Parietal Gray Matter Research Articles

Can Apparent Diffusion Coefficient Predict the Clinical Outcome in Drowned Children?

IntroductionPediatric cerebral hypoxic-ischemic injury frequently results in severe neurological outcome. Imaging with diffusion-weighted magnetic resonance imaging (DWi) demonstrates that the acute cerebral injury and apparent diffusion coefficient (ADC) allow the assessment of the severity of brain damage. The main objective was to examine if spatial distribution of reductions in ADC values is associated with clinical outcome in drowned children. MethodsThis is a retrospective study of 7 children (7 examinations) suffering from a hypoxic-ischemic event who underwent DWi. Seven subjects with normal DWi served as controls. The mean patient age was 4.88 ± 2.93 years and the male-to-female ratio was 5:2. The neurological outcome was divided into 2 categories: 4 children with Apallic syndrome and 3 deaths. We analysed the differences between the drowned children and the control group regarding clinical data, DWi abnormalities, and ADC values. ResultsThe ADC values in the occipital and parietal grey matter were significantly different between the drowned children (765.14 ± 65.47 vs 920.95 ± 69.62; P = .003) and the control group (670.82 ± 233.99 vs 900.66 ± 92.72; P = .005). The ADC showed low values in the precentral area also (P = .044). ConclusionThe ADC reduction may be useful to predict the poor outcome in drowned children and can be a valuable tool for clinical assessment.

Interictal diffusion and perfusion magnetic resonance imaging features of cats with familial spontaneous epilepsy.

OBJECTIVE To evaluate the usefulness of diffusion and perfusion MRI of the cerebrum in cats with familial spontaneous epilepsy (FSECs) and identify microstructural and functional deficit zones in affected cats. ANIMALS 19 FSECs and 12 healthy cats. PROCEDURES Diffusion-weighted, diffusion tensor, and perfusion-weighted MRI of the cerebrum were performed during interictal periods in FSECs. Imaging findings were compared between FSECs and control cats. Diffusion (apparent diffusion coefficient and fractional anisotropy) and perfusion (relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF], and mean transit time) variables were measured bilaterally in the hippocampus, amygdala, thalamus, parietal cortex gray matter, and subcortical white matter. Asymmetry of these variables in each region was also evaluated and compared between FSECs and control cats. RESULTS The apparent diffusion coefficient of the total amygdala of FSECs was significantly higher, compared with that of control cats. The fractional anisotropy of the right side and total hippocampus of FSECs was significantly lower, compared with that of control cats. The left and right sides and total hippocampal rCBV and rCBF were significantly lower in FSECs than in control cats. The rCBV and rCBF of the parietal cortex gray matter in FSECs were significantly lower than in control cats. CONCLUSIONS AND CLINICAL RELEVANCE In FSECs, diffusion and perfusion MRI detected microstructural changes and hypoperfusion (lowered function) in the cerebrum during interictal periods from that of healthy cats. These findings indicated that diffusion and perfusion MRI may be useful for noninvasive evaluation of epileptogenic foci in cats.

Cortical features of distinct developmental trajectories in patients with delusional infestation

BackgroundAlthough there is strong neuroimaging evidence that cortical alterations are a core feature of schizophrenia spectrum disorders, it still remains unclear to what extent such abnormalities occur in monothematic delusional disorders. In individuals with delusional infestation (DI), the delusional belief to be infested with pathogens, previous structural MRI studies have shown prefrontal, temporal, parietal, insular, thalamic and striatal gray matter volume changes. Differential contributions of cortical features of evolutionary and genetic origin (such as cortical thickness, area and folding) which may distinctly contribute to DI pathophysiology are unclear at present. MethodsIn this study, 18 patients with DI and 20 healthy controls (HC) underwent MRI scanning at 1.0T. Using surface-based analyses we calculated cortical thickness, surface area and local gyrification index (LGI). Whole-brain differences between patients and controls were investigated. ResultsSurface analyses revealed frontoparietal patterns exhibiting altered cortical thickness, surface area and LGI in DI patients compared to controls. Higher cortical thickness was found in the right medial orbitofrontal cortex (p<0.05, cluster-wise probability [CWP] corrected). Smaller surface area in patients was found in the left inferior temporal gyrus, the precuneus, the pars orbitalis of the right frontal gyrus, and the lingual gyrus (p<0.05, CWP corr.). Lower LGI was found in the left postcentral, bilateral precentral, right middle temporal, inferior parietal, and superior parietal gyri (p<0.01, CWP corr.). ConclusionThis study lends further support to the hypothesis that cortical features of distinct evolutionary and genetic origin differently contribute to the pathogenesis of delusional disorders. Regions in which atrophy was observed are part of neural circuits associated with perception, visuospatial control and self-awareness. The data are in line with the notion of a content-specific neural signature of DI.

Binge drinking differentially affects cortical and subcortical microstructure

Young adult binge drinkers represent a model for endophenotypic risk factors for alcohol misuse and early exposure to repeated binge cycles. Chronic or harmful alcohol use leads to neurochemical, structural and morphological neuroplastic changes, particularly in regions associated with reward processing and motivation. We investigated neural microstructure in 28 binge drinkers compared with 38 matched healthy controls. We used a recently developed diffusion magnetic resonance imaging acquisition and analysis, which uses three‐compartment modelling (of intracellular, extracellular and cerebrospinal fluid) to determine brain tissue microstructure features including neurite density and orientation dispersion index (ODI). Binge drinkers had reduced ODI, a proxy of neurite complexity, in frontal cortical grey matter and increased ODI in parietal grey matter. Neurite density was higher in cortical white matter in adjacent regions of lower ODI in binge drinkers. Furthermore, binge drinkers had higher ventral striatal grey matter ODI that was positively correlated with binge score. Healthy volunteers showed no such relationships. We demonstrate disturbed dendritic complexity of higher‐order prefrontal and parietal regions, along with higher dendritic complexity of a subcortical region known to mediate reward‐related motivation. The findings illustrate novel microstructural abnormalities that may reflect an infnce of alcohol bingeing on critical neurodevelopmental processes in an at‐risk young adult group.

Prematurity and brain perfusion: Arterial spin labeling MRI.

PurposeAbnormal brain perfusion is a critical mechanism in neonatal brain injury. The aim of the present study was to compare Cerebral Blood Flow (CBF) evaluated with ASL MRI in three groups of neonates: preterms without brain lesions on MRI (PN), preterms with periventricular white matter lesions (PNp) and term neonates with normal MRI (TN). The correlation between CBF and clinical outcome was explored.Materials and methodsThe institutional review board approved this prospective study and waived informed consent. The perfusion ASL data from 49 consecutive preterm neonates (PN) studied at term-equivalent age and 15 TN were evaluated. Statistically significant differences in gray matter CBF were evaluated by using a linear mixed-model analysis and Mann-Whitney U test. Logistic regression analysis was used to assess the relation between CBF and neuromotor outcome at 12 months.ResultsComparison of means indicated that the CBF of the whole brain were significantly higher in PN compared to TN (P = 0.011). This difference remained significant when considering the frontal (P = 0.038), parietal (P = 0.002), temporal (P = 0.030), occipital (P = 0.041) and cerebellar (P = 0.010) gray matter. In the PN group, lower CBF in basal ganglia was associated with a worse neuromotor outcome (P = 0.012).ConclusionsASL MRI demonstrated differences in brain perfusion of the basal ganglia between PN and TN. In PN, a positive correlation between CBF and neuromotor outcome was demonstrated in this area.

Brain structure, working memory and response inhibition in childhood leukemia survivors

IntroductionSurvival rates for children with acute lymphoblastic leukemia (ALL) approach 95%. At the same time, there is growing concern that chemotherapy causes alterations in brain development and cognitive abilities. We performed MRI measurements of white and gray matter volume to explore how variation in brain structure may be related to cognitive abilities in ALL survivors and healthy controls.MethodsThe sample included 24 male ALL survivors who had completed contemporary treatment 3–11 years prior, and 21 age‐ and sex‐matched controls. Participants were between 8 and 18 years old. Working memory and motor response inhibition were measured with the N‐Back and Stop Signal Tasks (SST), respectively. Participants underwent 3T structural MRI to assess white and gray matter volumes overall, lobe‐wise, and in cortical and atlas‐identified subcortical structures. Mental health was assessed with the Child Behavioral Checklist.Results ALL survivors performed more poorly on measures of working memory and response inhibition than controls. Frontal and parietal white matter, temporal and occipital gray matter volume, and volumes of subcortical white and gray matter structures were significantly reduced in ALL survivors compared with controls. Significant structure‐function correlations were observed between working memory performance and volume of the amygdala, thalamus, striatum, and corpus callosum. Response inhibition was correlated with frontal white matter volume. No differences were found in psychopathology.ConclusionsCompared with controls, a reduction in volume across brain regions and tissue types, was detectable in ALL survivors years after completion of therapy. These structural alterations were correlated with neurocognitive performance, particularly in working memory. Confirming these observations in a larger, more representative sample of the population is necessary. Additionally, establishing the time course of these changes—and the treatment, genetic, and environmental factors that influence them—may provide opportunities to identify at‐risk patients, inform the design of treatment modifications, and minimize adverse cognitive outcomes.

AV-1451 TAU-PET BINDING IN TYPICAL AND ATYPICAL SYNDROMIC VARIANTS OF ALZHEIMER’S DISEASE

Patients with Alzheimer’s disease typically present with episodic memory loss (dementia of the Alzheimer’s type (DAT)). However, 25% can have an atypical presentation dominated by language difficulties (logopenic aphasia (lvPPA)), or visuo-spatial/perceptual deficits (posterior cortical atrophy (PCA)). Tau-PET imaging using AV-1451 demonstrates striking uptake in DAT. It remains unclear whether elevated uptake occurs in atypical AD and whether regional patterns of uptake differ from DAT. We aimed to investigate tau-PET imaging in atypical AD. Tau-PET imaging using AV-1451 was performed in three patients with PCA and three with lvPPA; all six had a positive beta-amyloid PiB-PET scan. These six patients were compared to an age-matched group of 101 controls and 19 patients with DAT. Regional tau-PET uptake was assessed within medial and lateral temporal, parietal, frontal and occipital grey matter regions using the automated anatomical labelling atlas. Compared to controls, elevated tau uptake was observed in all PCA and lvPPA subjects. The PCA subjects all showed greatest uptake in occipital lobe and asymmetric patterns of uptake, with greatest involvement of the right hemisphere. Two PCA subjects showed additional widespread involvement of frontal, temporal and parietal lobes, with more focal and mild patterns observed in the third. The lvPPA subjects all showed left-sided patterns of uptake with the lateral temporal lobes showing striking uptake in two subjects. The third lvPPA subject showed widespread uptake throughout the cortex. Regional patterns of uptake in PCA and lvPPA overlapped with those observed in DAT, although there was a tendency for the left hippocampus to be involved to a greater degree in DAT.

Regional brain volume changes in alcohol-dependent individuals during early abstinence: associations with relapse following treatment

Cross-sectional structural magnetic resonance (MR) imaging studies of individuals with an alcohol use disorder (AUD) report that those who relapse after treatment, relative to individuals who maintain a period of extended abstinence, show greater morphological abnormalities in multiple brain regions near the inception of treatment, particularly in the frontal lobe. However, given the cross-sectional design of previous studies, it is unclear if the baseline morphological differences between future abstainers and relapsers were maintained over the course of early recovery. The primary goal of this study was to determine if frontal lobe tissue volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared frontal, parietal, temporal and occipital grey matter (GM) and white matter (WM) volumes, at 1 and 4 weeks of abstinence, among individuals who resumed alcohol consumption within 12 months of treatment (Relapsers) and those who showed sustained abstinence over 12 months following treatment (Abstainers). At 1 and 4 weeks of sobriety, both Abstainers and Relapsers demonstrated significantly smaller GM volumes than Controls in the majority of ROIs, but Relapsers exhibited significantly smaller bilateral frontal GM volumes than Abstainers. No significant group differences were observed for any WM region of interest. The persistent bilateral frontal GM volume deficits in Relapsers over 4 weeks from last alcohol use may represent an endophenotype that differentiates those who respond more favorably to the typical psychosocial and pharmacological interventions provided for AUD.

Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a (1)H-magnetic resonance spectroscopy study.

In utero exposure to alcohol leads to a spectrum of fetal alcohol related disorders (FASD). However, few studies used have used proton magnetic resonance spectroscopy ((1)H-MRS) to understand how neurochemical disturbances relate to the pathophysiology of FASD. Further, no studies to date have assessed brain metabolites in infants exposed to alcohol in utero. We hypothesize that neonates exposed to alcohol in utero will show decreased glutamatergic activity, pre-emptive of their clinical diagnosis or behavioural phenotype. Single voxel (1)H-MRS data, sampled in parietal white and gray matter, were acquired from 36 neonates exposed to alcohol in utero, and 31 control unexposed healthy neonates, in their 2nd-4th week of life. Metabolites relative to creatine with phosophocreatine and metabolites absolute concentrations using a water reference are reported. Male infants exposed to alcohol in utero were found to have reduced concentration of glutamate with glutamine (Glx) in their parietal white matter (PWM), compared to healthy male infants (p=0.02). Further, male infants exposed to alcohol in utero had reduced concentration and ratio for glutamate (Glu) in their PWM (p=0.02), compared to healthy male infants and female infants exposed to alcohol in utero. Female infants showed higher relative Glx and Glu ratios for parietal gray matter (PGM, p<0.01), compared to male infants. We speculate that the decreased Glx and Glu concentrations in PWM are a result of delayed oligodendrocyte maturation, which may be a result of dysfunctional thyroid hormone activity in males exposed to alcohol in utero. Further study is required to elucidate the relationship between Glx and Glu, thyroid hormone activity, and oligodendrocyte maturation in infants exposure to alcohol in utero.

Apnea-hypopnea index, nocturnal arousals, oxygen desaturation and structural brain changes: A population-based study

Sleep apnea has been related to brain changes such as atrophy. However, which component of sleep apnea, the apnea-hypopnea index (AHI), nocturnal oxygen desaturation or arousals, can explain this association is unclear. In this large population-based study (n=681, mean age 62.1 years), we investigated the associations of AHI, nocturnal oxygen desaturation and arousals with global and regional gray matter and white matter volumes and with white matter lesion volumes. All participants underwent one night of polysomnography and MRI scanning of their brain. Gray matter, white matter and white matter lesion volumes adjusted for intracranial volume were studied as markers of brain atrophy. Nocturnal oxygen desaturation was related to whole brain white matter atrophy independent of covariates (multivariable adjusted B=−8.3, 95% CI=−16.7; −0.02). This association was most prominently reflected in the association between more oxygen desaturation and a smaller white matter parietal volume (B=−3.95ml, 95% CI=−6.02; −1.88). Furthermore, oxygen desaturation was related to a smaller hippocampus (B=−0.22ml, 95% CI=−0.42; −0.01). Although a higher AHI was related to smaller parietal gray (B=−0.05, 95% CI=−0.09; −0.004) and white matter (B=−0.06, 95% CI=−0.12; −0.10) volumes, these associations disappeared when adding oxygen desaturation to the model. We did not find a relation between arousals and gray and white matter brain atrophy and white matter lesion volumes. This suggests that oxygen desaturation mainly explains the association between sleep apnea and brain damage.

Clinically Isolated Syndrome Suggestive of Multiple Sclerosis: Dynamic Patterns of Gray and White Matter Changes-A 2-year MR Imaging Study.

To investigate the patterns of regional gray matter (GM) and white matter (WM) atrophy, WM microstructural tissue damage, and changes in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis at 2 years from clinical onset. Institutional review board approval and written informed consent from all patients were obtained. Neurologic assessment and conventional, diffusion-tensor, and volumetric brain MR imaging sequences were performed in 37 patients with CIS within 2 months of clinical onset, and after 3, 12, and 24 months. Fourteen healthy control subjects also were studied. Longitudinal GM and WM volume changes and WM microstructural abnormalities were assessed by using voxel-based morphometry (P < .001, uncorrected) and tract-based spatial statistics (P < .05, corrected). At 24 months, 33 of 37 (89%) patients had developed multiple sclerosis. At month 3, patients with CIS showed a transient volume increase in frontal, parietal, temporal, and cerebellar GM regions. At 12 months, patients with CIS developed atrophy of the thalami, caudate nuclei, cerebellum, and frontal, parietal, and temporal lobes. At 24 months GM volume of the frontal, temporal, and parietal cortical areas further decreased from that at 12 months. WM atrophy involved only a few WM regions at 2 months from clinical onset, with progressive involvement of additional WM tracts with time. A diffuse pattern of WM microstructural abnormalities was detected within 2 months of onset and had worsened at 24 months. After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis.

Genetic markers of cholesterol transport and gray matter diffusion: a preliminary study of the CETP I405V polymorphism.

Variations of the cholesteryl ester transfer protein polymorphism (CETP I405V/rs5882) have been associated with an increased risk for neurodegeneration, particularly when examined in conjunction with the epsilon 4 isoform of apolipoprotein E (ApoE4). Despite these identified relationships, the impact of I405V on gray matter microstructure remains unknown. The present study examined the impact of the CETP I405V polymorphism on gray matter integrity among 52 healthy adults between ages 51 and 85. Gray matter was measured bilaterally using diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Participants were grouped according to a dominant statistical model (II genotype vs. IV/VV genotypes) and secondary analyses were completed to examine the interactive effects of CETP and ApoE4 on DTI metrics. Compared to individuals with the IV/VV genotypes, II homozygotes demonstrated significantly higher MD in bilateral temporal, parietal, and occipital gray matter. Secondary analyses revealed higher FA and AD in the left temporal lobe of IV/VV genotypes with an ApoE4 allele. Our results provide preliminary evidence that CETP II homozygosity is a predisposing risk factor for gray matter abnormalities in posterior brain regions in healthy older adults, independent of an ApoE4 allele.

Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson's disease?

The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging. Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study and completed cognitive assessments and 3T structural and diffusion tensor MR imaging. Voxel-based morphometry was performed to investigate the relationship between gray matter volume and cognitive ability. Microstructural white matter changes were assessed with diffusion tensor imaging measures of fractional anisotropy and mean diffusivity using tract-based spatial statistics. Increased mean diffusivity was observed bilaterally in subjects with PD, relative to controls (P = 0.019). Increased mean diffusivity was associated with performance on the semantic fluency and Tower of London tasks in frontal and parietal white matter tracts, including the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. There was no difference in total gray matter volume between groups; however, bilateral reductions in frontal and parietal gray matter volume were associated with reduced performance on measures of executive function in PD subjects. At the earliest stages of PD, regionally specific increases in central white matter mean diffusivity are present and suggest early axonal damage. Such changes are not accompanied by significant gray matter volume loss and are consistent with proposed models of pathological progression of the disease. Structural MRI, especially diffusion tensor imaging analysis, offers potential as a noninvasive biomarker reflecting cognitive impairment in PD.

P12. Neural correlates of apraxia in mild dementia of Alzheimer’s disease – A voxel-based morphometry study

Introduction Apraxia is a neuropsychological syndrome with the hallmark of impaired imitation and/or pantomiming of gestures and postures despite normal motor function and comprehension. Whereas key brain regions for apraxia in patients with left-hemispheric stroke have been suggested, it is unclear whether similar areas contribute to praxis disturbances observed in Alzheimer’s disease (AD). Methods 18 patients with mild AD received high-resolution 3.0 Tesla T1-weighted MRI scans of the brain and were tested for praxis disturbances with the help of a modern apraxia screening test (Cologne Apraxia Screening; CAS) incorporating tasks on limb and face imitation as well as pantomime of object-use. We used a voxel-based morphometry (VBM) analysis to explore associations between gray matter (GM) volume and CAS scores. Results All apraxia scores showed significant associations with GM volume within posterior brain regions. Limb imitation (CAS 2.2) was associated with GM volume in bilateral inferior occipital gyrus, right middle temporal gyrus as well as medial parietal areas, mainly the precuneus. Pantomime of object-use (CAS 1) showed a pattern of right lateralized clusters in posterior middle temporal gyrus, and both inferior and superior parietal areas, again stretching into the precuneus. Imitation of face postures (CAS 2.1) was mainly correlated with GM volume in inferior occipital and left fusiform gyrus. Discussion Limb apraxia in patients after stroke has consistently been associated with lesions in a left lateralized temporo-parieto-frontal brain network with an emphasis on the inferior parietal lobe. Our results from apraxic patients with AD are compatible with the suggested networks, however a more posterior and more bilateral (or even right-lateralized) distribution of associated brain areas emerged, suggesting a stronger influence of visuo-perception on apraxic phenomena in AD. In line with this, both tasks of limb apraxia (imitation and pantomime) showed associations with medial/dorsal areas within the parietal lobe, in particular with the precuneus. The precuneus is a target of early neurodegeneration in AD, shows extensive connections to both, inferior parietal lobe and supplementary motor cortex and is involved in motor imagery processes (i.e., mental visualization of spatially complex motor actions). It may thus constitute a key region for limb apraxia in AD. Face imitation however, was not correlated with parietal GM volume, corroborating previous results of body-part specificity in apraxia.

Calorie restriction improves brain health in aging rhesus macaques

Calorie restriction (CR) without malnutrition slows the aging and disease process, prolonging median and maximum lifespan in yeast, worms, fish, flies, and rodents. Studies of CR in non-human primates (Macaca mulatta) indicate a protective effect of CR against aging-related diseases and a salutary effect on brain health. Our group has studied the specific effects of CR on the non-human primate brain using neuroimaging, behavioral, and post-mortem histological techniques and this talk will provide an overview of these findings. Animals in this study were part of the longitudinal “Dietary Restriction and Aging Study” at the Wisconsin National Primate Research Center (WNPRC). Animals were either fed a normal diet or maintained on a moderately restricted diet (approximately 30% reduced intake from baseline), with both groups receiving comparable diet supplements. Using volumetric imaging we demonstrated that CR preserves gray matter cortex in limbic and heteromodal association areas, indicating a positive effect of CR against age-related brain atrophy. Diffusion tensor imaging showed preservation of white matter integrity in the corpus callosum and fronto-occipital fasciculus, superior longitudinal fasciculus, external capsule, and brainstem. CR also attenuated age-related iron accumulation in the basal ganglia, red nucleus, and parietal, temporal, and perirhinal cortex. Decreased iron accumulation was in turn associated with faster performance on fine motor function tests, signifying a protective effect against motor slowness that results during aging. CR moderated the effect of important plasma-based inflammatory markers (e.g. IL-6) on gray and white matter changes in several brain areas, including the parietal and temporal gray matter regions that are sensitive to aging. CR improved glucoregulatory profiles and positively influenced gray matter volume in the hippocampus. Histopathology studies reveal that CR monkeys express significantly lower (∼30%) levels of microglial activation in the hippocampus. Energy metabolism in the hippocampus as indexed by PGC1alpha and GSK3B was preserved in CR. Number of MTL amyloid plaques was however equivalent between groups. Overall, these results recapitulate the neuroprotective effects of CR from lower animal models. Taken together, these findings point to an overall beneficial effect of CR on the brain in this non-human primate model of aging.

Neuropathologic correlates of regional brain volumes in a community cohort of older adults

The objective of this work was 2-fold: to generate macrostructural brain signatures of age-related neuropathologies in a community cohort of older adults and to determine the contribution of brain macrostructure to the variation in antemortem cognition after accounting for the contributions of neuropathologies and demographics. Cerebral hemispheres from 165 participants of 2 cohort studies of aging were imaged with magnetic resonance imaging ex vivo (mean age at death = 90 years; standard deviation = 6 years). The volumes of white matter and 42 gray matter regions were measured. The same hemispheres also underwent neuropathologic examination. Alzheimer's disease pathology was negatively associated with volumes of mainly temporal, frontal, and parietal gray matter regions, and with total white matter volume (p < 0.05, false discovery rate-corrected). A negative association was also detected between hippocampal sclerosis and volumes of the hippocampus, as well as other temporal and frontal gray matter regions (p < 0.05, false discovery rate-corrected). The volume of mainly medial temporal lobe regions explained an additional 5%–6% of the variation in antemortem cognition, above and beyond what was explained by neuropathologies and demographics.

Magnetic Resonance Spectroscopy in Alzheimer's Disease: Systematic Review and Meta-Analysis.

The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with Alzheimer's disease (AD). However, whether these metabolites can serve as biomarkers for the diagnosis of AD remains unclear. Using meta-analysis, we aimed to investigate the patterns of cerebral metabolite changes in several cerebral regions that are strongly associated with cognitive decline in AD patients. Using Hedges' g effect size, a systematic search was performed in PubMed, Cochrane Library, Ovid, Embase, and EBSCO, and 38 studies were integrated into the final meta-analysis. According to the observational studies, N-acetyl aspartate (NAA) in AD patients was significantly reduced in the posterior cingulate (PC) (effect size (ES) =-0.924, p < 0.005) and bilateral hippocampus (left hippocampus: ES =-1.329, p < 0.005; right hippocampus: ES =-1.287, p < 0.005). NAA/Cr (creatine) ratio decreased markedly in the PC (ES =-1.052, p < 0.005). Simultaneously, significant elevated myo-inositol (mI)/Cr ratio was found not only in the PC but also in the parietal gray matter. For lack of sufficient data, we failed to elucidate the efficacy of pharmacological interventions with the metabolites changes. The available data indicates that NAA, mI, and the NAA/Cr ratio might be potential biomarkers of brain dysfunction in AD subjects. Choline (Cho)/Cr and mI/NAA changes might also contribute toward the diagnostic process. Thus, large, well-designed studies correlated with cerebral metabolism are needed to better estimate the cerebral extent of alterations in brain metabolite levels in AD patients.

Long-term structural changes after mTBI and their relation to post-concussion symptoms

Primary objective: To investigate sustained structural changes in the long-term (>1 year) after mild traumatic brain injury (mTBI) and their relationship to ongoing post-concussion syndrome (PCS).Research design: Morphological and structural connectivity magnetic resonance imaging (MRI) data were acquired from 16 participants with mTBI and nine participants without previous head injury.Main outcomes and results: Participants with mTBI had less prefrontal grey matter and lower fractional anisotropy (FA) in the anterior corona radiata and internal capsule. Furthermore, PCS severity was associated with less parietal lobe grey matter and lower FA in the corpus callosum.Conclusions: There is evidence for both white and grey matter damage in participants with mTBI over 1 year after injury. Furthermore, these structural changes are greater in those that report more PCS symptoms, suggesting a neurophysiological basis for these persistent symptoms.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection.

It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04). CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health.

The cognitive profile of prion disease: a prospective clinical and imaging study.

ObjectivesPrion diseases are dementing illnesses with poorly defined neuropsychological features. This is probably because the most common form, sporadic Creutzfeldt-Jakob disease, is often rapidly progressive with pervasive cognitive decline making detailed neuropsychological investigation difficult. This study, which includes patients with inherited, acquired (iatrogenic and variant) and sporadic forms of the disease, is the only large-scale neuropsychological investigation of this patient group ever undertaken and aimed to define a neuropsychological profile of human prion diseases.MethodsA tailored short cognitive examination of all of the patients (n = 81), with detailed neuropsychological testing in a subset with mild disease (n = 30) and correlation with demographic, clinical, genetic (PRNP mutation and polymorphic codon 129 genotype), and other variables (MRI brain signal change in cortex, basal ganglia or thalamus; quantitative research imaging, cerebrospinal fluid 14-3-3 protein).ResultsComparison with healthy controls showed patients to be impaired on all tasks. Principal components analysis showed a major axis of fronto-parietal dysfunction that accounted for approximately half of the variance observed. This correlated strongly with volume reduction in frontal and parietal gray matter on MRI. Examination of individual patients' performances confirmed early impairment on this axis, suggesting characteristic cognitive features in mild disease: prominent executive impairment, parietal dysfunction, a largely expressive dysphasia, with reduced motor speed.InterpretationTaken together with typical neurological features, these results complete a profile that should improve differential diagnosis in a clinical setting. We propose a tailored neuropsychological battery for early recognition of clinical onset of symptoms with potential for use in clinical trials involving at-risk individuals.