Sulcal Cerebrospinal Fluid Research Articles

Abnormal brain structure mediates the association between ApoE4 and slow gait among patients with pathological cognitive impairment: Results from the Ontario Neurodegenerative Research Initiative

AbstractBackgroundPresence of at least one copy of the polymorphic apolipoprotein E ε4 allele (ApoE4) increases the risk of impairments of gait performance, particularly in elderly individuals with cognitive impairment or at risk of dementia; however, its underlying neural mechanism are unclear. This study examined the association among ApoE4, gait performance, and brain structural changes among elderly individuals with cognitive impairment.MethodOverall, 269 older adults with Alzheimer’s disease, cerebrovascular disease with and without cognitive impairment, and mild cognitive impairment were included from the Ontario Neurodegenerative Disease Research Initiative, who were either ApoE4 carriers (n=98) or non‐ApoE4 (n=171) carriers. Gait speed was measured using an electronic walkway; speed <1 m/s was defined as slow gait. Participants were stratified into four groups according to the presence of at least one copy of ApoE4 and slow gait. Region of interest volumes were derived by automated segmentation using a 3.0T magnetic resonance imaging system.ResultAmong ApoE4 carriers, 65 (24.2%) participants had slow gait. ApoE4 carriers with slow gait showed significantly higher burden of white matter hyperintensities compared with ApoE4 carriers without slow gait. Moreover, they had significantly lower hippocampal volume and greater total sulcal cerebrospinal fluid volume compared with non‐ApoE4 carriers with slow gait. These differences remained significant despite controlling for covariates (e.g., demographic and clinical characteristics, including participant type).ConclusionOur results suggest that brain structural changes, attributable to Alzheimer’s pathology, may mediate the association between ApoE4 and slow gait among elderly individuals with pathological cognitive impairment.

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus.

Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

Automated detection of imaging features of disproportionately enlarged subarachnoid space hydrocephalus using machine learning methods.

ObjectiveCreate an automated classifier for imaging characteristics of disproportionately enlarged subarachnoid space hydrocephalus (DESH), a neuroimaging phenotype of idiopathic normal pressure hydrocephalus (iNPH).Methods1597 patients from the Mayo Clinic Study of Aging (MCSA) were reviewed for imaging characteristics of DESH. One core feature of DESH, the presence of tightened sulci in the high-convexities (THC), was used as a surrogate for the presence of DESH as the expert clinician-defined criterion on which the classifier was trained. Anatomical MRI scans were automatically segmented for cerebrospinal fluid (CSF) and overlaid with an atlas of 123 named sulcal regions. The volume of CSF in each sulcal region was summed and normalized to total intracranial volume. Area under the receiver operating characteristic curve (AUROC) values were computed for each region individually, and these values determined feature selection for the machine learning model. Due to class imbalance in the data (72 selected scans out of 1597 total scans) adaptive synthetic sampling (a technique which generates synthetic examples based on the original data points) was used to balance the data. A support vector machine model was then trained on the regions selected.ResultsUsing the automated classification model, we were able to classify scans for tightened sulci in the high convexities, as defined by the expert clinician, with an AUROC of about 0.99 (false negative ≈ 2%, false positive ≈ 5%). Ventricular volumes were among the classifier's most discriminative features but are not specific for DESH. The inclusion of regions outside the ventricles allowed specificity from atrophic neurodegenerative diseases that are also accompanied by ventricular enlargement.ConclusionAutomated detection of tight high convexity, a key imaging feature of DESH, is possible by using support vector machine models with selected sulcal CSF volumes as features.

The Impact of Covert Lacunar Infarcts and White Matter Hyperintensities on Cognitive and Motor Outcomes After Stroke

Background and AimsIn addition to overt stroke lesions, co-occurring covert lesions, including white matter hyperintensities (WMH) and covert lacunar infarcts (CLI), contribute to poststroke outcome. The purpose of this study was to examine the relationship between covert lesions, and motor and cognitive outcomes in individuals with chronic stroke. MethodsVolumetric quantification of clinically overt strokes, covert lesions (periventricular and deep: pWMH, dWMH, pCLI, dCLI), ventricular and sulcal CSF (vCSF, sCSF), and normal appearing white (NAWM) and gray matter (NAGM) was performed using structural magnetic resonance imaging. We assessed motor impairment and function, and global cognition, memory, and other cognitive domains. When correlation analysis identified more than one MR parameter relating to stroke outcomes, we used regression modeling to identify which factor had the strongest impact. ResultsNeuropsychological and brain imaging data were collected from 30 participants at least 6 months following a clinically diagnosed stroke. Memory performance related to vCSF (r = −0.52, P = .004). The strongest predictor of nonmemory domains was pCLI (r2 = 0.28, P = .004). Motor impairment and function were most strongly predicted by the volume of stroke and NAWM (r2 = 0.36; P = .001), and dWMH (r2 = 0.39; P = .001) respectively. ConclusionsCovert lesion type and location have important consequences for post-stroke cognitive and motor outcome. Limiting the progression of covert lesions in aging populations may enhance the degree of recovery post-stroke.

Quantitative Diffusion Tensor Tractography of the Superior Thalamic Radiation and the Corticospinal tract in relation to Ventricular and Sulcal CSF Volumes in Patients with Ventriculomegaly Diagnosed with Normal Pressure Hydrocephalus (P4.192)

Quantitative Diffusion Tensor Tractography of the Superior Thalamic Radiation and the Corticospinal tract in relation to Ventricular and Sulcal CSF Volumes in Patients with Ventriculomegaly Diagnosed with Normal Pressure Hydrocephalus (P4.192)

DISPROPORTIONATE INCREASE IN VENTRICULAR RELATIVE TO SULCAL CEREBROSPINAL FLUID VOLUME AND COGNITIVE FUNCTIONING: THE SMART-MR STUDY

Global cerebral volume loss is associated with neurodegenerative diseases but also with normal aging. To understand their etiology studies aim to pinpoint specific brain tissue regions that are affected early in the disease process or investigate disproportionate volume loss of specific brain tissue regions. Here, we take a different perspective by examining the disproportionate increase in ventricular relative to sulcal cerebrospinal fluid (CSF) and the association with age and cognitive functioning. Within the SMART-MR study a 1.5T MRI was performed in 1232 patients with vascular disease (mean age 58±10 years, 80% male). Automated brain segmentation was used to quantify brain tissue volumes, CSF and lesions. The ventricular-sulcal CSF (VS) ratio was calculated by dividing ventricular volume by sulcal CSF volume. Z-scores for the domains memory and executive functioning were calculated. Multiple linear regression analysis was used to estimate the associations of VS ratio with age and with memory performance and executive functioning. The mean ventricular and sulcal CSF volumes were 31±15ml and 276±43ml, respectively. The VS ratio was 0.11±0.05. Pearson correlation coefficients between the natural log-transformed VS ratio and total brain volume, intracranial volume, brain parenchymal fraction, log-deep WMH, log-periventricular WMH, and age were 0.02 (p=0.52), 0.18, -0.40, 0.21, 0.33, and 0.35, respectively (p-values <0.0001). The VS ratio increased with older age (p<0.0001) independent of sex, total WMH, and ICV. It was also significantly associated with poorer memory performance (b of Z-score=-1.29; 95% CI -2.41 to -0.17) and poorer executive functioning (b of Z-score=-1.72; 95% CI -2.78 to -0.67), adjusted for age, sex, log-WMH, and ICV. In this population, a disproportionate increase in ventricular volume relative to sulcal CSF is associated with older age and with poorer memory and executive functioning. Future studies should investigate to what extent this is a biomarker of accelerated cognitive aging.

Diffusion Tensor Imaging-Defined Sulcal Enlargement Is Related to Cognitive Impairment in Multiple Sclerosis.

Cerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricular CSF and subarachnoid space (sulcal CSF). Changes in CSF volumetry are seen in many neurological conditions including multiple sclerosis (MS) and found to correlate with clinical outcomes. We aimed to test the relation between the volumetry of sulcal and ventricular CSF and cognitive impairment (CI) based on the minimal assessment of cognitive function in MS (MACFIMS) in patients with MS. Forty-six patients with MS underwent the MACFIMS battery and classified as nonimpaired (MSNI) (n = 10) and cognitively impaired (MSCI) (n = 30) and borderline (MSBD) MS patients (n = 6). Volumes of sulcal and ventricular CSF along with global gray and white matter volumes and cortical thickness were obtained by diffusion tensor imaging (DTI) and T1-weighted (T1w)-based segmentation. These measures were statistically analyzed for associations with CI after adjusting for the age, education in years, lesion load, and disease duration. Sulcal CSF showed the strongest correlation with CI (r = .51, P = .001) in our cohort, whereas ventricular CSF (P = .28, P = .19) along with cortical thickness and gray matter volume failed to show a significant correlation. Group analyses unadjusted for multiple comparisons showed significant difference in volumes of sulcal CSF and ventricular CSF between MSNI and MSCI groups (P < .05). Sulcal CSF correlates with CI in patients with MS, possibly explained by cortical atrophy. DTI/T1w-based sulcal CSF segmentation method might be used as an indirect and simple neuroimaging marker to monitor CI in MS patients.

Apolipoprotein E ε4 genotype status is not associated with neuroimaging outcomes in a large cohort of HIV+ individuals.

Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM), and basal ganglia were examined. Secondary analyses explored this relationship separately in individuals ≥50years old (n = 173) and <50years old (n = 63). No significant differences were observed between ApoE ε4+ (ApoE ε3/ε4 and ApoE ε4/ε4) individuals (n = 69) and ApoE ε4- (ApoE ε2/ε3 and ApoE ε3/ε3) individuals (n = 167). When individuals were further divided by age, no significant genotype group differences were identified in individuals <50 or ≥50years of age on any neuroimaging outcome. The ApoE ε4 allele did not affect brain integrity in this large, diverse sample of HIV+ individuals. The effects of ApoE ε4 may not be apparent until more advanced ages and may be more prominent when present along with other risk factors for neuronal damage.

Structural brain differences in alcohol-dependent individuals with and without comorbid substance dependence

BackgroundOver 50% of individuals with alcohol use disorders (AUD) also use other substances; brain structural abnormalities observed in alcohol dependent individuals may not be entirely related to alcohol consumption. This MRI study assessed differences in brain regional tissue volumes between short-term abstinent alcohol dependent individuals without (ALC) and with current substance use dependence (polysubstance users, PSU). MethodsNineteen, one-month-abstinent PSU and 40 ALC as well as 27 light-drinkers (LD) were studied on a 1.5T MR system. Whole brain T1-weighted images were segmented automatically into regional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes. MANOVA assessed group differences of intracranial volume-normalized tissue volumes of the frontal, parietal, occipital, and temporal lobes and regional subcortical GM volumes. The volumetric measures were correlated with neurocognitive measures to assess their functional relevance. ResultsDespite similar lifetime drinking and smoking histories, PSU had significantly larger normalized WM volumes than ALC in all lobes. PSU also had larger frontal and parietal WM volumes than LD, but smaller temporal GM volumes and smaller lenticular and thalamic nuclei than LD. ALC had smaller frontal, parietal, and temporal GM, thalamic GM and cerebellar volumes than LD. ALC had more sulcal CSF volumes than both PSU and LD. ConclusionOne-month-abstinent ALC and PSU exhibited different patterns of gross brain structural abnormalities. The larger lobar WM volumes in PSU in the absence of widespread GM volume loss contrast with widespread GM atrophy in ALC. These structural differences may demand different treatment approaches to mitigate specific functionally relevant brain abnormalities.

Brain morphometric correlates of metabolic variables in HIV: the CHARTER study.

Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.

Dynamic oxygen-enhanced MRI of cerebrospinal fluid.

Oxygen causes an increase in the longitudinal relaxation rate of tissues through its T1-shortening effect owing to its paramagnetic properties. Due to such effects, MRI has been used to study oxygen-related signal intensity changes in various body parts including cerebrospinal fluid (CSF) space. Oxygen enhancement of CSF has been mainly studied using MRI sequences with relatively longer time resolution such as FLAIR, and T1 value calculation. In this study, fifteen healthy volunteers were scanned using fast advanced spin echo MRI sequence with and without inversion recovery pulse in order to dynamically track oxygen enhancement of CSF. We also focused on the differences of oxygen enhancement at sulcal and ventricular CSF. Our results revealed that CSF signal after administration of oxygen shows rapid signal increase in both sulcal CSF and ventricular CSF on both sequences, with statistically significant predominant increase in sulcal CSF compared with ventricular CSF. CSF is traditionally thought to mainly form from the choroid plexus in the ventricles and is absorbed at the arachnoid villi, however, it is also believed that cerebral arterioles contribute to the production and absorption of CSF, and controversy remains in terms of the precise mechanism. Our results demonstrated rapid oxygen enhancement in sulcal CSF, which may suggest inhaled oxygen may diffuse into sulcal CSF space rapidly probably due to the abundance of pial arterioles on the brain sulci.

Brain volumes and risk of cardiovascular events and mortality. The SMART-MR study

Brain atrophy is a strong predictor for cognitive decline and dementia, and these are, in turn, associated with increased mortality in the general population. Patients with cardiovascular disease have more brain atrophy and a higher morbidity and mortality. We investigated if brain volumes on magnetic resonance imaging were associated with the risk of cardiovascular events and mortality in patients with manifest arterial disease (n = 1215; mean age 58 years). Automated brain segmentation was used to quantify intracranial volume, and volumes of total brain, sulcal cerebrospinal fluid, and ventricles. After a median follow-up of 8.3 years, 184 patients died, 49 patients had an ischemic stroke, and 100 patients had an ischemic cardiac complication. Smaller relative brain volumes increased the risk of all-cause death (hazard ratio [HR] per standard deviation decrease in total brain volume: 1.58, 95% confidence interval [95% CI]: 1.33–1.88), vascular death (HR 1.69, 95% CI: 1.35–2.13), and ischemic stroke (HR 1.96, 95% CI: 1.43–2.69), independent of cardiovascular risk factors. These results suggest that brain volumes are an important determinant of poor outcome in patients with high cardiovascular risk.

Comparison of 10 brain tissue segmentation methods using revisited IBSR annotations

Ground-truth annotations from the well-known Internet Brain Segmentation Repository (IBSR) datasets consider Sulcal cerebrospinal fluid (SCSF) voxels as gray matter. This can lead to bias when evaluating the performance of tissue segmentation methods. In this work we compare the accuracy of 10 brain tissue segmentation methods analyzing the effects of SCSF ground-truth voxels on accuracy estimations. The set of methods is composed by FAST, SPM5, SPM8, GAMIXTURE, ANN, FCM, KNN, SVPASEG, FANTASM, and PVC. Methods are evaluated using original IBSR ground-truth and ranked by means of their performance on pairwise comparisons using permutation tests. Afterward, the evaluation is repeated using IBSR ground-truth without considering SCSF. The Dice coefficient of all methods is affected by changes in SCSF annotations, especially on SPM5, SPM8 and FAST. When not considering SCSF voxels, SVPASEG (0.90 ± 0.01) and SPM8 (0.91 ± 0.01) are the methods from our study that appear more suitable for gray matter tissue segmentation, while FAST (0.89 ± 0.02) is the best tool for segmenting white matter tissue. The performance and the accuracy of methods on IBSR images vary notably when not considering SCSF voxels. The fact that three of the most common methods (FAST, SPM5, and SPM8) report an important change in their accuracy suggest to consider these differences in labeling for new comparative studies.

Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection

MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79% initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.

Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study

Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up.A total of 48 patients (13 females, mean age 15.9±1.5years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline.In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=−0.560, 95% CI: −0.270 to −0.850, r=−0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.

Eosinophilic meningoencephalitis caused by Angiostrongylus cantonesis

A 67-year-old man presented with fatigue, myalgia and progressive drowsiness for 10 days and finally slipped into a coma. Neurological examinations showed mild neck stiffness, increased deep tendon reflex in his four limbs and bilateral positive Babinski's sign. Blood count analysis showed 15 530 leukocytes/μl with 22.2% eosinophils. His cerebrospinal fluid (CSF) contained 550 leukocytes/μl with 74% eosinophils, glucose of 62 mg/dl (normal range: 40–80 mg/dl) and protein of 150 mg/dl (normal range: 15–45 mg/dl). The serum and CSF surveys for bacteria, herpes simplex virus, cytomegalovirus, amoeba, fungus and tuberculosis were all negative. An electroencephalogram (EEG) showed diffuse cortical dysfunction particularly involving the bilateral frontoparietal lobes. The chest X-ray was unremarkable. Magnetic resonance imaging (MRI) of the brain showed abnormal hyperintensity in the sulcal CSF spaces on T2-fluid-attenuated inversion recovery (T2-FLAIR) images, suggestive of meningitis. Also noted were multifocal disoriented linear and nodular T2-hyperintense lesions in the bilateral cerebral white matter (Figure 1). 99mTc-ethylene …

Brain Volume Shrinkage Parallels Rise in Antipsychotic Drug Dosage

Brain Volume Shrinkage Parallels Rise in Antipsychotic Drug Dosage

Clinical factors related to brain structure in HIV: the CHARTER study

Despite the widening use of combination antiretroviral therapy (ART), neurocognitive impairment remains common among HIV-infected (HIV+) individuals. Associations between HIV-related neuromedical variables and magnetic resonance imaging indices of brain structural integrity may provide insight into the neural bases for these symptoms. A diverse HIV+ sample (n = 251) was studied through the CNS HIV Antiretroviral Therapy Effects Research initiative. Multi-channel image analysis produced volumes of ventricular and sulcal cerebrospinal fluid (CSF), cortical and subcortical gray matter, total cerebral white matter, and abnormal white matter. Cross-sectional analyses employed a series of multiple linear regressions to model each structural volume as a function of severity of prior immunosuppression (CD4 nadir), current CD4 count, presence of detectable CSF HIV RNA, and presence of HCV antibodies; secondary analyses examined plasma HIV RNA, estimated duration of HIV infection, and cumulative exposure to ART. Lower CD4 nadir was related to most measures of the structural brain damage. Higher current CD4, unexpectedly, correlated with lower white and subcortical gray and increased CSF. Detectable CSF HIV RNA was related to less total white matter. HCV coinfection was associated with more abnormal white matter. Longer exposure to ART was associated with lower white matter and higher sulcal CSF. HIV neuromedical factors, including lower nadir, higher current CD4 levels, and detectable HIV RNA, were associated with white matter damage and variability in subcortical volumes. Brain structural integrity in HIV likely reflects dynamic effects of current immune status and HIV replication, superimposed on residual effects associated with severe prior immunosuppression.

Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics

Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a second haplotype tagging SNP, rs10370, were genotyped. The q-value package was used to correct for multiple comparisons. In the alcoholics, cerebrospinal fluid and intra-cranial volumes showed significant differences across the six diplotype categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was associated with lowest gray matter ratio (greater shrinkage; p=0.005). Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p=0.03) but not in alcoholics above this level. White matter ratio was associated with sex (p=0.002) and lifetime total alcohol consumption (p=0.01) but not with diplotypes. In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure. The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme.

Ventricular dilation: Association with gait and cognition

Normal pressure hydrocephalus is characterized by gait impairment, cognitive impairment, and urinary incontinence, and is associated with disproportionate ventricular dilation. Here we report the distribution of ventricular volume relative to sulcal cerebrospinal fluid (CSF) volume, and the association of increasing ventricular volume relative to sulcal CSF volume with a cluster of gait impairment, cognitive impairment, and urinary incontinence in a stroke-free cohort of elderly persons from the general population. Data are based on 858 persons (35.4% men; age range, 66-92 years) who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study. Gait was evaluated with an assessment of gait speed. Composite scores representing speed of processing, memory, and executive function were constructed from a neuropsychological battery. Bladder function was assessed with a questionnaire. Magnetic resonance brain imaging was followed by semiautomated segmentation of intracranial CSF volume. White matter hyperintensity (WMH) volume was assessed with a semiquantitative scale. For the analysis of ventricular dilation relative to the sulcal spaces, ventricular volume was divided by sulcal CSF volume (VV/SV). Disproportion between ventricular and sulcal CSF volume, defined as the highest quartile of the VV/SV z score, was associated with gait impairment (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3) and cognitive impairment (OR, 1.8; 95% CI, 1.1-3.0). We did not find an association between the VV/SV z score and bladder dysfunction. The prevalence and severity of gait impairment and cognitive impairment increases with ventricular dilation in persons without stroke from the general population, independent of WMH volume.