ABSTRACT
Introduction Biomarker positivity predicts cognitive decline and Alzheimer’s dementia. But what predicts biomarker positivity? We hypothesized that cognitive function and p-tau would predict progression from normal to abnormal levels of β-amyloid (Aβ).
Methods Baseline cognition in 292 non-demented, Aβ-negative Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants was measured with two cognitive composites and compared between those that progressed to Aβ-positivity versus Aβ-stable. Follow-up analyses included continuous CSF Aβ and p-tau levels to examine subthreshold effects.
Results Continuously measured baseline subthreshold Aβ and p-tau predicted progression to Aβ-positivity, but both baseline cognitive measures predicted progression to Aβ-positivity even after controlling for baseline biomarker levels.
Discussion Current Aβ thresholds may be ignoring relevant subthreshold pathology. Importantly, cognitive function can be an important early predictor of future risk, even earlier than the key biomarkers as currently measured. Moreover, A-/T+ individuals may still be on the AD pathway because p-tau also predicted progression to positivity.
Footnotes
↵* Co-first authors
Declaration of interest: None