Sighing Dynamics as a Candidate Digital Biomarker for Anxiety in Daily Life Using Wearable Respiratory Monitoring: Intensive Longitudinal Study.

The cognitive decline that characterizes Alzheimer's disease (AD) is preceded by neuropathologic changes, including intracellular accumulation of neurofibrillary tangles composed of phosphorylated tau protein and extracellular deposition of amyloid beta (Aβ) plaques., , Early detection of these changes may allow for the initiation of disease‐modifying treatments that can slow AD progression., Neurofibrillary tangles and amyloid plaques can be detected by positron emission tomography (PET), but the cost and limited accessibility of this technology are barriers to its routine use outside the hospital setting. Detection of blood‐based biomarkers by mass spectrometry or high‐sensitivity immunoassay is a less costly and time‐saving alternative compared to neuroimaging or cerebrospinal fluid biomarker measurement., , Tau protein phosphorylated at threonine 217 (p‐tau217) is a biomarker with high diagnostic accuracy in AD, including the early stages., , , , , In addition to reflecting tau pathology, plasma p‐tau217 levels have been shown to correlate strongly with Aβ accumulation and amyloid plaque levels detected by PET., , , , However, it is unclear whether the association between plasma p‐tau217 level and treatment‐related amyloid clearance (TRAC) is maintained over the course of AD treatment with amyloid‐targeting therapies in patients with early symptomatic AD. Donanemab is one of two amyloid‐targeting therapies currently approved and in clinical use for the treatment of early symptomatic AD., , In a phase 2 trial, donanemab treatment reduced amyloid plaque levels, and TRAC was associated with a slower spread of tau pathology, as determined by PET, and slower clinical decline. A post hoc cohort‐wide analysis showed that compared to placebo, plasma p‐tau217 levels decreased with donanemab treatment, which showed a weakly positive correlation with percent change in amyloid plaque level on PET imaging. Similarly, in the pivotal phase 3 TRAILBLAZER‐ALZ 2 trial, participants with early symptomatic AD treated with donanemab showed a statistically significant group‐level decrease in plasma p‐tau217, along with a reduction in amyloid burden and slower cognitive decline at 76 weeks.