Total Brain Volume Research Articles

#1058 Causal discovery for the volume of white matter in patients undergoing haemodialysis

Abstract Background and Aims White matter hyperintensity is linked to adverse outcomes and a heightened risk of overt stroke and cognitive impairment, with its prevalence being more pronounced in patients undergoing haemodialysis than in the general population. Despite this, the determinants of white matter hyperintensity volume in patients undergoing haemodialysis remain unknown. Here, we aimed to utilise a statistical causal search approach to examine the factors influencing white matter hyperintensity volume, as measured by MRI, in patients undergoing haemodialysis. Method MRI measurements of white matter hyperintensity volumes were taken in 133 patients on outpatient maintenance haemodialysis for >1 year. Factors included in the statistical causal discovery model encompassed sex, underlying diseases that led to dialysis, total brain volume measured using MRI, and age and dialysis vintage at the time of MRI. Additionally, values calculated and averaged over the year before the MRI scan, such as pre-dialysis blood pressure, pulse, weight, blood pressure during dialysis, blood pressure after dialysis completion, the volume of water removed in one session, Kt/V, and URR and occurrences of sudden drops in blood pressure during dialysis, were considered. Missing measurements were supplemented using random forest. A statistical causal search using DirectLiNGAM was conducted, and clear temporal pre- and post-relationships were incorporated into the LiNGAM model as per prior knowledge. To enhance internal validity, 1000 bootstrap samplings were performed, and edges with a frequency of occurrence of ≥50% were considered valid for Directed Acyclic Graphs (DAGs). Factors directly linked to white matter volume were included in the model, and linear regression was executed. Results Patients had a mean age of 69.0 (Standard Deviation: 10.4) years, with 96 (72.2%) being male. The mean history of dialysis was 6.63 [Interquartile Range (IQR): 4.10, 10.78] years, and 40 (39.2%) patients had diabetes as the primary disease. The mean white matter hyperintensity volume was 14334.9 [IQR: 5262.4,30637.2]. Age, pre-dialysis body weight, post-dialysis mean blood pressure, and total brain volume were directly influenced by white matter volume. DAGs displaying causality obtained through bootstrapping are shown in the Fig. The regression model results revealed that white matter hyperintensity increased by 8376.3 [95% Confidence Intervals (CI): 4899.5 to 11853.1] for every 10 years of age, decreased by −2726.0 [95% CI: −4311.5 to −1140.5] with a 5 kg increase in pre-dialysis body weight, increased by 2089.7 [95% CI: 693.3 to 3540.0] with a 5-mmHg rise in post-dialysis mean blood pressure, and a 1 standard deviation increase in total cerebrum volume increased white matter volume by 13057.4 [95% CI: 8958.1 to 17156.8]. Conclusion The causal diagram indicated that age, pre-dialysis weight, post-dialysis mean blood pressure, and total cerebrum volume directly influenced white matter hyper intensity volume. The sudden drop in blood pressure during dialysis impacted white matter hyperintensity volume via post-dialysis mean blood pressure. Furthermore, age, post-dialysis mean blood pressure and total cerebrum volume had a facilitative effect on the increase in white matter hyperintensity volume, while pre-dialysis weight had a protective effect.

Sex-differences in the association of social health and marital status with blood-based immune and neurodegeneration markers in a cohort of community-dwelling older adults

BackgroundThe immune system has been proposed to play a role in the link between social health and all-cause dementia risk. We explored cross-sectional and longitudinal associations between social health, immune system balance and plasma neurodegeneration markers in community-dwelling older adults, and explored whether the balance between innate and adaptive immunity mediates associations between social health and both cognition and total brain volume. MethodsSocial health markers (social support, marital status, loneliness) were measured in the Rotterdam Study between 2002–2008. Immune system cell counts and balance were assessed repeatedly from 2002 to 2016 using white blood-cell-based indices and individual counts (granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)). Plasma neurodegeneration biomarkers (amyloid-β40, amyloid-β42, total tau and neurofilament light chain) were measured once from blood samples collected between 2002–2008. Global cognitive function and total brain volume (MRI) were measured at the follow-up visit between 2009–2014. We used linear mixed models to study longitudinal associations and performed causal mediation analyses. ResultsIn 8374 adults (mean age 65.7, 57 % female), never married participants (n = 394) had higher GLR, PLR and SII compared to married peers at baseline and during follow-up, indicating imbalance towards innate immunity. Being never married was associated with higher plasma amyloid-β40, and being widowed or divorced with higher plasma total tau levels at baseline. Widowed or divorced males, but not females, had higher GLR, PLR and SII at baseline. Higher social support was associated with lower PLR in females, but higher PLR in males. Loneliness was not associated with any of the immune system balance ratios. Never married males had higher levels of all plasma neurodegeneration markers at baseline. Immune system balance did not mediate associations between social health and cognition or total brain volume, but does interact with marital status. ConclusionThis study indicates that marital status is associated with blood-based immune system markers toward innate immunity and higher levels of plasma neurodegeneration markers. This is particularly evident for never married or previously married male older adults compared to married or female peers.

Life-course neighbourhood deprivation and brain structure in older adults: the Lothian Birth Cohort 1936.

Neighbourhood disadvantage may be associated with brain health but the importance of exposure at different stages of the life course is poorly understood. Utilising the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and local neuroimaging measures at age 73. A total of 689 participants had at least one valid brain measures (53% male); to maximise the sample size structural equation models with fullinformation maximum likelihood were conducted. Residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (β = -0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (β = -0.11; SE = 0.03; N = 658; n = 390), and normal-appearing white matter volumes (β = -0.07; SE = 0.03; N = 658; n = 390), thinner cortex (β = -0.14; SE = 0.06; N = 636; n = 379), and lower general white matter fractional anisotropy (β = -0.19; SE = 0.06; N = 665; n = 388). We also found some evidence on the accumulating impact of neighbourhood deprivation from birth to late adulthood on age 73 total brain (β = -0.06; SE = 0.02; N = 658; n = 276) and grey matter volumes (β = -0.10; SE = 0.04; N = 658; n = 276). Local analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower social classes, the brain-neighbourhood associations were particularly strong, with the impact of neighbourhood deprivation on total brain and grey matter volumes, and general white matter fractional anisotropy accumulating across the life course. Our findings suggest that living in deprived neighbourhoods across the life course, but especially in mid- to late adulthood, is associated with adverse brain morphologies, with lower social class amplifying the vulnerability.

Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort.

We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities. We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N=299), mild cognitive impairment (MCI; N=192), or dementia (DEM; N=65). Biomarkers were compared across groups stratified by diagnosis, sex, race, and APOE ε4 carrier status. General linear models examined plasma-imaging associations before and after adjusting for demographics (age, sex, race, education), APOE ε4 status, medications, diagnosis, and other factors (estimated glomerular filtration rate [eGFR], body mass index [BMI]). Plasma biomarkers differed across diagnostic groups (DEM>MCI>CU), were altered in Aβ-PET-positive individuals, and were associated with poorer brain health and kidney function. eGFR and BMI did not substantially impact associations between plasma and neuroimaging biomarkers. Plasma biomarkers differ across diagnostic groups (DEM>MCI>CU) and are altered in Aβ-PET-positive individuals. Altered plasma biomarker levels are associated with poorer brain health and kidney function. Plasma and neuroimaging biomarker associations are largely independent of comorbidities.

Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder-Robinson syndrome.

Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder caused by a mutation in the SMS gene, which encodes spermine synthase, and aberrant polyamine metabolism. SRS is characterized by intellectual disability, thin habitus, seizure, low muscle tone/hypotonia and osteoporosis. Progress towards understanding and treating SRS requires a model that recapitulates human gene variants and disease presentations. Here, we evaluated molecular and neurological presentations in the G56S mouse model, which carries a missense mutation in the Sms gene. The lack of SMS protein in the G56S mice resulted in increased spermidine/spermine ratio, failure to thrive, short stature and reduced bone density. They showed impaired learning capacity, increased anxiety, reduced mobility and heightened fear responses, accompanied by reduced total and regional brain volumes. Furthermore, impaired mitochondrial oxidative phosphorylation was evident in G56S cerebral cortex, G56S fibroblasts and Sms-null hippocampal cells, indicating that SMS may serve as a future therapeutic target. Collectively, our study establishes the suitability of the G56S mice as a preclinical model for SRS and provides a set of molecular and functional outcome measures that can be used to evaluate therapeutic interventions for SRS.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

The impact of sunlight exposure on brain structural markers in the UK Biobank

Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers. General linear regression analysis was used to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Restricted cubic spline was performed to examine the dose–response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. A negative association of sunlight exposure time with brain structural markers was found in the upper tertile compared to the lower tertile. Prolonged natural sunlight exposure was associated with the volumes of total brain (β: − 0.051, P < 0.001), white matter (β: − 0.031, P = 0.023), gray matter (β: − 0.067, P < 0.001), and white matter hyperintensities (β: 0.059, P < 0.001). These associations were more pronounced in males and individuals under the age of 60. The results of the restricted cubic spline analysis showed a nonlinear relationship between sunlight exposure and brain structural markers, with the direction changing around 2 h of sunlight exposure. This study demonstrates that prolonged exposure to natural sunlight is associated with brain structural markers change.

Circulating sphingolipids and subclinical brain pathology: the cardiovascular health study.

Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults. Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% APOE ε4 allele carriers). We measured 8 ceramide and sphingomyelin species in plasma samples and examined the associations with several MRI, including worsening grades of white matter hyperintensities and ventricular size, number of brain infarcts, and measures of brain atrophy in a subset with quantitative measures. We also investigated the sphingolipid associations with serum NfL and GFAP. In the fully adjusted model, higher plasma levels of ceramides and sphingomyelins with a long (16-carbon) saturated fatty acid were associated with higher blood levels of NfL [β = 0.05, false-discovery rate corrected P (PFDR) = 0.004 and β = 0.06, PFDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex (P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), PFDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume. Overall, our comprehensive investigation supports the evidence that ceramides and sphingomyelins are associated with increased aging brain pathology and that the direction of association depends on the fatty acid attached to the sphingosine backbone.

Hippocampal volume mediates the association of arterial stiffness with cognitive impairment in adult population.

To investigate the association of arterial stiffness with brain perfusion, brain tissue volume and cognitive impairment in the general adult population. This prospective study included 1488 adult participants (age range: 22.8-83.9 years) from the Kailuan study. All participants underwent brachial-ankle pulse wave velocity (PWV) measurement, brain MRI, and Montreal Cognitive Assessment (MoCA). The association of PWV with cerebral blood flow (CBF), brain tissue volume and MoCA score was investigated. Mediation analysis was used to determine whether CBF and brain tissue volume changes mediated the associations between PWV and MoCA score. A 1 standard deviation (SD) increase in PWV was associated with lower total brain CBF [ β (95% CI) -0.67 (-1.2 to -0.14)], total gray matter CBF [β (95% CI) -0.7 [-1.27 to -0.13)], frontal lobe CBF [ β (95% CI) -0.59 (-1.17 to -0.01)], parietal lobe CBF [ β (95% CI) -0.8 (-1.43 to -0.18)], and temporal lobe CBF [ β (95% CI) -0.68 (-1.24 to -0.12)]. Negative associations were found for PWV and total brain volume [ β (95% CI) -4.8 (-7.61 to -1.99)] and hippocampus volume [ β (95% CI) -0.08 (-0.13 to -0.04)]. A 1 SD increase PWV was significantly associated with elevated odds of developing cognitive impairment [odds ratio (95% CI) 1.21 (1.01-1.45)]. Mediation analysis showed that hippocampal volume partially mediated the negative association between PWV and MoCA scores (proportion: 14.173%). High arterial stiffness was associated with decreased total and regional CBF, brain tissue volume, and cognitive impairment. Hippocampal volume partially mediated the effects of arterial stiffness on cognitive impairment.

THE POTENTIAL ROLE OF EXERCISE IN DELAYING GENETIC DESTINY: EXAMINING THE RELATIONSHIP BETWEEN EXERCISE AND KEY BIOMARKERS IN DOMINANTLY INHERITED ALZHEIMER’S DISEASE

INTRODUCTION Greater physical activity is associated with reduced risk for Alzheimer’s disease (AD), and lower levels of AD-related biomarkers, such as beta-amyloid (Aβ) and tau, measured in the cerebrospinal fluid (CSF) and brain. A small proportion of Alzheimer’s disease (&amp;lt;1%) cases are caused by a rare dominant genetic mutation. The aim of the current study was to examine associations between self-reported exercise participation and AD-related biomarkers (from CSF and brain imaging) over time, in individuals we know will develop Alzheimer’s disease at an early age (i.e., dominant AD mutation carriers). METHODS The sample included n = 308 mutation carriers from the Dominantly Inherited Alzheimer’s Network (DIAN) study with data available for self-reported exercise participation, brain imaging (hippocampal volume, total brain volume, gray matter volume, white matter hyperintensities, brain Aβ levels), and biomarkers quantified from CSF (several Aβ and tau species and ratios). Participants were assessed regularly (time interval depending on mutation type) from baseline to 10+ years post-baseline. Associations between exercise and AD biomarkers (i.e., from brain imaging and CSF) were examined using linear mixed models, corrected for various confounding variables. RESULTS The sample had a mean age of 39.7 ± 10.8 years and were 56% female. Greater baseline exercise was associated with a slower decrease in right (B=0.06, p &amp;lt; 0.001) and left (B=0.06, p&amp;lt;0.05) hippocampal volume; and slower accumulation of brain Aβ (B=0.04, p&amp;lt;0.001). CONCLUSION These findings demonstrate that exercise is associated with more favourable profiles of AD-related biomarkers in those with ADAD mutations. This work may have implications for our understanding of how exercise influences disease development in late-onset sporadic AD. Nevertheless, the causal direction of our findings is difficult to ascertain, and future study designs investigating the therapeutic potential of exercise in both ADAD and late-onset AD should be considered.

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.

MRI morphometry of the anterior and posterior cerebellar vermis and its relationship to sensorimotor and cognitive functions in children

IntroductionThe human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions. MethodsTypically developing children (TDC; n=38; age 9–15) and healthy adults (HAC; n=31; 18–40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV. ResultsTBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ. ConclusionsIn TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The "inverted U" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.

Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis.

Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study.

This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

Volumetric Alterations in Brain Structures Caused by Autism during Different Age Stages

Conclusions in literature regarding the effect of Autism on the size of different brain structures are contradictory. The aim of this study is to determine the effect of Autism on the volumes of different brain subcortical structures, and the age stage at which those changes occur. 7 main brain structures were segmented and their volumes were obtained. Volumes and the ratio of the volume to total brain volume (SBR) were compared in Autism group to their corresponding values in Control group. Then, each group was divided into 4 subgroups based on age; the comparison was repeated for each subgroup. Independent t-test was used to determine if significant differences existed between compared groups. Significant reductions were observed in the SBR of Autistic Pallidum and Accumbens compared to Control group when considering the full range of ages (5–25 years). However, Amygdala’s volume was significantly smaller in Autism in the 5–8 year subgroup. In addition, the SBR of Putaman, Pallidum, Hippocampus, and Accumbens were reduced in the 18–25 year Autism subgroup. In conclusion, the alteration in the ratio of structure’s volume to total brain volume is a better indicator of Autism diagnosis than change in the absolute volume alone.

Sex, gender diversity, and brain structure in early adolescence.

There remains little consensus about the relationship between sex and brain structure, particularly in early adolescence. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest-many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9-11 years old (N = 7195). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. Additional sensitivity analyses found that male versus female differences in gyrification and white matter were largely accounted for by total brain volume, rather than sex per se. The model with sex, but not gender diversity, was the best-fitting model in 60.1% of gray matter regions and 61.9% of white matter regions after adjusting for brain volume. The proportion of variance accounted for by sex was negligible to small in all cases. While models including felt-gender explained a greater amount of variance in a few regions, the felt-gender score alone was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9-11 years old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity.

The association between cannabis use and neuroimaging measures in older adults: findings from the UK biobank.

Cannabis use has increased in recent years. However, the long-term implications of cannabis use on brain health remain unknown. We explored the associations of cannabis use with volumetric brain magnetic resonance imaging (MRI) measures in dementia-free older adults. This cross-sectional and longitudinal study included dementia-free participants of the UK Biobank aged ≥60years. Linear regression models were used to evaluate the association of cannabis use and patterns of use with volumetric brain MRI measures. The association between cannabis use and change in brain MRI measures over time was also tested. All models were adjusted for potential confounders. The sample included 19,932 participants (mean age 68 ± 5years, 48% men), 3,800 (19%) reported lifetime use of cannabis. Cannabis use was associated with smaller total, white, grey and peripheral cortical grey matter volumes (B= -6,690 ± 1,157; P< 0.001, B= -4,396 ± 766; P< 0.001, B= -2,140 ± 690; P= 0.002 and B= -2,451 ± 606; P< 0.001, respectively). Among cannabis users, longer duration of use was associated with smaller total brain, grey and cortical grey matter volumes (B= -7,878 ± 2,396; P= 0.001, B= -5,411 ± 1,430; P< 0.001, B = -5,396 ± 1,254; P< 0.001, respectively), and with increased white matter hyperintensity volume (B= 0.09 ± 0.03; P= 0.008). Additionally, current vs. former users (B= -10,432 ± 4,395; P= 0.020) and frequent versus non-frequent users (B= -2,274 ± 1,125; P= 0.043) had smaller grey and cortical grey matter volumes, respectively. No significant associations were observed between cannabis use and change in brain MRI measures. Our findings suggest that cannabis use, particularly longer duration and frequent use, may be related to smaller grey and white matter volumes in older ages, but not to late-life changes in these measures over time.

Cardiometabolic disease, cognitive decline, and brain structure in middle and older age.

The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear. In the UK Biobank, 46,562 dementia-free participants completed a cognitive test battery at baseline and a follow-up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age-stratified (middle age [<60] versus older [≥ 60]) mixed-effects models and linear regression. A higher number of CMDs was associated with significantly steeper global cognitive decline in older (β=-0.008; 95% confidence interval: -0.012, -0.005) but not middle age. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, and hippocampal volume and larger white matter hyperintensity volume, even in middle age. CMDs are associated with cognitive decline in older age and poorer brain structural health beginning already in middle age. We explored the association of CMDs with cognitive decline and brain MRI measures.CMDs accelerated cognitive decline in older (≥60y) but not middle (<60) age.CMDs were associated with poorer brain MRI parameters in both middle and older age.Results highlight the connection between CMDs and cognitive/brain aging.

Comparative MRI analysis of the forebrain of three sauropsida models

The study of the brain by magnetic resonance imaging (MRI) allows to obtain detailed anatomical images, useful to describe specific encephalic structures and to analyze possible variabilities. It is widely used in clinical practice and is becoming increasingly used in veterinary medicine, even in exotic animals; however, despite its potential, its use in comparative neuroanatomy studies is still incipient. It is a technology that in recent years has significantly improved anatomical resolution, together with the fact that it is non-invasive and allows for systematic comparative analysis. All this makes it particularly interesting and useful in evolutionary neuroscience studies, since it allows for the analysis and comparison of brains of rare or otherwise inaccessible species. In the present study, we have analyzed the prosencephalon of three representative sauropsid species, the turtle Trachemys scripta (order Testudine), the lizard Pogona vitticeps (order Squamata) and the snake Python regius (order Squamata) by MRI. In addition, we used MRI sections to analyze the total brain volume and ventricular system of these species, employing volumetric and chemometric analyses together. The raw MRI data of the sauropsida models analyzed in the present study are available for viewing and downloading and have allowed us to produce an atlas of the forebrain of each of the species analyzed, with the main brain regions. In addition, our volumetric data showed that the three groups presented clear differences in terms of total and ventricular brain volumes, particularly the turtles, which in all cases presented distinctive characteristics compared to the lizards and snakes.

Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV–adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK–SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann–Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10−3, p < 0.001). The MBs volume/TBV ratio correlated with visual memory, as assessed, respectively, by the Rey–Osterrieth Complex Figure test delayed recall (ρ = 0.62, p < 0.001). In conclusion, retired athletes with rmTBI have MB atrophy, potentially contributing to memory impairment linked to the Papez circuit disconnection.