Visual read of [F‐18]florquinitau PET that includes and extends beyond the mesial temporal lobe is associated with increased plasma pTau217 and cognitive decline in a cohort that is enriched with risk for Alzheimer's disease

Abstract

INTRODUCTIONPatterns of signal from tau positron emission tomography (tau‐PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.METHODSVisual assessment of Tau‐PET [F‐18]florquinitau (FQT) exams from 728 initially non‐demented older adults yielded four uptake groups: tau‐negative (T−), MTL‐only (T+MTL), neocortex‐only (T+Neo), or both (T+MTL&Neo). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.RESULTST+MTL&Neo was the most common T+ group (n = 97; 93% A+) and exhibited the sharpest worsening in cognitive and pTau217 trajectories before tau PET.DISCUSSIONThe T+MTL&Neo category represents an intermediate to advanced stage of AD preceded by rising ptau217 and progressive cognitive decline. The pTau217 finding suggests that A+, T+ in MTL or neocortex could represent early AD stages, with a higher likelihood of progressing to more advanced stages.Highlights Visual assessments of Tau‐PET FQT revealed four distinct uptake groups: tau‐negative (T−), MTL‐only (T+MTL), neocortex‐only (T+Neo), or both (T+MTL&Neo). Amyloid positive participants in the T+MTL and T+MTL&Neo categories showed a retrospectively faster decline in their cognitive trajectories, and a sharper increase in pTau217 levels in plasma, compared to T−. The T+MTL&Neo group displayed sharper trajectories compared with the other Tau positive groups in both their cognitive scores and pTau217 plasma levels. Our results suggest that participants with Tau present in both MTL and neocortex represent an intermediate to advanced stage of AD, whereas participants with signals confined to either MTL or neocortex could represent earlier AD stages.