moderate efficacy DMT in a real-world clinical setting. MethodsA total of 438 pwMS with 2,439 MRI exams during treatment were analyzed: 252 pwMS treated with moderate efficacy DMT, 130 with NTZ and 56 with FTY. Evolution of brain atrophy was analyzed over an average follow-up of 6.6 years after treatment initiation. Brain segmentation was performed on clinical 3D-FLAIRs using SynthSeg and regional brain volume changes over time were compared between the treatment groups. ResultsTotal brain, white matter and deep gray matter atrophy rates did not differ between moderate efficacy DMTs, NTZ and FTY. Annualized ventricle growth rates were lower in pwMS treated with NTZ (1.1 %/year) compared with moderate efficacy DMT (2.4 %/year, p < 0.001) and similar to FTY (2.0 %/year, p = 0.051). Cortical atrophy rates were lower in NTZ (-0.08 %/year) compared with moderate efficacy DMT (-0.16 %/year, p = 0.048). ConclusionIn a real-world clinical setting, pwMS treated with NTZ had slower ventricular expansion and cortical atrophy compared to those treated with moderate efficacy DMT.

Perivascular Spaces, Diffusivity Along Perivascular Spaces, and Free Water in Cerebral Small Vessel Disease.

Previous studies have linked the MRI measures of perivascular spaces (PVSs), diffusivity along the perivascular spaces (DTI-ALPS), and free water (FW) to cerebral small vessel disease (SVD) and SVD-related cognitive impairments. However, studies on the longitudinal associations between the three MRI measures, SVD progression, and cognitive decline are lacking. This study aimed to explore how PVS, DTI-ALPS, and FW contribute to SVD progression and cognitive decline. This is a cohort study that included participants with SVD who underwent neuroimaging and cognitive assessment, specifically measuring Mini-Mental State Examination (MMSE), cognitive index, and processing speed, at 2 time points. Three MRI measures were quantified: PVS in basal ganglia (BG-PVS) volumes, FW fraction, and DTI-ALPS. We performed a latent change score model to test inter-relations between the 3 MRI measures and linear regression mixed models to test their longitudinal associations with the changes of other SVD MRI markers and cognitive performances. In baseline assessment, we included 289 participants with SVD, characterized by a median age of 67.0 years and 42.9% women. Of which, 220 participants underwent the follow-up assessment, with a median follow-up time of 3.4 years. Baseline DTI-ALPS was associated with changes in BG-PVS volumes (β = -0.09, p = 0.030), but not vice versa (β = -0.08, p = 0.110). Baseline BG-PVS volumes were associated with changes in white matter hyperintensity (WMH) volumes (β = 0.33, p-corrected < 0.001) and lacune numbers (β = 0.28, p-corrected < 0.001); FW fraction was associated with changes in WMH volumes (β = 0.30, p-corrected < 0.001), lacune numbers (β = 0.28, p-corrected < 0.001), and brain volumes (β = -0.45, p-corrected < 0.001); DTI-ALPS was associated with changes in WMH volumes (β = -0.20, p-corrected = 0.002) and brain volumes (β = 0.23, p-corrected < 0.001). Furthermore, baseline FW fraction was associated with decline in MMSE score (β = -0.17, p-corrected = 0.006); baseline FW fraction and DTI-ALPS were associated with changes in cognitive index (FW fraction: β = -0.25, p-corrected < 0.001; DTI-ALPS: β = 0.20, p-corrected = 0.001) and processing speed over time (FW fraction: β = -0.29, p-corrected < 0.001; DTI-ALPS: β = 0.21, p-corrected < 0.001). Our results showed that increased BG-PVS volumes, increased FW fraction, and decreased DTI-ALPS are related to progression of MRI markers of SVD, along with SVD-related cognitive decline over time. These findings may suggest that the glymphatic dysfunction is related to SVD progression, but further studies are needed.

Modern Magnetic Resonance Imaging Modalities to Advance Neuroimaging in Astronauts.

INTRODUCTION: The rapid development of the space industry requires a deeper understanding of spaceflight's impact on the brain. MRI research reports brain volume changes following spaceflight in astronauts, potentially affecting cognition. Recently, we have demonstrated that this evidence of volumetric changes, as measured by typical T1-weighted sequences (e.g., magnetization-prepared rapid gradient echo sequence; MPRAGE), is error-prone due to the microgravity-related redistribution of cerebrospinal fluid in the brain. More modern neuroimaging methods, particularly dual-echo MPRAGE (DEMPRAGE) and magnetization-prepared rapid gradient echo sequence utilizing two inversion pulses (MP2RAGE), have been suggested to be resilient to this error. Here, we tested if these imaging modalities offered consistent segmentation performance improvements in some commonly employed neuroimaging software packages.METHODS: We conducted manual gray matter tissue segmentation in traditional T1w MRI images to utilize for comparison. Automated tissue segmentation was performed for traditional T1w imaging, as well as on DEMPRAGE and MP2RAGE images from the same subjects. Statistical analysis involved a comparison of total gray matter volumes for each modality, and the extent of tissue segmentation agreement was assessed using a test of similarity (Dice coefficient).RESULTS: Neither DEMPRAGE nor MP2RAGE exhibited consistent segmentation performance across all toolboxes tested.DISCUSSION: This research indicates that customized data collection and processing methods are necessary for reliable and valid structural MRI segmentation in astronauts, as current methods provide erroneous classification and hence inaccurate claims of neuroplastic brain changes in the astronaut population.Berger L, Burles F, Jaswal T, Williams R, Iaria G. Modern magnetic resonance imaging modalities to advance neuroimaging in astronauts. Aerosp Med Hum Perform. 2024; 95(5):245-253.

Alzheimer’s and neurodegenerative disease biomarkers in blood predict brain atrophy and cognitive decline

BackgroundAlthough blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known about how these biomarkers predict future brain atrophy and cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer’s disease (AD) pathology (amyloid-β [Aβ42/40], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Additionally, we determined whether sex, APOEε4 status, and plasma amyloid-β status modified these associations.MethodsPlasma biomarkers were measured using Quanterix SIMOA assays. Regional brain volumes were measured by 3T MRI, and a battery of neuropsychological tests assessed five cognitive domains. Linear mixed effects models adjusted for demographic factors, kidney function, and intracranial volume (MRI analyses) were completed to relate baseline plasma biomarkers to baseline and longitudinal brain volume and cognitive performance.ResultsBrain volume analyses included 622 participants (mean age ± SD: 70.9 ± 10.2) with an average of 3.3 MRI scans over 4.7 years. Cognitive performance analyses included 674 participants (mean age ± SD: 71.2 ± 10.0) with an average of 3.9 cognitive assessments over 5.7 years. Higher baseline pTau-181 was associated with steeper declines in total gray matter volume and steeper regional declines in several medial temporal regions, whereas higher baseline GFAP was associated with greater longitudinal increases in ventricular volume. Baseline Aβ42/40 and NfL levels were not associated with changes in brain volume. Lower baseline Aβ42/40 (higher Aβ burden) was associated with a faster decline in verbal memory and visuospatial performance, whereas higher baseline GFAP was associated with a faster decline in verbal fluency. Results were generally consistent across sex and APOEε4 status. However, the associations of higher pTau-181 with increasing ventricular volume and memory declines were significantly stronger among individuals with higher Aβ burden, as was the association of higher GFAP with memory decline.ConclusionsAmong cognitively unimpaired older adults, plasma biomarkers of AD pathology (pTau-181) and astrogliosis (GFAP), but not neuronal injury (NfL), serve as markers of future brain atrophy and cognitive decline.

Increases in regional brain volume across two native South American male populations

Industrialized environments, despite benefits such as higher levels of formal education and lower rates of infections, can also have pernicious impacts upon brain atrophy. Partly for this reason, comparing age-related brain volume trajectories between industrialized and non-industrialized populations can help to suggest lifestyle correlates of brain health. The Tsimane, indigenous to the Bolivian Amazon, derive their subsistence from foraging and horticulture and are physically active. The Moseten, a mixed-ethnicity farming population, are physically active but less than the Tsimane. Within both populations (N = 1024; age range = 46–83), we calculated regional brain volumes from computed tomography and compared their cross-sectional trends with age to those of UK Biobank (UKBB) participants (N = 19,973; same age range). Surprisingly among Tsimane and Moseten (T/M) males, some parietal and occipital structures mediating visuospatial abilities exhibit small but significant increases in regional volume with age. UKBB males exhibit a steeper negative trend of regional volume with age in frontal and temporal structures compared to T/M males. However, T/M females exhibit significantly steeper rates of brain volume decrease with age compared to UKBB females, particularly for some cerebro-cortical structures (e.g., left subparietal cortex). Across the three populations, observed trends exhibit no interhemispheric asymmetry. In conclusion, the age-related rate of regional brain volume change may differ by lifestyle and sex. The lack of brain volume reduction with age is not known to exist in other human population, highlighting the putative role of lifestyle in constraining regional brain atrophy and promoting elements of non-industrialized lifestyle like higher physical activity.

Region-Specific Brain Volume Changes Emerge in Adolescence in the Valproic Acid Model of Autism and Parallel Human Findings

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats. Method: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively. Results: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females. Conclusion: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.

Mapping brain volume change across time in primary-progressive multiple sclerosis.

Detection and prediction of the rate of brain volume loss with age is a significant unmet need in patients with primary progressive multiple sclerosis (PPMS). In this study we construct detailed brain volume maps for PPMS patients. These maps compare age-related changes in both cortical and sub-cortical regions with those in healthy individuals. We conducted retrospective analyses of brain volume using T1-weighted Magnetic Resonance Imaging (MRI) scans of a large cohort of PPMS patients and healthy subjects. The volume of brain parenchyma (BP), cortex, white matter (WM), deep gray matter, thalamus, and cerebellum were measured using the robust SynthSeg segmentation tool. Age- and gender-related regression curves were constructed based on data from healthy subjects, with the 95% prediction interval adopted as the normality threshold for each brain region. We analyzed 495 MRI scans from 169 PPMS patients, aged 20-79years, alongside 563 exams from healthy subjects aged 20-86. Compared to healthy subjects, a higher proportion of PPMS patients showed lower than expected brain volumes in all regions except the cerebellum. The most affected areas were BP, WM, and thalamus. Lower brain volumes correlated with longer disease duration for BP and WM, and higher disability for BP, WM, cortex, and thalamus. Constructing age- and gender-related brain volume maps enabled identifying PPMS patients at a higher risk of brain volume loss. Monitoring these high-risk patients may lead to better treatment decisions and improve patient outcomes.