Previous studies indicate that elevated plasma total tau (T-tau) and neurofilament light (NfL) are, cross-sectionally and longitudinally, associated with worse cognition and neuroimaging measures of cortical thickness, cortical atrophy, and white matter hyperintensity, or white matter integrity. However, research comparing how these biomarkers cross-sectionally or longitudinally associate with cognition and neuroimaging measures are lacking. Among approximately 1,000 participants of the Mayo Clinic Study on Aging without dementia and with concurrent plasma NfL and T‐tau, cognitive status, and neuroimaging data, researchers repeated follow-up approximately every 15 months for a median of 6.2 years. Analyses were replicated among nearly 400 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) without dementia who were followed for a median of 3 years. When compared with T-tau, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes in all analyses, whereas the combination of elevated NfL and T-tau at baseline was more strongly associated at cross-section with worse global cognition and memory and with neuroimaging measures that included temporal cortex thickness and increased number of infarcts. T-tau did not add to the prognostic value of NfL longitudinally. Similar results were found upon ADNI analyses.
