BackgroundAfrican Americans have been reported to have a higher prevalence of Alzheimer’s disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.MethodsWe prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau181, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume).ResultsSixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau181 (difference of 7.4 pg/ml; 95% CI, 3.7–11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5–37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29–2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100–0.409; p = 0.001) and p-tau181/Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031–0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.ConclusionsDespite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.Trial registrationClinicalTrials.gov, NCT02089555. Retrospectively registered on 14 March 2014.

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These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.

Previous functional magnetic resonance imaging (fMRI) investigations suggest that the intrinsically organized large-scale networks and the interaction between them might be crucial for cognitive activities. A triple network model, which consists of the default-mode network, salience network, and central-executive network, has been recently used to understand the connectivity patterns of the cognitively normal brains versus the brains with disorders. This model suggests that the salience network dynamically controls the default-mode and central-executive networks in healthy young individuals. However, the patterns of interactions have remained largely unknown in healthy aging or those with cognitive decline. In this study, we assess the patterns of interactions between the three networks using dynamical causal modeling in resting state fMRI data and compare them between subjects with normal cognition and mild cognitive impairment (MCI). In healthy elderly subjects, our analysis showed that the salience network, especially its dorsal subnetwork, modulates the interaction between the default-mode network and the central-executive network (Mann-Whitney U test; p < 0.05), which was consistent with the pattern of interaction reported in young adults. In contrast, this pattern of modulation by salience network was disrupted in MCI (p < 0.05). Furthermore, the degree of disruption in salience network control correlated significantly with lower overall cognitive performance measured by Montreal Cognitive Assessment (r = 0.295; p < 0.05). This study suggests that a disruption of the salience network control, especially the dorsal salience network, over other networks provides a neuronal basis for cognitive decline and may be a candidate neuroimaging biomarker of cognitive impairment.

Our preliminary findings suggest that white matter FA may be a clinically useful biomarker for the assessment of treatment-related neurotoxicity in post-treatment childhood cancer survivors.

Purpose To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) signal can be used to create maps similar to time-to-maximum of the residue function (Tmax) in Moyamoya patients and to determine whether sfBOLD delays affect the results of brain connectivity mapping. Methods Ten patients were scanned at 3T using a gradient-echo EPI sequence for sfBOLD imaging. Cross correlation analysis was performed between each brain voxel signal and a reference signal comprised of either the superior sagittal sinus (SSS) or whole brain (WB) average time course. sfBOLD delay maps were created based on the time shift necessary to maximize the correlation coefficient, and compared to dynamic susceptibility contrast Tmax maps. Standard and time-shifted resting-state BOLD connectivity analyses of the default mode network were compared. Results Good linear correlations were found between sfBOLD delays and Tmax using the SSS as reference (r2=0.8, slope=1.4, intercept=-4.6) or WB (r2=0.7, slope=0.8, intercept=-3.2). New nodes of connectivity were found in delayed regions when accounting for delays in the analysis. Conclusions Resting-state sfBOLD imaging can create delay maps similar to Tmax maps without the use of contrast agents in Moyamoya patients. Accounting for these delays may affect the results of functional connectivity maps.

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (L // ), and radial diffusivity (L ? ) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in L // from 4 to 40 weeks postradiation, and an increase in L ? with return to baseline in L // at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in L // correlated with reactive astrogliosis (P < 0.01) and L ? correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in L // and L ? . DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

In the present study, we describe a fingerprinting approach to analyze the time evolution of the MR signal and retrieve quantitative information about the microvascular network. We used a Gradient Echo Sampling of the Free Induction Decay and Spin Echo (GESFIDE) sequence and defined a fingerprint as the ratio of signals acquired pre and post injection of an iron based contrast agent. We then simulated the same experiment with an advanced numerical tool that takes a virtual voxel containing blood vessels as input, then computes microscopic magnetic fields and water diffusion effects, and eventually derives the expected MR signal evolution. The parameters inputs of the simulations (cerebral blood volume [CBV], mean vessel radius [R], and blood oxygen saturation [SO2]) were varied to obtain a dictionary of all possible signal evolutions. The best fit between the observed fingerprint and the dictionary was then determined using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained using more conventional MR methods, steady-state contrast imaging for CBV and R and a global measure of oxygenation obtained from the superior sagittal sinus for SO2. The fingerprinting method enabled the creation of high-resolution parametric maps of the microvascular network showing expected contrast and fine details. Numerical values in gray matter (CBV=3.1±0.7%, R=12.6±2.4µm, SO2=59.5±4.7%) are consistent with literature reports and correlated with conventional MR approaches. SO2 values in white matter (53.0±4.0%) were slightly lower than expected. Numerous improvements can easily be made and the method should be useful to study brain pathologies.