The glymphatic system is crucial for clearing metabolic waste from the brain, maintaining neural health and cognitive function. This study explores the glymphatic system\'s role in Moyamoya disease (MMD), characterized by progressive cerebral artery stenosis and brain structural lesions. We assessed 33 MMD patients and 21 healthy controls using diffusion tensor imaging along the perivascular space (DTI-ALPS) and global cortical gray matter-cerebrospinal fluid (CSF) coupling indices (gBOLD-CSF), which are indirect measurements of the glymphatic system. Cerebral perfusion in patients was evaluated via computed tomography perfusion imaging. We also measured the peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity (WMH) burden, and cognitive function. MMD patients exhibited lower ALPS and gBOLD-CSF coupling indices compared to controls (P < 0.01), indicating disrupted glymphatic function. Significant cognitive impairment was also observed in MMD patients (P < 0.01). ALPS indices varied with cerebral perfusion stages, being higher in earlier ischemic stages (P < 0.05). Analysis of brain structure showed increased CSF volume, PSMD index, and higher WMH burden in MMD patients (P < 0.01). The ALPS index positively correlated with white matter volume and cognitive scores, and negatively correlated with CSF volume, PSMD, and WMH burden (P < 0.05). Mediation analysis revealed the number of periventricular WMH significantly mediated the relationship between glymphatic dysfunction and cognitive impairment. In summary, MMD patients exhibit significant glymphatic system impairments, associated with brain structural changes and cognitive deficits.

BACKGROUND: Respective changes in neurovascular coupling (NVC) and glymphatic function have been reported in post-stroke depression (PSD). Recent studies have found a link between NVC and waste clearance by the glymphatic system, which has not been illustrated in PSD.
METHODS: We prospectively recruited ninety-six stroke patients and forty-four healthy controls (HC), with fifty-nine patients undergoing a second MRI scan. NVC metrics were investigated by exploring Pearson correlation coefficients and ratios between cerebral blood flow (CBF) and BOLD-derived quantitative maps (ALFF, fALFF, REHO maps). Diffusion tensor imaging along the perivascular (DTI-ALPS) index was used to reflect glymphatic function. We first analyzed the altered NVC metrics in stroke patients relative to the HC group. Then, we explored the relationship between NVC metrics, ALPS index and depressive symptoms at baseline and during the follow-up period through correlation and mediation analyses.
RESULTS: Stroke patients exhibited significantly lower global CBF-fALFF coupling and ALPS index. At the regional level, abnormal NVC alterations in brain regions involved in cognition, emotion, and sensorimotor function in PSD. Baseline analyses showed that ALPS index exhibited positive associations with both global and local NVC and abnormal regional NVC may contribute to generation of PSD by reducing glymphatic function (β = -0.075, p < 0.05, CI = [-0.169 to -0.012]). Longitudinal analyses similarly showed that ALPS index changes were positively associated with changes in NVC and mediated improvements in depressive symptoms.
CONCLUSIONS: Our findings suggest that NVC abnormalities leading to impaired glymphatic system function may be a potential neurobiological mechanism of PSD.

Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system.

OBJECTIVE: The current study aimed to investigate the dynamic changes in brain glymphatic function during chemotherapy in breast cancer patients (BCP) and their correlation with cognitive function.
METHODS: A total of 40 healthy female participants (control group) and 80 female BCP were included. Various cognitive assessment tools were used to evaluate cognitive function. Diffusion tensor imaging along the perivascular space was employed to measure brain glymphatic function.
RESULTS: Following chemotherapy, BCP exhibited a significant decline in various cognitive scores. After chemotherapy, the along the perivascular space index, a parameter indicating brain glymphatic function, was slightly higher than that at baseline and the control group levels and was correlated with cognitive scores.
CONCLUSIONS: This study unveiled a close relationship between the dynamic changes in brain glymphatic function after chemotherapy and cognitive function in BCP. Our findings contribute to a deeper understanding of the brain mechanisms underlying chemotherapy-related cognitive impairment and provide a theoretical basis for future interventions and treatments. In addition, they offer a new perspective for exploring the relationship between brain function and cognitive states.

BACKGROUND: Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) are significant markers associated with various neurological diseases. Although quantitative analysis of PVS may enhance sensitivity and improve consistency across studies, the field lacks a universally validated method for analyzing images from multi-center studies.
METHODS: We annotated PVS on multi-center 3D T1-weighted (T1w) images acquired using scanners from three major vendors (Siemens, General Electric, and Philips). A neural network, mcPVS-Net (multi-center PVS segmentation network), was trained using data from 40 subjects and then tested in a separate cohort of 15 subjects. We assessed segmentation accuracy against ground truth masks tailored for each scanner vendor. Additionally, we evaluated the agreement between segmented PVS volumes and visual scores for each scanner. We also explored correlations between PVS volumes and various clinical factors such as age, hypertension, and white matter hyperintensities (WMH) in a larger sample of 1020 subjects. Furthermore, mcPVS-Net was applied to a new dataset comprising both T1w and T2-weighted (T2w) images from a United Imaging scanner to investigate if PVS volumes could discriminate between subjects with differing visual scores. We also compared the mcPVS-Net with a previously published method that segments PVS from T1 images.
RESULTS: In the test dataset, mcPVS-Net achieved a mean DICE coefficient of 0.80, with an average Precision of 0.81 and Recall of 0.79, indicating good specificity and sensitivity. The segmented PVS volumes were significantly associated with visual scores in both the basal ganglia (r = 0.541, p < 0.001) and white matter regions (r = 0.706, p < 0.001), and PVS volumes were significantly different among subjects with varying visual scores. Segmentation performance was consistent across different scanner vendors. PVS volumes exhibited significant associations with age, hypertension, and WMH. In the United Imaging scanner dataset, PVS volumes showed good associations with PVS visual scores evaluated on either T1w or T2w images. Compared to a previously published method, mcPVS-Net showed a higher accuracy and improved PVS segmentation in the basal ganglia region.
CONCLUSIONS: The mcPVS-Net demonstrated good accuracy for segmenting PVS from 3D T1w images. It may serve as a useful tool for future PVS research.

OBJECTIVE: The discovery of the glymphatic system, crucial for cerebrospinal and interstitial fluid exchange, has enhanced our grasp of brain protein balance and its potential role in neurodegenerative disease prevention and therapy. Detecting early neurodegenerative shifts via noninvasive biomarkers could be key in identifying at-risk individuals for Alzheimer\'s disease (AD). Our research explores a diffusion tensor imaging (DTI) method that measures cortical mean diffusivity (cMD), potentially a more sensitive indicator of neurodegeneration than traditional macrostructural methods.
METHODS: We analyzed 67 post-traumatic stress disorder (PTSD)-diagnosed veterans from the Alzheimer\'s Disease Neuroimaging Initiative database. Participants underwent structural MRI, DTI, Aβ PET imaging, and cognitive testing. We focused on the DTI-ALPS technique to assess glymphatic function and its relation to cMD, cortical Aβ accumulation, and thickness, accounting for age and APOE ε4 allele variations.
RESULTS: The cohort, all male with an average age of 68.1 (SD 3.4), showed a strong inverse correlation between DTI-ALPS and cMD in AD-affected regions, especially in the entorhinal, parahippocampal, and fusiform areas. Higher DTI-ALPS readings were consistently linked with greater cortical thickness, independent of Aβ deposits and genetic risk factors. Age and cMD emerged as inversely proportional predictors of DTI-ALPS, indicating a complex interaction with age.
CONCLUSIONS: The study confirms a meaningful association between glymphatic efficiency and cMD in AD-sensitive zones, accentuating cortical microstructural alterations in PTSD. It positions DTI-ALPS as a viable biomarker for assessing glymphatic function in PTSD, implicating changes in DTI-ALPS as indicative of glymphatic impairment.

UNASSIGNED: Mild cognitive impairment (MCI) is a heterogeneous condition that can precede various forms of dementia, including Alzheimer\'s disease (AD). Identifying MCI subjects who are at high risk of progressing to AD is of major clinical relevance. Enlarged perivascular spaces (EPVS) on MRI are linked to cognitive decline, but their predictive value for MCI to AD progression is unclear.
UNASSIGNED: This study aims to assess the predictive value of EPVS for MCI to AD progression and develop a predictive model combining EPVS grading with clinical and laboratory data to estimate conversion risk.
UNASSIGNED: We analyzed 358 patients with MCI from the ADNI database, consisting of 177 MCI-AD converters and 181 non-converters. The data collected included demographic information, imaging data (including perivascular spaces grade), clinical assessments, and laboratory test results. Variable selection was conducted using the Least Absolute Shrinkage and Selection Operator (LASSO) method, followed by logistic regression to develop predictive model.
UNASSIGNED: In the univariate logistic regression analysis, both moderate (OR = 5.54, 95% CI [3.04-10.18]) and severe (OR = 25.04, 95% CI [10.07-62.23]) enlargements of the centrum semiovale perivascular space (CSO-PVS) were found to be strong predictors of disease progression. LASSO analyses yielded 12 variables, refined to six in the final model: APOE4 genotype, ADAS11 score, CSO-PVS grade, and volumes of entorhinal, fusiform, and midtemporal regions, with an AUC of 0.956 in the training and 0.912 in the validation cohort.
UNASSIGNED: Our predictive model, emphasizing EPVS assessment, provides clinicians with a practical tool for early detection and management of AD risk in MCI patients.

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UNASSIGNED: The cingulate sulcus sign (CSS) has been observed in patients with idiopathic normal pressure hydrocephalus (iNPH), suggesting potential disruptions in cerebrospinal fluid circulation and compromised glymphatic system. Although there are similarities in the underlying mechanisms between cerebral small vessel disease (CSVD) and iNPH, the relationship between CSS and CSVD remains unclear. This study aimed to investigate the prevalence and potential mechanisms of CSS in patients with CSVD.
UNASSIGNED: Data from patients diagnosed with CSVD at Shengjing Hospital of China Medical University between January 2020 and October 2022 were retrospectively collected, including general information, global cognitive function [assessed by measuring Mini-Mental State Examination (MMSE)], and four CSVD magnetic resonance imaging (MRI) markers [(white matter hyperintensity (WMH), cerebral microbleeds (CMBs), lacunes, and enlarged perivascular spaces (EPVS)], CSS and the Evan\'s index (EI).
UNASSIGNED: A total of 308 patients were included, and CSS was detected in 80 patients (26%). Univariate analysis revealed that MMSE scores in the CSS group were significantly lower compared to the non-CSS group (p < 0.001). Multivariable analysis showed an independent correlation between CSS and the presence of lacunes (odds ratio [OR] 0.358, 95% confidence interval [CI] 0.193-0.663, p = 0.001), presence of lobar dominant CMBs (OR 2.683, 95%CI 1.385-5.195, p = 0.003), periventricular WMH Fazekas score (OR 1.693, 95% CI 1.133-2.529, p = 0.01), and EI (OR 1.276, 95% CI 1.146-1.420, p < 0.001).
UNASSIGNED: This preliminary study showed that CSS can be observed in some patients with CSVD. The presence of CSS may represent different mechanisms of CSVD pathogenesis and reflect differences in the degree of cerebrospinal fluid (CSF)/interstitial fluid (ISF) stasis.

The excessive usage of nanoplastics (NPs) has posed a serious threat to the ecological environment and human health, which can enter the brain and then result in neurotoxicity. However, research on the neurotoxic effects of NPs based on different exposure routes and modifications of functional groups is lacking. In this study, the neurotoxicity induced by NPs was studied using polystyrene nanoplastics (PS-NPs) of different modifications (PS, PS-COOH, and PS-NH2). It was found that PS-NH2 through intranasal administration (INA) exposure route exhibited the greatest accumulation in the mice brain after exposure for 7 days. After the mice were exposed to PS-NH2 by INA means for 28 days, the exploratory ability and spatial learning ability were obviously damaged in a dose-dependent manner. Further analysis indicated that these damages induced by PS-NH2 were closely related to the decreased ability of glymphatic system to clear β-amyloid (Aβ) and phosphorylated Tau (P-Tau) proteins, which was ascribed to the loss of aquaporin-4 (AQP4) polarization in the astrocytic endfeet. Moreover, the loss of AQP4 polarization might be regulated by the NF-κB pathway. Our current study establishes the connection between the neurotoxicity induced by PS-NPs and the glymphatic system dysfunction for the first time, which will contribute to future research on the neurotoxicity of NPs.