Total Gray Matter Research Articles

Effects of Sex, APOE4, and Lifestyle Activities on Cognitive Reserve in Older Adults.

Background and ObjectivesLifestyle activities, such as physical activity and cognitive stimulation, may mitigate age-associated cognitive decline, delay dementia onset, and increase cognitive reserve. Whether the association between lifestyle activities and cognitive reserve differs by sex and APOE4 status is an understudied yet critical component for informing targeted prevention strategies. The current study examined interactions between sex and physical or cognitive activities on cognitive reserve for speed and memory in older adults.MethodsResearch participants with unimpaired cognition, mild cognitive impairment, or dementia from the Washington Heights-Inwood Columbia Aging Cohort were included in this study. Cognitive reserve scores for speed and memory were calculated by regressing out hippocampal volume, total gray matter volume, and white matter hyperintensity volume from composite cognitive scores for speed and memory, respectively. Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire, converted to metabolic equivalents (METS). Self-reported cognitive activity (COGACT) was calculated as the sum of 3 yes/no questions. Sex by activity interactions and sex-stratified analyses were conducted using multivariable linear regression models, including a secondary analysis with APOE4 as a moderating factor.ResultsSeven hundred fifty-eight participants (mean age = 76.11 ± 6.31 years, 62% women) were included in this study. Higher METS was associated with greater speed reserve in women (β = 0.04, CI 0.0–08) but not in men (β = 0.004, CI −0.04 to 0.05). METS was not associated with memory reserve in women or men. More COGACT was associated with greater speed reserve in the cohort (β = 0.13, CI 0.05–0.21). More COGACT had a trend for greater memory reserve in women (β = 0.06, CI −0.02 to 0.14) but not in men (β = −0.04, CI −0.16 to 0.08). Only among women, APOE4 carrier status attenuated relationships between METS and speed reserve (β = −0.09, CI −0.22 to 0.04) and between COGACT and both speed (β = −0.26, CI −0.63 to 0.11) and memory reserves (β = −0.20, CI −0.50.0 to 093).DiscussionThe associations of self-reported physical and cognitive activities with cognitive reserve are more pronounced in women, although APOE4 attenuates these associations. Future studies are needed to understand the causal relationship among sex, lifestyle activities, and genetic factors on cognitive reserve in older adults to best understand which lifestyle activities may be most beneficial and for whom.

Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness

Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm3 and 654 cm3, respectively; p = 0.019) and lower IQ (104 and 107, respectively; p = 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical (p = 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.

Basic lifestyle habits and volume change in total gray matter among community dwelling middle-aged and older Japanese adults

The brain controls human behavior, and the gray matter is the main resource of neuronal cells. We examined the longitudinal relationship between six basic lifestyle habits (diet, exercise, sleep, alcohol consumption, smoking, and social activity including employment) and total gray matter volume in community-dwelling adults in Japan.This two-year follow-up study with data derived from the National Institute for Longevity Sciences, Longitudinal Study of Aging, Aichi, Japan, included adults aged 40–87 years (n = 1665, men: 51%). Lifestyle habits were assessed at baseline (2008–2010) using self-reported questionnaires and three-day dietary records. Total gray matter volume at baseline and after two years was estimated using T1-weighted brain magnetic resonance imaging and FreeSurfer software. The association between each lifestyle factor, the total number of healthy lifestyle habits, and gray matter volume change was determined via a multiple linear regression analysis adjusting for baseline age, total gray matter volume, and other confounders. The mean ± standard deviation decrease in total gray matter volume during the two-year follow-up period was 0.94 ± 1.86% in men and 0.61 ± 2.27% in women. In the multiple regression analysis, volume loss in total gray matter positively correlated with male smoking, while it was negatively correlated with male social activity and employment, female dietary diversity, and the total number of healthy lifestyle habits (standardized beta coefficient; −0.061 in men [p = 0.07], −0.113 in women [p < 0.05]). Therefore, engaging in social activities, non-smoking, a diverse diet, or adopting one healthy lifestyle habit may help prevent gray matter volume loss.

Distribution of Cortical Atrophy Associated with Cognitive Decline in Alzheimer's Disease: A Cross-Sectional Quantitative Structural MRI Study from PUMCH Dementia Cohort.

Quantitative measures of atrophy on structural MRI are sensitive to the neurodegeneration that occurs in AD, and the topographical pattern of atrophy could serve as a sensitive and specific biomarker. We aimed to examine the distribution of cortical atrophy associated with cognitive decline and disease stage based on quantitative structural MRI analysis in a Chinese cohort to inform clinical diagnosis and follow-up of AD patients. One hundred and eleven patients who were clinically diagnosed with probable AD were enrolled. All patients completed a systemic cognitive evaluation and domain-specific batteries. The severity of cognitive decline was defined by MMSE score: 1-10 severe, 11-20 moderate, and 21-30 mild. Cortical volume and thickness determined using 3D-T1 MRI data were analyzed using voxelbased morphometry and surface-based analysis supported by the DR. Brain Platform. The male:female ratio was 38:73. The average age was 70.8 ± 10.6 years. The mild: moderate: severe ratio was 48:38:25. Total grey matter volume was significantly related to cognition while the relationship between white matter volume and cognition did not reach statistical significance. The volume of the temporal-parietal-occipital cortex was most strongly associated with cognitive decline in group analysis, while the hippocampus and entorhinal area had a less significant association with cognitive decline. Volume of subcortical grey matter was also associated with cognition. Volume and thickness of temporoparietal cortexes were significantly correlated with the cognitive decline, with a left predominance observed. Cognitive deterioration was associated with cortical atrophy. Volume and thickness of the left temporal-parietal-occipital cortex were most important in early diagnosis and longitudinal evaluation of AD in clinical practice. Cognitively relevant cortices were left predominant.

Peripheral Hemolysis in Relation to Iron Rim Presence and Brain Volume in Multiple Sclerosis.

Background:Iron rim lesions (IRLs) represent chronic lesion activity and are associated with a more severe disease course in multiple sclerosis (MS). How the iron rims around the lesions arise in patients with MS (pwMS), and whether peripheral hemolysis may be a source of iron in rim associated macrophages, is unclear.ObjectiveTo determine a potential correlation between peripheral hemolysis parameters and IRL presence in pwMS.MethodsThis retrospective study included pwMS, who underwent a 3T brain MRI between 2015 and 2020 and had a blood sample drawn at ± 2 weeks. Patients with vertigo served as a control group.ResultsWe analyzed 75 pwMS (mean age 37.0 years [SD 9.0], 53.3% female) and 43 controls (mean age 38.3 years [SD 9.8], 51.2% female). Median number of IRLs was 1 (IQR 4), 28 (37.3%) pwMS had no IRLs. IRL patients showed significantly higher Expanded Disability Status Scale (EDSS) compared to non-IRL patients (median EDSS 2.3 [IQR 2.9] vs. 1.3 [IQR 2.9], p = 0.017). Number of IRLs correlated significantly with disease duration (rs = 0.239, p = 0.039), EDSS (rs = 0.387, p < 0.001) and Multiple Sclerosis Severity Scale (MSSS) (rs = 0.289, p = 0.014). There was no significant difference in hemolysis parameters between non-IRL, IRL patients (regardless of gender and/or disease type) and controls, nor between hemolysis parameters and the number of IRLs. Total brain volume was associated with fibrinogen (β= −0.34, 95% CI −1.32 to −0.145, p = 0.016), and absolute cortical and total gray matter volumes were associated with hemoglobin (β = 0.34, 95% CI 3.39–24.68, p = 0.011; β = 0.33, 95% CI 3.29–28.95, p = 0.015; respectively).ConclusionOur data do not suggest an association between hemolysis parameters and IRL presence despite a significant association between these parameters and markers for neurodegeneration.

Fibromyalgia impact in the prefrontal cortex subfields: An assessment with MRI

IntroductionPrevious studies have associated brain abnormalities in people with fibromyalgia with accelerated brain ageing. The prefrontal cortex is located in the anterior pole of the mammalian brain. It is defined as the part of the cerebral cortex that receives projections from the mediodorsal nucleus of the thalamus. AimThis study aimed to evaluate the volumetric differences in the prefrontal cortex subfields between healthy women and women with fibromyalgia using magnetic resonance imaging (MRI) and controlling for age, estimated intracranial volume, depression, and cognitive impairment. Material and methodsA total of 47 women with fibromyalgia (recruited from a fibromyalgia local association) and 43 healthy women (retrieved from the Open Access Series of Imaging Studies database) participated in this cross-sectional study. Multiple linear regressions were used to predict the value of the prefrontal cortex subfields as well as to determine if there were volumetric differences between the groups. ResultsVolume of all prefrontal cortex regions decreased with each year of age. Healthy women showed higher volume in all the prefrontal cortex subfields than women with fibromyalgia. Regarding partial correlations performed, no significant relation were found between the fibromyalgia impact and the brain volumes analyzed, controlling for depression. ConclusionsWomen with fibromyalgia showed reduced volume in the right caudal middle frontal gyrus, rostral middle frontal gyrus, left inferior frontal gyrus pars opercularis, inferior frontal gyrus pars triangularis, inferior frontal gyrus pars orbitalis, lateral orbitofrontal cortex, right medial orbitofrontal cortex, right rostral anterior cingulate gyrus subfields of the prefrontal cortex and total gray matter compared to healthy women. Furthermore, through an analysis of multiple linear regressions, the left rostral middle frontal gyrus and left lateral orbitofrontal cortex showed significantly volumetric decreases related to depression levels. The total gray matter also shows a significant decrease related to age observed through the analysis of multiple linear regressions. No significant relation were found between the impact of the disease and the brain volumes analyzed, controlling for depression in women with fibromyalgia.

Magnetic resonance imaging findings of two cases with West syndrome and hypomelanosis of Ito with hemimegalencephaly: a report of two cases

BackgroundHemimegalencephaly is an unusual congenital non-familial malformation of the brain which is characterized by enlargement of the whole or part of one hemisphere due to neural proliferation and dysfunction in the cell migration. The brain stem and cerebellum may also be involved. There are also the common cortical malformation, unusual white matter proliferation, gliosis, and abnormal myelination in hemimegalencephaly. In addition, structural brain abnormalities like atrophy/hypertrophy, demyelination, gliosis, increased thickness of the cortical grey matter, increase signal intensity in the subcortical white matter, abnormal gyral patterns, blurring of the grey-white matter transition, and hamartomatous aspect can be observed on magnetic resonance imaging.Case presentationTwo patients who underwent brain magnetic resonance imaging because of West syndrome and hypomelanosis of Ito were diagnosed as hemimegalencephaly. The first case was a 9-day-old male patient initially diagnosed with West syndrome. On the brain magnetic resonance imaging performed for epilepsy, right total hemimegalencephaly, diffuse polymicrogyria, and heterotopic grey matter foci on the right hemisphere were observed. In addition, right cerebellar dysgenesis, upward angulation in the lateral ventricle's anterior horn, and colpocephalic dilatation in the posterior horn were evident. The second case was a 2-year-old female patient with hypomelanosis of Ito disease. The main reason for her parents' hospital visit was the shortness of the right leg. Initial examination showed the hypopigmented lesions on the right side and hemihypertrophy in the left leg. Brain magnetic resonance imaging revealed mild hemimegalencephaly in the right cerebral hemisphere, T1-weighted isointense, T2-weighted hyperintense white matter lesions extending from the basal ganglia to the ventricular body and the periventricular fronto-parieto-occipital white matter, and dilatation of the lateral ventricle.ConclusionsHemimegalencephaly is a rare condition which may accompany syndromic cases with epilepsy or neurocutaneous disease. Brain magnetic resonance imaging should be performed in patients with a suspicious medical history in order to make the correct diagnosis of hemimegalencephaly and to determine the severity of brain involvement, if any.

Effects of Diastolic Blood Pressure on Brain Structures and Cognitive Functions in Middle and Old Ages: Longitudinal Analyses.

Hypertension is a pervasive public health concern due to strong associations with cardiovascular diseases and stroke. Alternatively, the associations between hypertension and the risk of Alzheimer’s disease are complex and recent large sample studies reported positive associations. In this paper, we examine the associations between diastolic blood pressure (BP) and subsequent changes in brain structure and cognitive function over several years by multiple regression analyses (with adjustment for a wide range of potential confounding variables) among a large cohort from the UK Biobank. Higher baseline diastolic BP was associated with a slightly smaller relative increase (relative improvements) in reaction time and a slightly greater reduction in depression scores. Higher baseline diastolic BP was also associated with a greater total gray matter volume (GMV) retention, while aging alone was associated with GMV reduction. White matter microstructural analyses revealed that a greater diastolic BP was associated with reduced longitudinal mean and regional fractional anisotropy, greater increases in mean and regional mean diffusivity, radial diffusivity, and axial diffusivity, a greater decline in mean intracellular volume fraction, and greater increases in mean and regional isotropic volume fraction. These white matter microstructural changes were consistent with those seen in the aging process. Additional analyses revealed a greater cheese intake level at baseline, which is associated with a subsequent decline in diastolic BP and a relative subsequent increase in depressive tendency together with a relative increase in fluid intelligence and visuospatial memory performance. These results are congruent with the view that a higher BP in the aging brain has a complex role.

Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants

BackgroundGrowth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term.Material/methodsInfants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)−1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age.ResultsIn total, 49 infants (median [range] GA 25.4 [22.9–27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, β = 0.90), white matter (p = 0.007, β = 0.33), cortical gray matter (p = 0.002, β = 0.43), deep gray matter (p = 0.008, β = 0.05), and cerebellar (p = 0.006, β = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors.ConclusionsEndogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants.ImpactHigh serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants.IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood.Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).

Gray Matter Brain Alterations in Type 1 Diabetes - Findings Based on Detailed Phenotyping of Neuropathy Status.

This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements. Sixty individuals with type 1 diabetes and 20 healthy controls were included in the study. Nineteen individuals with type 1 diabetes and neuropathic pain, 19 with type 1 diabetes and DPN, 18 with type 1 diabetes without DPN, and 20 healthy controls were included in the brain analyses. We utilized structural brain magnetic resonance imaging to investigate total and regional gray matter volume. Significant lower gray matter volume was found in type 1 diabetes with neuropathic pain and in type 1 diabetes without DPN compared to healthy controls (p=0.024 and p=0.019, respectively). Lower insula volume was observed in all three diabetes groups (all p≤0.050). Thalamus and hippocampus volume was lower in type 1 diabetes with neuropathic pain, cerebellum volume was lower in type 1 diabetes with DPN, and somatosensory cortex volume was lower in type 1 diabetes without DPN (all p≤0.018). Attenuated memory was associated with lower gray matter volume in type 1 diabetes with DPN. No associations were found between gray matter volume and clinical/peripheral measurements. We demonstrated lower gray matter volume in individuals with type 1 diabetes regardless of the presence of DPN and neuropathic pain. Hence, central gray matter alteration was not associated with peripheral alterations.

Structural and Functional Thalamic Changes in Progressive Supranuclear Palsy

AimsStudies of thalamic structure and function in Progressive Supranuclear Palsy (PSP) suggest it may play a role in key aspects of the clinical syndrome. This study examined thalamic changes across PSP phenotypes investigating (i) thalamic atrophy (ii) thalamic functional connectivity and (iii) the relationship between thalamic structural and functional connectivity changes with clinical severity.MethodsParticipants92 participants with PSP [63 PSP-Richardson's Syndrome (RS), 24 PSP-cortical, 5 PSP-subcortical] and 104 age-matched controls were recruited from the Cambridge Centre for Parkinson's Plus Disorders cohort. Clinical assessments and imaging were conducted within 1 year of diagnosis.Structural AnalysisThalamic volumes (TVs) were obtained using FreeSurfer. Bayesian multiple regression (brms, R) was used to model (i) mean TVs (ii) group differences in mean TVs (iii) relationships between Z-standardised clinical scores and TVs with age, gender, and total grey matter as covariates.Functional AnalysisVoxel-wise seed-based functional connectivity of the thalamus used the Functional Magnetic Resonance Imaging Expert Analysis Tool (FEAT) in FMRIB's Software Library (FSL). Inter-group differences and relationships between clinical scores and functional connectivity for each group were assessed using a general linear model with age and gender as covariates.ResultsStructural AnalysisTVs for all PSP subgroups were smaller than controls. No differences between PSP subgroups were detected. There was evidence for a relationship between TVs for the entire PSP group and Revised Addenbrooke's Cognitive Examination (ACER) scores [ß = 0.28, 95% credible interval (CI) = 0.04–0.53]. Subgroup analysis showed evidence for a relationship between ACER scores and TVs in PSP-RS [ß = 0.33, 95% CI = 0.09–0.57] and PSP-cortical [ß = 0.46, 95% CI = 0.12–0.83] phenotypes. A negative influence of TVs on total PSP rating scale scores was found for the PSP cohort a whole [ß = −0.51, 95% CI = −1.00 – −0.02].Functional AnalysisPSP patients as a group showed decreased thalamic functional connectivity in higher cortical regions. Subgroup analysis revealed decreased connectivity in those areas compared to controls but in distinct distributions and magnitude. Increased thalamic connectivity with the middle temporal gyrus correlated with ACER scores for PSP patients as a group and in the PSP-cortical subtype.ConclusionThalamic volume loss is a prominent aspect of PSP and is associated with a wide network of changes in functional connectivity that may be distinct between PSP subtypes. Changes in thalamic structure and function predict clinical severity, particularly in PSP-RS and PSP-cortical subtypes.

Herpes Simplex-1 and Toxoplasma gondii in Obsessive-Compulsive Disorder: clinical and brain imaging correlates

IntroductionObsessive-compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. While its aetiology remains unknown, several infectious agents have been associated to obsessive-compulsive symptoms, including herpes simplex virus 1 (HSV-1) and Toxoplasma gondii.ObjectivesTo evaluate the serostatus for HSV-1 and Toxoplasma gondii in sample of patients with OCD, as well as its clinical and brain imaging correlates.Methods Twenty-six patients with OCD and 30 healthy controls recruited in Lisbon were assessed for sociodemographic and clinical characteristics using the Yale-Brown Obsessive-Compulsive Scale-II (YBOCS-II) and the Beck Depression Inventory-II (BDI-II). Seropositivity for HSV-1 and Toxoplasma gondii was assessed in serum using ELISA, and volumes of cortical and subcortical structures were assessed using T1-weighted magnetic resonance imaging.ResultsYBOCS-II and BDI-II scores were significantly higher in patients, while age, sex, smoking status, and seropositivity for HSV-1 and Toxoplasma gondii were similar between the two groups. Among OCD patients, those seropositive for HSV-1 had significantly lower volumes of total white-matter, total grey-matter, left and right putamen, while for HSV-1 seropositive healthy controls, only the last two were significantly smaller. In multiple regression analyses to control for age, associations between HSV-1 and brain volumes were conserved, while the effect of age was not significant. No significant differences were found in brain volumes of patients with OCD according to seropositivity for Toxoplasma gondii.ConclusionsOur preliminary results suggest that in patients with OCD, seropositivity to HSV-1 is associated with smaller volumes of total white- and grey-matter in the brain.DisclosureNo significant relationships.

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study

BackgroundThe predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear.ObjectiveInvestigate the relation between sNfL levels over a 2-year period in patients...

Cardiometabolic multimorbidity, genetic risk, and dementia: a prospective cohort study

SummaryBackgroundIndividual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes.MethodsWe examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006–10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics.FindingsThe dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39–9·08, p<0·0001, and 1·68, 1·53–1·84, p<0·0001, respectively). Participants with both a high genetic risk and a cardiometabolic multimorbidity index of two or greater had an increased risk of developing dementia (HR 5·74, 95% CI 4·26–7·74, p<0·0001), compared with those with a low genetic risk and no cardiometabolic conditions. Crucially, we found no interaction between cardiometabolic multimorbidity and polygenic risk (p=0·18). Cardiometabolic multimorbidity was independently associated with more extensive, widespread brain structural changes including lower hippocampal volume (F2, 12 110 = 10·70; p<0·0001) and total grey matter volume (F2, 12 236 = 55·65; p<0·0001).InterpretationCardiometabolic multimorbidity was independently associated with the risk of dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help to reduce the risk of dementia, regardless of genetic risk.FundingWellcome Trust, Alzheimer's Research UK, Alan Turing Institute/Engineering and Physical Sciences Research Council, the National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, JP Moulton Foundation, and National Institute on Aging/National Institutes of Health.

Volumetric Assessment of Hippocampus and Subcortical Gray Matter Regions in Alzheimer Disease and Amnestic Mild Cognitive Impairment.

Quantitative MRI assessment methods have limited utility due to a lack of standardized methods and measures for Alzheimer disease (AD) and amnestic mild cognitive impairment (aMCI). To employ a relatively new and easy-to-use quantitative assessment method to reveal volumetric changes in subcortical gray matter (GM) regions, hippocampus, and global intracranial structures as well as the diagnostic performance and best thresholds of total hippocampal volumetry in individuals with AD and those with aMCI. A total of 74 individuals-37 with mild to moderate AD, 19 with aMCI, and 18 with normal cognition (NC)-underwent a 3T MRI. Fully automated segmentation and volumetric measurements were performed. The AD and aMCI groups had smaller volumes of amygdala, nucleus accumbens, and hippocampus compared with the NC group. These same two groups had significantly smaller total white matter volume than the NC group. The AD group had smaller total GM volume compared with the aMCI and NC groups. The thalamus in the AD group showed a subtle atrophy. There were no significant volumetric differences in the caudate nucleus, putamen, or globus pallidus between the groups. The amygdala and nucleus accumbens showed atrophy comparable to the hippocampal atrophy in both the AD and aMCI groups, which may contribute to cognitive impairment. Hippocampal volumetry is a reliable tool for differentiating between AD and NC groups but has substantially less power in differentiating between AD and aMCI groups. The loss of total GM volume differentiates AD from aMCI and NC.

0322 sleep disordered breathing and MRI makers of brain aging in the Hispanic Community Health Study/Study of Latinos

Abstract Introduction We aim to determine if white matter hyperintensities and decreased brain volumes are associated with sleep-disordered breathing (SDB), in a diverse sample of middle-aged and older Hispanic/Latino adults. Methods Our sample of 1,119 Hispanics/Latinos (ages older than 50-years; 70% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent brain magnetic resonance imaging (MRI) as part of the Study of Latinos - Investigation of Neurocognitive Aging MRI (SOL-INCA MRI) ancillary study. MRI outcomes of interest included global (gray matter, total brain) and regional (lobar cortices, hippocampus) brain volumes, lateral ventricle volume, and total white matter hyperintensity (WMH) volume. All MRI measures were residualized for total cranial volume. Our main exposure was visit-1 sleep data (2008-2011), which includes information about SDB defined with the respiratory event index 3% (REI), ≥5 and ≥15 (moderate-severe SDB) identified by home-sleep apnea test. Survey linear regression models to assess the association between sleep measures and MRI outcomes adjusted for age, sex, education, Hispanic/Latino background, body mass index, tobacco use, alcohol consumption, and physical activity factors and accounted for HCHS/SOL complex study design. We tested for effect modifications by age, sex and Hispanic/Latino background. Results Mean age was 63.9±7.0 years. Adjusting for age, sex, and education, individuals with a REI ≥15 (vs. &amp;lt;5) had decrements in total brain volume (Btotal=-6.115[-10.19 ; -2.04]; p&amp;lt;0.01), total gray matter volume(B= -3.702 [-6.7 ; -0.7]; p&amp;lt;0.05), and frontal cortical gray matter volume (B= -1.844[-3.48; -0.21]; p&amp;lt;0.05), and increments in hippocampal volume β= 0.138[0.04; 0.23]; p&amp;lt;0.01). The associations persisted after adjustment for Hispanic/Latino background and behavioral risk factors. Older age modified associations between the REI and age and total brain volumes (Bage*REI=-0.019[-0.04 ;~0.00]; p&amp;lt;0.05). There was no consistent evidence for effect moderation by sex or Hispanic/Latino background. Conclusion In a diverse sample of Hispanic/Latinos, moderate-severe SDB was associated with decreased total brain volumes and increments in hippocampal volumes. Our findings suggest that SDB related neuroimaging markers of brain health could serve to identify Hispanic/Latino participants with sleep related Alzheimer’s disease and related dementia risk. Support (If Any) This work is supported by National Institute on Aging (R01AG048642, RF1AG054548, and R01AG063868) and by the National Heart Lung Blood Institute (R01HL098297). Dr. González also receives additional support from P30AG59299. The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-philip glass beck HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements.

Hallucinations and Brain Morphology Across Early Adolescence: A Longitudinal Neuroimaging Study

BackgroundPsychotic disorders have been widely associated with structural brain abnormalities. However, it is unclear whether brain structure predicts psychotic experiences in youth from the general population, owing to an overall paucity of studies and predominantly cross-sectional designs. Here, the authors investigated longitudinal associations between brain morphology and hallucinations from childhood to early adolescence. MethodsThis study was embedded in the population-based Generation R Study. Children underwent structural neuroimaging at age 10 years (N = 2042); a subsample received a second scan at age 14 years (n = 964). Hallucinations were assessed at ages 10 and 14 years and studied as a binary variable. Cross-lagged panel models and generalized linear mixed-effects models were fitted to examine longitudinal associations between brain morphology and hallucinations. ResultsSmaller total gray and white matter volumes and total cortical surface area at baseline were associated with a higher occurrence of hallucinations between ages 10 and 14 years. The regions associated with hallucinations were widespread, including the frontal, parietal, temporal, and occipital lobes, as well as the insula and cingulate cortex. Analyses of subcortical structures revealed that smaller baseline hippocampal volumes were longitudinally associated with hallucinations, although this association was no longer significant following adjustment for intracranial volume. No evidence for reverse temporality was observed (i.e., hallucinations predicting brain differences). ConclusionsThe findings from this longitudinal study suggest that global structural brain differences are associated with the development of hallucinations. These results extend findings from clinical populations and provide evidence for a neurodevelopmental vulnerability across the psychosis continuum.

Lifespan Volume Trajectories From Non-harmonized T1-Weighted MRI Do Not Differ After Site Correction Based on Traveling Human Phantoms.

Multi–site imaging consortiums strive to increase participant numbers by pooling data across sites, but scanner related differences can bias results. This study combines data from three research MRI centers, including three different scanner models from two vendors, to examine non–harmonized T1–weighted brain imaging protocols in two cohorts. First, 23 human traveling phantoms were scanned twice each at all three sites (six scans per person; 138 scans total) to quantify within–participant variability of brain volumes (total brain, white matter, gray matter, lateral ventricles, thalamus, caudate, putamen and globus pallidus), and to calculate site–specific correction factors for each structure. Sample size calculations were used to determine the number of traveling phantoms needed to achieve effect sizes for observed differences to help guide future studies. Next, cross–sectional lifespan volume trajectories were examined in 856 healthy participants (5—91 years of age) scanned at these sites. Cross–sectional trajectories of volume versus age for each structure were then compared before and after application of traveling phantom based site–specific correction factors, as well as correction using the open–source method ComBat. Although small systematic differences between sites were observed in the traveling phantom analysis, correction for site using either method had little impact on the lifespan trajectories. Only white matter had small but significant differences in the intercept parameter after ComBat correction (but not traveling phantom based correction), while no other fits differed. This suggests that age–related changes over the lifespan outweigh systematic differences between scanners for volumetric analysis. This work will help guide pooling of multisite datasets as well as meta–analyses of data from non–harmonized protocols.

Higher Dietary Inflammatory Index scores are associated with brain MRI markers of brain aging: Results from the Framingham Heart Study Offspring cohort.

We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort. A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI). Higher (pro-inflammatory) DII scores, averaged across a maximum of three time points, were associated with smaller total brain volume (beta ± standard error: -0.16 ± 0.03; P < .0001) after adjustment for demographic, clinical, and lifestyle covariates. In addition, higher DII scores were associated with smaller total gray matter volume (-0.08 ± 0.03; P = .003) and larger lateral ventricular volume (0.04 ± 0.02; P = .03). No associations were observed with other brain MRI measures. Our findings showed associations between higher DII scores and global brain MRI measures. As we are one of the first groups to report on the associations between higher DII scores and brain volume, replication is needed to confirm our findings.

Brain structural alterations detected by an automatic quantified tool as an indicator for MCI diagnosing in type 2 diabetes mellitus patients: A magnetic resonance imaging study

Background and objectivesType 2 diabetes mellitus (T2DM) is an important risk factors for mild cognitive impairment (MCI). Structural magnetic resonance imaging (sMRI) is an effective and widely used method to investigate brain pathomorphological injury in neural diseases. In present study, we aimed to determine the brain regional alterations that correlated to the incidence of MCI in T2DM patients. Materials and methodsEighteen T2DM patients with and without MCI (DMCI/T2DM) respectively, and eighteen age/gender-matched healthy controls (HC) were recruited. Brain MRI imagines of all the individuals were subjected to automatic quantified brain sub-structure volume segmentation and measurement by Dr. brain ™ software. The relative volume of total gray matter (TGM), total white matter (TWM), and 68 pairs (left and right) of brain sub-structures were compared between the three groups. Cognitive function correlation analysis and receiver operating characteristic (ROC) curve analysis were conducted in the MCI-related brain regions in T2DM patients, and we utilized a machine learning method to classify the three group of subjects. Results10 and 27 brain sub-structures with significant relative volumetric alterations were observed in T2DM patients without MCI and T2DM patients with MCI, respectively (p < 0.05). Compared with T2DM patients without MCI, eight critical regions include right anterior orbital gyrus, right calcarine and cerebrum, left cuneus, left entorhinal area, left frontal operculum, right medial orbital gyrus, right occipital pole, left temporal pole had significant lower volumetric ratio in T2DM patients with MCI (p < 0.05). Among them, the decrease of volumetric ratio in several regions had a positive correlation with Montreal Cognitive Assessment (MoCA) scores and Mini-Mental State Examination (MMSE) scores. The classification results conducted based on these regions as features by random forest algorithm yielded good accuracies of T2DM/HC 69.4%, DMCI/HC 72.2% and T2DM/DMCI 69.4%. ConclusionsCertain brain regional structural lesions occurred in patients with T2DM, and this condition was more serious in T2DM patients combined with MCI. A systematic way of segmenting and measuring the whole brain has a potential clinical value for predicting the presence of MCI for T2DM patients.