Associations between the choroid plexus and tau in Alzheimer's disease using an active learning segmentation pipeline.

BACKGROUND: The cerebrospinal fluid (CSF), primarily generated by the choroid plexus (ChP), is the major carrier of the glymphatic system. The alternations of CSF production and the ChP can be associated with the Alzheimer's disease (AD). The present work investigated the roles of the ChP in the AD based on a proposed ChP image segmentation pipeline. METHODS: A human-in-the-loop ChP image segmentation pipeline was implemented with intermediate and active learning datasets. The performance of the proposed pipeline was evaluated on manual contours by five radiologists, compared to the FreeSurfer and FastSurfer toolboxes. The ChP volume and blood flow were investigated among AD groups. The correlations between the ChP volume and AD CSF biomarkers including phosphorylated tau (p-tau), total tau (t-tau), amyloid-ß42 (Aß42), and amyloid-ß40 (Aß40) was investigated using three models (univariate, multiple variables, and stepwise regression) on two datasets with 806 and 320 subjects. RESULTS: The proposed ChP segmentation pipeline achieved superior performance with a Dice coefficient of 0.620 on the test dataset, compared to the FreeSurfer (0.342) and FastSurfer (0.371). Significantly larger volumes (p < 0.001) and higher perfusion (p = 0.032) at the ChP were found in AD compared to CN groups. Significant correlations were found between the tau and the relative ChP volume (the ChP volume and ChP/parenchyma ratio) in each patient groups and in the univariate regression analysis (p < 0.001), the multiple regression model (p < 0.05 except for the t-tau in the LMCI), and in the step-wise regression model (p < 0.021). In addition, the correlation coefficients changed from - 0.32 to - 0.21 along with the AD progression in the multiple regression model. In contrast, the Aß42 and Aß40 shows consistent and significant associations with the lateral ventricle related measures in the step-wise regression model (p < 0.027). CONCLUSIONS: The proposed pipeline provided accurate ChP segmentation which revealed the associations between the ChP and tau level in the AD. The proposed pipeline is available on GitHub ( https://github.com/princeleeee/ChP-Seg ).

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Reproducibility and Sensitivity of Resting-State fMRI in Patients With Parkinson's Disease Using Cross Validation-Based Data Censoring.

BACKGROUND: Uncontrollable body movements are typical symptoms of Parkinson's disease (PD), which results in inconsistent findings regarding resting-state functional connectivity (rsFC) networks, especially for group difference clusters. Systematically identifying the motion-associated data was highly demanded. PURPOSE: To determine data censoring criteria using a quantitative cross validation-based data censoring (CVDC) method and to improve the detection of rsFC deficits in PD. STUDY TYPE: Prospective. SUBJECTS: Forty-one PD patients (68.63 ± 9.17 years, 44% female) and 20 healthy controls (66.83 ± 12.94 years, 55% female). FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted gradient echo and EPI sequences. ASSESSMENT: Clusters with significant differences between groups were found in three visual networks, default network, and right sensorimotor network. Five-fold cross-validation tests were performed using multiple motion exclusion criteria, and the selected criteria were determined based on cluster sizes, significance values, and Dice coefficients among the cross-validation tests. As a reference method, whole brain rsFC comparisons between groups were analyzed using a FMRIB Software Library (FSL) pipeline with default settings. STATISTICAL TESTS: Group difference clusters were calculated using nonparametric permutation statistics of FSL-randomize. The family-wise error was corrected. Demographic information was evaluated using independent sample t-tests and Pearson's Chi-squared tests. The level of statistical significance was set at P < 0.05. RESULTS: With the FSL processing pipeline, the mean Dice coefficient of the network clusters was 0.411, indicating a low reproducibility. With the proposed CVDC method, motion exclusion criteria were determined as frame-wise displacement >0.55 mm. Group-difference clusters showed a mean P-value of 0.01 and a 72% higher mean Dice coefficient compared to the FSL pipeline. Furthermore, the CVDC method was capable of detecting subtle rsFC deficits in the medial sensorimotor network and auditory network that were unobservable using the conventional pipeline. DATA CONCLUSION: The CVDC method may provide superior sensitivity and improved reproducibility for detecting rsFC deficits in PD. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

ASL lexicon and reporting recommendations: A consensus report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

The 2015 consensus statement published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group and the European Cooperation in Science and Technology ( COST) Action ASL in Dementia aimed to encourage the implementation of robust arterial spin labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, leading inevitably to further divergence of the technique and its associated terminology, which could cause confusion and hamper research reproducibility. On behalf of the ISMRM Perfusion Study Group, and as part of the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task Force has been working on the development of an ASL Lexicon and Reporting Recommendations for perfusion imaging and analysis, aiming to (1) develop standardized, consensus nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as for the physiological constants required for quantitative analysis; and (2) provide a community-endorsed recommendation of the imaging parameters that we encourage authors to include when describing ASL methods in scientific reports/papers. In this paper, the sequences and parameters in (pseudo-)continuous ASL, pulsed ASL, velocity-selective ASL, and multi-timepoint ASL for brain perfusion imaging are included. However, the content of the lexicon is not intended to be limited to these techniques, and this paper provides the foundation for a growing online inventory that will be extended by the community as further methods and improvements are developed and established.

Effect of Meditation on Brain Activity during an Attention Task: A Comparison Study of ASL and BOLD Task fMRI.

Focused attention meditation (FAM) training has been shown to improve attention, but the neural basis of FAM on attention has not been thoroughly understood. Here, we aim to investigate the neural effect of a 2-month FAM training on novice meditators in a visual oddball task (a frequently adopted task to evaluate attention), evaluated with both ASL and BOLD fMRI. Using ASL, activation was increased in the middle cingulate (part of the salience network, SN) and temporoparietal (part of the frontoparietal network, FPN) regions; the FAM practice time was negatively associated with the longitudinal changes in activation in the medial prefrontal (part of the default mode network, DMN) and middle frontal (part of the FPN) regions. Using BOLD, the FAM practice time was positively associated with the longitudinal changes of activation in the inferior parietal (part of the dorsal attention network, DAN), dorsolateral prefrontal (part of the FPN), and precentral (part of the DAN) regions. The effect sizes for the activation changes and their association with practice time using ASL are significantly larger than those using BOLD. Our study suggests that FAM training may improve attention via modulation of the DMN, DAN, SN, and FPN, and ASL may be a sensitive tool to study the FAM effect on attention.

[Design and application of a B-ultrasound-guided deep vein puncture precise positioning device].

Deep venipuncture catheterization is a routine and basic operation in the treatment of critically ill patients, and it is the most effective way to quickly correct the shock. Clinical B-ultrasound guided deep vein catheters can improve the success rate of puncture, but in the process of operation, the short axis needs to be replaced by the long axis. In the replacement process, the stability of the novice is insufficient, the positioning is difficult, and the operation time is too long. If only short axis puncture is used, it is impossible to know whether the current position of the puncture needle, and the puncture may be too deep and stray into the artery. The accuracy of the 45 degree angle of the injection point requires a very experienced operator. In view of the above shortcomings, doctors in the department of critical care medicine of Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine designed a B-ultrasound puncture equipment, which has obtained the National Invention Patent of China (ZL 2016 1 0571557.X). The device is composed of B-ultrasound probe fixing frame, sliding scale plate, simulation slide rule, puncture needle, sliding device. By sliding device the angle of the pinhole channel, it is conducive to the accurate positioning of the puncture target, optimizing the operation procedure, improving the puncture speed and accuracy, effectively reducing the occurrence of puncture complications, ensuring patient safety, reducing unnecessary waste of human and material resources. It can reduce the workload of medical staff and is worthy of clinical practice.

Mechanical hierarchy in the formation and modulation of cortical folding patterns.

The important mechanical parameters and their hierarchy in the growth and folding of the human brain have not been thoroughly understood. In this study, we developed a multiscale mechanical model to investigate how the interplay between initial geometrical undulations, differential tangential growth in the cortical plate, and axonal connectivity form and regulate the folding patterns of the human brain in a hierarchical order. To do so, different growth scenarios with bilayer spherical models that features initial undulations on the cortex and uniform or heterogeneous distribution of axonal fibers in the white matter were developed, statistically analyzed, and validated by the imaging observations. The results showed that the differential tangential growth is the inducer of cortical folding, and in a hierarchal order, high-amplitude initial undulations on the surface and axonal fibers in the substrate regulate the folding patterns and determine the location of gyri and sulci. The locations with dense axonal fibers after folding settle in gyri rather than sulci. The statistical results also indicated that there is a strong correlation between the location of positive (outward) and negative (inward) initial undulations and the locations of gyri and sulci after folding, respectively. In addition, the locations of 3-hinge gyral folds are strongly correlated with the initial positive undulations and locations of dense axonal fibers. As another finding, it was revealed that there is a correlation between the density of axonal fibers and local gyrification index, which has been observed in imaging studies but not yet fundamentally explained. This study is the first step in understanding the linkage between abnormal gyrification (surface morphology) and disruption in connectivity that has been observed in some brain disorders such as Autism Spectrum Disorder. Moreover, the findings of the study directly contribute to the concept of the regularity and variability of folding patterns in individual human brains.

Affine image registration of arterial spin labeling MRI using deep learning networks.

Convolutional neural networks (CNN) have demonstrated good accuracy and speed in spatially registering high signal-to-noise ratio (SNR) structural magnetic resonance imaging (sMRI) images. However, some functional magnetic resonance imaging (fMRI) images, e.g., those acquired from arterial spin labeling (ASL) perfusion fMRI, are of intrinsically low SNR and therefore the quality of registering ASL images using CNN is not clear. In this work, we aimed to explore the feasibility of a CNN-based affine registration network (ARN) for registration of low-SNR three-dimensional ASL perfusion image time series and compare its performance with that from the state-of-the-art statistical parametric mapping (SPM) algorithm. The six affine parameters were learned from the ARN using both simulated motion and real acquisitions from ASL perfusion fMRI data and the registered images were generated by applying the transformation derived from the affine parameters. The speed and registration accuracy were compared between ARN and SPM. Several independent datasets, including meditation study (10 subjects × 2), bipolar disorder study (26 controls, 19 bipolar disorder subjects), and aging study (27 young subjects, 33 older subjects), were used to validate the generality of the trained ARN model. The ARN method achieves superior image affine registration accuracy (total translation/total rotation errors of ARN vs. SPM: 1.17 mm/1.23° vs. 6.09 mm/12.90° for simulated images and reduced MSE/L1/DSSIM/Total errors of 18.07% / 19.02% / 0.04% / 29.59% for real ASL test images) and 4.4 times (ARN vs. SPM: 0.50 s vs. 2.21 s) faster speed compared to SPM. The trained ARN can be generalized to align ASL perfusion image time series acquired with different scanners, and from different image resolutions, and from healthy or diseased populations. The results demonstrated that our ARN markedly outperforms the iteration-based SPM both for simulated motion and real acquisitions in terms of registration accuracy, speed, and generalization.

Longitudinal Patterns of Brain Changes in a Community Sample in Relation to Aging and Cognitive Status.

BACKGROUND: Aging and Alzheimer's disease (AD) are characterized by widespread cortical and subcortical atrophy. Though atrophy patterns between aging and AD overlap considerably, regional differences between these two conditions may exist. Few studies, however, have investigated these patterns in large community samples. OBJECTIVE: Elaborate longitudinal changes in brain morphometry in relation to aging and cognitive status in a well-characterized community cohort. METHODS: Clinical and neuroimaging data were compiled from 72 participants from the Cardiovascular Health Study-Cognition Study, a community cohort of healthy aging and probable AD participants. Two time points were identified for each participant with a mean follow-up time of 5.36 years. MRI post-processing, morphometric measurements, and statistical analyses were performed using FreeSurfer, Version 7.1.1. RESULTS: Cortical volume was significantly decreased in the bilateral superior frontal, bilateral inferior parietal, and left superior parietal regions, among others. Cortical thickness was significantly reduced in the bilateral superior frontal and left inferior parietal regions, among others. Overall gray and white matter volumes and hippocampal subfields also demonstrated significant reductions. Cortical volume atrophy trajectories between cognitively stable and cognitively declined participants were significantly different in the right postcentral region. CONCLUSION: Observed volume reductions were consistent with previous studies investigating morphometric brain changes. Patterns of brain atrophy between AD and aging may be different in magnitude but exhibit widespread spatial overlap. These findings help characterize patterns of brain atrophy that may reflect the general population. Larger studies may more definitively establish population norms of aging and AD-related neuroimaging changes.

Levetiracetam Increases Hippocampal Blood Flow in Alzheimer's Disease as Measured by Arterial Spin Labelling MRI.

BACKGROUND: Patients with Alzheimer's disease (AD) have an increased risk of developing epileptiform discharges, which is associated with a more rapid rate of progression. This suggests that suppression of epileptiform activity could have clinical benefit in patients with AD. OBJECTIVE: In the current study, we tested whether acute, intravenous administration of levetiracetam led to changes in brain perfusion as measured with arterial spin labeling MRI (ASL-MRI) in AD. METHODS: We conducted a double-blind, within-subject crossover design study in which participants with mild AD (n = 9) received placebo, 2.5 mg/kg, and 7.5 mg/kg of LEV intravenously in a random order in three sessions. Afterwards, the participants underwent ASL-MRI. RESULTS: Analysis of relative cerebral blood flow (rCBF) between 2.5 mg of levetiracetam and placebo showed significant decreases in a cluster that included the posterior cingulate cortex, the precuneus, and the posterior part of the cingulate gyrus, while increased cerebral blood flow was found in both temporal lobes involving the hippocampus. CONCLUSION: Administration of 2.5 mg/kg of LEV in patients without any history of epilepsy leads to changes in rCBF in areas known to be affected in the early stages of AD. These areas may be the focus of the epileptiform activity. Larger studies are needed to confirm the current findings.

Prospective Longitudinal Perfusion in Probable Alzheimer's Disease Correlated with Atrophy in Temporal Lobe.

Reduced cerebral blood flow (CBF) in the temporoparietal region and gray matter volumes (GMVs) in the temporal lobe were previously reported in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the temporal relationship between reductions in CBF and GMVs requires further investigation. This study sought to determine if reduced CBF is associated with reduced GMVs, or vice versa. Data came from 148 volunteers of the Cardiovascular Health Study Cognition Study (CHS-CS), including 58 normal controls (NC), 50 MCI, and 40 AD who had perfusion and structural MRIs during 2002-2003 (Time 2). Sixty-three of the 148 volunteers had follow-up perfusion and structural MRIs (Time 3). Forty out of the 63 volunteers received prior structural MRIs during 1997-1999 (Time 1). The relationships between GMVs and subsequent CBF changes, and between CBF and subsequent GMV changes were investigated. At Time 2, we observed smaller GMVs (p<0.05) in the temporal pole region in AD compared to NC and MCI. We also found associations between: (1) temporal pole GMVs at Time 2 and subsequent declines in CBF in this region (p=0.0014) and in the temporoparietal region (p=0.0032); (2) hippocampal GMVs at Time 2 and subsequent declines in CBF in the temporoparietal region (p=0.012); and (3) temporal pole CBF at Time 2 and subsequent changes in GMV in this region (p = 0.011). Therefore, hypoperfusion in the temporal pole may be an early event driving its atrophy. Perfusion declines in the temporoparietal and temporal pole follow atrophy in this temporal pole region.

Global Functional Connectivity at Rest Is Associated with Attention: An Arterial Spin Labeling Study.

Neural markers of attention, including those frequently linked to the event-related potential P3 (P300) or P3b component, vary widely within and across participants. Understanding the neural mechanisms of attention that contribute to the P3 is crucial for better understanding attention-related brain disorders. All ten participants were scanned twice with a resting-state PCASL perfusion MRI and an ERP with a visual oddball task to measure brain resting-state functional connectivity (rsFC) and P3 parameters (P3 amplitudes and P3 latencies). Global rsFC (average rsFC across the entire brain) was associated with both P3 amplitudes (r = 0.57, p = 0.011) and P3 onset latencies (r = -0.56, p = 0.012). The observed P3 parameters were correlated with predicted P3 amplitude from the global rsFC (amplitude: r = +0.48, p = 0.037; latency: r = +0.40, p = 0.088) but not correlated with the rsFC over the most significant individual edge. P3 onset latency was primarily related to long-range connections between the prefrontal and parietal/limbic regions, while P3 amplitudes were related to connections between prefrontal and parietal/occipital, between sensorimotor and subcortical, and between limbic/subcortical and parietal/occipital regions. These results demonstrated the power of resting-state PCASL and P3 correlation with brain global functional connectivity.

Recent Technical Developments in ASL: A Review of the State of the Art.

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.

Meta-Analysis of the Efficacy and Safety of Chlorhexidine for Ventilator-Associated Pneumonia Prevention in Mechanically Ventilated Patients.

Objective: To explore the efficacy and safety of chlorhexidine oral care in the prevention of ventilator-associated pneumonia (VAP) by means of meta-analysis. Methods: Randomized controlled trials on the effect of chlorhexidine oral care on the incidence of VAP in patients on mechanical ventilation were searched in PubMed, Scopus, Cochrane Library, and Embase from May 1, 2022. Two researchers independently screened and included the study, extracted the data, and evaluated the literature quality. RevMan5.3 software was used for meta-analysis. Results: Meta-analysis of 13 included literature studies involving 1533 patients showed that oral care with chlorhexidine solution could reduce the incidence of VAP in patients with mechanical ventilation and the difference was statistically significant (RR = 0.61, 95% CI (0.46, 0.82), P=0.04). However, the results showed that the incidence of VAP of low concentration (0.02%, 0.12%, and 0.2%) and high concentration (2%) of chlorhexidine in the intervention group was lower than that in the control group and the difference was statistically significant (RR = 0.70, 95% CI (0.51, 0.96), P=0.03; RR = 0.41, 95% CI (0.27, 0.62)). There was no significant difference in mortality between the two groups (RR = 1.01, 95% CI (0.85, 1.21), P=0.87). There was no statistical significance in days ventilated or days in ICU between the two groups (RR = -0.02, 95% CI (-0.19, 0.16), P=0.84; RR = 0.01, 95% CI (-0.11, 0.14), P=0.85). Conclusion: Existing evidence shows that chlorhexidine used for oral care of patients with mechanical ventilation can reduce the incidence of VAP, and high concentration of chlorhexidine (2%) or low concentration of chlorhexidine (0.02%, 0.12%, 0.2%) has a significant effect on the prevention of VAP. Considering the safety of clinical application, it is recommended to use 0.02%, 0.12%, and 0.2% chlorhexidine solution for oral care.

Pattern of Altered Magnetization Transfer Rate in Alzheimer's Disease.

BACKGROUND: Biomarkers for Alzheimer's disease (AD) are crucial for early diagnosis and treatment monitoring once disease modifying therapies become available. OBJECTIVE: This study aims to quantify the forward magnetization transfer rate (kfor) map from brain tissue water to macromolecular protons and use it to identify the brain regions with abnormal kfor in AD and AD progression. METHODS: From the Cardiovascular Health Study (CHS) cognition study, magnetization transfer imaging (MTI) was acquired at baseline from 63 participants, including 20 normal controls (NC), 18 with mild cognitive impairment (MCI), and 25 AD subjects. Of those, 53 participants completed a follow-up MRI scan and were divided into four groups: 15 stable NC, 12 NC-to-MCI, 12 stable MCI, and 14 MCI/AD-to-AD subjects. kfor maps were compared across NC, MCI, and AD groups at baseline for the cross-sectional study and across four longitudinal groups for the longitudinal study. RESULTS: We found a lower kfor in the frontal gray matter (GM), parietal GM, frontal corona radiata (CR) white matter (WM) tracts, frontal and parietal superior longitudinal fasciculus (SLF) WM tracts in AD relative to both NC and MCI. Further, we observed progressive decreases of kfor in the frontal GM, parietal GM, frontal and parietal CR WM tracts, and parietal SLF WM tracts in stable MCI. In the parietal GM, parietal CR WM tracts, and parietal SLF WM tracts, we found trend differences between MCI/AD-to-AD and stable NC. CONCLUSION: Forward magnetization transfer rate is a promising biomarker for AD diagnosis and progression.

MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial.

BACKGROUND: This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM). METHODS: Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin® R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 Control-INI, 59 Control-Placebo; 109 female, 65.8 ± 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM). RESULTS: DM-INI had faster NW (~ 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain. CONCLUSION: There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline.

The Longitudinal Effect of Meditation on Resting-State Functional Connectivity Using Dynamic Arterial Spin Labeling: A Feasibility Study.

We aimed to assess whether dynamic arterial spin labeling (dASL), a novel quantitative MRI technique with minimal contamination of subject motion and physiological noises, could detect the longitudinal effect of focused attention meditation (FAM) on resting-state functional connectivity (rsFC). A total of 10 novice meditators who recorded their FAM practice time were scanned at baseline and at the 2-month follow-up. Two-month meditation practice caused significantly increased rsFC between the left medial temporal (LMT) seed and precuneus area and between the right frontal eye (RFE) seed and medial prefrontal cortex. Meditation practice time was found to be positively associated with longitudinal changes of rsFC between the default mode network (DMN) and dorsal attention network (DAN), between DMN and insula, and between DAN and the frontoparietal control network (FPN) but negatively associated with changes of rsFC between DMN and FPN, and between DAN and visual regions. These findings demonstrate the capability of dASL in identifying the FAM-induced rsFC changes and suggest that the practice of FAM can strengthen the efficient control of FPN on fast switching between DMN and DAN and enhance the utilization of attentional resources with reduced focus on visual processing.

Longitudinal effects of meditation on brain resting-state functional connectivity.

Changes in brain resting-state functional connectivity (rsFC) were investigated using a longitudinal design by following a 2-month focused attention meditation (FAM) practice and analyzing their association with FAM practice time. Ten novice meditators were recruited from a university meditation course. Participants were scanned with a resting-state fMRI sequence with multi-echo EPI acquisition at baseline and at the 2-month follow-up. Total FAM practice time was calculated from the daily log of the participants. We observed significantly increased rsFC between the posterior cingulate cortex (PCC) and dorsal attention network (DAN), the right middle temporal (RMT) region and default mode network (DMN), the left and right superior parietal lobules (LSPL/RSPL) and DMN, and the LSPL/RSPL and DAN. Furthermore, the rsFC between the LSPL and medial prefrontal cortex was significantly associated with the FAM practice time. These results demonstrate increased connectivity within the DAN, between the DMN and DAN, and between the DMN and visual cortex. These findings demonstrate that FAM can enhance the brain connection among and within brain networks, especially DMN and DAN, indicating potential effect of FAM on fast switching between mind wandering and focused attention and maintaining attention once in the attentive state.

Cerebral Blood Flow Predicts Conversion of Mild Cognitive Impairment into Alzheimer's Disease and Cognitive Decline: An Arterial Spin Labeling Follow-up Study.

BACKGROUND: This is the first longitudinal study to assess regional cerebral blood flow (rCBF) changes during the progression from normal control (NC) through mild cognitive impairment (MCI) and Alzheimer's disease (AD). OBJECTIVE: We aim to determine if perfusion MRI biomarkers, derived from our prior cross-sectional study, can predict the onset and cognitive decline of AD. METHODS: Perfusion MRIs using arterial spin labeling (ASL) were acquired in 15 stable-NC, 14 NC-to-MCI, 16 stable-MCI, and 18 MCI/AD-to-AD participants from the Cardiovascular Health Study (CHS) cognition study. Group comparisons, predictions of AD conversion and time to conversion, and Modified Mini-Mental State Examination (3MSE) from rCBF were performed. RESULTS: Compared to the stable-NC group: 1) the stable-MCI group exhibited rCBF decreases in the right temporoparietal (p = 0.00010) and right inferior frontal and insula (p = 0.0094) regions; and 2) the MCI/AD-to-AD group exhibited rCBF decreases in the bilateral temporoparietal regions (p = 0.00062 and 0.0035). Compared to the NC-to-MCI group, the stable-MCI group exhibited a rCBF decrease in the right hippocampus region (p = 0.0053). The baseline rCBF values in the posterior cingulate cortex (PCC) (p = 0.0043), bilateral superior medial frontal regions (BSMF) (p = 0.012), and left inferior frontal (p = 0.010) regions predicted the 3MSE scores for all the participants at follow-up. The baseline rCBF in the PCC and BSMF regions predicted the conversion and time to conversion from MCI to AD (p < 0.05; not significant after multiple corrections). CONCLUSION: We demonstrated the feasibility of ASL in detecting rCBF changes in the typical AD-affected regions and the predictive value of baseline rCBF on AD conversion and cognitive decline.

Blunted circadian cortisol in children is associated with poor cardiovascular health and may reflect circadian misalignment.

OBJECTIVES: Circadian cues in children (sunlight, exercise, diet patterns) may be associated with health outcomes. The primary objective was to assess associations of daily cortisol fluctuations (morning, night) with cardiovascular health outcomes. A secondary objective was to determine if 1-year longitudinal changes in circadian cortisol levels are associated with longitudinal changes in health outcomes. STUDY DESIGN: The Cardiovascular Health Intervention Program (CHIP) was a cross-sectional and longitudinal study of cardiovascular risk profiles in public elementary school children in Southern Maine. Participants were 689 students in 4th grade (baseline; age = 9.20 ± 0.41 years), and 647 students in 5th grade (age = 10.53 ± 0.52 years). Longitudinal data (4th and 5th grade) was available for 347 participants. Clinical outcomes were blood pressure, hip/waist ratios, body mass index, percent fat. Laboratory measures were fasting glucose, lipids, and salivary cortisol measures (morning and evening). RESULTS: Lower first-in-morning diurnal cortisol levels were associated with increased blood pressure (ß -0.23 ± 0.05; p < 0.001), increased body fat (ß -0.22 ± 0.05; p < 0.001), and poor lipid profiles (ß -0.15 ± 0.07; p < 0.05). Inclusion of night cortisol in the model (stress-related) improved associations of the model with bodyfat composition (morning ß -0.27 ± 0.05; p < 0.001; night ß +0.16 ± 0.06; p < 0.01). Adjustments for potential confounding variables improved associations of morning cortisol with lipids (ß -0.19 ± 0.07; p < 0.01). Longitudinal analysis showed that lower morning diurnal cortisol in 4th grade was associated with increases in blood pressure a year later (ß -0.18 ± 0.08; p = 0.017) after adjusting for confounding variables. CONCLUSION: Data presented suggest adding circadian misalignment (lower amplitude of first-in-morning cortisol) to existing models of metabolic syndrome in children. Further, circadian misalignment may be a factor contributing to high blood pressure.