Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum

Background@#Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer's disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply ATN (amyloid/taueurodegeneration) classification based on CSF results. @*Methods@#We performed CSF analysis in 51 normal controls (NC), 23 mild cognitive impairment (MCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We attempted to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied ATN classification scheme based on CSF biomarker abnormalities to characterize our participants. @*Results@#CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differed across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42 (0.994) followed by p-tau/Aβ42 (0.963), Aβ42 (0.960), t-tau (0.918), and p-tau (0.684). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, ATN classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-N-(73%), MCI as A+T-N-(30%)/A+T+N+(26%), and ADD as A+T+N+(57%). @*Conclusion@#CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The ATN subtypes based on CSF biomarkers may further serve to predict the prognosis.

Hypercoagulability and Mortality of Patients with Stroke and Active Cancer: The OASIS-CANCER Study / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Patients with active cancer are at an increased risk for stroke. Hypercoagulability plays an important role in cancer-related stroke. We aimed to test whether 1) hypercoagulability is a predictor of survival, and 2) correction of the hypercoagulable state leads to better survival in patients with stroke and active cancer. METHODS: We recruited consecutive patients with acute ischemic stroke and active systemic cancer between January 2006 and July 2015. Hypercoagulability was assessed using plasma D-dimer levels before and after 7 days of anticoagulation treatment. The study outcomes included overall and 1-year survival. Plasma D-dimer levels before and after treatment were tested in univariate and multivariate Cox regression models. We controlled for systemic metastasis, stroke mechanism, age, stroke severity, primary cancer type, histology, and atrial fibrillation using the forward stepwise method. RESULTS: A total of 268 patients were included in the analysis. Patients with high (3rd–4th quartiles) pre-treatment plasma D-dimer levels showed decreased overall and 1-year survival (adjusted HR, 2.19 [95% CI, 1.46–3.31] and 2.70 [1.68–4.35], respectively). After anticoagulation treatment, post-treatment D-dimer level was significantly reduced and independently associated with poor 1-year survival (adjusted HR, 1.03 [95% CI, 1.01–1.05] per 1 μg/mL increase, P=0.015). The successful correction of hypercoagulability was a protective factor for 1-year survival (adjusted HR 0.26 [CI 0.10–0.68], P=0.006). CONCLUSIONS: Hypercoagulability is associated with poor survival after stroke in patients with active cancer. Effective correction of hypercoagulability may play a protective role for survival in these patients.

The Need for a Coagulation Assay after Initiation of New Oral Anticoagulants in Patients with Renal Dysfunction: A Case Report

BACKGROUND: Dabigatran etexilate, a new oral anticoagulant, was recently approved as an efficacious alternative to warfarin for the prevention of first and recurrent stroke in patients with nonvalvular atrial fibrillation. Limited data are available for dabigatran use in patients with a creatinine clearance rate (CrCL) of 15-30 mL/min. Furthermore, current guidelines do not recommend frequent blood monitoring after dabigatran use. We report herein a patient with severe renal dysfunction who exhibited profound coagulopathy after 2 days of dabigatran use. CASE REPORT: An 87-year-old woman was admitted for altered mental status and left-side weakness. She was diagnosed with right middle cerebral artery infarction. The baseline assessment revealed a serum creatinine concentration of 1.29 mg/dL and a CrCL of 27.2 mL/min. Dabigatran therapy was started 5 weeks after admission at a dosage of 110 mg twice daily. After 2 days of dabigatran use, the patient developed multiple bruises and evidence of upper-gastrointestinal bleeding. Laboratory tests demonstrated a severe coagulopathy, with a prothrombin time of 85.9 sec, an international normalized ratio of 11.36, an activated partial thromboplastin time of 119.2 sec, and a thrombin time of 230.8 sec. Serial assessment of the patient's renal function revealed substantial fluctuation of the CrCL (range, 17.9-26.5 mL/min). CONCLUSIONS: The present case emphasizes the need for frequent checking of renal function and assessment using coagulation assays after commencing dabigatran therapy in patients with moderate-to-severe renal impairment.