Amyloid-beta, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data

Isabelle Bos*, Stephanie J. B. Vos, Willemijn J. Jansen, Rik Vandenberghe, Silvy Gabel, Ainara Estanga, Mirian Ecay-Torres, Jori Tomassen, Anouk den Braber, Alberto Lleo, Isabel Sala, Anders Wallin, Petronella Kettunen, Jose L. Molinuevo, Lorena Rami, Gael Chetelat, Vincent de la Sayette, Magda Tsolaki, Yvonne Freund-Levi, Peter JohannsenGerald P. Novak, Inez Ramakers, Frans R. Verhey, Pieter Jelle Visser, Alzheimer's Disease Neuroimaging Initiative

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


We investigated whether amyloid-beta (A beta) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had A beta status and neuropsychological data available. Linear mixed models were used to assess the associations of Ali and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without A beta pathology (A beta- norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the A beta- norms rightfully identified an additional group of individuals at risk of dementia. For non-memory test we found no difference. We confirmed the relationship between Ao and cognition in cognitively normal individuals. The Af3- norms for memory tests in combination with published norms improve prognostic accuracy of dementia.
Original languageEnglish
Article number193
Number of pages11
JournalFrontiers in Aging Neuroscience
Publication statusPublished - 25 Jun 2018


  • Alzheimer's disease
  • amyloid-beta
  • tau
  • cognition
  • neuropsychological examination
  • normative data
  • AGE

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