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

Ingvild Vøllo Eliassen; Bjørn-Eivind Kirsebom; Knut Waterloo; Ragnhild Eide Skogseth; Gøril Rolfseng Grøntvedt; Mathilde Suhr Hemminghyth; Berglind Gísladóttir; Fernando Gonzalez-Ortiz; Dag Aarsland; Tormod Fladby; Erik Hessen

doi:10.1080/23279095.2025.2518566

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

Appl Neuropsychol Adult. 2025 Jun 17:1-9. doi: 10.1080/23279095.2025.2518566. Online ahead of print.

Authors

Ingvild Vøllo Eliassen^{1

2}, Bjørn-Eivind Kirsebom^{3

4

5}, Knut Waterloo^{3

4}, Ragnhild Eide Skogseth⁶, Gøril Rolfseng Grøntvedt^{7

8

9}, Mathilde Suhr Hemminghyth^{10

11

12}, Berglind Gísladóttir^{1

13}, Fernando Gonzalez-Ortiz¹⁴, Dag Aarsland^{1

15

16}, Tormod Fladby^{1

5}, Erik Hessen^{1

2}

Affiliations

¹ Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
² Institute of Psychology, University of Oslo, Oslo, Norway.
³ Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
⁴ Department of Psychology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
⁵ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶ Department of Clinical Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
⁷ Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway.
⁸ Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁹ KG Jebsen Centre for Alzheimer's Disease, Kavli Institute for Systems Neuroscience, Trondheim, Norway.
¹⁰ Research Group for Age-Related Medicine, Department of Research and Innovation, Fonna Hospital Trust, Haugesund, Norway.
¹¹ Department of Neuropsychology, Helse-Fonna, Fonna Hospital Trust, Haugesund, Norway.
¹² Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway.
¹³ Clinical Molecular Biology (EpiGen), Medical Division, Akershus University Hospital, University of Oslo, Oslo, Norway.
¹⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹⁵ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁶ Center for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway.

PMID: 40528306
DOI: 10.1080/23279095.2025.2518566

Abstract

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 (Aβ_42/40, 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.

Keywords: Alzheimer’s disease; cerebrospinal fluid biomarkers; cognition; plasma biomarkers; preclinical.