Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer’s disease. We studied 150 cognitively unimpaired participants and 100 patients with mild cognitive impairment in the Swedish BioFINDER study. P-tau217 was measured repeatedly for up to 6 years (median three samples per person, median time from first to last sample, 4.3 years). Preclinical (amyloid-β-positive cognitively unimpaired, n = 62) and prodromal (amyloid-β-positive mild cognitive impairment, n = 49) Alzheimer’s disease had accelerated p-tau217 compared to amyloid-β-negative cognitively unimpaired (β  =  0.56, P < 0.001, using linear mixed effects models) and amyloid-β-negative mild cognitive impairment patients (β  =  0.67, P < 0.001), respectively. Mild cognitive impairment patients who later converted to Alzheimer’s disease dementia (n = 40) had accelerated p-tau217 compared to other mild cognitive impairment patients (β  =  0.79, P < 0.001). P-tau217 did not change in amyloid-β-negative participants, or in patients with mild cognitive impairment who did not convert to Alzheimer’s disease dementia. For 80% power, 109 participants per arm were required to observe a slope reduction in amyloid-β-positive cognitively unimpaired (71 participants per arm in amyloid-β-positive mild cognitive impairment). Longitudinal increases in p-tau217 correlated with longitudinal worsening of cognition and brain atrophy. In summary, plasma p-tau217 increases during early Alzheimer’s disease and can be used to monitor disease progression.

Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer’s Clinical Composite; R2 = 0.14, 95% CI [0.12–0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77–0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54–81]; P < 0.001) with cognition as trial endpoint, and by 63% (95% CI [53–70], P < 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.

Background: Venous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort. Methods: Observational, prospective study enrolling consecutive patients at a tertiary multidisciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVCrelated VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT. Results: Overall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5e36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVCrelated VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive. Conclusions: Paediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass. Clinical trial registration: ACTRN12615000442505.