Neurology

Home-based precuneus gamma tACS improves cognition and function in prodromal/mild Alzheimer disease

Fifty patients with prodromal or mild Alzheimer disease were randomized to 8 weeks of home-based gamma tACS versus sham, then open-label extension. Active tACS improved global cognition, activities of daily living, and associative memory versus sham on CDR-sum of boxes, ADAS-Cog, ADCS-ADL, and Face-Name tests. During the open-label phase, cognitive, functional, and associative memory gains remained significant on ADAS-Cog, ADCS-ADL, and Face-Name outcomes. Treatment was safe, feasible for caregiver-supervised home delivery, and well tolerated over double-blind and extension periods. 1

Plasma p-tau217 change is a robust pharmacodynamic endpoint for early Alzheimer disease trials

This retrospective analysis pooled 716 participants with longitudinal plasma p-tau217, baseline amyloid PET, and serial clinical assessments across four cohorts. In Aβ-positive cognitively unimpaired and impaired groups, annual p-tau217 change showed effect sizes around 0.6, enabling moderate-sized treatment trials. Detecting a 25% drug effect required roughly 610–664 participants per arm in unselected Aβ-positive samples at 80% power. Restricting to intermediate amyloid burden (Centiloid 20–40) raised effect sizes to 0.72–0.85 and reduced sample needs to about 342–492 per arm. 2

Deep-learning brain age gap from acute MRI predicts ischemic stroke recurrence

Investigators trained the Mask-based Brain Age Network on 5,353 healthy individuals, then applied it to 10,890 acute ischemic cerebrovascular disease patients. The model estimated contextual brain age from non-infarcted T2-FLAIR regions, yielding a brain age gap versus chronological age. Higher brain age gap independently predicted stroke recurrence at 3 months and 5 years, outperforming chronological age as a prognostic factor. Adding brain age gap to established prediction models significantly improved discrimination for recurrence risk. 3

Plasma p-tau217 and NfL plus midbrain–pons ratio differentiate PSP from Parkinson disease

This multicenter study measured plasma p-tau217, p-tau181, p-tau231, NfL, and GFAP in 275 participants, including PSP, corticobasal degeneration, Parkinson disease, and controls. PSP and corticobasal degeneration had higher p-tau species and NfL than Parkinson disease and controls, supporting a distinct biofluid signature. In PSP, higher p-tau217, NfL, and GFAP correlated with worse cognition, and NfL correlated with higher PSP Rating Scale scores. Combining plasma p-tau217 and NfL with midbrain-to-pons MRI ratio discriminated PSP from Parkinson disease with AUC 0.946, comparable to florzolotau PET. 4