Total Intracranial Volume Research Articles

Unsupervised neurobiology-driven stratification of clinical heterogeneity in depression

IntroductionOne of the main obstacles in providing effective treatments for major depressive disorder (MDD) is clinical heterogeneity, whose neurobiological correlates are not clearly defined. A biologically meaningful stratification of depressed patients is needed to promote tailored diagnostic procedures.ObjectivesUsing structural data, we performed an unsupervised clustering to define clinically meaningful clusters of depressed patients.MethodsT1-weighted and diffusion tensor images were obtained from 102 MDD patients. In 64 patients, clinical symptoms, number of stressful life events, severity and exposure to adverse childhood experiences were evaluated using the Beck Depression Inventory (BDI), Schedule of Recent Experiences (SRE), Risky Family Questionnaire (RFQ), and Childhood Trauma Questionnaire (CTQ). Clustering analyses were performed with extracted tract-based fractional anisotropy (TBSS, FSL), cortical thickness, surface area, and regional measures of grey matter volumes (CAT12). Gaussian mixture model was implemented for clustering, considering Support Vector Machine (SVM) as classifier. A 10x2 repeated cross-validation with grid search was performed for hyperparameters tuning and clusters’ stability. The optimal number of clusters was determined by normalized stability, Akaike and Bayesian information criterion. Analyses were adjusted for total intracranial volume, age, and sex. The clinical relevance of the identified clusters was assessed through MANOVA, considering domains of clinical scales as dependent variables and clusters’ labels as fixed factors. Discriminant analysis was subsequently performed to assess the discriminative power of these variables.ResultsCross-validated clustering approach identified 2 highly stable clusters (normalized stability=0.316, AIC=-80292.48, BIC=351329.16). MANOVA showed a significant between-clusters difference in clinical scales scores (p=0.038). Discriminant analysis distinguished the two clusters with an accuracy of 78.1%, with BDI behavioural and CTQ minimisation/denial domains showing the highest discriminant values (0.325 and 0.313).ConclusionsOur results defined two biologically informed clusters of MDD patients associated with childhood trauma and specific clinical profiles, which may assist in targeting effective interventions and treatments.Disclosure of InterestNone Declared

Association of Income with Post-Stroke Cognition and the Underlying Neuroanatomical Mechanism.

To investigate the association between income and post-stroke cognition at 3 months, and the underlying neuroanatomical mechanism. Patients with first-ever ischemic stroke were enrolled and analyzed. Baseline information on income and neuroimaging measurements with predictive values for post-stroke cognitive impairment (PSCI) were collected within 7 days of the admission. Three months after the index stroke, all participants underwent a detailed neuropsychological test battery. The associations between income and PSCI and between income and brain structural measurements were investigated. A total of 294 patients were recruited for this study. Lower income was independently associated with poor cognitive performance on Stroop tests, Clinical Dementia Rating, Boston Naming Test, and Verbal Fluency Test. Regarding neuroimaging parameters, lower income was associated with a lower total brain volume (TBV)/total intracranial volume (TICV) ratio (p = 0.004). Lower income is associated with an increased chance of post-stroke cognitive decline, particularly in executive function and language domains. Since global brain atrophy (measured by TBV/TICV ratio) is a strong predictor for PSCI, its correlation with income may help explain the neuroanatomical mechanism between income and post-stroke cognition.

Validity Assessment of an Automated Brain Morphometry Tool for Patients with De Novo Memory Symptoms.

Automated volumetric analysis of structural MR imaging allows quantitative assessment of brain atrophy in neurodegenerative disorders. We compared the brain segmentation performance of the AI-Rad Companion brain MR imaging software against an in-house FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. T1-weighted images of 45 participants with de novo memory symptoms were selected from the OASIS-4 database and analyzed through the AI-Rad Companion brain MR imaging tool and the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. Correlation, agreement, and consistency between the 2 tools were compared among the absolute, normalized, and standardized volumes. Final reports generated by each tool were used to compare the rates of detection of abnormality and the compatibility of radiologic impressions made using each tool, compared with the clinical diagnoses. We observed strong correlation, moderate consistency, and poor agreement between absolute volumes of the main cortical lobes and subcortical structures measured by the AI-Rad Companion brain MR imaging tool compared with FreeSurfer. The strength of the correlations increased after normalizing the measurements to the total intracranial volume. Standardized measurements differed significantly between the 2 tools, likely owing to differences in the normative data sets used to calibrate each tool. When considering the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline as a reference standard, the AI-Rad Companion brain MR imaging tool had a specificity of 90.6%-100% and a sensitivity of 64.3%-100% in detecting volumetric abnormalities. There was no difference between the rate of compatibility of radiologic and clinical impressions when using the 2 tools. The AI-Rad Companion brain MR imaging tool reliably detects atrophy in cortical and subcortical regions implicated in the differential diagnosis of dementia.

Three-Dimensional Assessment of Frontal Bossing and Temporal Pinching in Patients with Sagittal Craniosynostosis Using Curvature Analysis.

Sagittal craniosynostosis results in varying degrees of frontal bossing and bilateral temporal pinching. This study assessed the three-dimensional changes in these regions using curvature analysis and volumetric analysis before and 1 year after extended sagittal strip craniectomy (ESC) with postoperative helmet therapy. A retrospective review of three-dimensional photographs of 50 subjects treated with ESC with postoperative helmet therapy and 50 age-matched controls was performed. Images were collected preoperatively and 1 year postoperatively. Forehead convexity and temple concavity were quantified. Computed tomographic scans of subjects with and without sagittal synostosis were analyzed to assess the percentage of total intracranial volume (ICV) in the anterior cranial fossa before and after ESC with postoperative helmet therapy. Forehead convexity in the ESC with postoperative helmet therapy group preoperatively (24.49 ± 3.16 m -1 ) was significantly greater than controls (22.48 ± 3.84 m -1 ; P = 0.005). Forehead convexity significantly decreased after ESC with postoperative helmet therapy (18.79 ± 2.43 m -1 ; P < 0.001) and did not differ from controls (19.67 ± 3.08 m -1 ; P = 0.115). The ESC group had more concave temples preoperatively (-10.27 ± 4.37 m -1 ) as compared with controls (-6.99 ± 3.55 m -1 ; P < 0.001). Temple concavity significantly decreased after ESC (-4.82 ± 3.17 m -1 ; P < 0.001) and did not differ from controls (-5.64 ± 3.27 m -1 ; P = 0.075). In the ESC group, the percentage ICV in the anterior cranial fossa decreased from 22.03% to 18.99% after surgery, whereas the anterior volume in controls was stable (17.74% to 16.81%). The ESC group had significantly greater forehead convexity, temple concavity and anterior cranial fossa volume compared with controls. One year after ESC with postoperative helmet therapy, forehead convexity, temple concavity, and percentage ICV in the anterior fossa were comparable to controls. Therapeutic, IV.

Abstract TP159: Association Of Lesion Characteristics And Neurological Outcomes In Neonatal Arterial Ischemic Stroke Patients

Background: Neonatal arterial ischemic stroke (NAIS) occurs as a result of an acute focal cerebral arterial infarction between birth and 28 days of life in nearly 1:2500 live births. As there are few studies examining the relationship between NAIS lesion characteristics and clinical outcomes, this study aims to determine if lesion volume and lesion location are associated with abnormal neurological outcomes in NAIS. Methods: Semi-automated lesion segmentation of co-registered multi-modal images was conducted using ITK-SNAP. Semi-automated lesion segmentations with manual corrections were performed using ITK-SNAP software. Lesion volumes were corrected for head size by dividing lesion volumes by total intracranial volume, and correlated (using Kendall's Tau-b [τ b ]) with neurological outcome that was assessed with the Pediatric Stroke Outcome Measure (PSOM). Results: Participants included N=20 NAIS patients (mean [M] weeks gestation=39.5, +/-1.64; 55% male, 70% single infarct, 75% left-sided lesions). Outcome was assessed an average of 312, +/-7.6 days post-stroke. Neurological deficits were present in 50% (with seizures in 85%) at time of stroke, and infarct locations most commonly involved supratentorial cortical structures (75%), however none were correlated with outcome. Larger lesion volumes (M=5.35 mm 3 , +/-0.069) were correlated with poor outcome (τ b =.444, p=0.02). Conclusion: We found larger lesion volume to be associated with atypical clinical outcomes following NAIS. Further analysis is in progress that include changes over time in lesion characteristics and outcome. These results demonstrate a need for better characterize the relationship between lesion characteristics and outcomes in NAIS.

Fully Automatic Method for Reliable Spinal Cord Compartment Segmentation in Multiple Sclerosis.

Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS. The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer. The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (P < .05), and total anterior horn areas (P < .01 respectively), as measured with SCORE. We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.

Gray matter differences associated with menopausal hormone therapy in menopausal women: a DARTEL-based VBM study

Menopausal hormone therapy (MHT) in women can reduce troublesome menopause symptoms and prevent cognitive decline. This cross-sectional study investigated the MHT-related effect on brain morphology and its association with sex hormones in menopausal women by using an optimized diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL)-based voxel-based morphometry (VBM) method. Twenty-one menopausal women without MHT (noMHT) and 20 menopausal women with MHT were included in this study. Magnetic resonance imaging data were processed using SPM 12 with DARTEL-based VBM whole brain analysis approach. A 2-sample t-test and analysis of covariance (ANCOVA) adjusting for age and total intracranial volume were used to compare GM volume between noMHT and MHT women. The association between MHT (treatment period, hormones levels) and brain volume variations were analyzed by Spearman correlation. MHT women showed significantly larger volumes of the superior/middle/inferior frontal gyri, hypothalamus, inferior temporal gyrus, parahippocampal gyrus, hippocampus, cerebellar cortex, postcentral gyrus, precuneus, angular gyrus, supplementary motor area, superior occipital gyrus, and precentral gyrus compared to the noMHT women. The volumes of the angular gyrus and hypothalamus in MHT women positively correlated with treatment period. On the other hand, the hypothalamic volume negatively correlated with FSH and LH levels, and the volumes of the inferior frontal gyrus, and angular gyrus negatively correlated with progesterone levels, respectively. MHT-treated women showed larger GM volume than noMHT women. The anatomical structures that showed greater volume in association with MHT included the deep brain areas, frontal, temporal, parietal, and occipital gyri.

Influence of accessory sulci of the frontoparietal operculum on gray matter quantification.

Introduction: The perisylvian region is the cortical core of language and speech. Several accessory sulci have been described in this area, whose presence could modify the results of the automatic quantification of gray matter by popularly used software. This study aimed to assess the expression of accessory sulci in the frontoparietal operculum (FPO) and to evaluate their influence on the gray matter volume estimated by an automatic parcellation of cortical gyri and sulci. Methods: Brain MRI scans of 100 healthy adult volunteers were visually analyzed. The existence of the triangular and diagonal sulci, and the number of accessory sulci in the frontoparietal operculum, were assessed on T1 images. Also, the gray matter volume of gyri and sulci was quantified by an automatized parcellation method. Interhemispheric differences in accessory sulci were evaluated with Chi-square and Wilcoxon paired tests. The effects of the hemisphere, sex, age, total intracranial volume, and accessory sulci on morphometric variables were assessed by linear models. Results: These sulci were found in more than half of the subjects, mostly in the left hemisphere, and showed a significant effect on the gray matter content of the FPO. In particular, the volume of the inferior frontal sulcus, pars opercularis of the inferior frontal gyrus, horizontal ramus of the lateral sulcus, angular gyrus, and postcentral gyrus showed a significant influence on the presence of accessory sulci. Discussion: The prevalence of tertiary sulci in the FPO is high, although their meaning is not yet known. Therefore, they should be considered to reduce the risk of misclassifications of normal variation.

Sleep, 24-Hour Activity Rhythms, and Cognitive Reserve: A Population-Based Study.

The cognitive reserve hypothesis aims to explain individual differences in susceptibility to the functional impact of dementia-related pathology. Previous research suggested that poor subjective sleep may be associated with a lower cognitive reserve. The objective was to investigate if actigraphy-estimated sleep and 24-hour activity rhythms are associated with cognitive reserve. This cross-sectional study included 1,002 participants from the Rotterdam Study (mean age: 65.0 years, standard deviation (SD): 7.1) who were assessed with actigraphy, five cognitive tests, and brain-MRI between 2009- 2014. Sleep and 24-hour activity rhythms were measured using actigraphy (mean days: 6.7, SD: 0.5). Cognitive reserve was defined as a latent variable that captures variance across cognitive tests, while adjusting for age, sex, education, total brain volume, intracranial volume, and white matter hyperintensity volume. Associations of sleep and 24-hour activity rhythms with cognitive reserve were assessed using structural equation models. Longer sleep onset latency (adjusted mean difference: - 0.16, 95% CI: - 0.24; - 0.08) and lower sleep efficiency (0.14, 95% CI: 0.05; 0.22) were associated with lower cognitive reserve. Total sleep time and wake after sleep onset were not significantly associated with cognitive reserve. After mutual adjustment, only the association of longer sleep onset latency remained significant (- 0.12, 95% CI: - 0.20; - 0.04). The 24-hour activity rhythm was not significantly associated with cognitive reserve. In conclusion, our study suggests that longer sleep onset latency is particularly associated with lower cognitive reserve. Future longitudinal work is needed to assess whether shortening the sleep onset latency could enhance cognitive reserve, in order to limit the susceptibility to the functional impact of dementia-related pathology.

The role of the orbitofrontal cortex in exercise addiction and exercise motivation: A brain imaging study based on multimodal magnetic resonance imaging

BackgroundExcessive exercise may also lead to exercise addiction (EXA), which is harmful to people's physical and mental health. Behavioral and neuroimaging studies have demonstrated that addictive disorders are essentially motivational problems. However, little is known about the neuropsychological mechanism of EXA and the effects of motivation on EXA. MethodsWe investigated 130 regularly exercised participants with EXA symptoms to explore the neurobiological basis of EXA and its association with motivation. The correlation between EXA and gray matter volume (GMV) was evaluated by whole-brain regression analysis based on voxel-based morphometry. Then, regional brain function was extracted and the relationship between brain structure-function-EXA was analyzed. Finally, mediation analysis was performed to further detect the relationship between the brain, motivation, and EXA. ResultsWhole-brain correlation analyses showed that the GMV of the right orbitofrontal cortex (OFC) was negatively correlated with EXA. The function of the right OFC played an indirect role in EXA and affected EXA via the GMV of the OFC. Importantly, the GMV of the right OFC played a mediating role in the relationship between ability motivation and EXA. These results remain significant even when adjusting for sex, age, body mass index, family socioeconomic status, general intelligence, total intracranial volume, and head motion. LimitationThe results should be interpreted carefully because only the people with EXA symptoms were included. ConclusionThis study provided evidence for the underlying neuropsychological mechanism of the important role of the right OFC in EXA and revealed that there may be a decrease in executive control function in EXA.

Male-specific, replicable and functional roles of genetic variants and cerebral gray matter volumes in ADHD: a gene-wide association study across KTN1 and a region-wide functional validation across brain

Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their regulatory effects on mRNA expression and cortical and subcortical GMVs. We examined a total of 1020 KTN1 SNPs in one discovery sample (ABCD cohort: 5573 males and 5082 females) and three independent replication European samples (Samples #1 and #2 each with 802/122 and 472/141 male/female offspring with ADHD; and Sample #3 with 14,154/4945 ADHD and 17,948/16,246 healthy males/females) to identify replicable associations within each sex. We examined the regulatory effects of ADHD-risk alleles on the KTN1 mRNA expression in two European brain cohorts (n = 348), total intracranial volume (TIV) in 46 European cohorts (n = 18,713) and the ABCD cohort, as well as the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258) and of 118 cortical and subcortical regions in the ABCD cohort. We found that four KTN1 variants significantly regulated the risk of ADHD with the same direction of effect in males across discovery and replication samples (0.003 ≤ p ≤ 0.041), but none in females. All four ADHD-risk alleles significantly decreased KTN1 mRNA expression in all brain regions examined (1.2 × 10–5 ≤ p ≤ 0.039). The ADHD-risk alleles significantly increased basal ganglia (2.8 × 10–22 ≤ p ≤ 0.040) and hippocampus (p = 0.010) GMVs but reduced amygdala GMV (p = 0.030) and TIV (0.010 < p ≤ 0.013). The ADHD-risk alleles also significantly reduced some cortical (right superior temporal pole, right rectus) and cerebellar but increased other cortical (0.007 ≤ p ≤ 0.050) GMVs. To conclude, we identified a set of replicable and functional risk KTN1 alleles for ADHD, specifically in males. KTN1 may play a critical role in the pathogenesis of ADHD, and the reduction of specific cortical and subcortical, including amygdalar but not basal ganglia or hippocampal, GMVs may serve as a neural marker of the genetic effects.

Assessment of aortic and cerebral haemodynamics and vascular brain injury with 3 and 7 T magnetic resonance imaging in patients with aortic coarctation.

Coarctation of the aorta (CoA) is characterized by a central arteriopathy resulting in increased arterial stiffness. The condition is associated with an increased risk of stroke. We aimed to assess the aortic and cerebral haemodynamics and the presence of vascular brain injury in patients with previous surgical CoA repair. Twenty-seven patients with CoA (median age 22 years, range 12-72) and 25 age- and sex-matched controls (median age 24 years, range 12-64) underwent 3 T (heart, aorta, and brain) and 7 T (brain) magnetic resonance imaging scans. Haemodynamic parameters were measured using two-dimensional phase-contrast images of the ascending and descending aorta, internal carotid artery (ICA), basilar artery (BA), middle cerebral artery (MCA), and perforating arteries. Vascular brain injury was assessed by rating white matter hyperintensities, cortical microinfarcts, lacunes, and microbleeds. Pulse wave velocities in the aortic arch and descending aorta were increased and ascending aortic distensibility was decreased in patients with CoA vs. controls. Patients with CoA showed a higher mean flow velocity in the right ICA, left ICA, and BA and a reduced distensibility in the right ICA, BA, and left MCA. Haemodynamic parameters in the perforating arteries, total cerebral blood flow, intracranial volumes, and vascular brain injury were similar between the groups. Patients with CoA show an increased flow velocity and reduced distensibility in the aorta and proximal cerebral arteries, which suggests the presence of a generalized arteriopathy that extends into the cerebral arterial tree. No substantial vascular brain injury was observed in this relatively young CoA population, although the study was inadequately powered regarding this endpoint.

Testing the Ecophenotype Model: Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment

BackgroundChildhood maltreatment is common in youths with conduct disorder (CD), and both CD and maltreatment have been linked to neuroanatomical alterations. Nonetheless, our understanding of the contribution of maltreatment to the neuroanatomical alterations observed in CD remains limited. We tested the applicability of the ecophenotype model to CD, which holds that maltreatment-related psychopathology is (neurobiologically) distinct from psychopathology without maltreatment. MethodsSurface-based morphometry was used to investigate cortical volume, thickness, surface area, and gyrification in a mixed-sex sample of participants with CD (n = 114) and healthy control subjects (HCs) (n = 146), ages 9 to 18 years. Using vertexwise general linear models adjusted for sex, age, total intracranial volume, and site, the control group was compared with the overall CD group and the CD subgroups with (n = 49) versus without (n = 65) maltreatment (assessed by the Children’s Bad Experiences interview). These subgroups were also directly compared. ResultsThe overall CD group showed lower cortical thickness in the right inferior frontal gyrus. CD youths with a history of maltreatment showed more widespread structural alterations relative to HCs, comprising lower thickness, volume, and gyrification in inferior and middle frontal regions. Conversely, CD youths with no history of maltreatment only showed greater left superior temporal gyrus folding relative to HCs. When contrasting the CD subgroups, those with maltreatment displayed lower right superior temporal gyrus volume, right precentral gyrus surface area, and gyrification in frontal, temporal, and parietal regions. ConclusionsConsistent with the ecophenotype model, findings indicated that CD youths with versus without maltreatment differ neurobiologically. This highlights the importance of considering maltreatment history in neuroimaging studies of CD and other disorders.

Occupational stress is associated with sex and subregion specific modifications of the amygdala volumes

Background: Despite the rapid increase in reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. In the present study, we investigated whether occupational ES is associated with specific modifications of the subfields of the amygdala and hippocampus resembling those described in other chronic stress conditions. Special focus was paid to possible sex differences. Methods: As a follow up to our previous studies of occupational ES, we carried out MRI-based subfield segmentation of the hippocampus and amygdala volumes in 58 patients with occupational ES (22 males) and 65 age-matched controls (27 males) (age range 30–46 years). Results: There was a significant and bilateral enlargement of the lateral, basal and central nucleus of the amygdala in patients with ES (corrected for the total intracranial volume (ICV)). These differences were detected only in females. Higher values in the right central and right basal amygdala remained when the whole amygdala volume was used as reference, instead of the ICV. Notably, in female patients the volumes of these specific nuclei were positively correlated with the degree of perceived stress. No changes in the hippocampus subfields were detected in female or male patients. Conclusions: The findings underline that ES is a chronic stress condition, suggesting that not only extreme forms of stress, but also the everyday stress is associated with localized differences from controls in the amygdala. The absence of significant alterations among men with ES despite a similar degree of perceived stress supports the notion that women seem more susceptible to stress-related cerebral changes, and may explain the higher prevalence of ES among women.

Can basic magnetic resonance imaging along with neuropsychological assessment be used as a cost-effective means for the detection of early dementia in the Indian sub-continent?

ABSTRACT Introduction: The mild cognitive impairment (MCI) stage occurs sporadically between healthy aging and the onset of Alzheimer’s disease (AD). MCI shows significant defacement in magnetic resonance imaging (MRI) of the brain along with neuropsychological and behavioral parameters. Aim: Assessment of neuropsychological, behavioral, and structural MRI changes in MCI and their relation with each other. Methodology: Seventy-eight participants in the MCI group and healthy controls (HC) were assessed using Addenbrooke’s Cognitive Examination (ACE), Mini-Mental Status Examination (MMSE), Clinical Dementia Rating Scale (CDR); and behavioral assessment by using Behavioral Pathology In AD (BEHAVE-AD). MRI brain volumetric analysis was performed using the software MYRIAN. Statistical analysis was performed using the Mann–Whitney U test, unpaired t-test (P = &lt;0.05), and Spearman’s rank correlation. Results: MCI group showed significant impairments in ACE, MMSE, and CDR and significantly higher behavioral symptoms on BEHAVE-AD. Episodic memory had a significant positive correlation with normalized right hippocampal volume and total intracranial volume (TICV). Remote memory had a significant negative correlation with normalized left hippocampal volumes. Global CDR score had a moderately negative correlation with normalized right and left hippocampal volumes. Affective disturbances were negatively correlated with TICV. Conclusions: Comparable analysis of correctly scaled neuropsychological assessments may provide unbiased proxies for MRI-based measures of dementia risk.

Independent and additive contribution of white matter hyperintensities and Alzheimer’s disease pathology to basal forebrain cholinergic system degeneration

ObjectivesDegeneration of the cholinergic basal forebrain nuclei (CBFN) system has been studied extensively in Alzheimer's disease (AD). White matter hyperintensities are a hallmark of aging as well as a common co-morbidity of AD, but their contribution to CBFN degeneration has remained unclear. Therefore, we explored the influence of white matter hyperintensities within cholinergic subcortical-cortical projection pathways on CBFN volumes and regional gray matter volumes in AD and age- and gender-matched controls. MethodsWe analyzed magnetic resonance images (MRI) from 42 patients with AD and 87 age- and gender-matched control subjects. We assessed the white matter hyperintensity burden within the cholinergic projection pathways using the Cholinergic Pathways Hyperintensities Scale (CHIPS), and applied probabilistic anatomical maps for the analysis of CBFN volumes, i.e. the Ch1-3 compartment and the Ch4 cell group (nucleus basalis of Meynert), by diffeomorphic anatomical registration using exponentiated lie algebra analysis of voxel-based morphometry. Using multiple linear regression analyses, we explored correlations between regional gray matter volumes and the extent of white matter hyperintensities or CBFN volumes in both groups. ResultsIn AD, all CBFN volumes were significantly smaller than in controls, and white matter hyperintensity burden within the cholinergic projection pathways was not correlated with CBFN volume. In controls, white matter hyperintensity burden within the cholinergic projection pathways was inversely correlated with CBFN volume when corrected for sex and total intracranial volume, but this correlation was no longer significant after correction for age. Voxel-wise multiple linear regression analyses using threshold-free cluster enhancement revealed that in controls, cholinergic pathway hyperintensities correlated with gray matter loss in perisylvian areas, whereas the were no effects in AD. Moreover, we found that CBFN volumes correlated with distinct regional cortical atrophy patterns in both groups. ConclusionOur results indicate that white matter hyperintensities and AD pathology contribute independently but additively to the degeneration of cholinergic basal forebrain structures. Whereas AD is primarily associated with CBFN volume loss, cholinergic degeneration associated with white matter hyperintensities appears to involve disruption of cholinergic cortical projection fibers with less pronounced effects on CBFN volumes.

Effects of COVID-19 on brain and cerebellum: a voxel based morphometrical analysis.

COVID-19 is caused by SARS-CoV-2 virus and turned into a pandemic in a short time, affects many organs and systems, especially the nervous system. In the present study, it was aimed to determine the morphological and volumetric changes in cortical and subcortical structures in recovered COVID-19 patients. We think that COVID-19 has a long-term effect on cortical and subcortical structures. In our study, 50 post-COVID-19 patients and 50 healthy volunteers participated. In both groups, brain parcellations were made with Voxel-Based Morphometry (VBM) and regions showing density changes in the brain and cerebellum were determined. Gray matter (GM), white matter, cerebrospinal fluid and total intracranial volume were calculated. Neurological symptoms developed in 80% of COVID-19 patients. In post-COVID-19 patients, a decrease in GM density was detected in pons, gyrus frontalis inferior, gyri orbitales, gyrus rectus, gyrus cinguli, lobus parietalis, gyrus supramarginalis, gyrus angularis, hippocampus, lobulus semilunaris superior of cerebellum, declive, and Brodmann area 7-11-39-40. There was a significant decrease in GM density in these regions and an increase in GM density in amygdala (p<0.001). The GM volume of post-COVID-19 group was found to be less than in the healthy group. As a result, it was seen that COVID-19 negatively affected many structures related to the nervous system. This study is a pioneering study to determine the consequences of COVID-19, especially in the nervous system, and to determine the etiology of these possible problems (Tab. 4, Fig. 5, Ref. 25). Text in PDF www.elis.sk Keywords: COVID-19, pandemic, Voxel-based morphometry (VBM), brain, magnetic resonance imaging (MRI).

S-57-5: GUT MICROBIOME DIVERSITY AND BRAIN VOLUME AMONG GENERAL JAPANESE MEN

Objective: Accumulative evidence links gut microbiome diversity to the central nervous system, cognition, and mental disorders. However, little is known regarding the associations of gut microbiome diversity with brain volumes in human. We assessed the association of within-person gut microbiome diversity and brain volumes in general Japanese men. Methods: Healthy Japanese men (n = 623) aged 40–79 years participated in the examination of the Shiga Epidemiological Study of Subclinical Atherosclerosis II (SESSA II) between 2010 and 2015. They underwent assessments of gut microbiota diversity (Shannon Diversity Index and Chao Index) through 16S rRNA sequencing using DNA extracted from stool samples and brain volumes in milliliters (i.e., total brain volume, white matter, gray matter, and hippocampus) and white matter lesion volumes (WMLV, reflecting cerebral small vessel disease) via brain magnetic resonance imaging (MRI). Multivariable linear regression tested the effect of indexes per SD on the outcomes. Results: In unadjusted models, higher Shannon Index and Chao Index were associated with lower volumes in hippocampus (see table). After adjustments for age and total intracranial volume, higher Shannon Index and Chao Index showed associations with higher volumes in gray matter but were attenuated after additional adjustments for body mass index, physical activity, smoking, drinking, and hypertension. Conclusions: Among general Japanese men, higher within-person gut microbiota diversity was not associated with volumes in total brain volume, white matter, gray matter, hippocampus, and WMLV. Further studies are warranted to identify specific gut microbiome signatures associated with brain volumes in human.

S-50-4: INCREASED PLASMA NEUROFILAMENT LIGHT AND CEREBRAL ATROPHY IN PATIENTS WITH TYPE 2 DIABETES AND LEFT VENTRICULAR HYPERTROPHY

Objective: Left ventricular hypertrophy (LVH) is common in people with type 2 diabetes mellitus (T2DM), and both are independently associated with increased dementia risk. Neurofilament light chain protein (NfL) is exclusively expressed in neurons and is an emerging plasma marker of neurodegeneration. We investigated the relationship between LVH, plasma NfL levels and brain atrophy in people with T2DM. Design and method: Participants with T2DM aged ≧ 50 years (n = 137) from the Diabetes and Dementia study (ACTRN126160005464590) in Melbourne, Australia completed detailed assessments including 3T brain MRI, transthoracic echocardiograms, and 24-hour ambulatory blood pressure. FreeSurfer estimated brain volume measures; plasma NfL assayed on Simoa® Quanterix HD-X Analyzer. Differences in the mean cortical thickness and average cortical gray matter volume were examined using multivariate general linear models. Multiple linear regression models examined the relationship between NfL and LVH. Comparisons were made between those with and without LVH. Results: Participant details: age = 65 ± 7 (mean ± SD) years, BMI = 30 ± 6 kg/m2, 44% women, HbA1c = 60 ± 14 mmol/mol, median diabetes duration = 15 [25th, 75th quartiles 7, 22] years, 21% APOE ε4 carriers; 25% educated &lt; 12 years; 28% LVH. LVH was significantly associated with older age, female sex, obesity (BMI 33 ± 6 vs. 29 ± 5 kg/m2), hypertension history (95% vs. 67%), less education (37% vs. 20%), greater cortical thinning and lower cortical gray matter volume. Plasma NfL was correlated positively with age, HbA1c, and LV mass and negatively with cortical thickness. Median plasma NfL levels were significantly higher in LVH participants (21 [14, 28] vs. 15 [11, 22] pg/mL). Differences with LVH remained significant after adjustment for age, BMI, sex, education, and total intracranial volume for cortical thickness and average cortical gray matter volume, but not after adjustment for hypertension. LVH was an independent predictor of NfL levels (coefficient 0.19, p = 0.04). Conclusion: Accelerated structural brain aging is seen in people with LVH and T2DM. LVH and hypertension appear conflated as risk factors for brain atrophy. Plasma NfL levels are associated with LVH and cortical thickness. LVH and plasma NfL are potential early biomarkers of neurodegeneration in T2DM.

The association of prediabetes and type 2 diabetes with hippocampal subfields volume: The Maastricht study

Aims/hypothesisWe investigated whether prediabetes, type 2 diabetes, and continuous measures of hyperglycemia are associated with tissue volume differences in specific subfields of the hippocampus. MethodsWe used cross-sectional data from 4,724 participants (58.7 ± 8.5 years, 51.5% women) of The Maastricht Study, a population-based prospective cohort. Glucose metabolism status was assessed with an oral glucose tolerance test, and defined as type 2 diabetes (n = 869), prediabetes (n = 671), or normal glucose metabolism (n = 3184). We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1w and FLAIR 3T MRI images. We used multiple linear regression and linear trend analysis, and adjusted for total intracranial volume, demographic, lifestyle, and cardiovascular risk factors. ResultsType 2 diabetes was significantly associated with smaller volumes in the hippocampal subfield fimbria (standardized beta coefficient ± standard error (β ± SE) = -0.195 ± 0.04, p-value < 0.001), the hippocampus proper, i.e. Cornu Ammonis (CA) 1, CA2/3, CA4, dentate gyrus, subiculum and presubiculum (β ± SE < -0.105 ± 0.04, p-value < 0.006); as well as the hippocampal tail (β ± SE = -0.162 ± 0.04, p-value < 0.001). Prediabetes showed no significant associations. However, linear trend analysis indicated a dose–response relation from normal glucose metabolism, to prediabetes, to type 2 diabetes. Multiple continuous measures of hyperglycemia were associated with smaller volumes of the subfields fimbria (β ± SE < -0.010 ± 0.011, p-value < 0.001), dentate gyrus (β ± SE < -0.013 ± 0.010, p-value < 0.002), CA3 (β ± SE < -0.014 ± 0.011, p-value < 0.001), and tail (β ± SE < -0.006 ± 0.012, p-value < 0.003). Conclusions/interpretationType 2 diabetes and measures of hyperglycemia are associated with hippocampal subfield atrophy, independently of lifestyle and cardiovascular risk factors. We found evidence for a dose–response relationship from normal glucose metabolism, to prediabetes, to type 2 diabetes. Prediabetes stages could give a window of opportunity for the early prevention of brain disease.