Smaller Gray Matter Volume Research Articles

Altered Gray Matter Volume and Its Correlation With PTSD Severity in Chinese Earthquake Survivors.

Objective: To detect the changes of gray matter volume (GMV) and their correlation with severity of symptom in patients with post-traumatic stress disorder (PTSD) who were defined with updated DSM-5 diagnostic criteria.Method: 71 participants were assigned into PTSD group (n = 35) or trauma-exposed control (TEC) group (n = 36) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Voxel-based morphometry analysis was used to detect alterations in GMV in the PTSD group.Results: We found that the PTSD group had larger GMV in the left middle temporal gyrus (MTG) and in the right dorsal medial prefrontal cortex (dmPFC), and smaller GMV in the region of the right temporal pole (TP) than the TEC group. We also found that PTSD Checklist for DSM-5 (PCL-5) scores correlated positively with the left MTG and right dmPFC GMV, and negatively with left TP GMV. These correlations were consistent with the findings of the between-group comparisons.Conclusions: GMV alterations in the MTG, dmPFC, and TP are detected in the group comparisons and correlated with symptom severity when classifying PTSD individuals according to DSM-5 diagnostic criteria within an earthquake-exposed population.

Structural brain changes in perinatally HIV-infected young adolescents in South Africa

To describe the structural brain changes, neurocognitive and mental health associations in adolescents perinatally infected with HIV-1 infection. Cross-sectional. Two hundred and four adolescents with perinatally acquired HIV and 44 uninfected frequency-matched controls aged 9-11 years were enrolled within the Cape Town Adolescent Antiretroviral Cohort. Diffusion tensor imaging and structural brain MRI was done to determine fractional anisotropy, mean diffusivity, grey and white matter volumes, cortical thickness and cortical surfractional anisotropy area. Correlation coefficients were calculated between total grey and white matter volume, cortical surface area, cortical thickness, whole brain fractional anisotropy and whole brain mean diffusivity and clinical and laboratory parameters including general intellectual functioning, Becks Youth Inventory, Child Motivation Scale and Child Behaviour Checklist. HIV-infected adolescents performed worse than controls on the Wechsler Abbreviated Scale of Intelligence (WASI; P < 0.01). HIV-infected adolescents had significant fractional anisotropy decreases, mean diffusivity increases and decreases in cerebral grey matter volumes, cortical surface area and decreased gyrification. Whole-brain mean fractional anisotropy was significantly reduced in the HIV-infected group (P = 0.031). There were significant correlation coefficients between greater total grey (P = 0.008) and white matter volume (P = 0.004) with the WASI and the Becks self-concept subscale (P = 0.038). Lower whole brain fractional anisotropy was associated with higher scores on the Becks anger (P = 0.018) and disruptive behaviour subscales (P = 0.031). Higher whole brain mean diffusivity was associated with apathy (P = 0.046). The pattern of increased risk of white matter microstructure alterations, smaller grey matter volumes, reduced cortical surface area and decreased gyrification, suggests abnormal neurodevelopment in perinatally infected younger adolescents.

Individual differences in trait anxiety are associated with gray matter alterations in hypothalamus: Preliminary neuroanatomical evidence

Trait anxiety is particularly a prone phenotype for the development of anxiety disorders and depression. Studying the neural underpinnings of trait anxiety can further inform our understanding of the etiology of these disorders. To investigate the structural correlates of trait anxiety, high resolution structural images were acquired from 76 right-handed healthy participants and gray matter volumes were extracted from a priori regions of interest (ROIs) that were earlier implicated in anxiety like behaviour (i.e., hippocampus, amygdala, anterior cingulate cortex, thalamus, hypothalamus and prefrontal (dorsolateral, rostrolateral, ventrolateral) cortex. In a partial correlation analysis (with age, gender, and Beck Depression Inventory (BDI) scores as covariates of no interest), trait anxiety was found to be negatively correlated with the gray matter volume of hypothalamus bilaterally and positively correlated with the gray matter volume of left thalamus. In a hierarchical multiple regression analysis, grey matter volume of hypothalamus and left thalamus were found to be the significant predictors of trait anxiety. Our findings thus suggest that a smaller gray matter volume in the hypothalamus and an increase in the gray matter volume of left thalamus is related to a disposition to high anxiety personality trait.

Gray matter volume of the dorsolateral prefrontal cortex moderates the relationship between rumination and depressed mood

Previous studies have indicated that negative cognition and rumination represent two vulnerabilities to depression and moderate one another’s influence on depression. Building upon previous studies, higher inhibitory abilities potentially allow less negative memories to feed into the ruminative process, which may mitigate the deleterious impact of rumination. Additionally, dorsolateral prefrontal cortex (DLPFC) plays an important role in memory inhibition. In the current study, we explored the moderating role of DLPFC between rumination and depressed mood. We used the think/no-think paradigm to explore the brain mechanisms of memory inhibition, and subsequently investigated the moderation effect of areas of interest, related with the memory inhibition, on the relationship between rumination and depressed mood. The results showed that higher memory inhibition ability was associated with larger gray matter volume in the dorsolateral prefrontal cortex. In addition, smaller gray matter volume in this area aggravated the relationship between rumination and depressed mood. This finding might help elucidate when and why healthy individuals experience depressed mood.

C-Reactive Protein, Plasma Amyloid-β Levels, and Their Interaction With Magnetic Resonance Imaging Markers

Background and Purpose- Inflammation is involved in the pathogenesis of large artery atherosclerosis, ischemic stroke, and Alzheimer dementia. However, the role of inflammation in cerebral small vessel disease and neurodegeneration remains poorly understood. We hypothesize that CRP (C-reactive protein) is associated with brain structural changes and may interact with amyloid to produce vascular and degenerative damage. We examined the association of CRP levels with imaging markers of cerebral small vessel disease and neurodegeneration. Furthermore, we studied the association of CRP with plasma Aβ (amyloid-β) levels and their joint effects with imaging markers. Methods- We included 2814 persons (mean age, 56.9 years; 44.8% women) from the Rotterdam Study with complete data on CRP and 1.5 T brain magnetic resonance imaging scans. Aβ levels were measured in a subsample (n=736). Markers of cerebral small vessel disease included lacunes, white matter hyperintensities, microbleeds, and enlarged perivascular spaces. Neurodegeneration was assessed by smaller volumes of gray matter, white matter, and hippocampus. Plasma levels of Aβ1-38, Aβ1-40, and Aβ1-42 were assessed using ELISA. Results- Higher CRP levels were associated with larger white matter hyperintensities volume (β=0.07; 95% CI, 0.00-0.13), increasing lacunar (rate ratios, 1.61; 95% CI, 1.19-2.19), enlarged perivascular spaces (rate ratios, 1.01; 95% CI, 1.00-1.03), and deep/infratentorial microbleeds (rate ratios, 1.30; 95% CI, 1.00-1.69) counts. People with high CRP levels had small gray matter volume. We also found significant interaction between CRP and Aβ such that among persons in higher tertiles of Aβ1-42, a strong association was observed between CRP and lacunar ( P interaction, 0.004), enlarged perivascular spaces ( P interaction, 0.002), and microbleed counts ( P interaction, <0.001). Similarly, among persons in higher tertile of Aβ1-38, a strong association was observed between CRP and microbleed counts ( P interaction, 0.004). Conclusions- Higher CRP levels were associated with subclinical markers of cerebral small vessel disease and neurodegeneration. This effect was augmented by an interaction between CRP and Aβ levels. Future longitudinal studies focusing on joint effects of CRP and Aβ on progression of magnetic resonance imaging markers and cognitive decline are warranted.

Neuroanatomical abnormalities in fragile X syndrome during the adolescent and young adult years

Abnormal brain development and cognitive dysfunction have been reported both in children and in adults with fragile X syndrome (FXS). However, few studies have examined neuroanatomical abnormalities in FXS during adolescence. In this study we focus on adolescent subjects with FXS (N = 54) as compared to age- and sex-matched subjects with idiopathic intellectual disability (Comparison Group) (N = 32), to examine neuroanatomical differences during this developmental period. Brain structure was assessed with voxel-based morphometry and independent groups t-test in SPM8 software. Results showed that the FXS group, relative to the comparison group, had significantly larger gray matter volume (GMV) in only one region: the bilateral caudate nucleus, but have smaller GMV in several regions including bilateral medial frontal, pregenual cingulate, gyrus rectus, insula, and superior temporal gyrus. Group differences also were noted in white matter regions. Within the FXS group, lower FMRP levels were associated with less GMV in several regions including cerebellum and gyrus rectus, and less white matter volume (WMV) in pregenual cingulate, middle frontal gyrus, and other regions. Lower full scale IQ within the FXS group was associated with larger right caudate nucleus GMV. In conclusion, adolescents and young adults with FXS demonstrate neuroanatomical abnormalities consistent with those previously reported in children and adults with FXS. These brain variations likely result from reduced FMRP during early neurodevelopment and mediate downstream deleterious effects on cognitive function.

Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta-Analysis.

The current insight into the neurobiological pathogenesis underlying social anxiety disorder (SAD) is still rather limited. We implemented a meta-analysis to explore the neuroanatomical basis of SAD. We undertook a systematic search of studies comparing gray matter volume (GMV) differences between SAD patients and healthy controls (HC) using a whole-brain voxel-based morphometry (VBM) approach. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of SAD patients compared with HC. We included eleven studies with 470 SAD patients and 522 HC in the current meta-analysis. In the main meta-analysis, relative to HC, SAD patients showed larger GMVs in the left precuneus, right middle occipital gyrus (MOG) and supplementary motor area (SMA), as well as smaller GMV in the left putamen. In the subgroup analyses, compared with controls, adult patients (age ≥ 18 years) with SAD exhibited larger GMVs in the left precuneus, right superior frontal gyrus (SFG), angular gyrus, middle temporal gyrus (MTG), MOG and SMA, as well as a smaller GMV in the left thalamus; SAD patients without comorbid depressive disorder exhibited larger GMVs in the left superior parietal gyrus and precuneus, right inferior temporal gyrus, fusiform gyrus, MTG and superior temporal gyrus (STG), as well as a smaller GMV in the bilateral thalami; and currently drug-free patients with SAD exhibited a smaller GMV in the left thalamus compared with HC while no larger GMVs were found. For SAD patients with different clinical features, our study revealed directionally consistent larger cortical GMVs and smaller subcortical GMVs, including locationally consistent larger precuneus and thalamic deficits in the left brain. Age, comorbid depressive disorder and concomitant medication use of the patients might be potential confounders of SAD at the neuroanatomical level.

Cerebellar development and its mediation role in cognitive planning in childhood.

Recent evidence suggests that the cerebellum contributes not only to the planning and execution of movement but also to the high-order cognitive planning. Childhood is a critical period for development of the cerebellum and cognitive planning. This study aimed (a) to examine the development of cerebellar morphology and microstructure and (b) to examine the cerebellar mediation roles in the relationship between age and cognitive planning in 6- to 10-year-old children (n = 126). We used an anatomical parcellation to quantify cerebellar regional gray matter (GM) and white matter (WM) volumes, and WM microstructure, including fractional anisotropy (FA) and mean diffusivity (MD). We assessed planning ability using the Stockings of Cambridge (SOC) task in all children. We revealed (a) a measure-specific anterior-to-posterior gradient of the cerebellar development in childhood, that is, smaller GM volumes and greater WM FA of the anterior segment of the cerebellum but larger GM volumes and lower WM FA in the posterior segment of the cerebellum in older children; (b) an age-related improvement of the SOC performance at the most demanding level of five-move problems; and (c) a mediation role of the lateral cerebellar WM volumes in age-related improvement in the SOC performance in childhood. These results highlight the differential development of the cerebellum during childhood and provide evidence that brain adaptation to the acquisition of planning ability during childhood could partially be achieved through the engagement of the lateral cerebellum.

Relationships between cerebral structure and cognitive function in African Americans with type 2 diabetes

BackgroundRelationships between cognitive function and brain structure remain poorly defined in African Americans with type 2 diabetes. MethodsCognitive testing and cerebral magnetic resonance imaging in African Americans from the Diabetes Heart Study Memory IN Diabetes (n = 480) and Action to Control Cardiovascular Risk in Diabetes MIND (n = 104) studies were examined for associations. Cerebral gray matter volume (GMV), white matter volume (WMV) and white matter lesion volume (WMLV) and cognitive performance (Mini-mental State Exam [MMSE and 3MSE], Digit Symbol Coding (DSC), Stroop test, and Rey Auditory Verbal Learning Test) were recorded. Multivariable models adjusted for age, sex, BMI, scanner, intracranial volume, education, diabetes duration, HbA1c, LDL-cholesterol, smoking, hypertension and cardiovascular disease assessed associations between cognitive tests and brain volumes by study and meta-analysis. ResultsMean(SD) participant age was 60.1(7.9) years, diabetes duration 12.1(7.7) years, and HbA1c 8.3(1.7)%. In the fully-adjusted meta-analysis, lower GMV associated with poorer global performance on MMSE/3MSE (β̂ = 7.1 × 10−3, SE 2.4 × 10−3, p = 3.6 × 10−3), higher WMLV associated with poorer performance on DSC (β̂ = −3 × 10−2, SE 6.4 × 10−3, p = 5.2 × 10−5) and higher WMV associated with poorer MMSE/3MSE performance (β̂ = −7.1 × 10−3, SE = 2.4 × 10−3, p = 3.6 × 10−3). ConclusionsIn African Americans with diabetes, smaller GMV and increased WMLV associated with poorer performance on tests of global cognitive and executive function. These data suggest that WML burden and gray matter atrophy associate with cognitive performance independent of diabetes-related factors in this population.

Reduced gray matter volume and respiratory dysfunction in Parkinson\u2019s disease: a voxel-based morphometry study

BackgroundThe respiratory dysfunction of patients with Parkinson’s disease (PD) has drawn increasing attention. This study evaluated the relationship between gray matter volume (GMV), as determined by voxel-based morphometry (VBM), and respiratory dysfunction in patients with PD and correlated it with systemic inflammatory markers.MethodsWhole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 25 PD patients with abnormal pulmonary function (13 men, 12 women; mean age: 62.9 ± 10.8 years) and, for comparison, on 25 sex- and age-matched PD patients with normal pulmonary function (14 men, 11 women; mean age: 62.3 ± 6.9 years). Inflammatory markers were determined by flow cytometry. The differences and correlations in regional GMV, clinical severity and inflammatory markers were determined after adjusting for age, gender and total intracranial volume (TIV).ResultsCompared with the normal pulmonary function group, the abnormal pulmonary function group had smaller GMV in several brain regions, including the left parahippocampal formation, right fusiform gyrus, right cerebellum crus, and left postcentral gyri. Forced expiratory volume in 1 s (FEV1) and maximal expiratory flow after expiration of 50% of forced vital capacity (MEF50) were positively correlated with regional GMV. There were no significant differences in the level of serum inflammatory markers between two groups.ConclusionOur findings suggested that involvement of the central autonomic network and GM loss may underlie the respiratory dysfunction in PD patients.

Preliminary evidence of altered gray matter volume in subjects with internet gaming disorder: associations with history of childhood attention-deficit/hyperactivity disorder symptoms.

Attention-deficit/hyperactivity disorder (ADHD) is commonly comorbid with Internet gaming disorder (IGD). Although childhood ADHD symptoms may decline during late brain maturation, structural alterations in some brain areas may persist into adulthood. This study investigated whether young adults with IGD and a history of childhood ADHD symptoms had gray matter volume (GMV) alterations that were distinct from subjects without a history of childhood ADHD. As an exploratory investigation, we conducted a whole-brain voxel-based morphometry with the diffeomorphic anatomical registration using an exponentiated Lie algebra algorithm and applied an uncorrected threshold at the voxel level for multiple comparisons. GMVs of IGD subjects with a history of childhood ADHD (IGDADHD+ group; n = 20; 24.5 ± 2.5years) were compared to those of subjects without a history of childhood ADHD (IGDADHD- group; n = 20; 23.9 ± 2.5years) and controls (n = 20; 22.7 ± 2.4years). Compared with controls, both IGD groups had a smaller GMV in the right anterior cingulate cortex, the left inferior frontal gyrus, and the left insula, yet had a larger GMV in the right angular gyrus. The IGDADHD+ group had a larger GMV in the right precuneus than the IGDADHD- group and controls. When controlling for other comorbid psychiatric symptoms, the IGDADHD+ group also had a smaller GMV in the right inferior frontal gyrus. In conclusion, we found that young adults with IGD and a history of childhood ADHD symptoms had characteristic GMV alterations, which may be linked with their manifestation of childhood ADHD.

Progressive symptom-associated prefrontal volume loss occurs in first-episode schizophrenia but not in affective psychosis.

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal-retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

Age sensitive associations of adolescent substance use with amygdalar, ventral striatum, and frontal volumes in young adulthood

IntroductionThis study evaluated an age sensitive model of substance use across adolescence to determine if substance use was associated with smaller volumes for an earlier developing brain region, the amygdala, a later developing region, the inferior frontal gyrus, and the ventral striatum. MethodParticipants (N = 110) were African American young adults who were members of a longitudinal cohort across childhood and adolescence. Measures of substance use were collected across early (ages 12–15 yrs.), middle (ages 16–18 yrs.), and later (ages 19–21 yrs.) adolescence; then, at age 25, a representative subset of the sample completed magnetic resonance imaging (MRI) that assessed regional brain volumes. ResultsHigher levels of substance use during early adolescence, but not middle or later adolescence, were significantly associated with smaller amygdalar volume in young adulthood. Higher levels of substance use during middle adolescence, but not early or later adolescence, were significantly associated with smaller pars opercularis volume. Substance use was not associated with the pars triangularis or ventral striatum. ConclusionThese findings support age sensitive associations between substance use and smaller gray matter volumes at age 25 and are consistent with literature supporting the differential nature of substance use and brain maturation across adolescence and into young adulthood.

Community violence exposure correlates with smaller gray matter volume and lower IQ in urban adolescents

Adolescents' exposure to community violence is a significant public health issue in urban settings and has been associated with poorer cognitive performance and increased risk for psychiatric illnesses, including PTSD. However, no study to date has investigated the neural correlates of community violence exposure in adolescents. Sixty-five healthy adolescents (age = 14-18 years; 36 females, 29 males) from moderate- to high-crime neighborhoods in Los Angeles reported their violence exposure, parents' education level, and free/reduced school lunch status (socio-economic status, SES), and underwent structural neuroimaging and intelligence testing. Violence exposure negatively correlated with measures of SES, IQ, and gray matter volume. Above and beyond the effect of SES, violence exposure negatively correlated with IQ and with gray matter volume in the left inferior frontal gyrus and anterior cingulate cortex, regions involved in high-level cognitive functions and autonomic modulation, and previously shown to be reduced in PTSD and combat-exposed military populations. The current results provide first evidence that frontal brain regions involved in cognition and affect appear to be selectively affected by exposure to community violence, even in healthy nondelinquent adolescents who are not the direct victims or perpetrators of violence.

Mitochondrial dysfunction in myotonic dystrophy type 1

The pathophysiological mechanism linking the nucleotide expansion in the DMPK gene to the clinical manifestations of myotonic dystrophy type 1 (DM1) is still unclear. In vitro studies demonstrate DMPK involvement in the redox homeostasis of cells and the mitochondrial dysfunction in DM1, but in vivo investigations of oxidative metabolism in skeletal muscle have provided ambiguous results and have never been performed in the brain. Twenty-five DM1 patients (14M, 39 ± 11years) underwent brain proton MR spectroscopy (1H-MRS), and sixteen cases (9M, 40 ± 13 years old) also calf muscle phosphorus MRS (31P-MRS). Findings were compared to those of sex- and age-matched controls. Eight DM1 patients showed pathological increase of brain lactate and, compared to those without, had larger lateral ventricles (p < 0.01), smaller gray matter volumes (p < 0.05) and higher white matter lesion load (p < 0.05). A reduction of phosphocreatine/inorganic phosphate (p < 0.001) at rest and, at first minute of exercise, a lower [phosphocreatine] (p = 0.003) and greater [ADP] (p = 0.004) were found in DM1 patients compared to controls. The post-exercise indices of muscle oxidative metabolism were all impaired in DM1, including the increase of time constant of phosphocreatine resynthesis (TC PCr, p = 0.038) and the reduction of the maximum rate of mitochondrial ATP synthesis (p = 0.033). TC PCr values correlated with the myotonic area score (ρ = 0.74, p = 0.01) indicating higher impairment of muscle oxidative metabolism in clinically more affected patients. Our findings provide clear in vivo evidence of multisystem impairment of oxidative metabolism in DM1 patients, providing a rationale for targeted treatment enhancing energy metabolism.

Neural correlates of impaired self-regulation in male youths with autism spectrum disorder: A voxel-based morphometry study

Although recent studies revealed impaired self-regulation (dysregulation) in autism spectrum disorder (ASD), neural correlates of dysregulation and its impacts on autistic neuroanatomy remain unclear. Voxel-based morphometry was applied on structural MRI images in 81 ASD and 61 typically developing (TD) boys aged 7–17years. Dysregulation was defined by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales in the Child Behavior Checklist>180. There were 53 and 28 boys in the ASD+Dysregulation and ASD-Dysregulation groups, respectively. First, we compared regional gray matter (GM) volume for ASD and TD. Second, we investigated regional GM volumetric differences among the ASD+Dysregulation, ASD-Dysregulation and TD groups. Lastly, shared and distinct neurostructural correlates of dysregulation were investigated in the ASD and TD groups. The ASD-TD difference on neuroanatomy no longer existed after controlling the dysregulation severity. ASD+Dysregulation had larger regional GM volumes in the right fusiform gyrus, and smaller GM volumes in the anterior prefrontal cortex than ASD-Dysregulation and TD, respectively. ASD+Dysregulation had smaller GM volumes in the left lateral occipital/superior parietal cortex than TD boys. No GM difference was identified between ASD-Dysregulation and TD. ASD and TD had a shared association between GM volumes in the orbitofrontal cortex and dysregulation levels. Our findings suggest that atypical neuroanatomy associated with ASD might partially reflect a disproportionate level of impaired self-regulation. Categorical and dimensional considerations of dysregulation should be implemented in future ASD studies.

Brain and heart magnetic resonance imaging/spectroscopy in duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive and irreversible loss of muscular function. As muscular disease progresses, the repair mechanisms cannot compensate for cellular damage, leading inevitably to necrosis and progressive replacement by fibrous and fatty tissue. Cardiomyopathy and respiratory failure are the main causes of death in DMD. In addition to the well-described muscle and heart disease, cognitive dysfunction affects around 30% of DMD boys. Myocardial fibrosis, assessed by late gadolinium enhancement (LGE), using cardiovascular magnetic resonance imaging (CMR), is an early marker of heart involvement in both DMD patients and female carriers. In parallel, brain MRI identifies smaller total brain volume, smaller grey matter volume, lower white matter fractional anisotropy and higher white matter radial diffusivity in DMD patients. The in vivo brain evaluation of mdx mice, a surrogate animal model of DMD, showed an increased inorganic phosphate (P(i))/phosphocreatine (PCr) and pH. In this paper, we propose a holistic approach using techniques of magnetic resonance imaging, spectroscopy and diffusion tensor imaging as a tool to create a "heart and brain imaging map" in DMD patients that could potentially facilitate the patients' risk stratification and also future research studies in the field.

Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus

Relationships between early kidney disease, neurocognitive function, and brain anatomy are poorly defined in African Americans with type 2 diabetes mellitus (T2DM). Cross-sectional associations were assessed between cerebral anatomy and cognitive performance with estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) in African Americans with T2DM. African Americans with cognitive testing and cerebral magnetic resonance imaging (MRI) in the African American-Diabetes Heart Study Memory in Diabetes (AA-DHS MIND; n=512; 480 with MRI) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) MIND (n=484; 104 with MRI) studies. eGFR (CKD-EPI creatinine equation), spot UACR. MRI-based cerebral white matter volume (WMV), gray matter volume (GMV), and white matter lesion volume; cognitive performance (Mini-Mental State Examination, Digit Symbol Coding, Stroop Test, and Rey Auditory Verbal Learning Test). Multivariable models adjusted for age, sex, body mass index, scanner, intracranial volume, education, diabetes duration, hemoglobin A1c concentration, low-density lipoprotein cholesterol concentration, smoking, hypertension, and cardiovascular disease were used to test for associations between kidney phenotypes and the brain in each study; a meta-analysis was performed. Mean participant age was 60.1±7.9 (SD) years; diabetes duration, 12.1±7.7 years; hemoglobin A1c concentration, 8.3%±1.7%; eGFR, 88.7±21.6mL/min/1.73m2; and UACR, 119.2±336.4mg/g. In the fully adjusted meta-analysis, higher GMV associated with lower UACR (P<0.05), with a trend toward association with higher eGFR. Higher white matter lesion volume was associated with higher UACR (P<0.05) and lower eGFR (P<0.001). WMV was not associated with either kidney parameter. Higher UACR was associated with lower Digit Symbol Coding performance (P<0.001) and a trend toward association with higher Stroop interference; eGFR was not associated with cognitive tests. Cross-sectional; single UACR measurement. In African Americans with T2DM, mildly high UACR and mildly low eGFR were associated with smaller GMV and increased white matter lesion volume. UACR was associated with poorer processing speed and working memory.

Volumetric magnetic resonance imaging analysis in patients with short-term remission of Cushing's disease.

The data on patients with short-term remission of Cushing's disease (CD) might provide information that is not available from previous long-term remission studies. We aimed to investigate structural changes in the brain in these patients and to examine whether these changes were associated with clinical characteristics. A cross-sectional study was performed. Thirty-four patients with CD (14 with CD in short-term remission and 20 with active CD) and 34 controls matched for age, sex and education underwent clinical evaluation and magnetic resonance imaging brain scans. Biometric measurements, disease duration and remission duration data were collected. Grey matter volumes in the whole brain were examined using voxel-based morphometry (VBM). No differences were observed in the grey matter volumes of the medial frontal gyrus (MFG) and cerebellum between the patients with remitted CD and healthy controls, whereas patients with active CD had smaller grey matter volumes in these two regions compared with controls and patients with remitted CD. Furthermore, significant correlations were found between remission time and grey matter values in these regions in short-term remission patients with CD. Additionally, greater grey matter volumes in the bilateral caudate of short-term remission patients with CD were observed. Trends for structural restoration were found in CD patients with short-term remission. This finding was associated with the number of days elapsed since curative surgery and the current age of the patients. This study enhances our understanding of potential reversibility after the resolution of hypercortisolism in CD patients.

Regional Gray Matter Volumes as Related to Psychomotor Slowing in Adults with Type 1 Diabetes.

Psychomotor slowing is a common cognitive complication in type 1 diabetes (T1D), but its neuroanatomical correlates and risk factors are unclear. In nondiabetic adults, smaller gray matter volume (GMV) and presence of white matter hyperintensities are associated with psychomotor slowing. We hypothesize that smaller GMV in prefronto-parietal regions explains T1D-related psychomotor slowing. We also inspect the contribution of microvascular disease and hyperglycemia. GMV, white matter hyperintensities (WMH), and glucose levels were measured concurrently with a test of psychomotor speed (Digit Symbol Substitution Test [DSST]) in 95 adults with childhood-onset T1D (mean age/duration = 49/41 years) and 135 similarly aged non-T1D adults. Linear regression models tested associations between DSST and regional GMV, controlling for T1D, sex, and education; a bootstrapping method tested whether regional GMV explained between-group differences in DSST. For the T1D cohort, voxel-based and a priori regions-of-interest methods further tested associations between GMV and DSST, adjusting for WMH, hyperglycemia, and age. Bilateral putamen, but no other regions examined, significantly attenuated DSST differences between the cohorts (bootstrapped unstandardized indirect effects: -3.49, -3.26; 95% confidence interval = -5.49 to -1.80, -5.29 to -1.44, left and right putamen, respectively). Among T1D, DSST was positively associated with GMV of bilateral putamen and left thalamus. Neither WMH, hyperglycemia, age, nor other factors substantially modified these relationships. For middle-aged adults with T1D and cerebral microvascular disease, GMV of basal ganglia may play a critical role in regulating psychomotor speed, as measured via DSST. Studies to quantify the impact of basal ganglia atrophy concurrent with WMH progression on psychomotor slowing are warranted.