We characterized patients with discordant plasma p-tau217 results and amyloid status determined by the Aβ42/p-tau181 CSF ratio or Aβ-PET biomarkers in an ethnically diverse mixed memory clinic cohort. Among 539 patients,...We characterized patients with discordant plasma p-tau217 results and amyloid status determined by the Aβ42/p-tau181 CSF ratio or Aβ-PET biomarkers in an ethnically diverse mixed memory clinic cohort. Among 539 patients, 83.9% had concordant biomarker profiles, while 13.4% were amyloid negative and plasma p-tau217 positive discordant, and 2.8% were amyloid positive and plasma p-tau217 negative discordant. Discordant groups differed in cognitive syndrome severity and etiological diagnosis, but no other variables reached significance. However, analyses indicated small effects of BMI, kidney function, and certain neurological conditions. Amyloid negativity and plasma p-tau217 positivity discordance may reflect plasma p-tau217 detecting early amyloid pathology not detected by CSF or Aβ-PET. Further research is needed to clarify mechanisms underlying discordant biomarker profiles.
BACKGROUND: Clinical Amyloid positivity Prediction Score (CAPS) is a clinical tool developed on a small Canadian cohort with clinical Alzheimer's Disease (AD) to help predict amyloid-beta (Aβ) positivity. The Comprehensi...BACKGROUND: Clinical Amyloid positivity Prediction Score (CAPS) is a clinical tool developed on a small Canadian cohort with clinical Alzheimer's Disease (AD) to help predict amyloid-beta (Aβ) positivity. The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study is a national Canadian observational study of participants clinically diagnosed with various neurodegenerative disorders, including Alzheimer's syndrome, making it an ideal platform to validate CAPS on an independent but similar cohort of participants. METHODS: Participants from the COMPASS-ND cohort with Subjective Cognitive Impairment (SCI), Mild Cognitive Impairment (MCI) or dementia due to AD, and a known Aβ status were included. CAPS was assigned to the individuals as follows: cognitive decline of >2 points/year on the Mini-Mental State Examination (MMSE) = 1-point, Neuropsychiatric Inventory Questionnaire (NPI-Q) ≥2 = 2 points, and low Fazekas score (0 or 1) = 1 points. A total CAP score ≥ 2 was considered indicative of Aβ positivity. RESULTS: Total 86 participants fulfilled the inclusion criteria. Aβ + individuals had higher NPI-Q scores (2 vs 0.5, p = 0.005) and a lower baseline MMSE score (26.5 vs 28.0, p = 0.009). High WMH on brain MRI was reported more frequently in the Aβ- subgroup (50.0% vs 33.8%, p < 0.001). The frequency of people with a CAPS score of ≥2 is significantly higher in the Aβ + subgroup (75% vs 50%, p < 0.001). CAPS demonstrated a reasonable predictive value in this cohort, with 67% accuracy, and 73% sensitivity. CONCLUSION: This validation study in a larger Canadian cohort showed that CAPS demonstrated reasonable accuracy in distinguishing between Aβ + and Aβ- subgroups.
BACKGROUND: Autoimmune cerebellar ataxia (ACA) is potentially treatable; however, some patients initially suspected of having ACA are later diagnosed with neurodegenerative diseases. We examined clinical features, immuno...BACKGROUND: Autoimmune cerebellar ataxia (ACA) is potentially treatable; however, some patients initially suspected of having ACA are later diagnosed with neurodegenerative diseases. We examined clinical features, immunotherapy response, and diagnostic reclassification in patients with suspected ACA. METHODS: We retrospectively reviewed 130 consecutive patients admitted for cerebellar ataxia between January 2015 and December 2023. At admission, 24 were classified as clinically suspected ACA and 81 as SCA/MSA (spinocerebellar ataxia or multiple system atrophy). The 24 cases were subclassified as definite, probable, or non-criteria ACA according to the Dalmau-Graus criteria. Immunotherapy response was defined as a ≥ 3-point improvement in the Scale for the Assessment and Rating of Ataxia (SARA). RESULTS: Compared with the SCA/MSA group, the suspected ACA group had lower frequencies of cerebellar atrophy, brainstem atrophy, and cerebellar hypoperfusion (all p < 0.005). Among 20 evaluable treated patients, 11 responded; responders presented earlier than non-responders (median onset-to-presentation interval, 12.0 vs 24.0 months; p = 0.006). Based on the ACA criteria, 5/24 were definite and 6/24 probable. During follow-up through December 2025, 8/24 patients (33.3%) were reclassified as having neurodegenerative diseases. CONCLUSIONS: Approximately one-third of patients initially suspected of having ACA were later reclassified as having neurodegenerative diseases. Although fulfillment of the Dalmau-Graus criteria was less frequent among reclassified patients, routine baseline clinical and imaging features did not clearly distinguish them. Some patients with early neurodegenerative cerebellar ataxia may initially present with clinical features overlapping those of ACA, underscoring the importance of longitudinal follow-up and periodic diagnostic reassessment.
BACKGROUND: The efficacy of an implantable loop recorder (ILR) has been proven in detecting atrial fibrillation (AF) in embolic stroke of undetermined source (ESUS) patients. However, when patients should get ILR remains...BACKGROUND: The efficacy of an implantable loop recorder (ILR) has been proven in detecting atrial fibrillation (AF) in embolic stroke of undetermined source (ESUS) patients. However, when patients should get ILR remains uncertain. OBJECTIVE: We investigated whether ILR insertion timing was associated with the incidence of AF detection and clinical outcomes. METHODS: We identified ESUS patients receiving an ILR insertion between July 2016 and October 2021 using National Health Insurance claims data. Patients were classified based on the ILR insertion timing. The early implant was defined as ≤2 months from stroke, and the late implant was defined as >1 year. RESULTS: Among 1509 patients, 386 (25.6%) were classified into early and 772 (51.2%) into late implant groups. Patients in the early group were younger and had a lower prevalence of hypertension, diabetes, and heart failure than those in the late group. The incidence of AF was higher in the early group than in the late group (HR 1.49, 95% CI 1.21-1.85, p < 0.001). However, clinical outcomes, including recurrent stroke, all-cause mortality, and major bleeding, were not different between the groups. The risk of recurrent stroke and major bleeding did not increase following AF detection, although the mortality risk did. CONCLUSION: In this nationwide cohort study, the incidence of AF detection was higher in ESUS patients when ILR was inserted within 2 months than after a year from stroke. From the perspective of AF, inserting an ILR earlier is superior; however, delayed insertion may still offer potential advantages.
BACKGROUND: Broad 6-month death-or-dependency outcomes after acute ischemic stroke can conceal opposing early benefit and harm pathways after antithrombotic treatment. We examined these pathways in the corrected public-u...BACKGROUND: Broad 6-month death-or-dependency outcomes after acute ischemic stroke can conceal opposing early benefit and harm pathways after antithrombotic treatment. We examined these pathways in the corrected public-use International Stroke Trial dataset. METHODS: We analyzed 19,285 randomized participants with assignable 6-month outcome classification; 150 with missing classification were excluded. The mediator was the first recorded selected event within 14 days or earlier death/discharge: early death, intracranial hemorrhage or hemorrhagic stroke, major extracranial bleeding, pulmonary embolism, recurrent stroke, or no selected event. Standardized risks, risk differences per 1000 patients, and risk ratios were estimated using robust Poisson regression and g-computation. Interventional direct and indirect effects were estimated with multinomial mediator and outcome models, marginalizing factorial co-allocation. RESULTS: Aspirin was associated with a small reduction in 6-month death or dependency (risk difference, -12.1 per 1000; risk ratio, 0.981). The interventional direct component was -9.8 per 1000 and the first-event-mediated component was -2.3 per 1000. Low-dose heparin had a near-null total effect (3.0 per 1000), with opposing direct (6.4) and indirect (-3.4) components. Higher-dose heparin also had a near-null composite effect (-1.9 per 1000), but mortality sensitivity analysis showed an unfavorable signal (15.6 per 1000). CONCLUSIONS: In this historical megatrial, small or near-null disability-inclusive effects were compatible with divergent early ischemic-prevention and bleeding-hazard pathways. Recorded first early events explained only part of the treatment-outcome contrasts. These estimates are methodological and interpretive, not contemporary prescribing guidance.
OBJECTIVE: Effective treatments for amyotrophic lateral sclerosis (ALS) remain limited, underscoring the need to identify robust biomarkers associated with disease severity and prognosis. This study investigated whether...OBJECTIVE: Effective treatments for amyotrophic lateral sclerosis (ALS) remain limited, underscoring the need to identify robust biomarkers associated with disease severity and prognosis. This study investigated whether immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-glycolipid antibodies are associated with clinical manifestations of ALS, particularly decline in respiratory function. METHODS: This was a retrospective observational cohort study of the patients with ALS. Among patients with definite or probable limb-onset ALS, 11 patients in the glycolipid IgG-positive group were compared with 15 patients in the IgG-negative group, and 5 patients in the glycolipid IgM-positive group were compared with 9 patients in the IgM-negative group, with adjustment for age. Associations between anti-glycolipid antibody status and respiratory function were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: The time to decline of percent forced vital capacity (%FVC) below 80% and 60% was significantly shorter in the IgG-positive group than in the IgG-negative group (p = 0.002 and p = 0.025, respectively). Cox proportional hazards analysis demonstrated that IgG antibody positivity was an independent risk factor for earlier decline in %FVC to 80%. INTERPRETATION: These findings suggest that anti-glycolipid IgG antibodies may be associated with respiratory function decline in ALS. Larger comprehensive studies will be required to validate these results and to elucidate the underlying pathophysiological mechanisms.