Comparison of plasma biomarkers and amyloid PET for predicting memory decline in cognitively unimpaired individuals

Clifford R. Jack, Heather J. Wiste, Alicia Algeciras-Schimnich, Stephen D. Weigand, Dan J. Figdore, Val J. Lowe, Prashanthi Vemuri, Jonathan Graff-Radford, Vijay K. Ramanan, David S. Knopman, Michelle M. Mielke, Mary M. Machulda, Julie Fields, Christopher G. Schwarz, Petrice M. Cogswell, Matthew L. Senjem, Terry M. Therneau, Ronald C. Petersen

Research output: Contribution to journalArticlepeer-review


BACKGROUND: We compared the ability of several plasma biomarkers versus amyloid positron emission tomography (PET) to predict rates of memory decline among cognitively unimpaired individuals. METHODS: We studied 645 Mayo Clinic Study of Aging participants. Predictor variables were age, sex, education, apolipoprotein E (APOE) ε4 genotype, amyloid PET, and plasma amyloid beta (Aβ)42/40, phosphorylated tau (p-tau)181, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and p-tau217. The outcome was a change in a memory composite measure. RESULTS: All plasma biomarkers, except NfL, were associated with mean memory decline in models with individual biomarkers. However, amyloid PET and plasma p-tau217, along with age, were key variables independently associated with mean memory decline in models combining all predictors. Confidence intervals were narrow for estimates of population mean prediction, but person-level prediction intervals were wide. DISCUSSION: Plasma p-tau217 and amyloid PET provide useful information about predicting rates of future cognitive decline in cognitively unimpaired individuals at the population mean level, but not at the individual person level.

Original languageEnglish (US)
Pages (from-to)2143-2154
Number of pages12
JournalAlzheimer's and Dementia
Issue number3
StatePublished - Mar 2024


  • amyloid PET
  • cognitive decline
  • cognitive decline and Alzheimer's disease
  • plasma biomarkers and Alzheimer's disease

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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