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.
Consciousness is central to the human condition, but its inherent characteristics and underlying mechanisms remain poorly understood. Advances in neuroscience based on the concept of the vegetative state have expanded the understanding of disorders of consciousness (DoC), particularly the minimally conscious state (MCS) and emergence from the MCS. Despite this progress, diagnostic uncertainty persists due to the subtlety of clinical signs and variable outcomes. Although standardized behavioral scales remain the gold standard for diagnosing DoC, advanced imaging and electrophysiological tools increasingly highlight the importance of multimodal assessments. These approaches have demonstrated that patients who appear unresponsive in behavioral assessments may voluntarily engage in mental activities that can be detected using functional magnetic resonance imaging and electroencephalography, potentially revealing covert consciousness and suggesting possible therapeutic strategies. This review consolidates the current evidence on the diagnosis, prognosis, and mechanisms of DoC across various neurological conditions. We highlight the role of brain networks in producing diverse phenotypes as well as the need for well-designed studies that can improve multimodal diagnostic strategies. Building on recent initiatives aimed at standardizing definitions, prognostic guidelines, data collection, and clinical management practices, we show that further multimodal neuroimaging research is essential to improving diagnoses, prognostication, and outcomes for patients with DoC and their families.
BACKGROUND AND PURPOSE:This study investigated the impact of schizophrenia on the outcomes of hospitalizations for acute ischemic stroke (AIS). Previous studies have suggested that outcomes are worse for patients with both AIS and schizophrenia, but a definitive conclusion is lacking. METHODS:A retrospective analysis of the 2005-2020 United States Nationwide Inpatient Sample was conducted. Patients aged ≥20 years who were hospitalized for AIS were divided into two groups: with and without schizophrenia. The groups were matched using propensity-score matching at a 1:4 ratio. The assessed outcomes included in-hospital mortality, unfavorable discharge, length of hospital stay (LOS), and major complications. Logistic and linear regression analyses were used to assess outcome relationships. RESULTS:Matching resulted in 43,545 patients being analyzed: 8,709 with schizophrenia and 34,836 without schizophrenia. Schizophrenia was associated with higher risks of mortality (odds ratio [OR]=1.16), unfavorable discharge (OR=2.00), prolonged LOS (OR=1.61), and major complications (OR=1.39) including acute myocardial infarction, venous thromboembolism, pneumonia, sepsis, and acute kidney injury. Schizophrenia was also associated with higher total hospital costs (beta=6.73). The associations were consistent across most subgroups. CONCLUSIONS:Schizophrenia significantly worsens the outcomes in AIS patients, contributing to higher mortality, prolonged LOS, more complications, and increased hospital costs. These findings highlight the need to apply tailored management strategies to AIS patients with schizophrenia.
BACKGROUND AND PURPOSE:Spontaneous intracranial hypotension (SIH) is primarily caused by cerebrospinal fluid (CSF) leakage; however, precise localization of the leakage remains challenging. This study evaluated the outcomes of ultrafast CT myelography in Korea. METHODS:Data were prospectively collected from patients with SIH who underwent ultrafast CT myelography at Seoul National University Hospital between August 2023 and December 2024. Success rates and leakage sites were documented. We also examined whether the most prominent lateral extradural fluid collection observed on heavily T2-weighted magnetic resonance (MR) myelography could predict the actual leak site identified by ultrafast CT myelography. RESULTS:Fifty-one patients (22 males and 29 females) underwent ultrafast CT myelography, with a mean age of 42.9±10.3 years (range, 25-70 years). Technical success rate was 90.2% (46/51). Leakage sites were identified in 44 patients (95.7%) of the 46 with successful examinations. Among these 44 patients, 4 (9.1%) demonstrated spinal cord herniation at the dural defect site. The leak site was cervical in 2 patients (5.0%) and thoracic in 38 patients (95.0%): 28 at the upper, 8 at the mid, and 2 at the lower thoracic levels. Among the 40 patients with visible leakage, only 5 (12.5%) had exact concordance between the leakage site and the most prominent lateral extradural fluid collection seen on pre-procedural MR myelography. CONCLUSIONS:The upper thoracic level was the most common site of CSF leakage, which differed from assumptions based on noninvasive spine MR myelography or non-contrast spine CT.
Background and Purpose To investigate the association between sleep hygiene practices and sleep disturbance in patients with Parkinson's disease (PD). Methods A cross-sectional study was conducted involving 109 PD patients. Sleep disturbance and sleep hygiene were evaluated using the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and the Sleep Hygiene Practice Scale-Korean version (SHPS-K), respectively. Multivariate linear regression analysis was performed, adjusting for potential confounding factors, such as age, body mass index, education, Hoehn and Yahr stage, cognitive function and depressive symptoms. Results Higher SHPS-K scores, reflecting poorer sleep hygiene, were significantly associated with greater sleep disturbance (B=0.254, p<0.001). Among the SHPS-K subdomains, arousal-related behaviors and irregular sleep scheduling showed the strongest correlations with K-PDSS-2 scores, while eating/drinking and sleep environments were not significantly related. Conclusions Poor sleep hygiene is significantly associated with disturbed sleep in patients with early-stage PD. These findings support the potential utility of non-pharmacological interventions targeting modifiable behavioral factors to improve sleep-related outcomes in patients with PD.
BACKGROUND AND PURPOSE:Breast cancer is the most common malignancy in females, with osseous metastasis predominantly occurring in the spine. We investigated the prevalence of mutations in patients with metastatic breast cancer to the spine (MBCS) and evaluated genotypic and therapeutic prognostic factors associated with survival. METHODS:The medical records and molecular genetic profiles of 50 patients diagnosed with MBCS at a single comprehensive cancer center between May 2013 and October 2022 were reviewed retrospectively. Data on demographics, biomarkers from genetic sequencing and immunohistochemistry, and anticancer therapies were collected. Overall survival rates were calculated, and accelerated-failure-time (AFT) models were used to identify prognostic factors for survival. RESULTS:The median overall survival time was approximately 6 years. Ninety-nine biomarkers were identified, with the estrogen receptor (ER) (38.4%), GATA protein binding 3 (32.3%), progesterone receptor (28.3%), human epidermal growth factor receptor 2 (13.1%), and AE1/AE3 (8.1%) being the most common. ER⁺ was the only biomarker associated with better survival when accounting for smoking status and treatment in an AFT model. Worse survival was associated with a smoking history (time ratio [TR]=0.427, p=0.043) and immunotherapy or targeted therapy (TR=0.440, p=0.048), but not radiotherapy of spinal metastasis (TR=0.256, p=0.121). In an alternative AFT model, better survival was associated with eribulin (TR=3.374, p=0.009), whereas worse survival was associated with pertuzumab (TR=0.390, p=0.010) and capecitabine (TR=0.496, p=0.024). CONCLUSIONS:Only ER expression was associated with the overall survival time when other confounding factors such as smoking status and treatment type were considered. A smoking history was associated with shorter survival, while eribulin was associated with survival prolongation.
Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by demyelination and axonal degeneration. Astrocytes have emerged as pivotal regulators of MS pathology, playing both pathogenic and regulatory roles. This review explores the mechanisms underlying astrocyte heterogeneity in MS, with a focus on how astrocyte functional states are influenced by extrinsic environmental factors such as inflammatory signals and dynamic interactions with immune cells and other glial populations. We discuss how the astrocyte heterogeneity established during development and further modulated by local environmental factors influences lesion formation, blood-brain barrier integrity, and tissue repair. We further outline protective and pathogenic astrocyte states together with the molecular mechanisms that govern neuroinflammatory responses. Finally, we highlight emerging therapeutic strategies for modulating astrocyte pathogenic responses. Collectively this work highlights astrocyte functional heterogeneity as a central feature of MS pathology and an emerging therapeutic opportunity for progressive MS.
BACKGROUND AND PURPOSE:Ultrafast dynamic CT myelography and digital subtraction myelography are used to localize dural defects in spontaneous intracranial hypotension; however, their invasiveness and technical demands limit widespread availability. The "flow-void sign" on T2-weighted spine MRI has been proposed as a potential non-invasive marker of the ventral dural defect, but its clinical value remains unclear. This study aimed to evaluate the utility of the flow-void sign for predicting dural defect sites in ventral cerebrospinal fluid leaks. METHODS:This retrospective cohort study, using data from the headache registry at Seoul National University Hospital (March 2022-April 2025), included patients with ventral dural defects confirmed by ultrafast dynamic CT myelography or surgery. Three neurologists assessed the flow-void sign on T2-weighted spine magnetic resonance sequences and evaluated the spinal CT images for causative structural lesions. The concordance between the flow-void sign and ventral dural defect was analyzed using kappa statistics. Logistic regression analysis was performed to identify factors associated with this concordance. RESULTS:Among 64 patients (57.8% female; median age, 40.0 years), the flow-void sign was observed in 43 (67.2%) patients. In the flow-void-positive group, 32 (74.4%) patients demonstrated concordance with the ventral dural defect level (κ=0.660, 95% confidence interval [CI], 0.476-0.825). The presence of a causative spinal lesion was significantly associated with the concordance (odds ratio, 6.48; 95% CI, 1.41-29.71; p=0.016). CONCLUSIONS:The flow-void sign may provide an indirect clue for localizing a ventral dural defect and supplement the definitive imaging modalities.
