69 research outputs found
Bio-psycho-social factorsâ associations with brain age: a large-scale UK Biobank diffusion study of 35,749 participants
Brain age refers to age predicted by brain features. Brain age has previously been associated with various health and disease outcomes and suggested as a potential biomarker of general health. Few previous studies have systematically assessed brain age variability derived from single and multi-shell diffusion magnetic resonance imaging data. Here, we present multivariate models of brain age derived from various diffusion approaches and how they relate to bio-psycho-social variables within the domains of sociodemographic, cognitive, life-satisfaction, as well as health and lifestyle factors in midlife to old age (Nâ=â35,749, 44.6â82.8âyears of age). Bio-psycho-social factors could uniquely explain a small proportion of the brain age variance, in a similar pattern across diffusion approaches: cognitive scores, life satisfaction, health and lifestyle factors adding to the variance explained, but not socio-demographics. Consistent brain age associations across models were found for waist-to-hip ratio, diabetes, hypertension, smoking, matrix puzzles solving, and job and health satisfaction and perception. Furthermore, we found large variability in sex and ethnicity group differences in brain age. Our results show that brain age cannot be sufficiently explained by bio-psycho-social variables alone. However, the observed associations suggest to adjust for sex, ethnicity, cognitive factors, as well as health and lifestyle factors, and to observe bio-psycho-social factor interactionsâ influence on brain age in future studies.publishedVersio
Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later
Introduction: The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology. Methods: In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40â70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline. Results: Postmenopausal females showed higher levels of baseline blood lipids (HDL (Formula presented.) = 0.14, p < 0.001, LDL (Formula presented.) = 0.20, p < 0.001, triglycerides (Formula presented.) = 0.12, p < 0.001) and HbA1c ((Formula presented.) = 0.24, p < 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group ((Formula presented.) = â0.08, p < 0.001), while WHR increased to a similar extent in both groups ((Formula presented.) = â0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes ((Formula presented.) range = 0.03â0.13, p †0.002). HDL showed a significant inverse relationship with WMH volume ((Formula presented.) = â0.27, p < 0.001). Discussion: Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years.</p
Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later
Introduction: The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology.
Methods: In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40â70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline.
Results: Postmenopausal females showed higher levels of baseline blood lipids (HDL ÎČâ=â0.14, pâ
Discussion: Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years
Dissecting unique and common variance across body and brain health indicators using age prediction
Ageing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses interâindividual heterogeneity in the multisystem ageing process. Using machineâlearning regression models on the UK Biobank data set (N = 32,593, age range 44.6â82.3, mean age 64.1 years), we first estimated tissueâspecific brain age for white and gray matter based on diffusion and T1âweighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits, including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI, were combined to predict âbody ageâ. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusionâbased model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscleâfat infiltration were related to olderâappearing body age compared to brain age. Conversely, higher handâgrip strength and muscle volume were related to a youngerâappearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals
ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors
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Intracranial and subcortical volumes in adolescents with earlyâonset psychosis: A multisite megaâanalysis from the ENIGMA consortium
Earlyâonset psychosis disorders are serious mental disorders arising before the age of 18âyears. Here, we investigate the largest neuroimaging dataset, to date, of patients with earlyâonset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with earlyâonset psychosis (mean age: 16.4â±â1.4âyears, mean illness duration: 1.5â±â1.4âyears, 39.2% female) and 359 healthy controls (mean age: 15.9â±â1.7âyears, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with earlyâonset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixedâeffects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = â0.39) and hippocampal (d = â0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both earlyâonset schizophrenia (d = â0.34) and affective psychosis (d = â0.42), and earlyâonset schizophrenia showed lower hippocampal (d = â0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = â0.42). The findings demonstrate a similar pattern of brain alterations in earlyâonset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent earlyâonset psychosis
Incident acute coronary syndromes in chronic dialysis patients in the United States11The opinions are solely those of the authors and do not represent an endorsement by the Department of Defense or the National Institutes of Health. This is a U.S. Government work. There are no restrictions on its use.
Incident acute coronary syndromes in chronic dialysis patients in the United States.BackgroundPatients on dialysis have a disproportionately high rate of cardiovascular disease (CVD). However, the incidence and risk factors for incident acute coronary syndromes (ACS) have not been previously assessed in dialysis patients.MethodsWe analyzed the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave II in a historical cohort study of ACS. Data from 3374 patients who started dialysis in 1996 with valid follow-up times were available for analysis, censored at the time of renal transplantation and followed until March 2000. Cox regression analysis was used to model factors associated with time to first hospitalization for ACS (ICD9 code 410.x or 411.x) adjusted for comorbidities, demographic factors, baseline laboratory values, blood pressures and cholesterol levels, type of vascular access, dialysis adequacy, and cardioprotective medications (angiotensin-converting enzyme inhibitors, calcium channel blockers, HMG-CoA reductase inhibitors (statins), beta blockers, and aspirin). Follow-up was 2.19 ± 1.14 years.ResultsThe incidence of ACS was 29/1000 person-years. Factors associated with ACS were older age, the extreme high and low ranges of serum cholesterol level, history of coronary heart disease (CHD), male gender, and diabetes. No cardioprotective medications including statins had a significant association with ACS in this study. However, medications known to reduce mortality after ACS were used in less than 50% of patients with known CHD at the start of the study, and statins were used in less than 10% of patients with CHD.ConclusionsDialysis patients had similar risk factors for ACS compared to the general population. Cardioprotective medications were not associated with a significant benefit, possibly due to their striking underutilization in this at-risk population
Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA-Schizophrenia consortium
Objective: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. Method: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. Results: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ÎČstd = â0.052; P = 0.021; right: ÎČstd = â0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. Conclusion: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia
What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group
First published: 29 July 2020MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.Christopher R. K. Ching .... Bernhard T. Baune ... et al
What we learn about bipolar disorder from large-scale neuroimaging:Findings and future directions from the ENIGMA Bipolar Disorder Working Group
MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness
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