Tau-PET is superior to phospho-tau when predicting cognitive decline in symptomatic AD patients

Ruben Smith; Nicholas C Cullen; Alexa Pichet Binette; Antoine Leuzy; Kaj Blennow; Henrik Zetterberg; Gregory Klein; Edilio Borroni; Rik Ossenkoppele; Shorena Janelidze; Sebastian Palmqvist; Niklas Mattsson-Carlgren; Erik Stomrud; Oskar Hansson; Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.12875

Tau-PET is superior to phospho-tau when predicting cognitive decline in symptomatic AD patients

Alzheimers Dement. 2023 Jun;19(6):2497-2507. doi: 10.1002/alz.12875. Epub 2022 Dec 14.

Authors

Ruben Smith^{1

2}, Nicholas C Cullen¹, Alexa Pichet Binette¹, Antoine Leuzy¹, Kaj Blennow^{3

4}, Henrik Zetterberg^{3

4

5

6

7}, Gregory Klein⁸, Edilio Borroni⁸, Rik Ossenkoppele^{1

9}, Shorena Janelidze¹, Sebastian Palmqvist^{1

10}, Niklas Mattsson-Carlgren^{1

2

11}, Erik Stomrud^{1

10}, Oskar Hansson^{1

10}; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Clinical Sciences, Clinical Memory Research Unit, Malmö, Lund University, Lund, Sweden.
² Department of Neurology, Skåne University Hospital, Lund, Sweden.
³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁶ UK Dementia Research Institute at UCL, London, UK.
⁷ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
⁸ F. Hoffmann-La Roche Ltd., Basel, Switzerland.
⁹ Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁰ Memory Clinic, Skåne University Hospital, Malmö, Sweden.
¹¹ Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.

Abstract

Introduction: Biomarkers for the prediction of cognitive decline in patients with amnestic mild cognitive impairment (MCI) and amnestic mild dementia are needed for both clinical practice and clinical trials.

Methods: We evaluated the ability of tau-PET (positron emission tomography), cortical atrophy on magnetic resonance imaging (MRI), baseline cognition, apolipoprotein E gene (APOE) status, plasma and cerebrospinal fluid (CSF) levels of phosphorylated tau-217, neurofilament light (NfL), and amyloid beta (Aβ)_42/40 ratio (individually and in combination) to predict cognitive decline over 2 years in BioFINDER-2 and Alzheimer's Disease Neuroimaging Initiative (ADNI).

Results: Baseline tau-PET and a composite baseline cognitive score were the strongest independent predictors of cognitive decline. Cortical thickness and NfL provided some additional information. Using a predictive algorithm to enrich patient selection in a theoretical clinical trial led to a significantly lower required sample size.

Discussion: Models including baseline tau-PET and cognition consistently provided the best prediction of change in cognitive function over 2 years in patients with amnestic MCI or mild dementia.

Keywords: AD; PET; blood biomarkers; cognition; tau.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alzheimer Disease* / pathology
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction* / cerebrospinal fluid
Humans
Positron-Emission Tomography / methods
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
tau Proteins
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding