White matter retention on 18F-florbetapir positron emission tomography independently predicts cognitive decline and response to anti-amyloid therapy in Alzheimer’s disease
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White matter 18F-florbetapir PET signal, often dismissed as non-specific, is shown here to be a clinically relevant biomarker in Alzheimer’s disease (AD). We analyzed normal-appearing white matter (NAWM) retention in 672 participants spanning the AD continuum. NAWM retention displayed distinct temporal dynamics from cortical amyloid, increasing in preclinical stages. Higher NAWM retention independently predicted accelerated cognitive decline and clinical progression (p < 0.0001), with prognostic power comparable to established fluid biomarkers like plasma p-tau217. Furthermore, NAWM retention was responsive to lecanemab therapy. Combining NAWM and cortical amyloid measures significantly improved diagnostic accuracy for amyloid positivity to 92%, outperforming either measure alone. We conclude that NAWM 18F-florbetapir retention is an independent biomarker for AD prognostication and therapeutic monitoring, providing information beyond cortical amyloid burden. These findings support its incorporation into AD staging and clinical protocols.
