Tau accumulation observed using repeated PET measures is associated with cognitive decline in normal elderly - 27/03/18
Résumé |
Background |
Autopsy and early PET data suggest that cognition is more closely associated with tau than with amyloid pathology, including in clinically normal (CN) older adults. Recently acquired serial tau-PET data allowed us to assess the association between cognition, tau, and amyloid, over a two-year follow-up. We hypothesized that the rate of tau accumulation in the temporal lobe would best predict the rate of cognitive decline.
Methods |
Sixty CN (age=55–90) from the Harvard Aging Brain Study (Boston, USA) had baseline evaluations within a three-month period [0.0–0.7 y]: Cognitive assessment included the Preclinical Alzheimer Cognitive Composite (PACC); Flortaucipir-PET SUVr assessed tau; and PiB-PET SUVr assessed amyloid. Subsequently, participants had annual cognitive evaluations [follow-up duration: 1.9–4.2y] and repeated tau [1.1–3.0 y] and PiB-PET [1.4–4.1 y]. Tau was measured in bilateral inferior temporal gyri and amyloid in a large cortical aggregate. Data were z-transformed to allow fair comparison between biomarkers. We correlated the slope of PACC decline to baseline PET measures, and to the rate of PET changes. We computed a model in which PET predictors were competing to determine which had the closest association with cognitive decline, adjusting for age, sex, and education.
Results |
All measures (tau, amyloid, cognition) changed during the follow-up (P<0.05). Change rates were faster for tau (+0.23±0.18 z-score/y) than for cognition (−0.10±0.23 z/y) or amyloid (+0.04±0.07 z-score/y). At baseline, tau (R2=0.06, P=0.07) and amyloid (R2=0.02, P=0.24) were not significantly associated with cognition. Baseline tau (R2=0.12, P=0.008) and amyloid (R2=0.13, P=0.006) predicted subsequent cognitive decline. Faster rates of change in tau predicted faster cognitive decline (R2=0.22, P=0.0003). In contrast, faster rates of changes in amyloid did not (R2=0.04, P=0.15). When baseline and change measures in amyloid and tau competed in the same model, change in tau predicted change in cognition (semi-partial R2=0.13, P=0.001), while baseline tau (semi-partial R2=2.9%, P=0.12) and amyloid (semi-partial R2=2.4%, P=0.15) were no longer significant predictors.
Conclusions |
Cognitive decline in CN is associated with tau accumulation in the temporal lobe. Tau-PET signal changes faster than cognition or amyloid, which makes it a promising marker to track disease progression and evaluate the efficacy of potential new drugs.
Le texte complet de cet article est disponible en PDF.Keywords : Cognition, Amyloid, Tau
Plan
Vol 174 - N° S1
P. S176 - avril 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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