BACKGROUND AND PURPOSE:Cerebral small-vessel disease (CSVD) is a major cause of cognitive impairment, but its underlying mechanisms remain incompletely understood. This study investigated the interrelationships among deep medullary vein (DMV) disruption, glymphatic dysfunction as assessed using the diffusion-tensor imaging analysis along the perivascular space (DTI-ALPS) index, CSVD imaging markers, and cognitive impairment. METHODS:Fifty CSVD patients were enrolled from Chengdu Second People's Hospital between January 2022 and December 2024, while 29 healthy controls (HCs) were recruited from the local community. DMV disruption was assessed using susceptibility-weighted imaging, while glymphatic function was evaluated using the DTI-ALPS index. Clinical characteristics, Mini-Mental State Examination (MMSE) scores, and CSVD imaging markers were collected, and regression and mediation analyses were performed. RESULTS:Compared with HCs, CSVD patients showed significantly lower DTI-ALPS indices, higher DMV scores, and worse cognition (all p<0.05). Higher DMV scores were independently associated with lower MMSE scores (p=0.006) and greater CSVD burden. Lower DTI-ALPS indices were associated with greater CSVD burden and showed a tendency toward an association with MMSE scores (p=0.070). DMV scores were negatively correlated with DTI-ALPS indices (p=0.024). The mediation analyses showed that glymphatic dysfunction did not exert a significant indirect effect on the relationship between DMV disruption and cognition, whereas there was a significant direct effect of DMV disruption on cognition. CONCLUSIONS:This study found that DMV disruption and glymphatic dysfunction were associated with the CSVD imaging burden. Cognitive impairment was strongly associated with DMV disruption but weakly associated with glymphatic dysfunction. Combined assessments may provide complementary imaging markers for the CSVD severity and cognitive decline.
The diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) relies heavily on detecting serum MOG-IgG by cell-based assay, but seropositivity alone does not establish the disease. In selected clinical cohorts, the positive predictive value of MOG-IgG ranges from approximately 50%-70% at low titers, depending on the assay and cohort, to near 100% at high titers, and inter-laboratory agreement is markedly lower in the low-positive samples than for clearly positive or negative samples. The difficulty in interpreting low-positive MOG-IgG results largely reflects the interplay of two elements: biological factors (including antigen-related background reactivity and potential cross-reactive immunoreactivity) and methodological variability between assays (including differences in antigen presentation, live versus fixed assay platforms, secondary antibody selection, fluorescence readout, sample timing, and locally validated cutoffs). This ambiguity is unlikely to be resolved by assay optimization alone. The 2023 International MOGAD Panel criteria address these issues by requiring stronger clinical and radiological support when the serological evidence is weaker. Accordingly, MOG-IgG should be interpreted as probabilistic evidence within the clinical and MRI context, rather than as a stand-alone diagnostic marker.
Functional neurological disorder (FND) is a common condition characterized by involuntary neurological symptoms. The most common subtypes include functional/dissociative seizures and functional movement disorders, though other presentations such as persistent postural-perceptual dizziness and functional cognitive disorder are increasingly recognized. Patients may present with multiple types of functional neurological symptoms, and comorbid pain, fatigue, and sleep disturbance are common and may substantially affect quality of life. Despite its high prevalence, FND has historically been neglected, and the prognosis remains poor in a substantial proportion of patients. This article provides an overview of current treatment options for FND, including physical therapy, cognitive behavioral therapy, multidisciplinary approaches, and neuromodulation. Ongoing challenges including heterogeneous outcome measures, limited long-term follow-up data, the absence of validated biomarkers, and the need for expanded access to specialist care are also discussed.
BACKGROUND AND PURPOSE:A transient ischemic attack (TIA) is associated with a markedly higher risk of subsequent ischemic stroke even when guideline-directed prevention strategies are applied. There is evidence emerging from the LAMP trial that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can help to prevent secondary stroke. We therefore conducted this study to evaluate the association in a real-world cohort. METHODS:We conducted a retrospective cohort study using data from the TriNetX US Collaborative Network. Adults with TIA who received antithrombotic therapy between 7 days before and 7 days after a TIA diagnosis were included. GLP-1RA use was defined as its initiation between 3 months before to 7 days after a TIA diagnosis. Propensity-score matching (PSM) was performed at a 1:1 ratio to balance covariates. The primary outcomes were ischemic stroke and mortality, while the secondary outcomes were inpatient (IP) admissions and emergency department (ED) visits. Outcomes were assessed over a 5-year follow-up period. Sensitivity analyses stratified by body mass index, hemoglobin-A1c level, and atrial fibrillation status were conducted to generalize the findings. RESULTS:After applying PSM, 5,071 GLP-1RA users and 5,071 GLP-1RA nonusers were included. GLP-1RA use was associated with lower risks of ischemic stroke (6.9% vs. 10.9%, hazard ratio [HR]=0.76, p<0.001) and mortality (5.9% vs. 12.3%, HR=0.67, p<0.001), as well as fewer IP admissions and ED visits. The results of six sensitivity analyses were consistent with the primary cohort demonstrating the favorable outcomes not being confined to a specific metabolic or vascular risk phenotype. CONCLUSIONS:GLP-1RA is associated with lower risks of ischemic stroke, mortality, IP admissions, and ED visits in TIA patients. These preliminary findings suggest that GLP-1RAs can play a role in the secondary prevention of cerebrovascular disease.
BACKGROUND AND PURPOSE:Vestibular migraine (VM) is a common cause of episodic vertigo with heterogeneous presentations. Some VM patients show caloric abnormalities suggestive of peripheral vestibular dysfunction (PVD). This study compared clinical symptoms and vestibulo-ocular function between VM patients with caloric canal paresis (CP) >25% (VM-CP+), which was used as an operational definition of evidence of PVD, and those without caloric CP >25% (VM-CP-). METHODS:We enrolled 181 patients diagnosed with VM according to the Bárány Society criteria: 47 in the VM-CP+ group and 134 in the VM-CP- group. All patients underwent videonystagmography and caloric testing, while the video head impulse test (vHIT), vestibular-evoked myogenic potential (VEMP) measurements, and subjective visual horizontal (SVH) and subjective visual vertical (SVV) assessments were performed in available subsets. RESULTS:Compared with VM-CP- patients, those with VM-CP+ showed higher frequencies of external vertigo, rotational vertigo, spontaneous nystagmus, unidirectional horizontal positional nystagmus, horizontal head-shaking nystagmus, abnormal cervical VEMPs, and abnormal upright SVH/SVV. The vHIT findings were abnormal only in VM-CP+ patients with available data. Conversely, a history of motion sickness and a family history of migraine were more common in VM-CP-. Multivariable regression showed that rotational vertigo, external vertigo, and unidirectional horizontal positional nystagmus were independently associated with VM-CP+, whereas a history of motion sickness and a family history of migraine were negatively associated with VM-CP+. CONCLUSIONS:VM-CP+ and VM-CP- patients showed different clinical and vestibulo-ocular patterns, suggesting the presence of clinical heterogeneity within VM. VM-CP+ patients may show a phenotype related to peripheral vestibular asymmetry. Whether this reflects a comorbid or additive effect of migraine and PVD or a migraine-related functional state should be investigated in future prospective studies.
BACKGROUND AND PURPOSE:Aperiodic alternating nystagmus (AAN) is defined as spontaneous alternating nystagmus in which the direction of nystagmus reverses repeatedly but the reversals do not occur at a consistent cycle interval and the cycle durations and/or peak slow-phase velocities are irregular. The etiologic distribution of vestibular disorders associated with AAN and the underlying mechanisms remain unclear. This study aimed to identify the clinical characteristics and potential underlying mechanisms of AAN. METHODS:We analyzed quantitative eye-movement recordings, audiovestibular test results, and neuroimaging results of 22 patients with AAN, and conducted a systematic review of reported cases of AAN in both peripheral and central vestibular disorders. RESULTS:The systematic review identified an additional 29 patients with AAN. Peripheral vestibular causes accounted for 32 (62.7%) of all 51 patients, and comprised acute peripheral vestibulopathy (n=16), Ménière's disease (n=9), vestibular schwannoma (n=3), vestibular paroxysmia (n=2), labyrinthine fistula (n=1), and lateral semicircular canal dysplasia (n=1). Central vestibular disorders (19.6%, n=10) comprised acute infarction (n=6) most commonly involving the medulla, brainstem glioma with concurrent cerebellar damage (n=1), traumatic diffuse brain injury (n=2), and adult-onset Alexander disease (n=1). The remaining 17.6% of cases (n=9) had undetermined causes. Compared with peripheral cases, central vestibular disorders were associated with significantly greater duration asymmetry of AAN (p=0.041), higher prevalence of persistent AAN (p=0.037), and more-frequent abnormal ocular motor findings (p<0.001). In contrast, reduced bithermal caloric responses were more prevalent in peripheral than central vestibulopathy (p<0.001). CONCLUSIONS:AAN can result from various peripheral and central vestibular disorders. Greater duration asymmetry, persistence of AAN, and accompanying ocular motor abnormalities can suggest a central origin, whereas reduced bithermal caloric responses may support a peripheral origin.
BACKGROUND AND PURPOSE:Subjective cognitive decline (SCD) may precede mild cognitive impairment (MCI) and dementia. However, the prognosis of patients with amyloid-negative (A-) SCD remains unclear. We investigated whether baseline plasma and imaging biomarkers predict four-year clinical progression in A-SCD. METHODS:Sixty-five individuals with A-SCD were followed for four years. Baseline plasma biomarkers-phosphorylated tau 181 (pTau181), glial fibrillary acidic protein, neurofilament light chain (NfL), and pTau181/Aβ42 ratio-and MRI markers (hippocampal volume and white matter hyperintensity [WMH] grade) were assessed. Outcomes included MCI conversion and cognitive progression defined as ≥1-point (Prog-1) or ≥2-point (Prog-2) decline in Korean Mini-Mental State Examination. Predictive performance was evaluated using multivariable logistic regression and bootstrap-validated receiver operating characteristic analyses. RESULTS:Fourteen participants (21.5%) converted to MCI, and 24 (36.9%) were classified as Prog-1. Plasma biomarkers did not show consistent predictive performance across predefined endpoints (all p>0.05), although NfL demonstrated modest discrimination for MCI conversion (area under the curve [AUC] 0.686, p=0.008). Hippocampal volume demonstrated significant discriminative performance for MCI conversion (AUC 0.765, p=0.016) and Prog-1 (AUC 0.933, p<0.001). For Prog-2, hippocampal volume showed high discrimination (AUC 0.952, p<0.001). WMH grade also demonstrated significant discrimination for MCI conversion (AUC 0.835, p<0.001) and Prog-1 (AUC 0.857, p<0.001). Bootstrap analyses (1,000 iterations) tended to show higher AUC estimates for imaging markers compared with plasma biomarkers. CONCLUSIONS:In this A-SCD cohort, hippocampal atrophy demonstrated more consistent prognostic performance than Alzheimer's disease-focused plasma biomarkers for predicting four-year conversion to MCI and cognitive decline, suggesting a potential role for MRI-based neurodegeneration markers in clinical risk stratification.
BACKGROUND AND PURPOSE:Education is a well-established proxy for cognitive reserve and hence may influence the relationship between Alzheimer's disease pathology and brain structure. This is particularly relevant in South Korea, where historical sex disparities in educational level among current elderly populations create unique cohort characteristics. This study examined how educational level moderates the biomarker-cortical-thickness relationship in females with cognitive decline, with descriptive sex comparisons used to contextualize these findings within a cohort reflecting disparities in the history of educational opportunities in South Korea. METHODS:In 80 patients (58 females, 22 males) with cognitive decline, we assessed plasma amyloid-β 42 (Aβ42), phosphorylated tau 181 (p-tau), and total tau levels, p-tau/Aβ42 ratio, regional cortical thickness, and scores on the Mini-Mental State Examination. Given the substantial confounding between sex and educational level in this cohort, moderated mediation analyses examining the biomarker-cortical-thickness-cognition pathway were restricted to females (n=53 with complete data). RESULTS:Females had a higher p-tau/Aβ42 ratio (p=0.026) and thicker frontal cortex (p=0.049) despite the absence of a significant difference in age-adjusted cognition. No significant sex× educational level interaction was observed for the biomarkers or cognition. In females, educational level moderated the relationship between the p-tau/Aβ42 ratio and cortical thickness (p<0.05 in all five brain regions), with high-educational level females showing the expected cortical thinning with pathology, while low-educational level females exhibited preserved thickness, which did not mediate the cognitive performance. CONCLUSIONS:Descriptive sex comparisons revealed a higher biomarker burden yet greater cortical thickness in females. Importantly, educational level significantly moderated the biomarker-cortical thickness relationship specifically in females, with lower-educated individuals showing structural preservation despite the presence of pathology. These findings suggest that measurements of the cortical thickness can underestimate the disease burden in lower-educated females, which highlights the need for educational level-stratified interpretations of structural biomarkers.
BACKGROUND AND PURPOSE:The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) showed that a multidomain lifestyle intervention targeting vascular risk, cognitive training, physical activity, nutrition, and motivation is feasible in older adults. However, its resource-intensive delivery limited scalability, and conventional aerobic exercise alone may not sufficiently support long-term adherence, cognitive-motor engagement, and cultural acceptability in older adults with mild cognitive impairment (MCI). To address these gaps, we developed the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health via Behavioral, Optimized, Organized Movement therapy (SUPERBRAIN-BOOM) in MCI, a mobile-based multidomain program integrating dance-based movement, nutrition education, and meditation. METHODS:This multicenter randomized feasibility trial will enroll 45 adults aged 50-85 years with MCI and at least one modifiable dementia risk factor. Participants will be randomized (1:1:1) to a tablet-based multidomain intervention, a smartphone-based multidomain intervention, or a control group receiving no intervention. The 12-week program consists of daily 30-minute home-based sessions (physical activity 20 minutes, nutrition education 5 minutes, meditation 5 minutes) delivered over four 3-week cycles, with assessments at weeks 3, 6, and 9 to adjust difficulty. The primary outcomes focus on feasibility (recruitment, retention, adherence ≥70%, and data completeness), and secondary outcomes include exploratory measures of cognition, physical function, vascular risk, nutrition, mood, quality of life, and motivation. RESULTS:Recruitment and data collection are ongoing. CONCLUSIONS:This feasibility trial will inform the design of a future randomized trial evaluating a scalable, personalized mobile multidomain intervention for dementia prevention.
