Impact of comorbidities on relapsing rates of Neuromyelitis Optica Spectrum Disorders: Insights from a longitudinal study in Taiwan.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. METHODS: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. RESULTS: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. CONCLUSIONS: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

Clinical Research into Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.

Dominance of Tau Burden in Cortical Over Subcortical Regions Mediates Glymphatic Activity and Clinical Severity in PSP.

BACKGROUND: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated. PATIENTS AND METHODS: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score. CONCLUSIONS: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP.

Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

Safety and efficacy of intracranial vascularized submental lymph node transfer for treating hydrocephalus.

Hydrocephalus is routinely treated with ventriculoperitoneal shunt drainage of cerebrospinal fluid (CSF), a procedure plagued by high morbidity and frequent revisions. Vascularized submental lymph node (VSLN) transplants act as lymphatic pumps to drain interstitial fluid (ISF) from lymphedematous extremities. As the field of neuro-lymphatics comes to fruition, we hypothesize the efficacy of VSLN in the drainage of intracranial CSF-ISF. We report novel placement of VSLN in the temporal subdural space in two patients diagnosed with symptomatic communicating hydrocephalus. At a minimum follow-up of 1 month postoperatively, both experienced radiological and clinical improvements.

Visual reading for [18F]Florzolotau ([18F]APN-1607) tau PET imaging in clinical assessment of Alzheimer's disease.

Introduction: Tau-targeted positron emission tomography (tau-PET) is a potential tool for the differential diagnosis of Alzheimer's disease (AD) and to clarify the distribution of tau deposition. In addition to the quantitative analysis of tau-PET scans, visual reading supports the assessment of tau loading for clinical diagnosis. This study aimed to propose a method for visually interpreting tau-PET using the [18F] Florzolotau tracer and investigate the performance and utility of the visual reading. Materials and methods: A total number of 46 individuals with 12 cognitively unimpaired subjects (CU), 20 AD patients with mild cognitive impairment (AD-MCI), and 14 AD with dementia (AD-D) patients with both [18F]Florbetapir amyloid PET and [18F]Florzolotau tau PET scans were included. Clinical information, cognitive assessment, and amyloid PET scan results were recorded. For visual interpretation, a modified rainbow colormap was created and a regional tau uptake scoring system was proposed to evaluate the degree of tracer uptake and its spatial distribution within five cortical regions. Each region was scored on a scale of [0, 2] as compared to the background, and that resulted in a global scale range of [0, 10]. Four readers interpreted [18F]Florzolotau PET using the visual scale. The global and regional standardized uptake value ratios (SUVr) were also calculated for analysis. Results: The result indicates the average global visual scores were 0 ± 0 in the CU group, 3.43 ± 3.35 in the AD-MCI group, and 6.31 ± 2.97 in the AD-D group (p < 0.001). The consensus among the four observers on image scores was high with an intraclass correlation coefficient of 0.880 (95% CI: 0.767-0.936). The average global visual score was significantly associated with global SUVr (r = 0.884, p < 0.0001) and with the CDR-sum of box (r = 0.677, p < 0.0001). Conclusion: The visual reading method generated a visual score of [18F]Florzolotau tau-PET with good sensitivity and specificity to identify AD-D or CU individuals from the other patients. The preliminary result also showed that the global visual scores are significantly and reliably correlated with global cortical SUVr, and associated well with the clinical diagnosis and cognitive performance.

Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease.

OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans. METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation. INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.

Recovery of walking ability in stroke patients through postacute care rehabilitation.

BACKGROUND: Walking entails orchestration of the sensory, motor, balance, and coordination systems, and walking disability is a critical concern after stroke. How and to what extent these systems influence walking disability after stroke and recovery have not been comprehensively studied. METHODS: We retrospectively analyzed patients with stroke in the Post-acute care-Cerebrovascular Diseases (PAC-CVD) program. We compared the characteristics of patient groups stratified by their ability to complete the 5-m walk test across various time points of rehabilitation. We then used stepwise linear regression to examine the degree to which each stroke characteristic and functional ability could predict patient gait performance. RESULTS: Five hundred seventy-three patients were recruited, and their recovery of walking ability was defined by the timing of recovery in a 5-m walk test. The proportion of patients who could complete the 5-m walk test at admission, at 3 weeks of rehabilitation, at 6 weeks of rehabilitation, between 7 and 12 weeks of rehabilitation, and who could not complete the 5-m walk test after rehabilitation was 52.2%, 21.8%, 8.7%, 8.7%, and 8.6%, respectively. At postacute care discharge, patients who regained walking ability earlier had a higher chance of achieving higher levels of walking activity. Stepwise linear regression showed that Berg Balance Scale (BBS) (ß: 0.011, p < .001), age (ß: -0.005, p = .001), National Institutes of Health Stroke Scale (NIHSS) (6a + 6b; ß: -0.042, p = .018), Mini-Nutritional assessment (MNA) (ß: -0.007, p < .027), and Fugl-Meyer upper extremity assessment (FuglUE) (ß: 0.002, p = .047) scores predicted patient's gait speed at discharge. CONCLUSION: Balance, age, leg strength, nutritional status, and upper limb function before postacute care rehabilitation are predictors of walking performance after stroke.

Postpartum Spinal Cord Infarction: A Case Report and Review of the Literature.

Background: Postpartum spinal cord infarction is a very rare disease. Only two cases have been reported in the English literature. Methods: We reported a 26 year old female who received second doses of the mRNA-1273 vaccine 52 days before delivery. She presented as sudden onset of paraplegia, sensory level, and sphincter incontinence at postpartum period. No history of heparin exposure was noted. Imaging findings confirmed the T10-11 level infarction and her anti-human heparin platelet factor 4 (anti-PF4) antibody was positive. After 7 days of dexamethasone therapy, her paraplegia and urinary incontinence gradually improved. Results: The CT angiography (CTA) of the artery of Adamkiewicz (Aka) showed tandem narrowing, most conspicuous at the T10-11 level, which was presumably due to partial occlusion of the arteriolar lumen. The thoracolumbar spine magnetic resonance imaging with contrast medium showed owl's eyes sign at the T10 and T11 levels. We compared our case with two other case reports from the literature. Conclusions: Post-partum spinal cord infarction with positive anti-PF4 antibody and relatively thrombocytopenia are the characteristics of our case.

Retinal Thickness Associates with Cognition Dysfunction in Young Adult with Type 1 Diabetes in Taiwan.

Background: Several factors could affect the cognitive dysfunction in patients with type 1 diabetes (T1D). Objectives: To report the characteristic of cognitive dysfunction in T1D and find its association with the retinal thickness. Subjects: We recruited one hundred and seven patients with T1D in our study. Methods: Detailed clinical and demographic factors and Cambridge Automated Neuropsychological Test Battery (CANTAB) were performed in all participants. The age at onset>5 years old and ≤5 years old groups was defined as old- and young-onset groups. The levels of the average values of 5-year glycated hemoglobin (HbA1c_5) before study were collected. Ophthalmic study and central retinal thickness (CRT) were performed. Results: The median age of T1D was 24.9 years old and 57 participants were women. The median age at onset was 7.4 years old, and mean disease duration was 17.2 years. After adjusting off multiple covariates by the regression analyses, the young-onset group had significantly a longer latency in sustained attention than old-onset group (P = 0.02). The HbA1c_5 showed a significantly negative association with the sustained attention (P = 0.03). The average values of CRT showed significantly negative correlations with the reaction time in sustained attention and visual searching (P = 0.04 and P < 0.01, respectively). Conclusions: Our results suggest that age at onset and glycemic control had significant impacts on different cognitive domains in T1D. The CRT had a significant correlation with sustained attention, which could be a surrogate markers of brain structural changes in T1D.

Experiences of family caregivers of persons living with dementia with and without a smart- clothes assisted home nursing program during the heightened COVID-19 alert.

BACKGROUND: The COVID-19 pandemic has required restrictions of daily activities, which has been found to impact the lives of persons living with dementia (PLWDs) and their family caregivers, who have multiple care demands. The lack of relevant studies in Taiwan emphasized the need to explore the experiences of family caregivers of older PLWDs faced with the intensified restrictions to control the spread of COVID-19, and the impact of the availability of a smart-clothes home nursing program. METHODS: This qualitative study used semi-structured interviews with family caregivers of older PLWDs. Participants were recruited from dementia clinics of a medical center in northern Taiwan from a subset of a sample from a larger study on smart-clothes assisted home nursing care. A total of 12 family caregivers who participated in the original study were interviewed during the follow-up period; seven family caregivers of a PLWD wearing a smart-vest, which transmitted information to a home care nurse; five caregivers of a PLWD not wearing a smart-vest. Interviews were conducted by telephone because the conditions of the pandemic prevented face-to-face interviews. Recorded interviews were transcribed and analyzed using content analysis. RESULTS: Interview data showed family caregivers' felt the care recipient's health was compromised and functional conditions intensified as Covid-19-related pandemic restrictions increased. Specific concerns included a lack social interactions, decreased daily activity levels, loss of interest and lack of motivation for activities, increased mood and behavioral problems, a decline in physical function and an increase in health problems. Family caregivers were also impacted by these restrictions, with significant increases in severity of caregiver role strain, including feeling trapped, a lack of in-home support, profound powerlessness, and worries about the PLWD contracting the coronavirus. The smart-clothes assisted home nursing care program offered supplementary support to family caregivers by providing on-time interactions, helping them manage health problems, enhancing predictability of the care recipient's behaviors, and providing caregivers with emotional support. CONCLUSIONS: The findings of this study support alternative care such as implementation of technology-assisted home health services to meet caregiver needs to facilitate family caregiving of PLWDs during the necessary restrictions in activities implemented during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Record NCT05063045.

The correlation of small fiber neuropathy with pain intensity and age in patients with Fabry's disease: A cross sectional study within a large Taiwanese family.

BACKGROUND: The relationships among small fiber neuropathy, age, sex and pain intensity in the context of Fabry's disease remain unclear. We aim to study the correlations of small fiber neuropathy, age, sex and pain intensity in Fabry patients. METHODS: We evaluated C-fiber function by recording the withdrawal latencies to painful heat stimulus (WLPHS) when each subject's right hand was immersed in a 50 °C hot water bath and correlated this parameter with the patient's perceived pain intensity and quality of life assessed by the short-form McGill Pain Questionnaire (SF-MPQ) in a large Taiwanese Fabry family and normal controls. RESULTS: Male Fabry patients showed a significantly increased WLPHS compared to that of normal controls. Furthermore, male Fabry patients showed a positive correlation of increased WLPHS with patient age. The SF-MPQ of male Fabry patients showed a bell distribution with age, and maximal pain scores were detected between the ages of the early 20s and late 40s. In contrast, the female Fabry patients had variable associations of WLPHS and SF-MPQ with age. CONCLUSIONS: We proposed a probable mechanism by which globotriaosylceramide (Gb3) or globotriaosylsphingosine (lyso-Gb3) is gradually deposited into the small nerve bundles with increasing age, which induces continuous damage and produces injury discharges to sustain neuropathic pain in young male Fabry patients. However, once the small fibers are reduced to a certain degree, they no longer produce enough noxious discharges to sustain neuropathic pains in older male Fabry patients, which leads these patients to have lower SF-MPQ scores. In contrast, female Fabry patients had less and variable small fiber damage, pain intensity and clinical signs/symptoms.

The Role of Autophagy and Apoptosis in Neuropathic Pain Formation.

Neuropathic pain indicates pain caused by damage to the somatosensory system and is difficult to manage and treat. A new treatment strategy urgently needs to be developed. Both autophagy and apoptosis are critical adaptive mechanisms when neurons encounter stress or damage. Recent studies have shown that, after nerve damage, both autophagic and apoptotic activities in the injured nerve, dorsal root ganglia, and spinal dorsal horn change over time. Many studies have shown that upregulated autophagic activities may help myelin clearance, promote nerve regeneration, and attenuate pain behavior. On the other hand, there is no direct evidence that the inhibition of apoptotic activities in the injured neurons can attenuate pain behavior. Most studies have only shown that agents can simultaneously attenuate pain behavior and inhibit apoptotic activities in the injured dorsal root ganglia. Autophagy and apoptosis can crosstalk with each other through various proteins and proinflammatory cytokine expressions. Proinflammatory cytokines can promote both autophagic/apoptotic activities and neuropathic pain formation, whereas autophagy can inhibit proinflammatory cytokine activities and further attenuate pain behaviors. Thus, agents that can enhance autophagic activities but suppress apoptotic activities on the injured nerve and dorsal root ganglia can treat neuropathic pain. Here, we summarized the evolving changes in apoptotic and autophagic activities in the injured nerve, dorsal root ganglia, spinal cord, and brain after nerve damage. This review may help in further understanding the treatment strategy for neuropathic pain during nerve injury by modulating apoptotic/autophagic activities and proinflammatory cytokines in the nervous system.

Perceptions of community dementia friendliness: A cross-sectional study of people with dementia, family caregivers, service providers, and the general public in Taiwan.

Promoting dementia-friendly communities is an important strategy for improving quality of life for people with dementia and dementia-family caregivers. The process of building dementia-friendly communities should include all people living in the community. The objective of this study was to compare perceived dementia friendliness in the community among people with dementia, family caregivers, service providers, and the general public. In Taiwan, we surveyed 60 people with dementia, 140 family caregivers, and 200 members of the general public face to face, with 200 service providers surveyed by mail. Participants completed the Perceived Community Dementia Friendliness measure, consisting of seven subscales: care services, community members, community environment, community interactions, transportation, hospitals, and stores and organisations. This measure has acceptable convergent validity, construct validity, and internal consistency reliability for use in Taiwan. Differences in perceived dementia friendliness were examined by chi-square tests/analysis of variance. Among the seven subscales, hospitals were rated with good dementia friendliness by 70% of people with dementia (n = 42); however, care services were rated poor by 23.3% of people with dementia (n = 14). Hospitals were also rated with good dementia friendliness by 39.2% of family caregivers (n = 54). Care services were rated as having good dementia friendliness by 43.5% of service providers (n = 87) and 47% of the general public (n = 86). Furthermore, community interactions were rated as good by small percentages of family caregivers (11.4%, n = 16), service providers (22.2%, n = 44), and the general public (30.9%, n = 58). Family caregivers, service providers, and the general public rated hospitals with the highest mean dementia-friendliness score and community interactions with the lowest. Perceived community-dementia friendliness among participants with dementia differed from that of participants without. People with dementia prioritised improving care services, while people without dementia rated facilitating community interactions as more vital. These differences provide vital insights into understanding the policies and administration of dementia-friendly communities.

Peripheral inflammatory markers associated with brain volume reduction in patients with bipolar I disorder.

BACKGROUND: Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients. METHODS: Euthymic patients with bipolar I disorder (BD-I) aged 20-45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1ß, and transforming growth factor-ß1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others. RESULTS: We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes. CONCLUSIONS: The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.

Association of Sleep, Neuropsychological Performance, and Gray Matter Volume With Glymphatic Function in Community-Dwelling Older Adults.

BACKGROUND AND OBJECTIVES: The glymphatic system, which is robustly enabled during some stages of sleep, is a fluid-transport pathway that clears cerebral waste products. Most contemporary knowledge regarding the glymphatic system is inferred from rodent experiments and human research is limited. Our objective is to explore the associations between human glymphatic function, sleep, neuropsychological performance, and cerebral gray matter volumes. METHODS: This cross-sectional study included individuals 60 years or older who had participated in the Integrating Systemic Data of Geriatric Medicine to Explore the Solution for Health Aging study between September 2019 and October 2020. Community-dwelling older adults were enrolled at 2 different sites. Participants with dementia, major depressive disorders, and other major organ system abnormalities were excluded. Sleep profile was accessed using questionnaires and polysomnography. Administered neuropsychological test batteries included Everyday Cognition (ECog) and the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). Gray matter volumes were estimated based on MRI. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was used as the MRI marker of glymphatic function. RESULTS: A total of 84 participants (mean [SD] age 73.3 [7.1] years, 47 [56.0%] women) were analyzed. Multivariate linear regression model determined that age (unstandardized ß, -0.0025 [SE 0.0001]; p = 0.02), N2 sleep duration (unstandardized ß, 0.0002 [SE 0.0001]; p = 0.04), and the apnea-hypopnea index (unstandardized ß, -0.0011 [SE 0.0005]; p = 0.03) were independently associated with DTI-ALPS. Higher DTI-ALPS was associated with better ECog language scores (unstandardized ß, -0.59 [SE 0.28]; p = 0.04) and better CERAD-NB word list learning delayed recall subtest scores (unstandardized ß, 6.17 [SE 2.31]; p = 0.009) after covarying for age and education. Higher DTI-ALPS was also associated with higher gray matter volume (unstandardized ß, 107.00 [SE 43.65]; p = 0.02) after controlling for age, sex, and total intracranial volume. DISCUSSION: Significant associations were identified between glymphatic function and sleep, stressing the importance of sleep for brain health. This study also revealed associations between DTI-ALPS, neuropsychological performance, and cerebral gray matter volumes, suggesting the potential of DTI-ALPS as a biomarker for cognitive disorders.

Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury.

Our previous studies have shown that early systemic granulocyte colony-stimulating factor (G-CSF) treatment can attenuate neuropathic pain in rats with chronic constriction injury (CCI) by modulating expression of different proinflammatory cytokines, microRNAs, and proteins. Besides the modulation of inflammatory mediators' expression, previous studies have also reported that G-CSF can modulate autophagic and apoptotic activity. Furthermore, both autophagy and apoptosis play important roles in chronic pain modulation. In this study, we evaluated the temporal interactions of autophagy, and apoptosis in the dorsal root ganglion (DRG) and injured sciatic nerve after G-CSF treatment in CCI rats. We studied the behaviors of CCI rats with or without G-CSF treatment and the various levels of autophagic, proinflammatory, and apoptotic proteins in injured sciatic nerves and DRG neurons at different time points using Western blot analysis and immunohistochemical methods. The results showed that G-CSF treatment upregulated autophagic protein expression in the early phase and suppressed apoptotic protein expression in the late phase after nerve injury. Thus, medication such as G-CSF can modulate autophagy, apoptosis, and different proinflammatory proteins in the injured sciatic nerve and DRG neurons, which have the potential to treat neuropathic pain. However, autophagy-mediated regulation of neuropathic pain is a time-dependent process. An increase in autophagic activity in the early phase before proinflammatory cytokines reach the threshold level to induce neuropathic pain can effectively alleviate further neuropathic pain development.