Predicting Adverse Recanalization Therapy Outcomes in Acute Ischemic Stroke Patients Using Characteristic Gut Microbiota.

Recanalization therapy is the most effective treatment for eligible patients with acute ischemic stroke (AIS). Gut microbiota are involved in the pathological mechanisms and outcomes of AIS. However, the association of gut microbiota features with adverse recanalization therapy outcomes remains unclear. Herein, we investigated gut microbiota features associated with neurological deficits in patients with AIS after recanalization therapy and whether they predict the patients' functional outcomes. We collected fecal samples from 51 patients with AIS who received recanalization therapy and performed 16S rRNA gene sequencing (V3-V4). We compared the gut microbiota diversity and community composition between mild to moderate and severe disability groups. Next, the characteristic gut microbiota was compared between groups, and we noted that the characteristic gut microbiota in patients with mild to moderate disability included Bilophila, Butyricimonas, Oscillospiraceae_UCG-003, and Megamonas. Moreover, the relative abundance of Bacteroides fragilis, Fusobacterium sp., and Parabacteroides gordonii was high in patients with severe disability. The characteristic gut microbiota was correlated with neurological deficits, and areas under the receiver operating characteristic curves confirmed that the characteristic microbiota predicted adverse recanalization therapy outcomes. In conclusion, gut microbiota characteristics are correlated with recanalization therapy outcomes in patients with AIS. Gut microbiota may thus be a promising biomarker associated with early neurological deficits and predict recanalization therapy outcomes.

The Prognostic Biomarkers of Plasma Trimethylamine N-Oxide and Short-Chain Fatty Acids for Recanalization Therapy in Acute Ischemic Stroke.

Bidirectional communication of the microbiota-gut-brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0-3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.

Oxidative stress involves phenotype modulation of morbid soreness symptoms in fibromyalgia.

OBJECTIVES: Muscle soreness occurs after exercise and also in musculoskeletal diseases, such as fibromyalgia (FM). However, the nosography and pathoetiology of morbid soreness in FM remain unknown. This study aimed to investigate the morbid soreness of FM, evaluate its therapeutic responses and probe its pathophysiology with metabolomics profiling. METHODS: Patients with newly diagnosed FM were prospectively recruited and completed self-report questionnaires pertaining to musculoskeletal symptoms. The phenotypes and metabotypes were assessed with variance, classification and correlation analyses. RESULTS: Fifty-one patients and 41 healthy controls were included. Soreness symptoms were prevalent in FM individuals (92.2%). In terms of manifestations and metabolomic features, phenotypes diverged between patients with mixed pain and soreness symptoms (FM-PS) and those with pain dominant symptoms. Conventional treatment for FM did not ameliorate soreness severity despite its efficacy on pain. Moreover, despite the salient therapeutic efficacy on pain relief in FM-PS cases, conventional treatment did not improve their general disease severity. Metabolomics analyses suggested oxidative metabolism dysregulation in FM, and high malondialdehyde level indicated excessive oxidative stress in FM individuals as compared with controls (p=0.009). Contrary to exercise-induced soreness, lactate levels were significantly lower in FM individuals than controls, especially in FM-PS. Moreover, FM-PS cases exclusively featured increased malondialdehyde level (p=0.008) and a correlative trend between malondialdehyde expression and soreness intensity (r=0.337, p=0.086). CONCLUSIONS: Morbid soreness symptoms were prevalent in FM, with the presentation and therapeutic responses different from FM pain conditions. Oxidative stress rather than lactate accumulation involved phenotype modulation of the morbid soreness in FM. TRIAL REGISTRATION NUMBER: NCT04832100.

The Association between Electronegative Low-Density Lipoprotein Cholesterol L5 and Cognitive Functions in Patients with Mild Cognitive Impairment.

L5, the most electronegative subfraction of low-density lipoprotein cholesterol (LDL-C), may play a role in the pathogenesis of cerebrovascular dysfunction and neurodegeneration. We hypothesized that serum L5 is associated with cognitive impairment and investigated the association between serum L5 levels and cognitive performance in patients with mild cognitive impairment (MCI). This cross-sectional study conducted in Taiwan included 22 patients with MCI and 40 older people with normal cognition (healthy controls). All participants were assessed with the Cognitive Abilities Screening Instrument (CASI) and a CASI-estimated Mini-Mental State Examination (MMSE-CE). We compared the serum total cholesterol (TC), LDL-C, and L5 levels between the MCI and control groups and examined the association between lipid profiles and cognitive performance in these groups. The serum L5 concentration and total CASI scores were significantly negatively correlated in the MCI group. Serum L5% was negatively correlated with MMSE-CE and total CASI scores, particularly in the orientation and language subdomains. No significant correlation between the serum L5 level and cognitive performance was noted in the control group. Conclusions: Serum L5, instead of TC or total LDL-C, could be associated with cognitive impairment through a disease stage-dependent mode that occurs during neurodegeneration.

Association between proteinuria and the development of malignant middle cerebral artery infarction: A retrospective cohort study.

A disrupted blood-brain barrier (BBB) with extravasation of macromolecules plays a critical role in the development of malignant middle cerebral artery infarction (MMI). Proteinuria is considered a marker of generalized endothelial dysfunction, including BBB disruption. This study aimed to clarify whether proteinuria identified in the acute stage of stroke is associated with MMI development. Patients with infarctions involving the middle cerebral artery territory were reviewed. Urine samples collected within 8 hours after stroke were analyzed using urine dipsticks. Patients were divided into proteinuria (urine dipstick reading of 1 + to 4+) and nonproteinuria groups. MMI was present if either signs of uncal herniation or a progressive conscious disturbance were recorded along with a midline shift > 5 mm identified on follow-up computed tomography (CT). Among the 1261 patients identified between January 2010 and June 2019, 138 were eligible for final analyses. Patients in the MMI group had lower Alberta Stroke Program Early CT Scores (ASPECTS), higher National Institutes of Health Stroke Scale scores, and a greater proportion of proteinuria than those in the non-MMI group. Four multivariate logistic regression models were used to clarify the role of proteinuria in MMI development. In model 1, proteinuria was significantly associated with MMI after adjusting for age, sex, dyslipidemia and ASPECTS (OR = 2.987, 95% CI = 1.329-6.716, P = .0081). The risk of developing MMI in patients with proteinuria remained significant in model 2 (OR = 3.066, 95% CI = 1.349-6.968, P = .0075) after adjusting for estimated glomerular filtrate rate (eGFR) < 60ml/min/1.73 m2 in addition to variables in model 1. In model 3, proteinuria was still significantly associated with MMI after adjusting for age, sex, dyslipidemia, ASPECTS, hypertension, diabetes, and atrial fibrillation (OR = 2.521, 95% CI = 1.075-5.912, P = .0335). In model 4, the risk of developing MMI in patients with proteinuria remained significant (OR = 2.579, 95% CI = 1.094-6.079, P = .0304) after adjusting for eGFR < 60ml/min/1.73 m2 in addition to variables in model 3. Proteinuria is independently associated with MMI development. Proteinuria may be a clinically accessible predictor of MMI development.

Internal carotid artery occlusion related to poorly controlled rheumatoid arthritis presenting with continuous hand shaking: A case report and literature review.

RATIONALE: Limb-shaking syndrome is a special manifestation of transient ischemic attack, resulting from internal carotid artery (ICA) occlusion. Extra-articular manifestations of rheumatoid arthritis (RA) are likely to occur in patients with severe or active RA. RA may accelerate atherosclerotic processes through inflammation. Here, we present a case of ICA occlusion related to poorly controlled RA that presented with continuous hand shaking. PATIENT CONCERNS: A 73-year-old man with a history of poorly controlled RA developed total occlusion of the right ICA in recent 4 months. He presented with 2 days of continuous and rhythmic left-hand shaking before admission. DIAGNOSIS: The patient was suspected to have transient ischemic attack resulting from ICA occlusion. INTERVENTIONS: Antiplatelets and antiepileptic drugs were used for continuous nonepileptic focal myoclonus. A disease-modifying antirheumatic drug-based regimen for RA was developed to prevent further atherosclerosis. OUTCOMES: Following the initial intervention, continuous hand shaking subsided on hospital day 7. Prednisolone was titrated as an active RA control. At the 6-month follow-up visit, neither painful wrist swelling nor recurrent shaking of the hand was noted. LESSONS: Continuous hand shaking (nonepileptic focal myoclonus) can be the initial presentation of ICA occlusion in patients with poorly controlled RA. Every patient with RA should be treated aggressively with anti-rheumatic agents since RA is an independent risk factor for stroke. Additionally, every patient with RA should be surveyed for ICA stenosis, especially in those with poor control.

Abnormalities in Cutaneous Microcirculation in Patients with Alzheimer's Disease, Mild Cognitive Impairment, and Chronic Insomnia Disorder.

Impaired sympathetic response is frequently observed in neurodegenerative diseases, such as Alzheimer's disease (AD). On the other hand, chronic insomnia disorder (CID) is also often accompanied by activation of sympathetic nerves. Considering that cutaneous microcirculation reflects sympathetic tone, we hypothesized that baseline cutaneous microcirculation in fingers, as detected by laser Doppler flowmetry (LDF), differs among patients with mild cognitive impairment (MCI), AD, and CID. As light therapy is one of the adjunctive treatments for AD and CID, we designed a randomized controlled cross-over trial of light therapy through eyes for 12 weeks with red light as treatment and green light as control limb, and examined if light therapy has an impact on cutaneous microcirculation. Before light therapy, patients with AD had significantly lower baseline cutaneous perfusion than those with CID in left and right first to fourth fingers. After red light therapy, however, cutaneous perfusion of fingers in CID patients significantly decreased (right fingers, before vs. after = 227.25 ± 62.00 vs. 162.00 ± 49.34, p = 0.007; left fingers, before vs. after = 228.99 ± 58.80 vs. 177.41 ± 59.41, p = 0.003) while cutaneous perfusion of fingers in CID patients did not significantly change after green light therapy. Light therapy with red light also significantly increased cutaneous finger perfusion in patients with AD (right fingers, before vs. after = 130.13 ± 49.82 vs. 172.38 ± 38.32, p = 0.043). Our results suggest that cutaneous perfusion is a useful tool to detect sympathetic dysfunction in patients with CID and AD, and that light therapy with red light is a potential therapeutic intervention to reverse impaired sympathetic function in patients with CID and patients with AD.

Rapid eye movement sleep disturbance in patients with refractory epilepsy: A polysomnographic study.

OBJECTIVE/BACKGROUND: Patients with epilepsy have disrupted sleep architecture and a higher prevalence of sleep disturbance. Moreover, obstructive sleep apnea (OSA) is more common among patients with refractory epilepsy. Few studies have compared subjective sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and those with medically controlled epilepsy. Therefore, this study aimed to evaluate the differences in sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and patients with medically controlled epilepsy. PATIENTS: This retrospective case-control study included 38 patients with refractory epilepsy and 96 patients with medically controlled epilepsy. Sleep parameters and indices of sleep-related breathing disorders were recorded by standard in-laboratory polysomnography. The scores from sleep questionnaires on sleep quality and daytime sleepiness were compared between the two groups. RESULTS: Patients with refractory epilepsy versus medically controlled epilepsy had statistically significantly decreased rapid eye movement (REM) sleep (13.5 ± 6.1% vs. 16.2 ± 6.1%) and longer REM latency (152.2 ± 84.1 min vs. 117.2 ± 61.9 min). Further, no differences were found in the prevalence of sleep-related breathing disorders, subjective sleep quality, prevalence of daytime sleepiness, and quality of life. Although not statistically significant, patients with refractory epilepsy have a lower rate of OSA compared with those with medically controlled epilepsy (21.1% vs. 30.2%). CONCLUSIONS: Patients with refractory epilepsy had more disrupted REM sleep regulation than those with medically controlled epilepsy. Although patients with epilepsy have a higher risk of OSA, in this study patients with refractory epilepsy were not susceptible to OSA.

Activation of acid-sensing ion channel 3 by lysophosphatidylcholine 16:0 mediates psychological stress-induced fibromyalgia-like pain.

OBJECTIVES: Fibromyalgia is commonly considered a stress-related chronic pain disorder, and daily stressors are known triggers. However, the relation between stress and pain development remains poorly defined by clinical approaches. Also, the aetiology remains largely unknown. METHODS: We used a newly developed mouse model and lipidomic approaches to probe the causation and explore the biological plausibility for how perceived stress translates into chronic non-inflammatory pain. Clinical and lipidomic investigations of fibromyalgia were conducted for human validation. RESULTS: Using non-painful sound stimuli as psychological stressors, we demonstrated that mice developed long-lasting non-inflammatory hyperalgesia after repeated and intermittent sound stress exposure. Elevated serum malondialdehyde level in stressed mice indicated excessive oxidative stress and lipid oxidative damage. Lipidomics revealed upregulation of lysophosphatidylcholine 16:0 (LPC16:0), a product of lipid oxidisation, in stressed mice. Intramuscular LPC16:0 injection triggered nociceptive responses and a hyperalgesic priming-like effect that caused long-lasting hypersensitivity. Pharmacological or genetic inhibition of acid-sensing ion channel 3 impeded the development of LPC16:0-induced chronic hyperalgesia. Darapladib and antioxidants could effectively alleviate the stress-induced hyperalgesia by inhibiting LPC16:0 synthesis. Clinical investigations showed that excessive oxidative stress and LPC16:0 expression also exist in patients with fibromyalgia. Moreover, LPC16:0 expression was correlated with pain symptoms in patients with high oxidative stress and disease severity. CONCLUSIONS: Our study provides experimental evidence for the causal effect of psychological stressors on chronic pain development. The findings identify a possible pathophysiological mechanism of stress-induced chronic non-inflammatory pain at molecular, behavioural and clinical levels that might indicate a new therapeutic approach for fibromyalgia.

Infection-provoked reversible posterior leukoencephalopathy syndrome in an adult with nephrotic syndrome: a case report.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare and heterogeneous clinico-neuroradiological syndrome characterized by headache, altered mental status, seizures, and visual disturbances. Hypertension and immunosuppression are two of the main factors that predispose an individual to RPLS. However, RPLS can develop when no major risk factors are present. RPLS has been reported in pediatric nephrotic patients, but rarely in adults. CASE PRESENTATION: A 42-year-old Asian woman with nephrotic syndrome presented with seizures, headaches, and nausea. Her blood pressure was controlled, and no immunosuppressants had been prescribed. All symptoms and tests indicated RPLS following infection with pneumonia, which was successfully treated by immediate administration antibiotic and anti-epileptic medications. Seizures did not recur during a 2-year follow-up period. CONCLUSIONS: When patients with nephrotic syndrome have an infection, RPLS symptoms should be investigated thoroughly. With early diagnosis and appropriate treatment of RPLS, morbidity and mortality can be prevented.

Association of early-onset Alzheimer's disease with germline-generated high affinity self-antigen load.

Self-antigen presentation outside the central nervous system has crucial role regarding self-proteins tolerance and autoimmunity, leading to neuroinflammation. Self-antigen with strong-binding affinity is considered to be pathogenic. We aim to investigate whether strong-binding affinity self-antigen load is associated with early/late-onset Alzheimer's disease (AD). A total of 54 AD samples (22 early-onset, 32 late-onset) underwent next-generation sequencing (NGS) for whole-exome sequencing. Genotypes of HLA class I genes and germline mutations were obtained for estimation of the binding affinity and number of self-antigens. For each patient, self-antigen load was estimated by adding up the number of self-antigens with strong-binding affinity. Self-antigen load of early-onset AD was significantly higher than late-onset AD (mean ± SD: 6115 ± 2430 vs 4373 ± 2492; p = 0.011). An appropriate cutoff value 2503 for dichotomizing self-antigen load was obtained by receiver operating characteristic (ROC) curve analysis. Patients were then dichotomized into high or low self-antigen load groups in the binary multivariate logistic regression analysis. Adjusted odds ratio of the high self-antigen load (>2503) was 14.22 (95% CI, 1.22-165.70; p = 0.034) after controlling other covariates including gender, education, ApoE status, and baseline CDR score. This is the first study using NGS to investigate germline mutations generated self-antigen load in AD. As strong-binding affinity self-antigen is considered to be pathogenic in neuroinflammation, our finding indicated that self-antigen load did have a role in the pathogenesis of AD owing to its association with neuroinflammation. This finding may also contribute to further research regarding disease mechanism and development of novel biomarkers or treatment.

Parkinsonism with newly diagnosed flare-up rheumatoid arthritis mimicking progressive supranuclear palsy.

In order to make a correct diagnosis of idiopathic Parkinson's disease (PD), it is essential to exclude atypical parkinsonian features, such as early dementia, fall, and autonomic dysfunction. Rheumatoid arthritis (RA), which is a systemic inflammatory disorder, although most patients present in a polyarticular manner. Still some may also present with extra-articular involvement including skin, lung, heart, and the central or peripheral nervous systems. A possible pathogenetic link between RA and PD are proposed. However, the coexistence of RA and progressive supranuclear palsy (PSP) is rarely reported. Here, we report a parkinsonian patient with a newly diagnosed flare-up RA presenting with early falls, postural instability and supra-nuclear gaze palsy, which suggestive of clinically probable PSP. Furthermore, the parkinsonian features respond to anti-rheumatic agents, but not levodopa. Finally, the patient looks like a clinical possible PD. In summary, Parkinsonian patient with newly diagnosed flare-up RA can present with clinically probable PSP. Unbearably painful limb contracture is a clue of the coexistence of RA. Both typical and atypical parkinsonian features respond dramatically to anti-rheumatic medication, but not levodopa.

Apolipoprotein E e4 allele is associated with extrapyramidal symptoms in Alzheimer's disease.

BACKGROUND: Extrapyramidal symptoms (EPS) are not uncommon in Alzheimer's disease (AD). As apolipoprotein E(APOE) e4 allele is a major risk factor for late-onset AD, we intend to examine the association between APOE genotype and the development of EPS in AD. METHOD: This study describes two hundred and fifty-five clinically diagnosed AD patients aged 72 to 80 years from 2010 to 2014. We reviewed the medical charts to determine the development of EPS. APOE genotypes were also confirmed. RESULTS: APOE e4 allele was detected in 74 patients (29%) and rigidity was among the most common EPS (61%). After adjusting the age, gender, baseline clinical dementia rating, we found AD patients carrying APOE e4 allele are more likely to develop EPS (OR: 4.515, p=0.033). CONCLUSION: This study demonstrates the higher coexistence of EPS in AD patients with APOE e4 allele. Furthermore, the identification of APOE e4 allele in the development of EPS in AD patients supports the hypothesis that EPS may be partially attributed to AD pathology.

Compensatory Neural Recruitment for Error-Related Cerebral Activity in Patients with Moderate-To-Severe Obstructive Sleep Apnea.

(1) Background: Although it is known that obstructive sleep apnea (OSA) impairs action-monitoring function, there is only limited information regarding the associated cerebral substrate underlying this phenomenon. (2) Methods: The modified Flanker task, error-related event-related potentials (ERPs), namely, error-related negativity (ERN) and error positivity (Pe), and functional magnetic resonance imaging (fMRI) were used to evaluate neural activities and the functional connectivity underlying action-monitoring dysfunction in patients with different severities of OSA. (3) Results: A total of 14 control (Cont) subjects, 17 patients with moderate OSA (mOSA), and 10 patients with severe OSA (sOSA) were enrolled. A significant decline in posterror correction rate was observed in the modified Flanker task when patients with mOSA were compared with Cont subjects. Comparison between patients with mOSA and sOSA did not reveal any significant difference. In the analysis of ERPs, ERN and Pe exhibited declined amplitudes in patients with mOSA compared with Cont subjects, which were found to increase in patients with sOSA. Results of fMRI revealed a decreased correlation in multiple anterior cingulate cortex functional-connected areas in patients with mOSA compared with Cont subjects. However, these areas appeared to be reconnected in patients with sOSA. (4) Conclusions: The behavioral, neurophysiological, and functional image findings obtained in this study suggest that mOSA leads to action-monitoring dysfunction; however, compensatory neural recruitment might have contributed to the maintenance of the action-monitoring function in patients with sOSA.

REST rs3796529 Genotype and Rate of Functional Deterioration in Alzheimer's Disease.

Recently, REST (RE1-silencing transcription factor) gene has been shown to be lost in Alzheimer's disease (AD), and a missense minor REST allele rs3796529-T has been shown to reduce the rate of hippocampal volume loss. However, whether the REST rs3796529 genotype is associated with the rate of functional deterioration in AD is unknown. A total of 584 blood samples from Taiwanese patients with AD were collected from January 2002 to December 2013. The diagnosis of AD was based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. The allele frequency of rs3796529-T was compared between the AD cohort and 993 individuals from the general population in Taiwan. Kaplan-Meier analysis, the log rank test and a multivariate Cox model were then used to evaluate the association between rs3796529-T and functional deterioration in the AD cohort. The allele frequency of rs3796529-T was significantly lower in the AD cohort compared to the general population cohort (36.82% vs. 40.73%, p=0.029). Kaplan-Meier analysis and the log rank test showed that the AD patients carrying the rs3796529 T/T genotype had a longer progression-free survival than those with the C/C genotype (p=0.012). In multivariate analysis, the rs3796529 T/T genotype (adjusted HR=0.593, 95% CI: 0.401-0.877, p=0.009) was an independent protective factor for functional deterioration. The rs3796529 T/T genotype was associated with slower functional deterioration in patients with AD. This finding may lead to a to better understanding of the molecular pathways involved, and prompt further development of novel biomarkers to monitor AD.

Impaired conflict monitoring in cognitive decline.

Resolving conflicts is an important cognitive ability of executive function, and it may decrease with cognitive decline. The flanker task is a practical test used to assess the ability to suppress responses that are inappropriate in a particular context. The aims of the present study were to investigate conflict monitoring of cognitive control in subjects with different levels of cognitive impairment, and clarify the usefulness of the flanker task in screening cognitive decline. We recruited 50 subjects with mild cognitive impairment (MCI) and 34 patients with Alzheimer's disease (AD), and 44 mentally healthy elderly subjects as a control group. To evaluate cognitive performance, each participant underwent a neuropsychological assessment using the Cognitive Abilities Screening Instrument and a modified flanker task. Compared with the normal controls and those with MCI, the patients with AD had a significantly lower accuracy rate and longer reaction time in both congruent and incongruent trials. The diagnosis of AD predicted significantly poorer performances on the flanker tasks. Furthermore, behavioral data of the patients with AD were significantly correlated with the results of neuropsychological tests. Our results indicated that executive cognitive deficits in conflict monitoring as detected by the flanker task were significantly impaired in the patients with AD. The flanker task could be a quick and easier alternative tool for screening AD among elderly people with suspicious cognitive impairment.

Obstructive sleep apnea and cerebral white matter change: a systematic review and meta-analysis.

Obstructive sleep apnea (OSA) can cause sleep fragmentation and intermittent hypoxemia, which are linked to oxidative stress. White matter changes (WMCs) representing cerebrovascular burden and are at risk factor for oxidative ischemic injury. The current study explores the mutual relationships between OSA and WMCs. We performed a systematic review of electronic databases for clinical studies investigating OSA and WMCs. Random-effects models were used for pooled estimates calculation. A total of 22 studies were included in the meta-analysis. The results revealed a significantly higher prevalence rate of WMCs [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.52-2.80, p < 0.001] and significantly higher severity of WMCs (Hedges' g = 0.23, 95% CI 0.06-0.40, p = 0.009) in the patients with OSA than in controls. Furthermore, the results revealed a significantly higher apnea-hypopnea index (Hedges' g = 0.54, 95% CI 0.31-0.78, p < 0.001) and significantly higher prevalence rate of moderate-to-severe OSA (OR 2.86, 95% CI 1.44-5.66, p = 0.003) in the patients with WMCs than in controls, however there was no significant difference in the prevalence rate of mild OSA between the patients with WMCs and controls (OR 0.71, 95% CI 0.20-2.54, p = 0.603). OSA was associated with a higher prevalence and more severe WMCs, and the patients with WMCs had an increased association with moderate-to-severe OSA. Future large-scale randomized controlled trials with a longitudinal design are essential to further evaluate treatment in patients with OSA.