Variations In Cerebral Blood Flow Research Articles

Association between cerebral blood flow variation and cognitive decline in older patients undergoing hemodialysis.

The mechanism of cognitive impairment in hemodialysis patients is multifactorial. The relationship between cerebral blood flow and the decline of cognitive function is poorly understood. To investigate the association between cerebral blood flow variation and decline of cognitive function in older patients undergoing hemodialysis. In this prospective observational cohort study of 121 older patients undergoing hemodialysis, we used transcranial Doppler ultrasound (TCD) to measure cerebral arterial mean flow velocity (MFV) throughout dialysis, assessed cognitive function at baseline and 12-month follow-up, and then analyzed associations between MFV and changes on cognitive scores. TCD recordings demonstrated a significant reduction in MFV throughout dialysis, which were significantly correlated with cumulative ultrafiltration volume (rho 0.356, p < 0.001), ΔSBP (rho 0.251, p = 0.005), and ΔMAP (rho 0.194, p = 0.032). Compared with the baseline assessments, cognitive scores of participants at the 12-month follow-up were significantly worsened in global cognition (MOCA), some tests of memory (CFT-memory), executive function (TMT-B, SCWT-C, and SCWT-T), attention/processing speed (SDMT), and visuospatial function (CFT-copy) (p < 0.05). The worsening scores in global cognition (MOCA) (β = 0.066, 95% CI 0.018-0.113, p = 0.007) and some tests of memory (AVLT5) (β = 0.050, 95% CI 0.004-0.097, p = 0.035) and executive function (TMT-B, SCWT-C, SCWT-T) (β = 1.955, 95% CI 0.457-3.453, p = 0.011; β = 0.298, 95% CI 0.112-0.484, p = 0.002 and β = 1.371, 95% CI 0.429-2.303, p = 0.004, respectively) were significantly associated with the reduction of MFV. Hemodialysis may significantly reduce cerebral blood flow in older patients; Repetitive intradialytic decreases in CBF may be one of the mechanisms underlying the decline of cognitive function. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000C5B5&selectaction=Edit&uid=U0003QEL&ts=4&cx=-djoi2.

Magnetic resonance imaging patterns and perfusion changes of posterior reversible encephalopathy syndrome in children with clinical outcome correlation.

Posterior reversible encephalopathy syndrome (PRES) in children has a propensity towards atypical features on magnetic resonance (MR) imaging, with limited literature on perfusion changes and clinicoradiological correlation. We aimed to comprehensively study MR imaging patterns of pediatric PRES, including cerebral blood flow variations on arterial spin labeling, and looked for any MR biomarkers of poor clinical outcome. In this retrospective observational study conducted in a tertiary hospital setting, MR records over a 4-year period (May 2019 to May 2023) were systematically searched along with their clinical details. Patients with an age less than 18years and a clinicoradiological constellation consistent with PRES were included. MR scans were analyzed by two neuroradiologists with 8years' and 10years' experience. Association was sought with poor clinical outcome (defined as modified Rankin Scale score at discharge of > 2). A total of 45 patients (29 boys) were included in the study, with a mean age (± standard deviation) of 11.19 (± 4.53) years. On MR imaging, 95.6% of patients (n = 43) showed atypical features and/or atypical areas of involvement. The superior frontal sulcus (n = 18) was the most predominant MR pattern, and cerebellar involvement was not uncommon (n = 15). Unilateral involvement (n = 3), isolated central pattern (n = 1), and spinal cord involvement (PRES-SCI: n = 1) were also encountered. Brainstem involvement (n = 4) showed a characteristic "V-sign" of anterior medullary hyperintensity. Patchy restricted diffusion (46.6%), punctate hemorrhages (37.7%), and leptomeningeal contrast enhancement (36%) were not uncommon. Arterial spin labeling sequence (available in 24 patients) showed increased cerebral blood flow in the involved areas in 79.2% of patients. Univariate analysis showed a significant association of the presence of hemorrhage (P = 0.003), involvement of brainstem (P = 0.007), deep white matter (P = 0.008), and thalamus (P = 0.026) with poor clinical outcome. Multivariate regression analysis found that hemorrhage on MRI (P = 0.011, odds ratio 8) was an independent factor associated with poor clinical outcome. The conventionally described atypical features in PRES are common in children and therefore may no longer be considered exceptions. Raised perfusion on arterial spin labeling sequence was seen in the majority of cases. Hemorrhage on MRI was an independent predictor of poor clinical outcome in pediatric PRES.

Diffusion model enables quantitative CBF analysis of Alzheimer's Disease.

Cerebral blood flow (CBF) measured by arterial spin labeling (ASL) is a promising biomarker for Alzheimer's Disease (AD). ASL data from multiple vendors were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. However, the M0 images were missing in Siemens ASL data, prohibiting CBF quantification. Here, we utilized a generative diffusion model to impute the missing M0 and validated generated CBF data with acquired data from GE. A conditional latent diffusion model was trained to generate the M0 image and validate it on an in-house dataset (N=55) based on image similarity metrics, accuracy of CBF quantification, and consistency with the physical model. This model was then applied to the ADNI dataset (Siemens: N=211) to impute the missing M0 for CBF calculation. We further compared the imputed data (Siemens) and acquired data (GE) regarding regional CBF differences by AD stages, their classification accuracy for AD prediction, and CBF trajectory slopes estimated by a mixed effect model. The trained diffusion model generated the M0 image with high fidelity (Structural similarity index, SSIM=0.924±0.019; peak signal-to-noise ratio, PSNR=33.348±1.831) and caused minimal bias in CBF values (mean difference in whole brain is 1.07±2.12ml/100g/min). Both generated and acquired CBF data showed similar differentiation patterns by AD stages, similar classification performance, and decreasing slopes with AD progression in specific AD-related regions. Generated CBF data also improved accuracy in classifying AD stages compared to qualitative perfusion data. This study shows the potential of diffusion models for imputing missing modalities for large-scale studies of CBF variation with AD.

Transient Changes in Cerebral Tissue Oxygen, Glucose, and Temperature by Microstrokes: A Computational Study.

This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity. A mathematical model was developed to simulate the changes in cerebral tissue pO2, glucose concentration, and temperature due to blood flow interruptions. The model considers variations in baseline cerebral blood flow (CBF), capillary density, and blood oxygen/glucose levels, as well as ambient temperature changes. Simulations indicate that complete blood flow obstruction still allows for limited glucose availability, supporting nonoxidative metabolism and potentially exacerbating lactate buildup and acidosis. Partial obstructions decrease tissue pO2, with minimal impact on glucose level, which can remain almost unchanged or even slightly increase. Reduced CBF, capillary density, or blood oxygen due to aging or disease enhances hypoxia risk at lower obstruction levels, with capillary density having a significant effect on stroke severity by influencing both pO2 and glucose levels. Conditions could lead to co-occurrence of hypoxia/hypoglycemia or hypoxia/hyperglycemia, each worsening outcomes. Temperature effects were minimal in deep brain regions but varied near the skull by 0.2-0.8°C depending on ambient temperature. The model provides insights into the conditions driving severe stroke outcomes based on estimated levels of hypoxia, hypoglycemia, hyperglycemia, and temperature changes.

Evaluation of the correlation between cerebral hemodynamics and blood pressure by comparative analysis of variation in cerebral blood flow in hypertensive versus normotensive individuals: A systematic review and meta-analysis.

Current understanding of the cerebral vascular response to variations in blood pressure (BP) among individuals with hypertension is limited. The aim of this meta-analysis was to determine the correlation between hypertension, risk of stroke, and cerebral blood flow (CBF). We reviewed studies published between 2000 and 2023 from PubMed, Google Scholar, and Science Direct that compared mean CBF in normotensive (NTN) and hypertensive (HTN) patients. A random effects model was used to construct the risk ratio (RR), 95% confidence interval (CI), forest plot, and inverse variance weighting. Additionally, a mixed-effects meta-regression was employed to examine the impact of study-specific patient variables. This meta-analysis included eight prospective cross-sectional studies published from 2002 to 2023. It revealed a significant average difference in the standard mean CBF of -0.45 (95% CI -0.60 to -0.30, I2 = 69%, P < 0.00001), distinguishing NTN from HTN subjects. A RR of 0.90 (95% CI 0.63 to 1.30, I2 = 89%, P = 0.04) indicated a significant decrease in CBF among individuals with hypertension. We found a statistically significant relationship between changes in diastolic and systolic BPs and the mean CBF (R -0.81, P = 0.001 and R = -0.90, P = 0.005, respectively). Our research demonstrates a strong relationship between elevated BP and reduced CBF, with hypertension reducing CBF compared to NTN individuals, by increasing cerebrovascular resistance.

Arterial Lesion Location and Outcomes of Intracranial Atherosclerotic Disease.

Intracranial atherosclerosis is a leading cause of stroke with a high recurrence rate despite treatment. Numerous factors are proposed to influence stroke recurrence due to intracranial atherosclerosis including lesion eccentricity, plaque characteristics, and computational fluid dynamic metrics, such as wall shear stress. An overlooked variable that intrinsically relates to intracranial atherosclerosis is the location of the arterial segment where the lesion occurs. Variations in cerebral blood flow, arterial anatomy, and flow dynamics are likely drivers of initial lesion development and thus likely to influence stroke recurrence. To date, treatment trials of intracranial atherosclerosis have not considered arterial segment lesion location as an independent variable, failing to account for variations in flow dynamics between each artery. There are limited available data on differences between arterial segments, confined to only post hoc analyses. In this review, we summarize available data on such differences between arterial segments. With the limited arterial segment data available, multiple differences in recurrence of stroke in territory of lesion were identified across trials.

Quantifying cerebral blood flow changes using arterial spin labeling: A comparative study of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease

IntroductionIdiopathic rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) have been found to have changes in cerebral perfusion and overlap of some of the lesioned brain areas. However, a consensus regarding the specific location and diagnostic significance of these cerebral blood perfusion alternations remains elusive in both iRBD and PD. The present study evaluated the patterns of cerebral blood flow changes in iRBD and PD. Material and methodsA total of 59 right-handed subjects were enrolled, including 15 patients with iRBD, 20 patients with PD, and 24 healthy controls (HC). They were randomly divided into groups at a ratio of 4 to 1 for training and testing. A PASL sequence was employed to obtain quantitative cerebral blood flow (CBF) maps. The CBF values were calculated from these acquired maps. In addition, AutoGluon was employed to construct a classifier for CBF features selection and classification. An independent t-test was performed for CBF variations, with age and sex as nuisance variables. The performance of the feature was evaluated using receiver operating characteristic (ROC) curves. A significance level of P < 0.05 was considered significant. CBF in several brain regions, including the left median cingulate and paracingulate gyri and the right middle occipital gyrus (MOG), showed significant differences between PD and HC, demonstrating good classification performance. The combined model that integrates all features achieved even higher performance with an AUC of 0.9380. Additionally, CBF values in multiple brain regions, including the right MOG and the left angular gyrus, displayed significant differences between PD and iRBD. Particularly, CBF values in the left angular gyrus exhibited good performance in classifying PD and iRBD. The combined model achieved improved performance, with an AUC of 0.8533. No significant differences were found in brain regions when comparing CBF values between iRBD and HC subjects. ConclusionsASL-based quantitative CBF change features can offer reliable biomarkers to assist in the diagnosis of PD. Regarding the characteristic of CBF in the right MOG, it is anticipated to serve as an imaging biomarker for predicting the progression of iRBD to PD.

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants. DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

The association between cerebral blood flow variations during on-pump coronary artery bypass grafting surgery and postoperative delirium.

Postoperative delirium (POD) has a major impact on patient recovery after cardiac surgery. Although its pathophysiology remains unclear, there could be a correlation between cerebral blood flow (CBF) variations during cardio-pulmonary bypass (CPB) and POD. Our study aimed to evaluate whether variations in on-pump CBF, compared to pre-anesthesia and pre-CPB values, are associated with POD following coronary artery bypass grafting (CABG) surgery. This prospective observational cohort study included 95 adult patients undergoing elective on-pump CABG surgery. Right middle cerebral artery blood flow velocity (MCAV) was assessed using Transcranial Doppler before anesthesia induction, before CPB and every fifteen minutes during CPB. Pre-anesthesia and pre-CPB values were chosen as baselines. Individual values, measured during CPB, were converted as percentage changes relative to these baselines and named as %MCAV0 and %MCAV1, respectively. POD was assessed using the Confusion Assessment Method for ICU (CAM-ICU) during the first 48 post-operative hours and with the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) on the fifth post-surgical day. Overall POD incidence was 17.9%. At 30minutes of CPB, %MCAV0 was higher in POD group than in no-POD group (p = .05). %MCAV0 at 45minutes of CPB was significantly higher in POD group (87 (±17) %) than in no-POD group (68 (±24) %), p = .04. %MCAV1 at 30 and 45minutes of CPB were higher in POD group than in no-POD group, at the limit of statistical significance. We found %MCAV1 > 100% in POD group, but not in no-POD group. Significant differences in %MCAV0 became evident after 30minutes of CPB, whereas differences in %MCAV1 at 45 minutes of CPB were at limit of statistical significance. In POD group %MCAV1 was higher than 100% at 30 and 45minutes of CPB, which is supposed to be a sign of cerebral hyperperfusion. Monitoring CBF during CPB could have prognostic value for POD.

Circadian and Diurnal Regulation of Cerebral Blood Flow.

Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular reactivity, autoregulation, and neurovascular coupling. We review the evidence for the circadian and diurnal variation in each of these mechanisms and their integration, from the detailed evidence for mechanisms underlying the nocturnal nadir and morning surge in blood pressure to identifying limited available evidence for circadian and diurnal variation in cerebrovascular compensatory mechanisms. We, thus, identify key systemic hemodynamic factors related to the diurnal variation in the risk of stroke but particularly identify the need for further research focused on cerebrovascular regulatory mechanisms.

Diurnal variation of cerebral blood flow in healthy humans under normal entrained conditions.

The presence of a circadian cycle of cerebral blood flow may have implications for the occurrence of daily variations in cerebrovascular events in humans, but how cerebral blood flow varies throughout the day and its mechanism are still unclear. The study aimed to explore the diurnal variation of cerebral blood flow in healthy humans and its possible mechanisms. Arterial spin labelling images were collected at six time-points (09:00 hours, 13:00 hours, 17:00 hours, 21:00 hours, 01:00 hours, 05:00 hours) from 18 healthy participants (22-39 years old; eight females) to analyse diurnal variations in cerebral blood flow. Resting heart rate and blood pressure at six time-points and blood indicators (20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids, prostaglandin E2, noradrenaline and nitric oxide) related to cerebral vascular tone at two time-points (09:00 hours and 21:00 hours) were collected to analyse possible influences on diurnal variations in cerebral blood flow. From 21:00 hours to 05:00 hours, parietal cortical relative cerebral blood flow tended to increase, while frontal cortical and cerebellar relative cerebral blood flow tended to decrease. There was a time-dependent negative correlation between parietal cortical relative cerebral blood flow and resting heart rate, whereas there was a time-dependent positive correlation between cerebellar relative cerebral blood flow and resting heart rate. The change of parietal cortical relative cerebral blood flow was positively correlated with the change of nitric oxide. There was also a time-dependent positive correlation between mean arterial pressure and mean whole-brain cerebral blood flow. The findings indicated that parietal cortical relative cerebral blood flow and frontal cortical/cerebellar relative cerebral blood flow showed roughly opposite trends throughout the day. The diurnal variations in relative cerebral blood flow were regional-specific. Diurnal variation of nitric oxide and neurogenic regulation may be potential mechanisms for diurnal variation in regional relative cerebral blood flow.

Unraveling diurnal and technical variability in cerebral hemodynamics from neurovascular 4D-Flow MRI

Neurovascular 4D-Flow MRI enables non-invasive evaluation of cerebral hemodynamics including measures of cerebral blood flow (CBF), vessel pulsatility index (PI), and cerebral pulse wave velocity (PWV). 4D-Flow measures have been linked to various neurovascular disorders including small vessel disease and Alzheimer’s disease; however, physiological and technical sources of variability are not well established. Here, we characterized sources of diurnal physiological and technical variability in cerebral hemodynamics using 4D-Flow in a retrospective study of cognitively unimpaired older adults (N = 750) and a prospective study of younger adults (N = 10). Younger participants underwent repeated MRI sessions at 7am, 4 pm, and 10 pm. In the older cohort, having an MRI earlier on the day was significantly associated with higher CBF and lower PI. In prospective experiments, time of day significantly explained variability in CBF and PI; however, not in PWV. Test-retest experiments showed high CBF intra-session repeatability (repeatability coefficient (RPC) =7.2%), compared to lower diurnal repeatability (RPC = 40%). PI and PWV displayed similar intra-session and diurnal variability (PI intra-session RPC = 22%, RPC = 24% 7am vs 4 pm; PWV intra-session RPC = 17%, RPC = 21% 7am vs 4 pm). Overall, CBF measures showed low technical variability, supporting diurnal variability is from physiology. PI and PWV showed higher technical variability but less diurnal variability.

Gradients of O-information highlight synergy and redundancy in physiological applications.

The study of high order dependencies in complex systems has recently led to the introduction of statistical synergy, a novel quantity corresponding to a form of emergence in which patterns at large scales are not traceable from lower scales. As a consequence, several works in the last years dealt with the synergy and its counterpart, the redundancy. In particular, the O-information is a signed metric that measures the balance between redundant and synergistic statistical dependencies. In spite of its growing use, this metric does not provide insight about the role played by low-order scales in the formation of high order effects. To fill this gap, the framework for the computation of the O-information has been recently expanded introducing the so-called gradients of this metric, which measure the irreducible contribution of a variable (or a group of variables) to the high order informational circuits of a system. Here, we review the theory behind the O-information and its gradients and present the potential of these concepts in the field of network physiology, showing two new applications relevant to brain functional connectivity probed via functional resonance imaging and physiological interactions among the variability of heart rate, arterial pressure, respiration and cerebral blood flow.

Time-resolved Laser Speckle Contrast Imaging (TR-LSCI) of Cerebral Blood Flow.

To address many of the deficiencies in optical neuroimaging technologies, such as poor tempo-spatial resolution, low penetration depth, contact-based measurement, and time-consuming image reconstruction, a novel, noncontact, portable, time-resolved laser speckle contrast imaging (TR-LSCI) technique has been developed for continuous, fast, and high-resolution 2D mapping of cerebral blood flow (CBF) at different depths of the head. TR-LSCI illuminates the head with picosecond-pulsed, coherent, widefield near-infrared light and synchronizes a fast, high-resolution, gated single-photon avalanche diode camera to selectively collect diffuse photons with longer pathlengths through the head, thus improving the accuracy of CBF measurement in the deep brain. The reconstruction of a CBF map was dramatically expedited by incorporating convolution functions with parallel computations. The performance of TR-LSCI was evaluated using head-simulating phantoms with known properties and in-vivo rodents with varied hemodynamic challenges to the brain. TR-LSCI enabled mapping CBF variations at different depths with a sampling rate of up to 1 Hz and spatial resolutions ranging from tens/hundreds of micrometers on rodent head surfaces to 1-2 millimeters in deep brains. With additional improvements and validation in larger populations against established methods, we anticipate offering a noncontact, fast, high-resolution, portable, and affordable brain imager for fundamental neuroscience research in animals and for translational studies in humans.

Impact of Codonopsis decoction on cerebral blood flow and cognitive function in rats with chronic cerebral ischemia

Ethnopharmacological relevanceSome species of Codonopsis (local name in Shanxi: Ludang) have long demonstrated high medicinal and economic value. Radix Codonopsis, the dried root of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. modesta (Nannf.) L.D.Shen (C. pilosula var. modesta), or Codonopsis pilosula subsp. tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), was recorded as a traditional Chinese medicine back in the Qing Dynasty in Ben Cao Cong Xin. Radix Codonopsis, a valuable medicinal herb certified by the Chinese National Geographic Indication, is known for invigorating the spleen, nourishing the lungs, promoting blood circulation, and generating fluid properties. Given that chronic cerebral ischemia (CCI) is often associated with the symptoms of qi and blood deficiencies and fluid depletion, we explored the potential of Codonopsis decoction in the treatment of CCI. Study aimsWe investigated the effects of Codonopsis decoction on cerebral blood flow (CBF) and cognitive function in rats with bilateral carotid artery occlusion after surgery; explored whether Codonopsis decoction alleviates pathological injuries in brain tissue of rats after 2-VO surgery; and assessed the impact of Codonopsis decoction on the expression of chemokines, hypoxia-inducible factors, and inflammatory mediators in rats after 2-VO surgery. Materials and methodsWe used a 2-VO rat model to simulate CCI. We used a laser speckle imaging (LSI) system to observe changes in CBF before and after surgery. The goal was to examine variations in CBF at different time points after 2-VO surgery. For 4 weeks, the rats were orally administered Codonopsis decoction at doses of 2.7, 5.4, and 10.8 g/kg/day, or Ginaton at a dose of 43.2 mg/kg/day. To assess the effect of Codonopsis on cerebral hypoperfusion symptoms in rats, we conducted the Morris water maze (MWM), Barnes maze (BM), and forelimb grip strength tests. Additionally, pathological experiments including hematoxylin and eosin, Nissl, and Luxol fast blue staining were conducted. Furthermore, we used western blotting to detect changes in the levels of proteins such as the chemotactic factor CKLF1 and hypoxia-inducible actor 1-alpha (HIF-1α). ResultsOne week after 2-VO surgery, cerebral arterial blood supply in the rats rapidly reduced to approximately 43.39% ± 3.53% of the preoperative level. Cerebral cortex perfusion reached its nadir within 24 h of surgery, gradually recovering and stabilizing by the fourth week after surgery. An integration of the results from the BM, MWM, and grip strength tests, which assessed cognitive function and forelimb strength in rats after 2-VO surgery, unequivocally revealed that Codonopsis treatment significantly reduced the latency period and increased the number of platform crossings in the MWM test. Ginaton exhibited a comparable effect. Moreover, both Codonopsis and Ginaton decreased the number of errors and the time required to locate the target hole in the BM test. Histopathological staining revealed that Codonopsis and Ginaton could ameliorate pathological damage in rats after CCI and reduce the release of factors such as CKLF1 and HIF-1α. ConclusionCodonopsis decoction exerted its protective effects on CCI rats possibly by modulating the levels of chemokines, hypoxia-inducible factors, and neuroinflammatory mediators.

Cerebral Blood Flow and Arterial Transit Time Variations in Elders with Long COVID

AbstractBackgroundMany COVID‐19 patients experience persistant neurological symptoms that often extend beyond the period of acute infection, referred to as “Long COVID”, where most patients reported brain fog and cognitive dysfunction. While elderly individuals are more vulnerable to possible enduring cognitive impairments after acute COVID‐19 requiring hospitalization, there is increasing concern that older patients with Long COVID will be at high risk for developing Alzheimer’s disease (AD) and dementia. Although there is emerging recognition of Long COVID, its underlying neuropathology remains unknown. This study aimed to investigate neurovascular function using advanced MRI perfusion in elder patients with Long COVID.MethodWell‐matched elderly Long COVID patients (n = 14, mean age = 60.1±4.3 years, 12F, 2M) and control subjects (n = 25, mean age = 60.4±7.2 years, 19F, 6M) underwent neurocognitive testing as well as neuroimaging. Patients were seen 711.57 ± 165.02 days after the initial mild non‐hospitalized COVID‐19 infection. Clinical cognitive complaints of Long COVID patients included memory changes (n = 12, 85.7%), attention (n = 12, 85.7%), speech/writing (n = 9, 64.3%), and multitasking (n = 9, 64.3%). Brain perfusion was evaluated using an advanced 3D pseudo‐continuous arterial spin labeling (pCASL) sequence with Hadamard encoded multiple post‐labeling delays (PLDs), enabling estimation of Cerebral Blood Flow (CBF) and Arterial Transit Time (ATT) ATT and ATT corrected CBF.ResultConventional MRI scans (T1, T2, and FlAIR) appear normal in all subjects. Voxelwise comparisons between Long‐COVID and control subjects showed a significant global decrease in the ATT (p &lt; 0.05, cluster corrected at a &lt; 0.05), along default mode and other key networks, where there is a trend of decreased CBF (p&lt;0.05, uncorrected) specifically in the frontal lobe in those with Long COVID.ConclusionThese preliminary results in an aging group indicate that neurocognitive effects of Long COVID could be attributed to neurovascular dysfunction, even in those cases with initial non‐hospitalized mild COVID‐19 of more than 500 days. The novel finding of diffusely decreased ATT could be something attributable to the unique neurovascular mechanism of Long COVID. Future longitudinal research following the progression of those elderly Long COVID patients with known abnormal neurovascular function to fully evaluate their risk for developing AD and dementia.

Cerebral Blood Flow and Arterial Transit Time Variations in Elders with Long COVID

AbstractBackgroundMany COVID‐19 patients experience persistant neurological symptoms that often extend beyond the period of acute infection, referred to as “Long COVID”, where most patients reported brain fog and cognitive dysfunction. While elderly individuals are more vulnerable to possible enduring cognitive impairments after acute COVID‐19 requiring hospitalization, there is increasing concern that older patients with Long COVID will be at high risk for developing Alzheimer’s disease (AD) and dementia. Although there is emerging recognition of Long COVID, its underlying neuropathology remains unknown. This study aimed to investigate neurovascular function using advanced MRI perfusion in elder patients with Long COVID.MethodWell‐matched elderly Long COVID patients (n = 14, mean age = 60.1±4.3 years, 12F, 2M) and control subjects (n = 25, mean age = 60.4±7.2 years, 19F, 6M) underwent neurocognitive testing as well as neuroimaging. Patients were seen 711.57 ± 165.02 days after the initial mild non‐hospitalized COVID‐19 infection. Clinical cognitive complaints of Long COVID patients included memory changes (n = 12, 85.7%), attention (n = 12, 85.7%), speech/writing (n = 9, 64.3%), and multitasking (n = 9, 64.3%). Brain perfusion was evaluated using an advanced 3D pseudo‐continuous arterial spin labeling (pCASL) sequence with Hadamard encoded multiple post‐labeling delays (PLDs), enabling estimation of Cerebral Blood Flow (CBF) and Arterial Transit Time (ATT) ATT and ATT corrected CBF.ResultConventional MRI scans (T1, T2, and FlAIR) appear normal in all subjects. Voxelwise comparisons between Long‐COVID and control subjects showed a significant global decrease in the ATT (p &lt; 0.05, cluster corrected at α &lt; 0.05), along default mode and other key networks, where there is a trend of decreased CBF (p&lt;0.05, uncorrected) specifically in the frontal lobe in those with Long COVID.ConclusionThese preliminary results in an aging group indicate that neurocognitive effects of Long COVID could be attributed to neurovascular dysfunction, even in those cases with initial non‐hospitalized mild COVID‐19 of more than 500 days. The novel finding of diffusely decreased ATT could be something attributable to the unique neurovascular mechanism of Long COVID. Future longitudinal research following the progression of those elderly Long COVID patients with known abnormal neurovascular function to fully evaluate their risk for developing AD and dementia.

Associations between ASL‐derived cerebrovascular health and cognitive performance: results from the Insight 46 study

AbstractBackgroundCardiovascular and cerebrovascular pathology may accelerate brain aging and cognitive decline. Structural cerebrovascular imaging biomarkers, such as white matter hyperintensities, reflect mostly irreversible accumulated damage. In contrast, cerebral blood flow (CBF), measured with arterial spin labelling (ASL) perfusion MRI, is a potential early haemodynamic biomarker of cognitive impairment. However, our understanding of physiological CBF variability and its relation with cognition is limited.MethodWe included 245 cognitively unimpaired participants from the Insight 46 birth cohort study, who underwent 3D T1‐weighted and pseudo‐continuous ASL‐MRI (labelling duration = 1800ms; post‐labelling delay = 1800ms) on a 3T Siemens Biograph mMR PET‐MRI scanner. Cognitive assessment included tests for logical memory (Wechsler Memory Scale‐Revised), associative memory (Face‐Name Associative Memory Exam), attention and processing speed (Digit‐symbol substitution and response inhibition test), non‐verbal reasoning (Matrix test), executive functioning (Choice Reaction Time), visuomotor integration (circle‐tracing task), and two composite scores (Mini‐Mental State Examination (MMSE) and the Preclinical Alzheimer Cognitive Composite).ResultSample characteristics are reported in Table 1. Associations were found between GM sCoV and MMSE (Male/Female ß = 0.74/‐0.75, p = 0.028, Figure 1), and GM sCoV and Logical Memory (Male/Female ß = 1.05/‐0.25, p = 0.005, Figure 2), but not between CBF and any cognitive scores (p&gt;0.05).ConclusionIn a cognitively unimpaired population, cognitive performance was associated with GM sCoV but not with other CBF parameters. However, in males, the relationship was opposite to what we expected. Further work should investigate to what extent this indicates macrovascular change occurs before perfusion alterations and could relate to future cognitive decline, and how they differ between sex.

Cognitive status modifies the association between elevated cerebrospinal fluid phosphorylated tau and longitudinal cerebral blood flow changes over a 7‐year follow‐up period

AbstractBackgroundAlzheimer’s disease (AD) is associated with widespread reductions in cerebral blood flow (CBF), but the precise link between AD pathology and CBF is unclear. Hypoperfusion is a late‐stage event associated with tau, but not amyloid, pathology. We assessed whether baseline levels of cerebrospinal fluid (CSF)‐measured core AD pathology [β‐amyloid42 (Aβ42), phosphorylated tau (p‐tau)] related to CBF changes over a 7‐year period and if associations differed by baseline cognitive status.MethodsVanderbilt Memory and Aging Project participants free of clinical dementia or stroke at enrollment [n = 153, 72±6 years, 37% mild cognitive impairment (MCI), 33% female] underwent lumbar puncture to obtain CSF at study entry and serial multimodal 3T brain magnetic resonance imaging over a 7‐year follow‐up period (mean = 5.4 years). Enzyme‐linked immunosorbent assays quantified CSF Aβ42 and p‐tau181. Pseudo‐continuous arterial spin‐labeling captured CBF in total and lobar grey matter regions of interest (ROI). Linear mixed‐effects models related biomarker x time to longitudinal CBF variables adjusting for baseline age and cognitive status, sex, race/ethnicity, education, Framingham Stroke Risk Profile (minus age), ROI volume, APOE‐ε4 status, and time. Models were repeated testing a cognitive status x biomarker x time interaction term.ResultsIn main effect models, neither CSF Aβ42 (p‐values&gt;0.31) nor p‐tau (p‐values&gt;0.28) related to CBF outcomes. Aβ42 did not interact with cognitive status on CBF outcomes (p‐values&gt;0.37), but p‐tau interacted with baseline cognitive status on longitudinal frontal, temporal, parietal, occipital, and total grey matter CBF trajectories (p‐values&lt;0.005). Among cognitively unimpaired participants, higher p‐tau was associated with slower reductions in frontal (β = 0.01, p = 0.03), parietal (β = 0.01, p = 0.04), occipital (β = 0.01, p = 0.02), and total grey matter CBF (β = 0.01, p = 0.04). Among individuals with MCI, higher p‐tau was associated with faster reductions in frontal (β = ‐0.03, p = 0.008), temporal (β = ‐0.02, p = 0.01), parietal (β = ‐0.04, p = 0.002), occipital (β = ‐0.03, p = 0.0004), and total grey matter CBF (β = ‐0.03, p = 0.005).ConclusionsResults linking CSF p‐tau to CBF decline in MCI support the theory that grey matter hypoperfusion is a later‐stage event tied to neurofibrillary tangle pathology. Associations between higher p‐tau and slower rates of CBF decline among cognitively unimpaired individuals warrants further investigation. Funding: R01‐AG034962, K24‐AG046373, F31‐AG079640, T32‐AG058524, P20‐AG068082

Diurnal oscillations of MRI metrics in the brains of male participants

Regulation of biological processes according to a 24-hr rhythm is essential for the normal functioning of an organism. Temporal variation in brain MRI data has often been attributed to circadian or diurnal oscillations; however, it is not clear if such oscillations exist. Here, we provide evidence that diurnal oscillations indeed govern multiple MRI metrics. We recorded cerebral blood flow, diffusion-tensor metrics, T1 relaxation, and cortical structural features every three hours over a 24-hr period in each of 16 adult male controls and eight adult male participants with bipolar disorder. Diurnal oscillations are detected in numerous MRI metrics at the whole-brain level, and regionally. Rhythmicity parameters in the participants with bipolar disorder are similar to the controls for most metrics, except for a larger phase variation in cerebral blood flow. The ubiquitous nature of diurnal oscillations has broad implications for neuroimaging studies and furthers our understanding of the dynamic nature of the human brain.