Multi-Racial Normative Data for Lobar and Subcortical Brain Volumes in Old Age: Korean and Caucasian Norms May Be Incompatible With Each Other†

Brain aging is becoming an increasingly important topic, and the norms of brain structures are essential for diagnosing neurodegenerative diseases. However, previous studies of the aging brain have mostly focused on Caucasians, not East Asians. The aim of this paper was to examine ethnic differences in the aging process of brain structures or to determine to what extent ethnicity affects the normative values of lobar and subcortical volumes in clinically normal elderly and the diagnosis in multi-racial patients with Alzheimer's disease (AD). Lobar and subcortical volumes were measured using FreeSurfer from MRI data of 1,686 normal Koreans (age range 59–89) and 851 Caucasian, non-Hispanic subjects in the ADNI and OASIS datasets. The regression models were designed to predict brain volumes, including ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and MRI scanner manufacturers as independent variables. Ethnicity had a significant effect for all lobar (|β| > 0.20, p < 0.001) and subcortical regions (|β| > 0.08, p < 0.001) except left pallidus and bilateral ventricles. To demonstrate the validity of the z-score for AD diagnosis, 420 patients and 420 normal controls were selected evenly from the Korean and Caucasian datasets. The four validation groups divided by race and diagnosis were matched on age and sex using a propensity score matching. We analyzed whether and to what extent the ethnicity adjustment improved the diagnostic power of the logistic regression model that was built using the only z-scores of six regions: bilateral temporal cortices, hippocampi, and amygdalae. The performance of the classifier after ethnicity adjustment was significantly improved compared with the classifier before ethnicity adjustment (ΔAUC = 0.10, D = 7.80, p < 0.001; AUC comparison test using bootstrap). Korean AD dementia patients may not be classified by Caucasian norms of brain volumes because the brain regions vulnerable to AD dementia are bigger in normal Korean elderly peoples. Therefore, ethnicity is an essential factor in establishing normative data for regional volumes in brain aging and applying it to the diagnosis of neurodegenerative diseases.

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Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

Molecular Psychiatry ◽

10.1038/s41380-021-01098-x ◽

2021 ◽

Author(s):

Sean R. McWhinney ◽

◽

Christoph Abé ◽

Martin Alda ◽

Francesco Benedetti ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Bipolar Disorders ◽

Ventricular Volume ◽

Group Differences ◽

Intracranial Volume ◽

Brain Volumes ◽

Lateral Ventricles ◽

Mixed Effects Modeling ◽

Subcortical Volumes

AbstractIndividuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

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A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites

Microbiome ◽

10.1186/s40168-021-01172-0 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Hongli Shi ◽

Xing Ge ◽

Xi Ma ◽

Mingxuan Zheng ◽

Xiaoying Cui ◽

...

Keyword(s):

Cognitive Impairment ◽

Gut Microbiota ◽

Neurodegenerative Diseases ◽

Dietary Fiber ◽

Brain Aging ◽

Synaptic Proteins ◽

Aging Brain ◽

Normal Brain ◽

Fiber Intake ◽

Synaptic Ultrastructure

Abstract Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis. Results In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment. Conclusions This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.

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Relationship Between Verbal Fluency Performance, Fight Exposure, and Subcortical Region Brain Volumes in Professional Fighters

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz026.05 ◽

2019 ◽

Vol 34 (5) ◽

pp. 735-735

Author(s):

L Bennett ◽

C Bernick ◽

S Banks

Keyword(s):

Verbal Fluency ◽

Brain Structures ◽

Brain Regions ◽

Health Study ◽

Semantic Fluency ◽

Cognitive Changes ◽

Brain Volumes ◽

Subcortical Brain ◽

Subcortical Region ◽

Subcortical Brain Structures

Abstract Purpose Verbal fluency performance has been shown to be sensitive to preclinical cognitive changes in neurodegenerative diseases and may detect early, trauma-related cognitive and volumetric changes amongst professional fighters. Baseline verbal fluency performance and volumes of relevant subcortical brain structures were expected to decline as number of professional fights (NoPF) increased, while controlling for education. Methods Baseline letter and semantic fluency performance, NoPF, and structural brain imaging from 548 active and retired fighters who participated in the Professional Fighters Brain Health Study were considered. ANCOVAs were conducted to assess differences in verbal fluency performance by NOPF, while controlling for years of education. Number of professional fights were stratified into low (0-20 fights), medium (21-40 fights), and high (41 or more fights). Results Semantic fluency performance differed across the three levels of NoPF (F(2, 542)=4.56; p<.02). In addition, significant positive correlations between semantic fluency performance and volumes in the following regions were observed: left thalamus, left putamen, left pallidum, bilateral caudates, bilateral amygdalae, bilateral hippocampi, and bilateral accumbens (all p’s<.05). In contrast, letter fluency performance was not significantly associated with NoPF or volumes of relevant subcortical brain structures (all p’s>.05). Conclusion Semantic fluency may be low-cost, easy-to-administer harbinger of emerging cognitive dysfunction and lower volumes in related subcortical brain regions. Additional assessment of clinical utility is necessary.

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Metabolism modulates network synchrony in the aging brain

10.1101/2020.04.17.047233 ◽

2020 ◽

Author(s):

Corey Weistuch ◽

Lilianne R Mujica-Parodi ◽

Anar Amgalan ◽

Ken A Dill

Keyword(s):

Statistical Physics ◽

Quantitative Methods ◽

Brain Aging ◽

Brain Activity ◽

High Sensitivity ◽

Brain Regions ◽

Aging Brain ◽

Global Changes ◽

Abrupt Changes ◽

Network Synchrony

AbstractBrain aging is associated with hypometabolism and associated global changes in functional connectivity. Using fMRI, we show that network synchrony, a collective property of brain activity, decreases with age. Applying quantitative methods from statistical physics, we provide a generative (Ising) model for these changes as a function of the average communication strength between brain regions. In particular, we find healthy brains to be poised at a critical point of this communication strength, enabling a balance between segregated (to functional domains) and integrated (between domains) patterns of synchrony. However, one characteristic of criticality is a high sensitivity to small changes. Thus, minute weakening of pairwise communication between regions, as seen in the aging brain, gives rise to qualitatively abrupt changes in synchrony. Finally, by experimentally modulating metabolic activity in younger adults, we show how metabolism alone–independent of other changes associated with aging–can provide a mechanism for global changes in synchrony.

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Smaller Volume in Left-Lateralized Brain Structures Correlates with Greater Experience of Negative Non-target Emotions in Neurodegenerative Diseases

Cerebral Cortex ◽

10.1093/cercor/bhaa193 ◽

2020 ◽

Vol 31 (1) ◽

pp. 15-31 ◽

Cited By ~ 1

Author(s):

Kuan-Hua Chen ◽

Alice Y Hua ◽

Sandy J Lwi ◽

Claudia M Haase ◽

Howard J Rosen ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Left Hemisphere ◽

Subjective Experience ◽

Emotional Experience ◽

Brain Structures ◽

Brain Regions ◽

Contaminated Food ◽

Positive Target ◽

Withdrawal Behaviors

Abstract Subjective emotional experience that is congruent with a given situation (i.e., target emotions) is critical for human survival (e.g., feeling disgusted in response to contaminated food motivates withdrawal behaviors). Neurodegenerative diseases including frontotemporal dementia and Alzheimer’s disease affect brain regions critical for cognitive and emotional functioning, resulting in increased experience of emotions incongruent with the situation (i.e., non-target emotions, such as feeling happy when seeing someone grieving). We examined neuroanatomical correlates of subjective experience of non-target emotions in 147 patients with neurodegenerative diseases and 26 healthy individuals. Participants watched three films intended to elicit particular target emotions and rated their experience of negative and positive target and non-target emotions after watching each film. We found that smaller volume in left hemisphere regions (e.g., caudate, putamen, and dorsal anterior insula) was associated with greater experience of negative non-target emotions. Follow-up analyses confirmed that these effects were left-lateralized. No correlates emerged for positive non-target emotions. These findings suggest that volume loss in left-hemisphere regions produces a more diffuse, incongruent experience of non-target emotions. These findings provide a potential neuroanatomical basis for understanding how subjective emotional experience is constructed in the brain and how this can be disrupted in neurodegenerative disease.

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The Effect of Anxiety on Regional Brain Volumes in the National Alzheimer’s Coordinating Center Uniform Data Set

Innovation in Aging ◽

10.1093/geroni/igaa057.1197 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 371-372

Author(s):

Shanna Burke ◽

Tan Li ◽

Adrienne Grudzien ◽

Christopher Barnes ◽

Kevin Hanson ◽

...

Keyword(s):

Parietal Lobe ◽

Secondary Analysis ◽

Occipital Lobe ◽

Ventricular Volume ◽

Brain Regions ◽

Brain Morphology ◽

Intracranial Volume ◽

Data Set ◽

Brain Volumes ◽

Regional Brain

Abstract Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk.

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Regional Brain Volumes Associated With Depression in the National Alzheimer’s Coordinating Center Uniform Data Set

Innovation in Aging ◽

10.1093/geroni/igaa057.1196 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 371-371

Author(s):

Shanna Burke ◽

Tan Li ◽

Adrienne Grudzien ◽

Christopher Barnes ◽

Kevin Hanson ◽

...

Keyword(s):

Gray Matter ◽

Parietal Lobe ◽

Brain Regions ◽

Intracranial Volume ◽

Data Set ◽

Brain Volumes ◽

Brain White Matter ◽

Regional Brain ◽

Total Brain ◽

Gray Matter Volumes

Abstract Depression has been associated with greater risk of Alzheimer’s disease (AD), and existing research has identified structural differences in brain regions in depressed subjects compared to healthy samples, but results have been heterogeneous. We sought to determine the effect of depression on regional brain volumes by cognitive and APOE e4 status. Secondary analysis of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of depression (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRIs. Depression in the prior two years was associated with lower total brain, cerebrum,, and gray matter volumes and greater total brain white matter hyperintensities (p<.05). Greater volumes were also observed in all ventricular volume measures. Lower mean volumes were observed in six additional frontal lobe and parietal lobe cortical regions. Alternately, depression antecedent to the past 2 years correlated only with occipital lobe gray matter volumes (right, left, total). Our findings suggest that depression in the prior two years is associated with atrophy across multiple brain regions and related ventricular enlargement, even after controlling for intracranial volume and demographic covariates. The duration of depression influences results, however, as depression prior to 2 years before assessment was correlated with significantly fewer and different regional brain volume changes.

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Sex-Dependent Age Trajectories of Subcortical Brain Structures: Analysis of Large-Scale Percentile Models and Shape Morphometry

10.1101/2020.09.30.321711 ◽

2020 ◽

Cited By ~ 1

Author(s):

Christopher R. K. Ching ◽

Zvart Abaryan ◽

Vigneshwaran Santhalingam ◽

Alyssa H. Zhu ◽

Joanna K. Bright ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Spatial Distribution ◽

Large Scale ◽

Brain Aging ◽

Brain Structures ◽

Large Sample Size ◽

Subcortical Brain ◽

Subcortical Brain Structures ◽

Subcortical Volumes

ABSTRACTModeling of structural brain variation over the lifespan is important to better understand factors contributing to healthy aging and risk for neurological conditions such as Alzheimer’s disease. Even so, we lack normative data on brain morphometry across the adult lifespan in large, well-powered samples. Here, in a large population-based sample of 26,440 adults from the UK Biobank (age: 44-81 yrs.), we created normative percentile charts for MRI-derived subcortical volumes. Next, we investigated associations between these morphometric measures and the strongest known genetic risk factor for late-onset Alzheimer’s disease (APOE genotype) and mapped the spatial distribution of age-by-sex interactions using computational surface mesh modeling and shape analysis. Vertex-wise shape mapping supplements traditional gross volumetric approaches to reveal finer-grained variations across functionally important brain subcompartments. Normative curves revealed volumetric loss with age, as expected, for all subcortical brain structures except for the lateral ventricles, which expanded with age. Surprisingly, no volumetric associations with APOE genotype were detected, despite the very large sample size. Age-related trajectories for volumes differed in women versus men, and surface-based statistical maps revealed the spatial distribution of the age-by-sex interaction. Subcortical volumes declined faster in men than women over the full age range, but after age 60, fewer structures showed sex-dependent trajectories, indicating similar volumetric changes in older men and women. Large-scale statistical modeling of age effects on brain structures may drive new insights into individual differences in brain aging and help to identify factors that promote healthy brain aging and risk for disease.

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Brain MRI Phenotypes Associated with Polymorphisms at or near the MAPT (Microtubule Associated Protein Tau) and COASY (Coenzyme A Synthase) Genes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_004 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1246-1246

Author(s):

Emily Chambers ◽

Evan Hermann ◽

Danielle Davis ◽

Mckale Montgomery ◽

Edralin Lucas ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Metal Accumulation ◽

Brain Aging ◽

Brain Mri ◽

Brain Regions ◽

Chromosome 17 ◽

P Value ◽

Candidate Snps ◽

A Genome ◽

Independent Association

Abstract Objectives Impaired metal homeostasis in the brain has been reported in neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease and can be detected using magnetic resonance imaging (MRI). Many factors, including genetics, affect brain metal accumulation and the risk of neurodegeneration or premature brain aging. Our objective is to uncover independent association signals at chromosome 17 associated with susceptibility-weighted MRI (swMRI) intensities in the caudate and putamen. Methods Conditional and joint association analysis by GCTA-COJO was performed on the summary statistics dataset from a genome-wide association study (GWAS) on brain swMRI phenotypes from 7778 healthy adults of European descent aged 40–69 years from the UK BioBank. Independent association signals (single nucleotide polymorphisms or SNPs) found by GCTA-COJO were grouped further by SNPclip to identify additional candidate SNPs in high linkage disequilibrium (LD) (R2 > 0.8, P < 5.0 × 10–8) with the independent lead/index SNP at each signal. Correlations were performed to show the similarity of impacts (beta) of SNPs significantly associated with MRI differences in both caudate and putamen at one locus. Results There are 2 independent and distinct loci at chromosome 17 associated with MRI differences in the putamen, whereas there is only 1 locus for the caudate. One locus for the putamen is associated with the MAPT H2 haplotype, which has been linked to different neurological diseases. Another locus for both putamen and caudate is located near the genes COASY, NAGLU, and MLX, which are all plausible candidate genes for brain metal accumulation. For one locus identified by GCTA-COJO, there are 19 SNPs in LD (R2 > 0.8) and overlapping in both the caudate and the putamen. The effects (beta) of the SNPs in the putamen and caudate are highly correlated across both brain regions (R2 = 0.907, P-value = 0.000921). Conclusions There is likely 1 signal from the COASY/NAGLU locus on chromosome 17 affecting both brain regions. The signal from the MAPT locus only affects the MRI pattern seen in the putamen. These results connect genetics with brain MRI patterns and an individual's risk for neurodegenerative diseases. Funding Sources This work was funded by grants from the Oklahoma Center for the Advancement of Science & Technology and the Oklahoma Agricultural Experiment Station.

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Lifetime antipsychotic use and brain structures in schizophrenia and other psychoses – 43-year study of the Northern Finland Birth Cohort 1966

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.077 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S100-S101

Author(s):

S. Huhtaniska ◽

I. Korkala ◽

T. Heikka ◽

J. Tohka ◽

J. Manjon ◽

...

Keyword(s):

Birth Cohort ◽

Antipsychotic Medication ◽

Lateral Ventricle ◽

Brain Structures ◽

Brain Morphology ◽

Psychotic Symptoms ◽

Intracranial Volume ◽

Brain Volumes ◽

Left Lateral Ventricle ◽

Brain Changes

IntroductionThe effects of long-term antipsychotic medication use on structural brain changes in psychoses are still unknown. Severity and duration of illness are key confounders when evaluating antipsychotic effects on brain morphology.ObjectivesUnderstanding the role of antipsychotic medication on brain morphology in psychoses.AimsTo analyze whether cumulative lifetime or current antipsychotic medication dose relates to brain morphology in schizophrenia and other psychoses at age of 43 years.MethodsForty-four schizophrenia cases and 35 with other psychoses from the Northern Finland Birth Cohort 1966 were scanned on a 1.5T GE Signa scanner and brain structures were extracted using volBrain automated volumetry system (http://volbrain.upv.es). Data of antipsychotic medication were collected from medical records and interviews. We used linear regression model to analyze the effect of antipsychotic medication on brain volumes and used intracranial volume and onset age as covariates. We also performed additional analyses adding psychotic symptoms (PANSS Total score) as a covariate.ResultsHigher lifetime and current dose associated to left lateral ventricle increase (b = 0.33, P = 0.033; b = 0.307, P = 0.042, respectively) and right and left accumbens decrease (b = −0.405, P = 0.013, b = −0.404, P = 0.010; b = −0.302, P = 0.027, b = −0.282, P = 0.036, respectively) in schizophrenia but not in other psychoses. When PANSS was added to the model, the findings remained regarding right and left accumbens, but not regarding left lateral ventricle.ConclusionsIt seems that antipsychotic medication affects the brain in schizophrenia, but not in the heterogeneous group of other psychoses. In schizophrenia, brain changes associated to antipsychotic medication cannot be explained by illness duration or symptom severity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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