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bioRxiv · 10.1101/523787

Aβ-Positivity Predicts Cognitive Decline but Cognition Also Predicts Progression to Aβ-Positivity

Elman, J. A.·Panizzon, M. S.·Franz, C. E.·Gustavson, D. E.·Sanderson, M. E.·Lyons, M. J.·Kremen, W. S.
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Abstract

IntroductionBiomarker positivity predicts cognitive decline and Alzheimers dementia. But what predicts biomarker positivity? We hypothesized that cognitive function and p-tau would predict progression from normal to abnormal levels of {beta}-amyloid (A{beta}). MethodsBaseline cognition in 292 non-demented, A{beta}-negative Alzheimers Disease Neuroimaging Initiative (ADNI) participants was measured with two cognitive composites and compared between those that progressed to A{beta}-positivity versus A{beta}-stable. Follow-up analyses included continuous CSF A{beta} and p-tau levels to examine subthreshold effects. ResultsContinuously measured baseline subthreshold A{beta} and p-tau predicted progression to A{beta}-positivity, but both baseline cognitive measures predicted progression to A{beta}-positivity even after controlling for baseline biomarker levels. DiscussionCurrent A{beta} 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.

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Elman, J. A., Panizzon, M. S., Franz, C. E., Gustavson, D. E., Sanderson, M. E., Lyons, M. J., Kremen, W. S.. 2019-01-17. Aβ-Positivity Predicts Cognitive Decline but Cognition Also Predicts Progression to Aβ-Positivity. https://doi.org/10.1101/523787

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