Applied Neuropsychology Adult · Jun 17, 2025

Pathological biomarkers for Alzheimer's disease in cognitively unimpaired individuals are not associated with cognitive decline at two-year follow-up

By Eliassen IV, Kirsebom BE, Waterloo K et al.

BACKGROUND: Alzheimer's disease (AD) pathology may be present in cognitively unimpaired individuals, but the clinical implications of this are unclear. Subtle cognitive decline is a potential marker of preclinical AD. OBJECTIVE: To investigate whether two-year cognitive change scores are influenced by AD-linked cerebrospinal fluid (Aβ42/40, p-tau, t-tau, NfL) or plasma (p217, BD-tau, NfL) biomarker pathology in individuals who are cognitively unimpaired at baseline. METHODS: Participants were 148 cognitively unimpaired older adults (mean age = 68.11). Mean cognitive change over two years was compared between participants with normal and pathological biomarker status, for each biomarker separately. RESULTS: We found no significant difference between mean change scores in people with abnormal biomarker values compared to normal biomarker groups. CONCLUSION: Regardless of baseline CSF biomarker positivity, no significant cognitive change was observed in this group.

doi.org/10.1080/23279095.2025.2518566 Open access PubMed 40528306 Biomarkers