Day, Gregory S.

This cross-sectional study evaluates the performance of the US Food and Drug Administration–cleared phosphorylated tau 217 (p-tau217) to β-amyloid 42 ratio cut points used to detect amyloid pathology associated with Alzheimer disease.

ABSTRACT Early identification of patients with treatment‐responsive rapidly progressive dementia (RPD) is important as early treatment improves outcomes. The STAM 3 P score identifies treatment‐responsive RPD using “high risk” presenting features. We optimized performance by adding a time component (i.e., dementia within 3 months) and validated the modified “STAM3 m P score” in two independent cohorts ( n = 302). A STAM3 m P score ≥ 1 identified 96% of patients with treatment‐responsive RPD; ≥ 3 features were highly specific (98%). These data suggest that ≥ 1 STAM3 m P features effectively identifies treatment‐responsive RPD and may be used to prioritize investigations, whereas ≥ 3 STAM3 m P features are highly specific and may inform early treatment decisions.

Abstract INTRODUCTION Research into cognitive dispersion – a cognitive process score measuring the intra‐individual variability (IIV) across a single testing session – suggests utility in neurodegenerative populations. Given widespread deficits observed in sporadic early‐onset Alzheimer's disease (EOAD), however, it is unclear if examining cognitive dispersion shows benefit in this condition. METHODS A total of 309 participants (188 amyloid‐positive EOAD, 43 amyloid‐negative early‐onset dementia [EOnonAD], 78 cognitively normal [CN]) completed neuropsychological testing twice over 12 months. Dispersion‐related differences among groups were assessed, as was cognitive dispersion's capacity to predict domain‐specific cognitive trajectories, and its convergence with imaging biomarkers. RESULTS EOAD participants displayed higher cognitive dispersion than EOnonAD participants, and associations with EOAD‐specific biomarkers. Additionally, cognitive dispersion was associated with 12‐month reliable change across several cognitive domains. DISCUSSION These preliminary results examine cognitive dispersion in sporadic EOAD. When used with baseline cognitive performance, cognitive dispersion measures may enrich future clinical trials in EOAD by enhancing treatment monitoring over time.