UNASSIGNED: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer\'s disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition.
UNASSIGNED: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed.
UNASSIGNED: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN.
UNASSIGNED: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.

OBJECTIVE: The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS).
METHODS: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions.
RESULTS: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = -0.004, p = 0.026), tumor grade (β = -0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = -0.005, p < 0.001), tumor grade (β = -0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = -0.002, p = 0.001), and peritumoral edema volume (β = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = -0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001).
CONCLUSIONS: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

Several risk factors contribute to the development of Alzheimer\'s disease (AD), including genetics, metabolic health, cardiovascular history, and diet. It has been observed that women appear to face a higher risk of developing AD. Among the various hypotheses surrounding the gender disparity in AD, one pertains to the potential neuroprotective properties of estrogen. Compared to men, women are believed to be more susceptible to neuropathology due to the significant decline in circulating estrogen levels following menopause. Studies have shown, however, that estrogen replacement therapies in post-menopausal women do not consistently reduce the risk of AD. While menopause and estrogen levels are potential factors in the elevated incidence rates of AD among women, this review highlights the possible roles estrogen has in other pathways that may also contribute to the sex disparity observed in AD such as olfaction, sleep, and glymphatic functionality.

Background: The impediment to β-amyloid (Aβ) clearance caused by the invalid intracranial lymphatic drainage in Alzheimer\'s disease is pivotal to its pathogenesis, and finding reliable clinical available solutions to address this challenge remains elusive. Methods: The potential role and underlying mechanisms of intranasal oxytocin administration, an approved clinical intervention, in improving intracranial lymphatic drainage in middle-old-aged APP/PS1 mice were investigated by live mouse imaging, ASL/CEST-MRI scanning, in vivo two-photon imaging, immunofluorescence staining, ELISA, RT-qPCR, Western blotting, RNA-seq analysis, and cognitive behavioral tests. Results: Benefiting from multifaceted modulation of cerebral hemodynamics, aquaporin-4 polarization, meningeal lymphangiogenesis and transcriptional profiles, oxytocin administration normalized the structure and function of both the glymphatic and meningeal lymphatic systems severely impaired in middle-old-aged APP/PS1 mice. Consequently, this intervention facilitated the efficient drainage of Aβ from the brain parenchyma to the cerebrospinal fluid and then to the deep cervical lymph nodes for efficient clearance, as well as improvements in cognitive deficits. Conclusion: This work broadens the underlying neuroprotective mechanisms and clinical applications of oxytocin medication, showcasing its promising therapeutic prospects in central nervous system diseases with intracranial lymphatic dysfunction.

BACKGROUND: The neural mechanisms underlying congenital sensorineural hearing loss (CSNHL) remain elusive.
OBJECTIVE: This study evaluated the function of the glymphatic system in children with CSNHL compared to normal-hearing children using the DTI-ALPS approach, which utilizes diffusion tensor imaging along the perivascular space.
METHODS: Twenty-six children with CSNHL and 30 age- and sex-matched healthy controls (HCs) with normal hearing thresholds were recruited. The DTIALPS index was calculated for each group. We analyzed the discrepancies in the DTI-ALPS index between patients with CSNHL and healthy controls. Additionally, Spearman\'s correlation analysis was performed to investigate the relationship between the DTI-ALPS index and age in children with CSNHL.
RESULTS: Significant differences in the DTI-ALPS index were observed between the two groups. Compared with HCs, the DTI-ALPS index in CSNHL patients was significantly lower (1.49388±0.11441 vs. 1.61402±0.15430, p=0.002). In addition, diffusivity along the z-axis in the association fiber (Dzzassoc) index was significantly higher in the CSNHL group than in the HC group (0.00041±0.00006 vs. 0.00036±0.00004, p=0.003). Furthermore, we discovered a noteworthy downward correlation between the DTI-ALPS index and age in children with CSNHL (rho = -0.544, p=0.005).
CONCLUSIONS: In this present study, glymphatic system activity in CSNHL children was investigated for the first time using the DTI-ALPS index. A significant decrease in glymphatic system function was detected in CSNHL children, which correlated well with age. The DTI-ALPS index could serve as a valuable biomarker for tracking disease progression and treatment in CSNHL and unraveling the neural mechanisms of early hearing deprivation in children with CSNHL.

BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized.
OBJECTIVE: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index.
METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed.
RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels.
CONCLUSIONS: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution in the acute phase of ICH, though the precise mechanisms remain unclear. Recent findings have highlighted the glymphatic system (GS) as a crucial component in intracranial cerebrospinal fluid circulation, playing a significant role in hematoma clearance post-ICH. This study investigates the link between SIM efficacy in hematoma resolution and the GS. Our experimental results show that SIM alleviates GS damage in ICH-induced rats, resulting in improved outcomes such as reduced brain edema, neuronal apoptosis, and degeneration. Further analysis reveals that SIM\'s effects are mediated through the VEGF-C/VEGFR3/PI3K-Akt pathway. This study advances our understanding of SIM\'s mechanism in promoting intracranial hematoma clearance and underscores the potential of targeting the GS for ICH treatment.

The perivascular space (PVS) surrounds cerebral blood vessels and plays an important role in clearing waste products from the brain. Their anatomy and function have been described for arteries, but PVS around veins remain poorly characterized. Using in vivo 2-photon imaging in mice, we determined the size of the PVS around arteries and veins, and their connection with the subarachnoid space. After infusion of 70 kD FITC-dextran into the cerebrospinal fluid via the cisterna magna, labeled PVS were evident around arteries, but veins showed less frequent labeling of the PVS. The size of the PVS correlated with blood vessel size for both pial arteries and veins, but not for penetrating vessels. The PVS around pial arteries and veins was separated from the subarachnoid space by a thin meningeal layer, which did not form a barrier for the tracer. In vivo, FITC-dextran signal was observed adjacent to the vessel wall, but minimally within the wall itself. Post-mortem, there was a significant shift in the tracer\'s location within the arterial wall, extending into the smooth muscle layer. Taken together, these findings suggest that the PVS around veins has a limited role in the exchange of solutes between CSF and brain parenchyma.

The blood-brain barrier (BBB) is a selectively semi-permeable layer, crucial in shielding the brain from external pathogens and toxic substances while maintaining ionic homeostasis and sufficient nutrient supply. However, it poses a significant challenge for drugs to penetrate the BBB in order to effectively target brain tumors. Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive technique that employs thermal energy to cauterize intracranial lesions with the potential to temporarily disrupt the BBB. This further opens a possible therapeutic window to enhance patient outcomes. Here, we review the impact of MRg-LITT on BBB and blood tumor barrier (BTB) and the duration of the BBB disruption. Studies have shown that MRg-LITT is effective due to its minimally invasive nature, precise tumor targeting, and low complication rates. Although the disruption duration varies across studies, the average peak disruption is within the initial two weeks post-ablation period and subsequently exhibits a gradual decline. However, further research involving larger groups with extended follow-up periods is required to determine disruption duration more accurately. In addition, evaluating toxicity and glymphatic system disruption is crucial to circumvent potential risks associated with this procedure.

Currently, there is unavailability of disease-modifying medication for Alzheimer\'s disease (AD), a debilitating neurological disorder. The pathogenesis of AD appears to be complex and could be influenced by the glymphatic system present in the central nervous system (CNS). Amyloid-beta (Aβ) and other metabolic wastes are eliminated from the brain interstitium by the glymphatic system, which encompasses perivascular channels and astroglial cells. Dysfunction of the glymphatic system, which could occur due to decreased aquaporin 4 (AQP4) expression, aging-related alterations in the human brain, and sleep disruptions, may contribute to the pathogenesis of AD and also accelerate the development of AD by causing a buildup of harmful proteins like Aβ. Promising approaches have been examined for reducing AD pathology, including non-pharmacological therapies that target glymphatic function, like exercise and sleep regulation. In addition, preclinical research has also demonstrated the therapeutic potential of pharmaceutical approaches targeted at augmenting AQP4-mediated glymphatic flow. To identify the precise processes driving glymphatic dysfunction in AD and to find new treatment targets, more research is required. Innovative diagnostic and treatment approaches for AD could be made possible by techniques such as dynamic contrast-enhanced MRI, which promises to evaluate glymphatic function in neurodegenerative diseases. Treatment options for AD and other neurodegenerative diseases may be improved by comprehending and utilizing the glymphatic system\'s function in preserving brain homeostasis and targeting the mechanisms involved in glymphatic functioning. This review intends to enhance the understanding of the complex link between AD and the glymphatic system and focuses on the function of AQP4 channels in promoting waste clearance and fluid exchange.