Gray Matter Volume Loss Research Articles

Longitudinal evaluation of resting-state connectivity, white matter integrity and cortical thickness in stable HIV infection: Preliminary results.

Purpose The objectives of this study were to determine if HIV-infected patients treated with highly active antiretroviral therapy (HAART), without dementia, suffer from longitudinal gray matter (GM) volume loss, changes in white matter (WM) integrity and deterioration in functional connectivity at rest, in an average interval of 30 months. Methods Clinically stable HIV-positive patients (on HAART, CD4 + T lymphocyte > 200 cells/μl, and viral loads <50 copies/μl) were recruited. None of them had HIV-associated dementia. Each patient underwent two scans, performed in a 1.5-T magnetic resonance imaging (MRI) scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of GM structures. WM integrity was assessed using tract-based spatial statistics to post-process diffusion tensor imaging data, and FMRIB's Software Library tools were used to post-process resting-state functional magnetic resonance imaging (RS-fMRI). Results There were no significant differences in cortical thickness, deep GM volumes, or diffusivity parameters between the scans at the two time points. Five resting-state networks were identified in our patients. In the second MRI, HIV-positive patients presented increased areas of functional connectivity in visual pathways, frontoparietal and cerebellar networks, compared with the first MRI (considering p < 0.05). Conclusions RS-fMRI revealed potentially compensatory longitudinal alterations in the brains of HIV-positive patients, attempting to compensate for brain damage related to the infection.

Structure-function correlations in Retinitis Pigmentosa patients with partially preserved vision: a voxel-based morphometry study

Retinitis Pigmentosa is a group of hereditary retinal dystrophy disorders associated with progressive peripheral visual field loss. The impact of this retinal loss in cortical gray matter volume has not been addressed before in Retinitis Pigmentosa patients with low vision. Voxel-based morphometry was applied to study whole brain gray matter volume changes in 27 Retinitis Pigmentosa patients with partially preserved vision and 38 age- and gender-matched normally sighted controls to determine whether peripheral visual loss can lead to changes in gray matter volume. We found significant reductions in gray matter volume that were restricted to the occipital cortex of patients. The anteromedial pattern of reduced gray matter volume in visual primary and association cortices was significantly correlated with the extent of the peripheral visual field deficit in this cohort. Moreover, this pattern was found to be associated with the extent of visual field loss. In summary, we found specific visual cortical gray matter loss in Retinitis Pigmentosa patients associated with their visual function profile. The spatial pattern of gray matter loss is consistent with disuse-driven neuronal atrophy which may have clinical implications for disease management, including prosthetic restoration strategies.

P 1 Effect of ocrelizumab on magnetic resonance imaging markers of neurodegeneration in patients with relapsing multiple sclerosis – analysis of the phase III, double-blind, double-dummy, interferon beta-1a- controlled OPERA I and OPERA II studies

Background Ocrelizumab (OCR) is a humanised monoclonal antibody that selectively targets CD20+B cells. The pathogenesis of multiple sclerosis (MS), including neurodegeneration, is thought to be influenced by B cells. Volumetric magnetic resonance imaging (MRI) measurements can be used to assess neurodegeneration. Objective To evaluate the effect of OCR vs interferon beta-1a (IFN β -1a) on brain MRI markers of neurodegeneration in patients with relapsing MS enrolled in two identical Phase III, randomised, double-blind, double-dummy trials (OPERA I and OPERA II). Methods In OPERA I and OPERA II, patients were randomised (1:1) to receive OCR 600 mg via intravenous infusion every 24 weeks or subcutaneous IFN β -1a 44 μ g three-times weekly over 96 weeks. MRI endpoints thought to be related to neurodegeneration included the change in whole brain volume, change in cortical grey matter volume and change in cerebral white matter volume. Results Compared with IFN β -1a, OCR reduced the rate of whole brain volume loss from baseline to Week 96 by 23.5% ( p p = 0.0001), and from Week 24 to Week 96 by 22.8% ( p = 0.0042) and 14.9% ( p = 0.0900) in OPERA I and OPERA II, respectively. OCR-treated patients showed a smaller mean percentage of cortical grey matter volume loss compared with IFN β -1a from baseline to Week 96, with a mean difference of 0.273% ( p = 0.0005) in OPERA I and 0.516% ( p β -1a from baseline to Week 96, with a mean difference of 0.261% ( p = 0.0024); in OPERA II, there was no difference ( p = 0.2748) in cerebral white matter volume loss in patients treated with OCR compared with IFN β -1a from baseline to Week 96. Conclusion The rate of neurodegeneration as measured by whole brain, cortical grey and cerebral white matter volume loss on MRI was reduced by OCR compared with IFN β -1a in patients with relapsing MS over 96 weeks. This study is sponsored by F. Hoffmann-La Roche Ltd.

A specific pattern of gray matter atrophy in Alzheimer's disease with depression.

Considering the high incidence of depressive symptoms in Alzheimer's disease (AD), we conducted a large-sample study to investigate the pattern of gray matter (GM) abnormalities that differentiates depressive from non-depressive AD patients. We included 201 AD patients who underwent MRI assessment and categorized them into depressive and non-depressive subgroups based on the Geriatric Depression Scale (GDS; cut-off score: ≤9). We performed whole-brain voxel-based morphometry analysis in 173 patients after MRI quality control and used between-group comparisons and regression analysis models to analyze the volumetric data controlling for nuisance variables. Depressive AD patients had extensive GM volume loss mainly in the paracentral region, specifically in post- and pre-central gyrus, supplementary motor areas and thalamus compared to non-depressive patients. Similar findings were obtained for the group of 173 patients using regression analysis and GDS score as predictor variable. We provided the first clear demonstration of a unique pattern of GM atrophy that characterizes AD patients with depression which is consistent with regions implicated in the phenomenon of psychomotor retardation that characterizes depression.

Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion.

To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion (C9orf72RE). Presymptomatic C9orf72RE carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter. Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic C9orf72RE compared with HC. In a subgroup of C9orf72RE carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter. This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic C9orf72RE carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.

Association between change in brain gray matter volume, cognition, and depression severity: Pre- and post- antidepressant pharmacotherapy for late-life depression

Late-life depression (LLD) is associated with cognitive impairments and reduced gray matter volume (GMV); however the mechanisms underlying this association are not well understood. The goal of this study was to characterize changes in depression severity, cognitive function, and brain structure associated with pharmacologic antidepressant treatment for LLD. We administered a detailed neurocognitive battery and conducted structural magnetic resonance imaging (MRI) on 26 individuals with LLD, pre-/post-a 12-week treatment trial with venlafaxine. After calculating changes in cognitive performance, GMV, and depression severity, we calculated Pearson's correlations, performed permutation testing, and false discovery rate correction. We found that loss of GMV over 12 weeks in the superior orbital frontal gyrus was associated with less improvement in depression severity and that increased GMV in the same was associated with greater improvement in depression severity. We detected no associations between changes in cognitive performance and improvements in either depressive symptoms or changes in GMV.

Tracking Cognitive Decline in Amnestic Mild Cognitive Impairment and Early-Stage Alzheimer Dementia: Mini-Mental State Examination versus Neuropsychological Battery

Background/Aims: Although the Mini-Mental State Examination (MMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and neuropsychological batteries are widely used for evaluating cognitive function, it remains elusive which instrument best reflects the longitudinal disease progression in amnestic mild cognitive impairment (aMCI) and probable Alzheimer disease (AD). We investigated whether changes in these three instruments over time correlate with loss of cortical gray matter volume (cGMV). Methods: We retrospectively investigated 204 patients (aMCI, n = 114; AD, n = 90) who had undergone MMSE, CDR-SOB, the dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D), and 3-dimensional T1-weighted magnetic resonance images at least twice. We investigated the partial correlation between annual decline in test scores and percent change of cGMV. Results: In aMCI patients, changes in the SNSB-D total score (r = 0.340, p < 0.001) and CDR-SOB (r = 0.222, p = 0.020), but not MMSE, showed a correlation with cGMV loss, with the SNSB-D total score showing the strongest correlation. In AD patients, decline in all three test scores correlated significantly with cGMV loss, with MMSE exhibiting the strongest correlation (r = 0.464, p < 0.001). Conclusion: In aMCI patients, neuropsychological battery, though time-consuming, was the most adequate tool in tracking disease progression. In AD patients, however, MMSE may be the most effective longitudinal monitoring tool when considering cost-effectiveness.

PATTERNS OF GRAY MATTER VOLUME LOSS IN ALZHEIMER’S DISEASE WITH SLEEP DISTURBANCE

Previous studies using animal model and imaging modalities showed anatomical structures related to sleep physiology. Also recent researches revealed the relationship between sleep problems and cognitive dysfunction. Despite these evidences, there have been few studies of structural changes in Alzheimer's disease with sleep problems. We aimed to evaluate the effects of nighttime sleep on cognition and neuropsychological symptoms in AD, and to investigate whether there are differences of gray matter(GM) loss patterns between Alzheimer's disease (AD) with sleep problems (poor sleeper AD) and without sleep problems(good sleeper AD). We included consecutive 32 patients with AD and 14 controls. All of the participants underwent detailed neuropsychological evaluation using SNSB and NPI-K, the sleep characteristic questionnaire using Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) and 3D T1-weighted MRI at 3 Tesla. VBM analysis using FSL and hippocampal subfields volume analyses using Freesurfer were performed. AD patients showed significantly lower PSQI-K total score and higher NPI total score than controls (p<0.05). In AD, sleep latency was found to be negatively correlated with visual memory (p<0.05) after adjusting for age and education, while sleep duration was positively correlated with visual and verbal memory (p<0.05). Comparison of cognitive function showed worse performances of verbal memory and visual memory in poor sleeper AD (PSQI total score >5) than in good sleeper AD (p<0.05). GM volume was significantly reduced in bilateral cingulate gyrus in poor sleeper AD compared to good sleeper AD. Our results suggest that prolonged sleep duration and seep latency were correlated with cognitive dysfunction, especially memory dysfunction. GM volume loss in bilateral cingulate gyrus in poor sleeper AD support previous neuroimaging results in insomnia.

GLYCEMIC STATES MODULATE CORTICAL THICKNESS AND STRUCTURAL CONNECTIVITY IN OLD AGE

Diabetes mellitus (DM) is a common chronic disease and is known to increase risk of cognitive decline and dementia, including AD. The level of glycated hemoglobin (HbA1c) is positively associated with the risk of developing dementia. DM is associated with global gray matter volume loss, though this remains inconsistent across studies. Therefore, this study aims to investigate the associations between glycemic states, gray matter thickness, and white matter structural connectivity in a senior volunteer cohort. Twenty senior volunteers between the age of 60 and 80 were enrolled from local communities in Hualien, Taiwan. Venous blood was drawn from every participant, with glycemic indices including HbA1c, fasting glucose, and fasting insulin. From each participant, we obtained T1-weighted MRI (TR/TE=1.16/0.8 ms; flip angle =15°; matrix size =512x512; slice thickness =1.0 mm; final voxel size of 160.x60.5 mm) and diffusion tensor images (DTI) (3 mm axial slices, 256*256 matrix, 1*1 mm in-plane resolution, 30 directions) using a 3T GE scanner. Gray matter thickness was extracted from T1 scans, and fractional anisotropy (FA) and mean diffusivity (MD) were determined from DTI data. Both T1 and DTI data were co-registered to the MNI152 template. Correlation between these data and each of the glycemic indices was examined in regions previously shown to be susceptible to DM and AD using the Spearman correlation coefficient. Participants had a mean age of 66.5±5.0 years, and were 75% female. After controlling for age and gender, significant correlations were found between insulin with MD (ρ=-0.47, p=0.047) and cortical thickness of parahippocampus (ρ=0.56, p=0.02), HbA1c with MD (ρ=0.51, p=0.03) and cortical thickness of insular (ρ=0.52, p=0.02), and glucose with middle temporal cortical thickness (ρ=-0.49, p=0.04). Gray matter thickness and white matter structural connectivity are significantly correlated with glycemic state, particularly in the posterior regions related to AD and memory capacity. These correlations were strongest for fasting glucose and HbA1c, which may help explain cognitive decline in individuals with DM.

Impairments in Walking Ability, Dexterity, and Cognitive Function in Multiple Sclerosis Are Associated with Different Regional Cerebellar Gray Matter Loss.

Both histological and neuroimaging studies highlight the role of the cerebellum in multiple sclerosis (MS). There is at least some evidence for associations of cerebellar gray matter (GM) loss with motor and cognitive ability. We therefore correlated motor and cognitive ability scores (the multiple sclerosis functional composite MSFC) with regional cerebellar GM volumes. We used voxel-based morphometry (VBM) to assess the regional GM volume loss in a cohort of 45 MS patients. For the regression analysis, we used the clinical subscores of the multiple sclerosis functional composite (25-ft walk test (T25FW), nine-hole peg test (9HPT), paced auditory serial addition task (PASAT)). Decreased GM in distinct cerebellar areas was associated with different subscores of the MSFC in Larsell's lobule VI with the T25FW (t=5.16), in lobule IX with the 9HPT (t=3.95), and in lobule IX with the PASAT (t=4.81). Regional volume decrease in distinct cerebellar areas involved in motor and cognitive domains were associated with clinical impairment in these fields. Our data confirm the relationship between cerebellar GM volume loss and disability, extending the knowledge in the functional neuroanatomical perspective.

Frontotemporal lobar degeneration and social behaviour: Dissociation between the knowledge of its consequences and its conceptual meaning

Inappropriate social behaviour is an early symptom of frontotemporal lobar degeneration (FTLD) in both behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Knowledge of social behaviour is essential for appropriate social conduct. The superior anterior temporal lobe (ATL) has been identified as one key neural component for the conceptual knowledge of social behaviour, but it is unknown whether this is dissociable from knowledge of the consequences of social behaviour. Here, we used a newly-developed test of knowledge about long-term and short-term consequences of social behaviour to investigate its impairment in patients with FTLD relative to a previously-developed test of social conceptual knowledge. We included 19 healthy elderly control participants and 19 consecutive patients with features of bvFTD or SD and defined dissociations as performance differences between tasks for each patient (Bonferroni-corrected p < .05). Knowledge of long-term consequences was selectively impaired relative to short-term consequences in five patients and the reverse dissociation occurred in one patient. Six patients showed a selective impairment of social concepts relative to long-term consequences with the reverse dissociation occurring in one patient. These results corroborate the hypothesis that knowledge of long-term consequences of social behaviour is dissociable from knowledge of short-term consequences, as well as of social conceptual knowledge. Confirming our hypothesis, we found that patients with more marked grey matter (GM) volume loss in frontopolar relative to right superior ATL regions of interest exhibited poorer knowledge of the long-term consequences of social behaviour relative to the knowledge of its conceptual meaning and vice versa (n = 15). These findings support the hypothesis that frontopolar and ATL regions represent distinct aspects of social knowledge. This suggests that rather than being unable to suppress urges to behave inappropriately, FTLD patients often lose the knowledge of what appropriate social behaviour is and can therefore not be expected to behave accordingly.

Cortical brain volume abnormalities associated with few or multiple neuropsychiatric symptoms in Alzheimer's disease.

New research on assessing neuropsychiatric manifestations of Alzheimer´s Disease (AD) involves grouping neuropsychiatric symptoms into syndromes. Yet this approach is limited by high inter-subject variability in neuropsychiatric symptoms and a relatively low degree of concordance across studies attempting to cluster neuropsychiatric symptoms into syndromes. An alternative strategy that involves dichotomizing AD subjects into those with few versus multiple neuropsychiatric symptoms is both consonant with real-world clinical practice and can contribute to understanding neurobiological underpinnings of neuropsychiatric symptoms in AD patients. The aim of this study was to address whether the number of neuropsychiatric symptoms (i.e., presence of few [≤2] versus multiple [≥3] symptoms) in AD would be associated with degree of significant gray matter (GM) volume loss. Of particular interest was volume loss in brain regions involved in memory, emotional processing and salience brain networks, including the prefrontal, lateral temporal and parietal cortices, anterior cingulate gyrus, temporo-limbic structures and insula. We recruited 19 AD patients and 13 healthy controls, which underwent an MRI and neuropsychiatric assessment. Regional brain volumes were determined using voxel-based morphometry and other advanced imaging processing methods. Our results indicated the presence of different patterns of GM atrophy in the two AD subgroups relative to healthy controls. AD patients with multiple neuropsychiatric manifestations showed more evident GM atrophy in the left superior temporal gyrus and insula as compared with healthy controls. In contrast, AD subjects with few neuropsychiatric symptoms displayed more GM atrophy in prefrontal regions, as well as in the dorsal anterior cingulate ad post-central gyri, as compared with healthy controls. Our findings suggest that the presence of multiple neuropsychiatric symptoms is more related to the degree of atrophy in specific brain networks rather than dependent on the global severity of widespread neurodegenerative brain changes.

Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis

ObjectiveImaging is recommended to support the clinical diagnoses of dementias, yet imaging research studies rarely have pathological confirmation of disease. This study aims to characterise patterns of brain volume loss...

Resting-state connectivity and modulated somatomotor and default-mode networks in Huntington disease.

To analyze brain functional connectivity in the somatomotor and default-mode networks (DMNs) of patients with Huntington disease (HD), its relationship with gray matter (GM) volume loss, and functional changes after pridopidine treatment. Ten patients and ten untreated controls underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (fMRI); four patients were also assessed after 3months of pridopidine treatment (90mg/d). The seed-based functional connectivity patterns from the posterior cingulate cortex and the supplementary motor area (SMA), considered cortical hubs of the DMN and somatomotor networks, respectively, were computed. FMRIB Software Library voxel-based morphometry measured GM volume. Patients had GM volume decrease in all cortical and subcortical areas of the somatomotor network with preservation of the SMA, and increased somatomotor and DMN connectivity. In DMN structures, functional connectivity impairment preceded volume loss. Pridopidine reduced the intensity of these aberrant connections. The abnormal connectivity of the somatomotor and DMN observed in HD patients may represent an early dysfunction marker, as it preceded volume loss in DMN. Pridopidine reduced connectivity of these networks in all four treated patients, suggesting that connectivity is sensitive to treatment response.

Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging

BackgroundOmega-3 polyunsaturated fatty acids (n-3 PUFA) are structural components of the brain and are indispensable for neuronal membrane synthesis. Along with decline in cognition, decreased synaptic density and neuronal loss, normal aging is accompanied by a reduction in n-3 PUFA concentration in the brain in both humans and rodents. Recently, many clinical and experimental studies have demonstrated the importance of n-3 PUFA in counteracting neurodegeneration and age-related dysfunctions.MethodsMethods: This review will focus on the neuroprotective effects of n-3 PUFA on cognitive impairment, neuroinflammation and neurodegeneration during normal aging. Multiple pathways of n-3 PUFA preventive action will be examined.ResultsNamely, n-3 PUFA have been shown to increase the levels of several signaling factors involved in synaptic plasticity, thus leading to the increase of dendritic spines and synapses as well as the enhancement of hippocampal neurogenesis even at old age. In elderly subjects n-3 PUFA exert anti-inflammatory effects associated with improved cognitive functions. Interestingly, growing evidence highlights n-3 PUFA efficacy in preventing the loss of both gray and white matter volume and integrity.ConclusionThis review shows that n-3 PUFA are essential for a successful aging and appear as ideal cognitive enhancers to be implemented in nutritional interventions for the promotion of healthy aging.

Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

Peripheral apoE isoform levels in cognitively normal APOE \u03b53/\u03b54 individuals are associated with regional gray matter volume and cerebral glucose metabolism

BackgroundCarriers of the APOE ε4 allele are at increased risk of developing Alzheimer’s disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated.MethodsUsing quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE ε3/ε4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV).ResultsOur results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex.ConclusionsOur study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study.

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.