Lower Brain Volume Research Articles

Abstract P191: Association Between Blood Pressure And Brain Volumes Vary By Sex And Age.

Objective: To quantify the association between blood pressure (BP) across its full range and brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), antihypertensive medication, and other risk factors. Methods: UK Biobank participants ( N =36,260) aged 40 to 70 years were included and stratified by sex and age into four groups (age ≤ 45, 46-55, 56-65 and > 65 years old). Multi-level regression analyses were used to assess the association between mean arterial (MAP), systolic (SBP), and diastolic (DBP) blood pressure, and brain volumes segmented using the FreeSufer software (gray matter [GMV], white matter [WMV], left [L] and right hippocampal volume [RHCV]) and WMLs. We also investigated the interaction effects between body mass index (BMI) and antihypertensive medication and BP in predicting brain volumes and WMLs. Results: Every 10-mmHg higher DBP was associated with lower brain volumes (GMV: -1300– -2800) [SE=34–90]; WMV: -903.44– -1171.7[SE=34.66–53.03]; LHCV: -7.7– -14.26 [SE=0.44–0.57]; RHCV: -6.25– -22.64[SE=0.32–0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker, in men. Also, every 10-mmHg higher MAP was associated with larger WMLs across all age groups but peaked > 65 years (0.1 [SE=0.002]). Both lower BMI and anti-hypertensive medication appeared to afford a protective effect. Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and across the life course. Therefore, it is important that prevention efforts be directed at younger adults with focus on achieving optimal BP to decrease future risk of developing dementia.

Supplemental Material for Lower Brain Volume and Poorer Emotional Regulation in Partner Coercive Men and Other Offenders

Supplemental Material for Lower Brain Volume and Poorer Emotional Regulation in Partner Coercive Men and Other Offenders

Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

RationaleKetamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis.ObjectivesWe tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group.MethodsKetamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users.ResultsKetamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms.ConclusionsChronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms.

Higher Framingham Risk Scores are associated with greater loss of brain volume over time in multiple sclerosis

BackgroundFew studies have evaluated the association between comorbidities associated with increased vascular risk and brain volume changes in multiple sclerosis (MS). To date, findings have not been consistent with respect to which comorbidities are associated with lower brain volumes or whether comorbidities associated with increased vascular risk are associated with greater brain volume loss over time. ObjectivesWe aimed to evaluate the association between the Framingham Risk Score (FRS) which evaluates vascular risk and normalized whole brain volume in MS. MethodsWe included 98 participants with MS who underwent two brain MRIs two years apart, from which whole brain volumes were calculated. Each participant reported their comorbidities and medications taken. Blood pressure, height and weight were recorded and we calculated the FRS. We tested the association between the FRS at baseline and brain volume at the second time point using quantile regression adjusting for baseline normalized brain volume, age, gender and use of disease-modifying therapy. ResultsAs the FRS increased, brain volume was lower, both at enrollment (β= -0.24; 95%CI: -0.42, -0.04) and at follow-up (-0.27; 95%CI: -0.45, -0.08). After further adjustment for age, gender, and use of disease modifying therapy, higher FRS remained associated with lower brain volume at follow-up at the 90th percentile of brain volume (β= -2.22; 95%CI: -3.40, -1.04) but not at the 10th or 50th percentiles. ConclusionHigher FRS were associated with lower brain volumes in persons with MS at baseline, and with brain volume loss over time. This effect was most pronounced for persons with higher brain volumes at baseline, which suggests that prevention, detection and effective management of comorbidities associated with vascular risk in people with MS is particularly important early in the disease course.

Abstract MP25: Brain Atrophy And White Matter Injury In Relation To Cardiovascular Risk Factors And Race/ethnicity: The Multi-ethnic Study Of Atherosclerosis

Introduction: Cardiovascular risk factors are associated with cognitive decline and dementia. Brain magnetic resonance imaging (MRI) provides sensitive measurement of cerebral atrophy and small vessel disease, reflecting multiple pathologies leading to dementia. However, large brain MRI studies include primarily white participants. We investigated associations in the diverse Multi-Ethnic Study of Atherosclerosis (MESA). Hypothesis: Cardiovascular and sociodemographic risk factors are associated with brain morphology and white matter injury in a racially and ethnically diverse population. Methods: In MESA, brain MRI was performed in 2018-2019 with automated measurement of total brain volume, gray and white matter (GM, WM) volume, and measures of WM injury including WM lesion volume, WM fractional anisotropy, and WM apparent diffusion coefficient. In cross-sectional analyses, we assessed the association of race/ethnicity with MRI measures, with and without adjustment for cardiovascular risk factors, education, and socioeconomic status. In a multivariable model, we assessed the association of cardiovascular risk factors with brain MRI measures. All analyses of volumes, including WM lesion volume, were adjusted for total intracranial volume. Results: MRI data were complete in 1,051 participants; 40% were white, 15% Chinese-American, 25% African-American, and 20% Hispanic. Mean (standard deviation, SD) age was 73 (8) years and 53% of participants were women. Adjusted for age and sex, African-American participants had slightly greater total brain and WM volume than white participants. Adjusted for age and sex, African-American participants had on average more WM injury than whites as measured by higher WM lesion volume (46.7% higher, 95% CI: 19.9, 79.4%) and lower fractional anisotropy (-0.20 SD, 95% CI: -0.34, -0.05); these associations were attenuated after additional adjustment for cardiovascular risk factors and socioeconomic status (24.3% higher WM lesion volume, 95% CI: 0.0, 54.3; -0.06 SD fractional anisotropy, 95% CI: -0.22, 0.09). Conversely, all non-white race/ethnic groups had slightly less WM injury than white participants as estimated by apparent diffusion coefficient. Overall, greater age, diabetes, current smoking, high systolic blood pressure, and treated hypertension were strongly associated with more WM injury; in addition, age and diabetes were strongly associated with lower brain volumes. Conclusions: We found little evidence of differences in measures of brain atrophy and WM injury by race/ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. Findings of differences by race/ethnicity in apparent diffusion coefficient are intriguing and need further investigation. Consistent with previous studies, age, diabetes, current smoking and hypertension were strongly and consistently associated with WM injury.

A matter of atrophy: differential impact of brain and spine damage on disability worsening in multiple sclerosis

As atrophy represents the most relevant driver of progression in multiple sclerosis (MS), we investigated the impact of different patterns of brain and spinal cord atrophy on disability worsening in MS. We acquired clinical and MRI data from 90 patients with relapsing–remitting MS and 24 healthy controls (HC). Clinical progression at follow-up (mean 3.7 years) was defined according to the Expanded Disability Status Scale-Plus. Brain and spinal cord volumes were computed on MRI brain scans. After normalizing each participants’ brain and spine volume to the mean of the HC, z-score cut-offs were applied to separate pathologically atrophic from normal brain and spine volumes (accepting a 2.5% error probability). Accordingly, MS patients were classified into four groups (Group I: no brain or spinal cord atrophy N = 40, Group II: brain atrophy/no spinal cord atrophy N = 11, Group III: no brain atrophy/ spinal cord atrophy N = 32, Group IV: both brain and spinal cord atrophy N = 7). All patients’ groups showed significantly lower brain volume than HC (p < 0.0001). Group III and IV showed lower spine volume than HC (p < 0.0001 for both). Higher brain lesion load was identified in Group II (p = 0.049) and Group IV (p = 0.023) vs Group I, and in Group IV (p = 0.048) vs Group III. Spinal cord atrophy (OR = 3.75, p = 0.018) and brain + spinal cord atrophy (OR = 5.71, p = 0.046) were significant predictors of disability progression. The presence of concomitant brain and spinal cord atrophy is the strongest correlate of progression over time. Isolated spinal cord atrophy exerts a similar effect, confirming the leading role of spinal cord atrophy in the determination of motor disability.

Higher Blood Pressure is Associated with Greater White Matter Lesions and Brain Atrophy: A Systematic Review with Meta-Analysis.

Background: To summarise and quantify the evidence on the association between Blood pressure (BP), white matter lesions (WMLs), and brain volumes. Method: Electronic databases PubMed, Scopus, and Clarivate were searched in February 2020 using an established methodology and pre-determined search terms. Studies were eligible for inclusion if they reported on the association between BP and WMLs or brain volume in cognitively healthy individuals, while adjusting for age and intra-cranial volume. Results: Searches yielded 7509 articles, of which 52 (26 longitudinal and 33 cross-sectional), were eligible and had a combined sample size of 343,794 individuals. Analyses found that 93.7% of studies reported that higher BP was associated with poorer cerebral health (higher WMLs and lower brain volumes). Meta-analysis of compatible results indicated a dose-dependent relationship with every one standard deviation increase in systolic BP (SBP) above 120 mmHg being associated with a 11.2% (95% CI 2.3, 19.9, p = 0.0128) increase in WMLs and −0.13% (95% CI −0.25, −0.023, p = 0.0183) smaller hippocampal volume. Conclusion: The association between BP and brain volumes appears across the full range of BP measurements and is not limited to hypertensive individuals. Higher BP in community-residing individuals is associated with poorer cerebral health.

Vascular comorbidity is associated with lower brain volumes and lower neuroperformance in a large multiple sclerosis cohort

Objective: The objective of this study is to assess the association between vascular comorbidity burden with clinical and imaging features of disease burden in a large population of people with multiple sclerosis (MS). Methods: We included participants from the MS Partners Advancing Technology Health Solutions (MS PATHS) cohort. We evaluated if vascular comorbidities (diabetes, hypertension, and dyslipidemia) or a composite sum of comorbidities was associated with MS characteristics, including objective neurologic function assessments and quantitative brain magnetic resonance imaging (MRI) measurements in propensity score–weighted models. Results: In total, 11,506 participants (6409 (55%) with brain MRI) were included. Individuals with 2+ vascular comorbidities had slower walking speed (standard deviation (SD) = −0.49; 95% confidence interval (CI) = −0.78, −0.19; p = 0.001), slower manual dexterity (SD = −0.41; 95% CI = −0.57, −0.26; p < 0.0001), and fewer correct scores on cognitive processing speed (SD = −0.11; 95% CI = −0.20, −0.02; p = 0.02) versus those with no comorbidities. Those with 2+ had lower brain parenchymal (−0.41%, 95% CI = −0.64, −0.17) and gray matter fractions (−0.30%, 95% CI = −0.49, −0.10), including reduced cortical (−10.10 mL, 95% CI = −15.42, −4.78) and deep (−0.44 mL, 95% CI = −0.84, −0.04) gray matter volumes versus those with no comorbidity. Conclusion: Increased vascular comorbidity burden was associated with clinical and imaging markers of neurologic dysfunction and neurodegeneration in MS. Strategies to optimize comorbidity management in people with MS are warranted.

Systematic Review of Studies on Telomere Length in Patients with Multiple Sclerosis.

Telomeres are protective cap structures at the end of chromosomes that are essential for maintaining genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases. We aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS). A comprehensive literature search was conducted to identify original studies that presented data on TL in samples from persons with MS. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies. A total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in patients with MS were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes. Despite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the pathomechanisms of MS.

Chapter 8 - Neurological complications of heart failure

Heart failure (HF) is a major global cause of death with increasing absolute worldwide numbers of HF patients. HF results from the interaction between cardiovascular aging with specific risk factors, comorbidities, and disease modifiers. The failing heart and neuronal injury have a bidirectional interaction requiring specific management strategies. Decreased cardiac output has been associated with lower brain volumes. Cerebral blood flow (CBF) may normalize following heart transplantation among severe HF patients. Stroke and cognitive impairment remain the main neurologic conditions associated with HF. However, HF patients may also suffer from chronic cerebral hypoperfusion. It seems likely that HF-related ischemic strokes are primarily the result of cardiac embolism. Atrial fibrillation (AF) is present in half of stroke patient with HF. The increased risk of hemorrhagic strokes is less well characterized and likely multifactorial, but may in part reflect a higher use of long-term antithrombotic therapy. The steady improvement of neuroimaging techniques has demonstrated an increased prevalence of silent ischemic lesions among HF patients. The populations most likely to benefit from long-term anticoagulant therapy are HF patients with AF. Cognitive impairment in HF can have a variety of clinical manifestations from mild memory problems to dementia.

Association of plasma EFEMP1 with brain aging and dementia

AbstractBackgroundBiological pathways underlying the association between white matter hyperintensities (WMH) and Alzheimer’s disease (AD) dementia remain poorly understood. Epidermal growth factor containing fibulin extracellular matrix protein‐1 (EFEMP1) has been associated with increased WMH burden and disorders of premature aging. However, it is unknown if elevated circulating EFEMP1 is associated with clinical dementia. We determined the association between plasma EFEMP1 levels and incident dementia and Alzheimer’s disease (AD) dementia in a community‐based sample of cognitively healthy individuals.MethodPlasma EFEMP1 levels were measured in 1597 [53% women, mean age 68.7 (SD 5.7) yr] Framingham Heart Study Offspring cohort participants who were free of dementia at examination cycle seven (1998‐2001). We related plasma EFEMP1 levels to risk of incident dementia and Alzheimer’s disease (AD) dementia. Structural MRI brain measures and neurocognitive test performance were included as secondary outcomes.ResultDuring a median 11.8 [Q1, Q3: 7.1, 13.3] year follow‐up, 131 participants developed dementia and 98 were diagnosed with AD dementia. On Cox proportional‐hazards analysis adjusting for vascular risk factors and ApoE4 carrier status, the highest quintile of plasma EFEMP1, compared to the bottom four quintiles, was associated with an almost 80% increased risk of time to incident all‐cause dementia (HR 1.77, 95% CI 1.18‐2.64) and AD dementia (HR 1.76, 95% CI 1.11‐2.81). The highest quintile of EFEMP1, compared to the bottom four quintiles, was also associated with lower total brain volume (SE, ‐0.28±0.11, p=0.01) and hippocampal volume (‐0.006±0.003, p=0.04) but not WMH burden. Higher circulating EFEMP1 concentrations were associated with impairment in abstract reasoning (Similarities test, ‐0.18±0.08, p=0.018 per standard deviation increment in EFEMP1).ConclusionElevated circulating EFEMP1 levels are associated with an increased risk of incident dementia and AD dementia as well as lower brain volumes and impaired cognitive performance. EFEMP1 may play an important biological role in the development of AD and all‐cause dementia mediated through nonvascular pathways (e.g. microglial activation or via regulatory effects on metalloproteases), although additional studies are warranted to replicate our findings.

Relationships Among Circulating Levels of Hemostasis Inhibitors, Chemokines, Adhesion Molecules, and MRI Characteristics in Multiple Sclerosis.

Background: Several studies suggested cross talk among components of hemostasis, inflammation, and immunity pathways in the pathogenesis, neurodegeneration, and occurrence of cerebral microbleeds (CMBs) in multiple sclerosis (MS).Objectives: This study aimed to evaluate the combined contribution of the hemostasis inhibitor protein C (PC) and chemokine C-C motif ligand 18 (CCL18) levels to brain atrophy in MS and to identify disease-relevant correlations among circulating levels of hemostasis inhibitors, chemokines, and adhesion molecules, particularly in CMB occurrence in MS.Methods: Plasma levels of hemostasis inhibitors (ADAMTS13, PC, and PAI1), CCL18, and soluble adhesion molecules (sNCAM, sICAM1, sVCAM1, and sVAP1) were evaluated by multiplex in 138 MS patients [85 relapsing-remitting (RR-MS) and 53 progressive (P-MS)] and 42 healthy individuals (HI) who underwent 3-T MRI exams. Association of protein levels with MRI outcomes was performed by regression analysis. Correlations among protein levels were assessed by partial correlation and Pearson's correlation.Results: In all patients, regression analysis showed that higher PC levels were associated with lower brain volumes, including the brain parenchyma (p = 0.002), gray matter (p < 0.001), cortex (p = 0.001), deep gray matter (p = 0.001), and thalamus (p = 0.001). These associations were detectable in RR-MS but not in P-MS patients. Higher CCL18 levels were associated with higher T2-lesion volumes in all MS patients (p = 0.03) and in the P-MS (p = 0.003). In the P-MS, higher CCL18 levels were also associated with lower volumes of the gray matter (p = 0.024), cortex (p = 0.043), deep gray matter (p = 0.029), and thalamus (p = 0.022). PC-CCL18 and CCL18-PAI1 levels were positively correlated in both MS and HI, PC–sVAP1 and PAI1–sVCAM1 only in MS, and PC–sICAM1 and PC–sNCAM only in HI. In MS patients with CMBs (n = 12), CCL18–PAI1 and PAI1–sVCAM1 levels were better correlated than those in MS patients without CMBs, and a novel ADAMTS13–sVAP1 level correlation (r = 0.78, p = 0.003) was observed.Conclusions: Differences between clinical phenotype groups in association of PC and CCL18 circulating levels with MRI outcomes might be related to different aspects of neurodegeneration. Disease-related pathway dysregulation is supported by several protein level correlation differences between MS patients and HI. The integrated analysis of plasma proteins and MRI measures provide evidence for new relationships among hemostasis, inflammation, and immunity pathways, relevant for MS and for the occurrence of CMBs.

Brain MRI characteristics in neuromyelitis optica spectrum disorders: A large multi-center retrospective study in China

PurposeTo investigate the brain MRI features in neuromyelitis optica spectrum disorders (NMOSD) and its clinical relevance in a large multi-center cohort in China. Methods270 NMOSD patients were recruited from seven centers. The brain MRI were classified as normal, NMOSD-specific lesions, multiple sclerosis-like, nonspecific white matter changes. Brain volumes including whole brain, white, gray matter, cortex and subcortex gray matter volume were measured. The relationship between MRI measures, clinical disability and cognitive impairment were investigated. Results98 patients (36.3%) had normal brain MRI; 48 patients (17.7%) had NMOSD-specific lesions located in dorsal brainstem, corticospinal tract corpus, callosum and periependymal lesions surrounding the ventricular system; 16 patients (6%) had multiple sclerosis-like lesions; and 108 patients (40%) had nonspecific white matter changes. NMOSD patients with brain lesions had a trend of lower subcortex gray matter volume compared to patients without lesions. 52.5% patients with normal brain MRI and 50.8% patients with abnormal brain MRI showed cognitive impairment. No significant differences were identified in brain volume between cognitive impairment and cognitive preserved groups. ConclusionIn this large multicenter NMOSD cohort, nonspecific white matter changes were the most common findings (40%). NMOSD patients with brain lesions demonstrated a trend of having lower brain volume than patients without lesions. Approximately 50% NMOSD patients presented cognitive impairment independent of brain lesions.

Detecting Amyloid Positivity in Elderly With Increased Risk of Cognitive Decline.

The importance of early interventions in Alzheimer’s disease (AD) emphasizes the need to accurately and efficiently identify at-risk individuals. Although many dementia prediction models have been developed, there are fewer studies focusing on detection of brain pathology. We developed a model for identification of amyloid-PET positivity using data on demographics, vascular factors, cognition, APOE genotype, and structural MRI, including regional brain volumes, cortical thickness and a visual medial temporal lobe atrophy (MTA) rating. We also analyzed the relative importance of different factors when added to the overall model. The model used baseline data from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) exploratory PET sub-study. Participants were at risk for dementia, but without dementia or cognitive impairment. Their mean age was 71 years. Participants underwent a brain 3T MRI and PiB-PET imaging. PiB images were visually determined as positive or negative. Cognition was measured using a modified version of the Neuropsychological Test Battery. Body mass index (BMI) and hypertension were used as cardiovascular risk factors in the model. Demographic factors included age, gender and years of education. The model was built using the Disease State Index (DSI) machine learning algorithm. Of the 48 participants, 20 (42%) were rated as Aβ positive. Compared with the Aβ negative group, the Aβ positive group had a higher proportion of APOE ε4 carriers (53 vs. 14%), lower executive functioning, lower brain volumes, and higher visual MTA rating. AUC [95% CI] for the complete model was 0.78 [0.65–0.91]. MRI was the most effective factor, especially brain volumes and visual MTA rating but not cortical thickness. APOE was nearly as effective as MRI in improving detection of amyloid positivity. The model with the best performance (AUC 0.82 [0.71–0.93]) was achieved by combining APOE and MRI. Our findings suggest that combining demographic data, vascular risk factors, cognitive performance, APOE genotype, and brain MRI measures can help identify Aβ positivity. Detecting amyloid positivity could reduce invasive and costly assessments during the screening process in clinical trials.

Vitamin E Intake Is Associated with Lower Brain Volume in Haptoglobin 1-1 Elderly with Type 2 Diabetes.

The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype. To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes. Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n = 24, Hp 2-1: n = 77, Hp 2-2: n = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype. Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus' volume; p = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p = 0.0348), increased by 0.429% for Hp 2-1 (p = 0.0457), and by 0.077% for Hp 2-2 (p = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p = 0.6011) and superior (p = 0.2025) frontal gyri or for the middle temporal gyrus (p = 0.503). The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype.

Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia

BackgroundThere are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to...

Combined Use of Clinical, Lesion Topography, and Thalamic Volume Helps Differentiating Multiple Sclerosis from its Mimickers

Early diagnosis of multiple sclerosis (MS) is important. Non-specific white matter changes usually confound earlier diagnosis. Cross-sectional, global and regional studies have shown that brain volume estimates are of diagnostic and prognostic relevance to the management of the disease; however, it did not reach an individual patient level of precision. We aimed to use both conventional (subjective lesion count) and advanced (brain volume and thalamic volume) magnetic resonance imaging (MRI) measures to investigate the ability of these measures to differentiate MS from other mimickers. Seventy MS patients and seventy-two age- and sex-matched healthy controls were recruited for this study. A third group of patients diagnosed with MS mimickers who presented with symptoms that might be attributed to MS, and had multiple white matter lesions was also included. Whole brain volume and thalamic volume were evaluated for all groups using FSL software pipelines (SIENAX and FIRST respectively). Z scores were calculated for brain and thalamic volume from healthy controls group and two standard deviations below the mean were considered the cut-off value for comparison. Brain and thalamic volumes differed significantly between the study groups. Brain volume correlated significantly with thalamic volume in healthy controls (p<0.00, r=0.59) and MS group (p<0.00, r=0.76), but not in the MS mimickers group (p=0.26, r=0.27). A significantly low brain volume was observed in 7 MS patients (10%) and a significantly low thalamic volume was observed in 15 MS patients (21%). Only one subject from MS mimickers group showed a significant low brain volume (5%); otherwise no significant thalamic atrophy was observed in this group. Thalamic and brain atrophy occur early in MS. Non-specific white matter changes do not contribute significantly to brain volume changes. Hemispheric volume changes may occur in MS mimickers but not particularly thalamic atrophy. Cross-sectional volumetric evaluation may add some valuable information in distinguishing MS patients from common radiological mimickers of the disease.

Brain Volumes of very Low Birth Weight Infants Measured by Two-dimensional Cranial Ultrasonography: A Prospective Cohort Study.

Cranial ultrasonography is the main neuroimaging technique for very low birth weight infants. Low brain volume is associated with poor neurologic outcome. This study aimed to calculate brain volumes of preterm infants with two-dimensional measurements of cranial ultrasonography. Intracranial height, anteroposterior diameter, bi-parietal diamater, ventricular height, thalamo-occipital distance and ventricular index were measured with routine cranial ultrasonographic scanning. Brain considered a spheric, ellipsoid model and estimated brain volume (EBV) was calculated by subtracting two lateral ventricular volumes from the total brain volume. One hundred and twenty-one preterm infants under a birth weight of 1500 g and 32 weeks of gestational age were included in this study. The mean gestational age of study population was 27.7 weeks, and mean birthweight was 1057 grams. Twenty-two of 121 infants had dilated ventricle, in this group, EBV was lower than normal group (202 ± 58 cm3 vs 250 ± 53 cm3, respectively, p<0.01). Advanced resuscitation, bronchopulmonary dysplasia and late-onset sepsis were found to be independent risk factors for low brain volume in our data. Estimated brain volume can be calculated by two-dimensional measurements with cranial ultrasonography.

Editors' note: Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study

Using cross-sectional data from the Framingham Heart Study including nondemented middle-aged adults, Echouffo-Tcheugui et al. identified an association between higher serum cortisol levels and lower brain volume and poorer performance on a variety of cognitive assessments. Although the serum cortisol measurement was acquired at a single point in time, and may not be reflective of chronic elevations in cortisol as Barbosa et al. assert, the data are strongly suggestive of a correlation. The investigators also agree that hair cortisol might be a better indicator of long-term cortisol levels; however, these data were not available in this observational cohort. Drs. Jimenez-Pavon and Carbonell-Baeza comment on the role that physical activity (PA) and cardiorespiratory fitness (CRF) may have on structural brain integrity and cognitive performance. Some of these associations from the Framingham Heart Study have been previously published in Neurology ® in 2016. Although analysis of these physiologic variables may be worthy of further investigation, Echouffo-Tcheugi et al. argue that PA and CRF may alter cortisol levels (and thereby, neural structure and function), but that such a mediation could lead to an overadjustment. Based on the results of this analysis, the investigators emphasize that cortisol levels may be the bridge the between PA/CRF and brain volume and cognitive performance. Using cross-sectional data from the Framingham Heart Study including nondemented middle-aged adults, Echouffo-Tcheugui et al. identified an association between higher serum cortisol levels and lower brain volume and poorer performance on a variety of cognitive assessments. Although the serum cortisol measurement was acquired at a single point in time, and may not be reflective of chronic elevations in cortisol as Barbosa et al. assert, the data are strongly suggestive of a correlation. The investigators also agree that hair cortisol might be a better indicator of long-term cortisol levels; however, these data were not available in this observational cohort. Drs. Jimenez-Pavon and Carbonell-Baeza comment on the role that physical activity (PA) and cardiorespiratory fitness (CRF) may have on structural brain integrity and cognitive performance. Some of these associations from the Framingham Heart Study have been previously published in Neurology ® in 2016. Although analysis of these physiologic variables may be worthy of further investigation, Echouffo-Tcheugi et al. argue that PA and CRF may alter cortisol levels (and thereby, neural structure and function), but that such a mediation could lead to an overadjustment. Based on the results of this analysis, the investigators emphasize that cortisol levels may be the bridge the between PA/CRF and brain volume and cognitive performance.

The effect of age of first exposure to competitive fighting on cognitive and other neuropsychiatric symptoms and brain volume

It has long been established that fighting sports such as boxing and mixed martial arts can lead to head injury. Prior work from this group on the Professional Fighters Brain Health Study found that exposure to repetitive head impacts is associated with lower brain volumes and decreased processing speed in fighters. Current and previously licensed professional fighters were recruited, divided into active and retired cohorts, and matched with a control group that had no prior experience in sports with likely head trauma. This study examined the relationship between age of first exposure (AFE) to fighting sports and brain structure (MRI regional volume), cognitive performance (CNS Vital Signs, iComet C3), and clinical neuropsychiatric symptoms (PHQ-9, Barratt Impulsiveness Scale). Brain MRI data showed significant correlations between earlier AFE and smaller bilateral hippocampal and posterior corpus callosum volumes for both retired and active fighters. Earlier AFE in active fighters was correlated with decreased processing speed and decreased psychomotor speed. Retired fighters showed a correlation between earlier AFE and higher measures of depression and impulsivity. Overall, the results help to inform clinicians, governing bodies, parents, and athletes of the risks associated with beginning to compete in fighting sports at a young age.