Regional Cortical Volumes Research Articles

Associations between polygenic scores for cognitive and non-cognitive factors of educational attainment and measures of behavior, psychopathology, and neuroimaging in the adolescent brain cognitive development study.

Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a 'genome-wide association study (GWAS) by subtraction,' subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal 'cognitive' and 'non-cognitive' factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear. Using data from up to 5517 youth (ages 9-11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects. Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects. While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.

Abstract 56: High Blood Pressure Is Associated with Lower Brain Volume and Cortical Thickness in Healthy Young Adults

Background: High blood pressure (BP) in middle-aged and older adults is associated with lower brain volume and cortical thickness assessed with structural MRI. However, little evidence is available in young adults. Objective: We investigated the associations of high BP with brain volumes and cortical thickness in healthy young adults. We hypothesized that high BP is associated with lower brain volume and cortical thickness in young adults. Methods: This cross-sectional study included 1095 young adults (54% women, 22-37 years) from the Human Connectome Project (HCP) who self-reported not having a history of hypertension or taking antihypertensive medications. Brachial systolic (SBP) and diastolic BP (DBP) were measured with semi-automatic or manual sphygmomanometer during study visits. Structural MRI was used to measure gray matter (GM) and white matter (WM) volume and mean cortical thickness. Associations of BP and hypertension stage with total and regional brain volumes and cortical thickness were analyzed using linear regression and analysis of covariance (ANCOVA) after adjusting for age, sex, education years, body mass index (BMI), smoking, alcohol consumption history, zygosity, and total intracranial volume. Results: SBP and DBP were (mean ± SD) 123.6 ± 14.2 and 76.5 ± 10.6 mmHg, respectively (n = 1095). High DBP was associated with lower total GM ( p = 0.012), cortical GM ( p = 0.004), subcortical GM ( p = 0.012), and total WM volumes ( p = 0.031). There were no associations of SBP and hypertension stage with total brain volume and cortical thickness. High SBP and DBP were associated with lower regional cortical thickness in the parietal lobe and lingual gyrus, and lower regional cortical volume in the postcentral gyrus, inferior parietal lobe, lateral occipital gyrus, and middle temporal gyrus. Conclusion: Associations of high BP, particularly DBP, with lower total and regional brain volume and cortical thickness were observed in healthy young adults. These findings suggest the importance of prevention or control of high BP early in life for brain health.

Association of Cortical Lesions With Regional Glutamate, GABA, N-Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region. In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, N-acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls. Data were collected at a single center between August 2018 and September 2020. Linear mixed-effects models were used to test for associations between metabolite concentrations and cortical lesion volumes within the same MR-spectroscopy voxel. Forty-seven patients with MS (34 RRMS, 13 SPMS; 45.1 ± 12.5 years; 31 women) and 23 healthy controls (44.4 ± 13 years, 15 women) were studied. In patients, higher regional glutamate and lower regional GABA concentrations were associated with larger cortical lesion volume within the MR-spectroscopy voxel [glutamate: 0.61 (95% CI 0.19-1.03) log(mm3), p = 0.005, GABA: -0.71 (-1.24 to -0.18) log(mm3), p = 0.01]. In addition, lower N-acetylaspartate levels [-0.37 (-0.67 to -0.07) log(mm3), p = 0.016] and higher myoinositol levels [0.48 (0.03-0.93) log(mm3), p = 0.037] were associated with a larger regional cortical lesion volume. Furthermore, glutamate concentrations were reduced in patients with SPMS compared with healthy participants [-0.75 (-1.3 to -0.19) mM, p = 0.005] and patients with RRMS [-0.55 (-1.07 to -0.02) mM, p = 0.04]. N-acetylaspartate levels were lower in both patients with RRMS [-0.81 (-1.39 to -0.24) mM, p = 0.003] and SPMS [-1.31 (-2.07 to -0.54) mM, p < 0.001] when compared with healthy controls. Creatine-normalized N-acetylaspartate levels were associated with performance in the 9-hole peg test of the contralateral hand [-0.004 (-0.007 to -0.002) log(s), p = 0.002], and reduced mean creatine-normalized glutamate was associated with increased Expanded Disability Status Scale (R = -0.39, p = 0.02). Cortical lesions are associated with local increases in glutamate and a reduction in GABA concentration within the lesional or perilesional tissue. Further studies are needed to investigate the causal relationship between cortical lesions and changes in neurotransmitter concentrations.

Examining the neurostructural architecture of intelligence: The Lothian Birth Cohort 1936 study

Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or ‘g’)? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .7). Associations between the extracted cognitive factor scores for each domain and g were computed for each brain measure covarying for age, sex and intracranial volume, and corrected for false discovery rate.There were a range of significant associations between cognitive domains and global MRI brain structural measures (r range .008 to .269, p < .05). Regions implicated by vertex-wise regional cortical volume included a widespread number of medial and lateral areas of the frontal, temporal and parietal lobes. However, at both global and regional level, much of the domain-MRI associations were shared (statistically accounted for by g). Removing g-related variance from cognitive domains attenuated association magnitudes with global brain MRI measures by 27.9–59.7% (M = 46.2%), with only processing speed retaining all significant associations. At the regional cortical level, g appeared to account for the majority (range 22.1–88.4%; M = 52.8% across cognitive domains) of regional domain-specific associations. Crystallised and memory domains had almost no unique cortical correlates, whereas processing speed and visuospatial ability retained limited cortical volumetric associations. The greatest spatial overlaps across cognitive domains (as denoted by g) were present in the medial and lateral temporal, lateral parietal and lateral frontal areas.

High Blood Pressure Is Associated With Lower Brain Volume and Cortical Thickness in Healthy Young Adults.

High blood pressure (BP) in middle-aged and older adults is associated with lower brain volume and cortical thickness assessed with structural magnetic resonance imaging (MRI). However, little evidence is available on young adults. We investigated the associations of high BP with brain volumes and cortical thickness in healthy young adults. This cross-sectional study included 1,095 young adults (54% women, 22-37 years) from the Human Connectome Project (HCP) who self-reported not having a history of hypertension or taking antihypertensive medications. Brachial systolic (SBP) and diastolic BP (DBP) were measured with a semi-automatic or manual sphygmomanometer during study visits. Structural MRI was used to measure gray matter (GM) and white matter (WM) volume and mean cortical thickness. Associations of BP and hypertension stage with total and regional brain volumes and cortical thickness were analyzed using linear regression and analysis of covariance (ANCOVA) after adjusting for age, sex, education years, body mass index (BMI), smoking, alcohol consumption history, zygosity, and total intracranial volume. SBP and DBP were (mean ± SD) 123.6 ± 14.2 and 76.5 ± 10.6 mm Hg, respectively, (n = 1,095). High DBP was associated with lower total GM (P = 0.012), cortical GM (P = 0.004), subcortical GM (P = 0.012), and total WM volumes (P = 0.031). High SBP and DBP were associated with lower regional cortical volume and cortical thickness. These findings suggest that high BP may have deleterious effects on brain health at the early stage of adulthood.

Changes in brain structure and function in youth at familial risk for schizophrenia or bipolar disorder: implications for early intervention

Abstract The evaluation of child and adolescent offspring of patients with schizophrenia or bipolar disorder seeks to understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. In this session I will present findings from the BASYS (Bipolar And Schizophrenia Young offspring Study) cohort, which has recruited young offspring of patients with schizophrenia or bipolar disorder ages 6 to 17 years, using clinical, cognitive and brain imaging measures for over 15 years in Spain. I will begin by reviewing our baseline and 2 year findings using structural magnetic resonance imging (MRI) measures, where we found whole brain and regional cortical grey matter volume and surface area reductions, specifically in offspring of patients with schizophrenia relative to controls, but not in offspring of patients with bipolar disorder, which I will compare with results from the ENIGMA relatives working group analyses. Within our cohort I will expain the relevance of baseline brain structural findings to clinical and cognitive outcome over time. I will then present longitudinal analyses of structural anf functional MRI measures at up to 8 year follow-up, examining the influence of development of psychotic spectrum symptoms over time and cognitive and functional outcomes, on longitudinal brain imaging measures. I will finish the talk explaining avenues for future research in the field, which include incorporating other imaging modalities and validating our findings in other cohorts, while I will also present avenues for increasing understanding of the neurobiological changes underpinning our MRI findings.This project has received funding from Instituto de Salud Carlos III (PI151500467; PI1700741; PI1800696; PI1800976, PI2100330), Fundació Marato TV3 (091630, 202232-30-31), the Catalonia Government (2021SGR01319), PERIS (SLT006/17/00346), Fundació Clínic Recerca Biomèdica (Ajut a la Recerca Pons Bartran), co-financed by ERDF Funds from the European Commission and CIBERSAM.Disclosure of InterestNone Declared

Ocrelizumab reduces cortical and deep grey matter loss compared to the S1P-receptor modulator in multiple sclerosis.

Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. To compare the effect of OCR and FGL on clinical and MRI endpoints. 95 relapsing-remitting patients (57 OCR, 38 FGL) clinically followed for 36months underwent a 3-Tesla MRI at baseline and after 24months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (- 0.12% vs - 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (- 0.45% vs - 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65-0.71), frontal gyrus (d-range = 0.47-0.60), cingulate (d-range = 0.41-0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss.

Regional cortical brain volumes at treatment entry relates to post treatment WHO risk drinking levels in those with alcohol use disorder

Abstinence following treatment for alcohol use disorder (AUD) is associated with significant improvements in psychiatric and physical health, however, recent studies suggest resumption of low risk levels of alcohol use can also be beneficial. The present study assessed whether post-treatment levels of alcohol use were associated with cortical brain volumedifferences at treatment entry. Individuals seeking treatment for AUD (n=75) and light/non-drinking controls (LN, n=51) underwent 1.5T magnetic resonance imaging. The volumes of 34 bilateral cortical regions of interest (ROIs) were quantitated via FreeSurfer. Individuals with AUD were classified according to post-treatment alcohol consumption using the WHO risk drinking levels (abstainers: AB; low risk: RL; or higher risk: RH). Regional volumes for AB, RL and RH, at treatment entry, were compared to LN. Relative to LN, AB demonstrated smaller volumes in 18/68 (26%), RL in 24/68 (35%) and RH in 34/68 (50%) ROIs with the largest magnitude volume differences observed between RH and LN. RH and RL reported a higher frequency of depressive disorders than AB. Among RH and RL, level of depressive and anxiety symptomatology were associated with daily number of drinks consumed after treatment. Volumetric differences, at treatment entry, in brain regions implicated in executive function and salience networks corresponded with post-treatment alcohol consumption levels suggesting that pre-existing differences in neural integrity may contribute to treatment outcomes. Depressive and anxiety symptomatology was also associated with brain morphometrics and alcohol use patterns, highlighting the importance of effectively targeting these conditions during AUD treatment.

Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients

Introduction: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. Methods: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. Results: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. Conclusion: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

A Case Report of Changes in Regional Cortical Blood Volume and Oxygenation During Induction of General Anaesthesia with Sevoflurane Versus Propofol in a Paediatric Moyamoya Disease, Evaluated by Near-Infrared Spectroscopy.

A safe induction method of general anaesthesia for paediatric moyamoya disease patients has not been fully established. We had the opportunity to administer general anaesthesia twice to a two-year-old girl diagnosed with moyamoya disease. We used different induction methods for general anaesthesia at each session, i.e. slow induction with sevoflurane and rapid induction with propofol, and were able to evaluate changes in her left regional cortical blood volume (rCBV) and oxygenation (rCBO) during both anaesthesia inductions using near-infrared spectroscopy (NIRS). The mean change value of total-Hb (rCBV) (mean±SD; μmol/L) in the rapid induction was lower than that in the slow induction (-0.54±1.43 vs. 1.82±1.74). However, the TOI (rCBO) levels during both anaesthesia inductions were constantly higher than these respective baseline values (64% in the slow induction, 71% in the rapid induction), and these mean change values in each of the anaesthesia induction were about the same. The present results suggested that both the slow induction method with sevoflurane and the rapid induction method with propofol might be safe and effective for anaesthesia induction in paediatric patients with moyamoya disease.

Association of low frequency variants with regional cortical grey matter volumes in genetic frontotemporal dementia: Results from GENFI

AbstractBackgroundFrontotemporal dementia (FTD) is a neurodegenerative condition characterized by heterogeneous clinical, pathological, and genetic features. Mutations in three genes account for the majority of autosomal dominant FTD: GRN, MAPT, and C9orf72. We tested whether gene‐based aggregate burden of genome‐wide low‐frequency variants contribute to variation in regional cortical and subcortical grey matter volumes in the GENetic Frontotemporal dementia Initiative (GENFI), after controlling for effects of autosomal dominant mutations.MethodGENFI recruits symptomatic and presymptomatic participants from families segregating genetic FTD. We included 517 participants with genotype (Neurochip; imputed against TOPMed), and T1w‐MRI brain volumetric data. Gene‐based burden tests that aggregate the number of uncommon/rare variants by gene were used to examine the association of low‐frequency variants (minor allele frequency: 0.000001 to &lt;0.05) with regional cortical and subcortical grey matter volumes, controlling for age, sex, total intracranial volume, mutation status, population stratification, and family membership (kinship matrix). In two separate analyses, we used the following set of annotations to account for (i) loss of function mutations (LOF): start gain, stop loss, start loss, essential splice site, stop gain, normal splice site, and non‐synonymous, (ii) insertions, deletions, and frameshift mutations (indel‐fs).ResultOf the 517 participants (300 women), 307 were mutation carriers (symptomatic = 82). For LOF mutations (731 genes tested; significance threshold: p = 0.05/731 = 6.8×10−5), aggregate burden of variants in BSND were associated with lower volumes in: temporal (p = 6.6×10−6), left insula (p = 5.0×10−5), and ventromedial prefrontal cortical (p = 2.8×10−5) regions. For indel‐fs mutations (826 genes tested; significance threshold: p = 0.05/826 = 6.05×10−5), aggregate burden of variants in: (i) E2F2 was associated with lower volumes in occipital (p = 8.7×10−6) regions; (ii) TMEM61 was associated with lower volumes in left temporal (p = 7.8×10−7), and left cingulate regions (p = 5.5×10−5); (iii) KDM4A‐AS1 was associated with lower volumes in the right temporal (p = 3.2×10‐7) region. All genes are variably expressed in the brain.ConclusionIdentification of deleterious or protective low‐frequency variants contributing to FTD imaging phenotypes may help identify genetic modifiers of familial FTD. Replication of results followed by functional studies are needed.

Clinical Phenotypes of Alzheimer’s Disease: Pathological Correlates of Regional Cortical Volume

AbstractBackgroundRecent studies highlight distinct patterns of cortical atrophy in amnestic (typical) and non‐amnestic (atypical – behavioural, dysexecutive and visuospatial) clinical phenotypes of Alzheimer’s disease (AD). The current study aimed to assess regional phenotypic MRI patterns of cortical atrophy, and their association with Amyloid‐beta (Aβ), phosphorylated Tau (pTau), and axonal degeneration (NfL).MethodPostmortem In‐situ 3DT1 3T‐MRI data were collected for 28 AD (14 typical, 14 atypical) and 10 control brain donors. Images were segmented using QyScore® and regional volumes according to the AAL3 atlas were obtained. At subsequent autopsy, Eight brain regions from the right hemisphere were selected and immunostained for Aβ (4G8), pTau (AT8), and Neurofilament light (NfL), and quantified for area% load. Group comparisons and MRI volume‐pathology associations were analyzed using linear models with covariates age, gender, postmortem delay, and intracranial volume when applicable.ResultsWhen assessing regional cortical volumes, compared to controls, typical AD showed a more parietal‐temporal, while atypical AD showed a more a frontal‐temporal atrophy pattern (fig1).Typical and atypical phenotypes showed different pathological load across all selected regions in both Aβ and NFL (p = 0.032,p = 0.0007, respectively). Subsequent explorative assessment indicates a difference in regional pTau distribution between behavioural, dysexecutive and visuospatial subtypes, specifically in the occipital region (fig2).Addressing MRI‐pathology associations across all selected regions, we observed a positive association between cortical volume and Aβ in typical AD (β = 1.98,p = 0.026), while both pTau and NFL showed a negative association (β = ‐0.26,p = 0.004; β = ‐2.00,p = 0.001, respectively). In atypical AD, only NFL showed a significant negative association (β = ‐2.27,p&lt;0.001) with cortical volume. Regionally (fig3), only NfL associated with MRI volume; with the precuneus in both typical and atypical AD (β = ‐2.81,p = 0.044; β = ‐3.81,p = 0.011, respectively), and with posterior cingulate cortex volume in atypical AD (β = ‐3.24,p = 0.045).ConclusionThis study found varying atrophy patterns in AD phenotypes when compared to controls. Across all selected regions, typical AD showed volume‐pathology associations with Aβ, pTau and axonal damage, while atypical AD only showed associations with axonal damage, indicating a possible difference in volume‐pathology associations between phenotypes. Regionally, cortical volume was predominantly associated with axonal damage, rather than Aβ or pTau protein accumulation, in parietal regions.

Regional brain atrophy is associated with measures of impaired blood‐CSF barrier in patients with prodromal and overt dementia with Lewy bodies and Alzheimer’s disease dementia

AbstractBackgroundAlzheimer’s disease (ADdem) and Lewy body dementia (DLB) are characterized by cholinergic impairment and regional brain atrophy including the medial‐temporal and temporo‐parietal regions. In DLB, the overlapping AD pathology is associated with more prominent atrophy. However, other factors than AD pathology play role in brain atrophy and clinical impairmentl. The choroid plexus (CP), part of blood‐CSF barrier, is central in regulating inflammation and monitoring the CSF synthesis, composition, and circulation. However, association between measures of blood‐CSF barrier impairment and regional brain atrophy, and the effect of AD biomarkers in this association, remain unknown in prodromal and overt AD and DLB.MethodWe included 108 participants from the Czech Brain Aging Study (n = 30 prodromal AD, n = 24 ADdem, n = 10 prodromal DLB, n = 20 overt DLB, n = 24 cognitively unimpaired controls, CN) who underwent clinical/cognitive testing, brain MRI and CSF sampling. FreeSurfer automated algorithm and cholinergic basal forebrain ROIs were used to measure CP volumes and nucleus basalis of Meynert (NBM) and other regional cortical thickness and volumes. From CSF, the established AD biomarkers and an albumin quotient (QAlb), a proxy of blood‐CSF barrier impairment, were derived. Associations were measured using multivariate analysis of variance adjusted for age, sex; mediation analysis was used to assess effect of CSF AD biomarkers on associations between atrophy and blood‐CSF impairment.ResultCP volume was significantly larger and NBM volume was smaller in both DLB and AD compared to CN, and the CP volume increased from prodromal to overt dementia stages. Larger CP volumes were associated with smaller NBM volumes in AD and DLB prodromal and overt stages. Larger CP volumes were associated with abnormal QAlb, and with more abnormal levels of AD biomarkers. More abnormal AD biomarker levels mediated the association between larger CP volumes, abnormal AlbQ and regional atrophy in AD and DLB.ConclusionMeasures of impaired blood‐CSF barrier by enlarged CP and AlbQ are associated with more profound regional atrophy including cholinergic regions from prodromal to overt dementia stages. Whereas AD‐related pathology likely plays role in this, investigating the blood‐CSF barrier as a potential treatment target may be beneficial for AD and DLB patients.

Comprehensive assessment of sleep duration, insomnia, and brain structure within the UK Biobank cohort.

To assess for associations between sleeping more than or less than recommended by the National Sleep Foundation (NSF), and self-reported insomnia, with brain structure. Data from the UK Biobank cohort were analyzed (N between 9K and 32K, dependent on availability, aged 44 to 82 years). Sleep measures included self-reported adherence to NSF guidelines on sleep duration (sleeping between 7 and 9 hours per night), and self-reported difficulty falling or staying asleep (insomnia). Brain structural measures included global and regional cortical or subcortical morphometry (thickness, surface area, volume), global and tract-related white matter microstructure, brain age gap (difference between chronological age and age estimated from brain scan), and total volume of white matter lesions. Longer-than-recommended sleep duration was associated with lower overall grey and white matter volumes, lower global and regional cortical thickness and volume measures, higher brain age gap, higher volume of white matter lesions, higher mean diffusivity globally and in thalamic and association fibers, and lower volume of the hippocampus. Shorter-than-recommended sleep duration was related to higher global and cerebellar white matter volumes, lower global and regional cortical surface areas, and lower fractional anisotropy in projection fibers. Self-reported insomnia was associated with higher global gray and white matter volumes, and with higher volumes of the amygdala, hippocampus, and putamen. Sleeping longer than recommended by the NSF is associated with a wide range of differences in brain structure, potentially indicative of poorer brain health. Sleeping less than recommended is distinctly associated with lower cortical surface areas. Future studies should assess the potential mechanisms of these differences and investigate long sleep duration as a putative marker of brain health.

Discrepancies in Patient and Caregiver Ratings of Personality Change in Alzheimer's Disease and Related Dementias.

Personality change in Alzheimer's disease and related dementias (ADRD) is complicated by the patient and informant factors that confound accurate reporting of personality traits. We assessed the impact of caregiver burden on informant report of Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness) and investigated the regional cortical volumes associated with larger discrepancies in the patient and informant report of the Big Five personality traits. Sixty-four ADRD participants with heterogeneous neurodegenerative clinical phenotypes and their informants completed the Big Five Inventory (BFI). Caregiver burden was measured using the Zarit Burden Interview. Discrepancy scores were computed as the difference between patient and informant ratings for the BFI. Regional gray matter volumes from T1-weighted 3T MRI were normalized to intracranial volume and related to global Big Five discrepancy scores using linear regression. Higher levels of caregiver burden were associated with higher informant ratings of patient neuroticism (ß = 0.08, p =.012) and with lower informant ratings of patient agreeableness (ß = 0.11, p =.021) and conscientiousness (ß = 0.04, p =.034) independent of disease severity. Patients with greater Big Five discrepancy scores showed smaller cortical volumes in the right medial prefrontal cortex (β = -5.24, p =.045) and right superior temporal gyrus (β = -7.91, p =.028). Informant ratings of personality traits in ADRD can be confounded by the caregiver burden, highlighting the need for more objective measures of personality and behavior in dementia samples. Discrepancies between informant and patient ratings of personality may additionally reflect loss of insight secondary to cortical atrophy in the frontal and temporal structures.

Associations among prenatal exposure to gestational diabetes mellitus, brain structure, and child adiposity markers.

The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity. This was a cross-sectional study of 9- to 10-year-old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self-reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates. The sample included 8521 children (7% GDM-exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM-exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers. The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.

Non-abstinent recovery in alcohol use disorder is associated with greater regional cortical volumes than heavy drinking.

Harm-reduction (i.e., non-abstinent recovery) approaches to substance use treatment have garnered increasing attention. Reduced levels of alcohol consumption post-treatment have been associated with better psychosocial functioning and physical health, yet less is known regarding differences in brain structures associated with varying levels of alcohol consumption. This study investigated regional cortical volumes after alcohol use disorder (AUD) treatment among individuals who achieved complete abstinence and those who returned to lower and higher levels of consumption. Data were collected from individuals with AUD (n = 68) approximately 8 months after the initiation of treatment. Using risk drinking levels defined by the World Health Organization, participants were classified as abstaining (AB) or relapsing with low (RL) or higher (RH) levels. Data were also obtained from 34 age-matched light/non-drinking controls (LN). All participants completed a 1.5 T magnetic resonance imaging session and volumes for 34 bilateral cortical regions of interest were quantitated with FreeSurfer. Generalized linear models were used to examine group differences in cortical volume. All group findings are significant at an FDR-corrected value of 0.018. Adjusting for age and intracranial volume, significant group differences were found in 13/34 cortical regions. AB showed greater volumes than RL in 2/13 regions and RH in 6/13 regions. RH demonstrated significantly smaller volumes than LN in 12/13 ROIs, whereas RL differed from LN in 9/13 regions. RH and RL differed in only two cortical regions. Individuals who consumed low-risk levels of alcohol post-treatment exhibited regional cortical volumes more similar to abstainers than individuals who returned to higher-risk levels. This suggests that low-risk levels of alcohol consumption are associated with brain integrity that is comparable to that seen with complete abstinence. Given the previously demonstrated improvement in psychosocial and physical health with reduced levels of alcohol consumption post-treatment, harm reduction may be a beneficial and more attainable goal for some individuals with AUD who are seeking treatment.

The association among plasma p‐tau181, cognitive progression and structural brain change in early Alzheimer’s disease

AbstractBackgroundPlasma levels of phosphorylated tau 181 (p‐tau181) is one of the potential blood‐based biomarkers for the diagnosis of Alzheimer’s disease (AD). However, the association among plasma p‐tau181 and cognitive progression and structural brain change still needs to be investigated.MethodAD and mild cognitive impairment (MCI) patients diagnosed with a multidisciplinary consensus meeting were recruited. Cognitive function was assessed at baseline and at annual follow‐ups. Plasma p‐tau181 levels at baseline were measured using Quanterix SIMOA kits. The regional cortical thickness and volumes of baseline brain MRI were measured using the FreeSurfer image analysis suite. T‐tests and multiple regression were used for analyses. FDR tests were performed for multiple comparisons.ResultA total of 162 AD and 19 MCI patients were recruited (mean age = 77.4 ± 7.3 years, 42% male, 37% APOE ɛ4 carrier, and mean MMSE = 20 ± 5.4). There were 137 patients (75.7%) having at least two annual follow‐up and the mean follow‐up time was 2.1 ± 0.4 years. The baseline plasma p‐tau181 levels were correlated with the rates of MMSE decline per year (r = 0.284, p &lt; 0.001). After adjusting for age, gender, education, APOE ɛ4 status and baseline MMSE, the baseline plasma p‐tau181 levels were still correlated with the yearly MMSE decline (β = 0.292, p = 0.001) and was able to predict MMSE decline&gt;3 per year (OR = 4.03, 95% CI 1.47–11.05). There were 152 patients (135 AD and 17 MCI) with valid brain MRI. The cross‐sectional analyses with adjustments of age, gender, education and APOE ɛ4 status showed significant association between plasma p‐tau181 levels and left hippocampus volume (β = ‐0.205, p = 0.010), right hippocampus volume (β = ‐0.213, p = 0.009) and right middle temporal thickness (β = ‐0.292, p &lt; 0.001).ConclusionHigher plasma p‐tau181 levels were associated with the faster rate of MMSE decline in AD and MCI patients as well as the decreased volume and cortical thickness of several AD‐specific brain areas. Our study suggested that the plasma p‐tau181 could be a potential biomarker for tracking cognitive decline and reflecting structural brain changes in AD and MCI patients.

Protective Effect of APOE-ɛ2 on Cortical Thickness and Volume in a Cerebrovascular Registry (S36.010)

<h3>Objective:</h3> To compare cortical thickness across APOE genotypes, and to assess the potential protective effect of APOE2 on brain cortical thinning and grey matter volume. <h3>Background:</h3> Studies have shown a negative association of APOE-ɛ4 allele with regional cortical thickness and volume. The role of the APOE-ɛ3 allele has been considered neutral in several studies. The protective role of APOE-ɛ2 against cortical thinning has not been well established. <h3>Design/Methods:</h3> From a biomarker cerebrovascular registry, 187 individuals with APOE testing and MRI brain from 2010 to 2020 were included. APOE genotype tested were ɛ2ɛ2, ɛ2ɛ3, ɛ2ɛ4, ɛ3ɛ3, ɛ3ɛ4, ɛ4ɛ4, stratified to APOE-ɛ2 carrier or APOE-ɛ2 non-carrier. Cortical thickness, cortical volume and gray matter volume were estimated on T1-weighted images using FreeSurfer. Measures of brain atrophy were compared across APOE genotypes, and between ɛ2 vs non-ɛ2 allele carriers. Mini-Mental Status Examination (MMSE) were compared between groups. <h3>Results:</h3> In our cohort (n=187), mean age was 60±16 years and 55.4% were female. Of the APOE genotypes, 18.5% were APOE-ɛ2 carriers (ɛ2ɛ2 3, ɛ2ɛ3 33), 81.5% were APOE-ɛ2 non-carriers (ɛ3ɛ3 114, ɛ3ɛ4 43, ɛ4ɛ4 2). Compared to ɛ2 non-carriers, ɛ2 carriers were less likely to have hypertension, diabetes, coronary artery disease, and had higher LDL (p&lt;0.05). Across APOE genotypes, cortex was thickest in ɛ2ɛ2 (2.35 mm) and thinnest in ɛ4ɛ4 (1.92 mm) (p = 0.0137). APOE-ɛ2 carriers had significantly thicker cortex (2.13 mm vs 1.96 mm, p=0.001), larger cortical volume (313.26 cm3 vs 266.09 cm3, p=&lt;0.001) and grey matter volumes (459.93 cm3 vs 411.01 cm3, p=0.001), compared to ɛ2 non-carriers. There was no difference in MMSE between ɛ2carriers vs non-carriers (24.4 vs 25.6, p=0.316). <h3>Conclusions:</h3> Our study suggested a protective effect of APOE-ɛ2 allele against cortical thinning and grey matter volume loss. Future study may examine the effect of APOE-ɛ2 on brain resilience after brain injury such as stroke. <b>Disclosure:</b> Mr. Youssef has nothing to disclose. Mr. Mateti has nothing to disclose. Erik Middlebrooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Varian Medical Systems Inc. Erik Middlebrooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Corp. The institution of Erik Middlebrooks has received research support from Varian Medical Systems Inc. The institution of Dr. Taner has received research support from NIH. The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS. Dr. Lin has nothing to disclose.

Assessing the Equivalence of Brain-Derived Measures from Two 3D T1-Weighted Acquisitions: One Covering the Brain and One Covering the Brain and Spinal Cord.

In MS, it is common to acquire brain and spinal cord MR imaging sequences separately to assess the extent of the disease. The goal of this study was to see how replacing the traditional brain T1-weighted images (brain-T1) with an acquisition that included both the brain and the cervical spinal cord (cns-T1) affected brain- and spinal cord-derived measures. Thirty-six healthy controls (HC) and 42 patients with MS were included. Of those, 18 HC and 35 patients with MS had baseline and follow-up at 1 year acquired on a 3T magnet. Two 3D T1-weighted images (brain-T1 and cns-T1) were acquired at each time point. Regional cortical thickness and volumes were determined with FastSurfer, and the percentage brain volume change per year was obtained with SIENA. The spinal cord area was estimated with the Spinal Cord Toolbox. Intraclass correlation coefficients (ICC) were calculated to check for consistency of measures obtained from brain-T1 and cns-T1. Cortical thickness measures showed an ICC >0.75 in 94% of regions in healthy controls and 80% in patients with MS. Estimated regional volumes had an ICC >0.88, and the percentage brain volume change had an ICC >0.79 for both groups. The spinal cord area measures had an ICC of 0.68 in healthy controls and 0.92 in patients with MS. Brain measurements obtained from 3D cns-T1 are highly equivalent to those obtained from a brain-T1, suggesting that it could be feasible to replace the brain-T1 with cns-T1.