Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study
Year: 2024
Type: article
Study design: Observational Study
Abstract: Background: Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care. Methods: We measured plasma Aβ42/Aβ40, P-tau181, NfL, and GFAP in 1007 individuals without dementia, aged 79-94 years, from the longitudinal, primary care-based German AgeCoDe study. We assessed the association with cognitive decline, disease progression, and the capacity to predict future dementia of the Alzheimer's type (DAT). We also evaluated biomarker dynamics in 305 individuals with a follow-up sample (∼8 years later). Findings: Higher levels of P-tau181 (HR = 1.32 [95% CI: 1.17-1.51]), NfL (HR = 1.19 [95% CI: 1.03-1.36]), and GFAP (HR = 1.36 [95% CI: 1.22-1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68-0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT. Additionally, higher levels of P-tau181 (β = -0.49 [95% CI: -0.71 to 0.26]), NfL (β = -0.29 [95% CI: -0.52 to 0.06]), and GFAP (β = -0.60 [95% CI: -0.83 to 0.38]) were linked to faster cognitive decline. A two-step DAT prediction strategy combining initial MMSE with biomarkers improved the identification of individuals in the prodromal stage for potential treatment eligibility. Biomarker levels changed over time, with increases in P-tau181 (β = 0.19 [95% CI: 0.14-0.25]), NfL (β = 2.88 [95% CI: 2.18-3.59]), and GFAP (β = 8.23 [95% CI: 6.71-9.75]). NfL (β = 2.47 [95% CI: 1.04-3.89]) and GFAP (β = 4.45 [95% CI: 1.38-7.51]) exhibited a faster increase in individuals progressing to DAT. Interpretation: Evaluating plasma biomarkers, alongside brief cognitive assessments, might enhance the precision of risk assessment for DAT progression in primary care. Funding: Alzheimer Forschung Initiative, Bundesministerium für Bildung und Forschung.
Institutions: University of Cologne, University Hospital Cologne, German Center for Neurodegenerative Diseases, University of Bonn, University Hospital Bonn, Heidelberg University, Medizinische Fakultät Mannheim, Technical University of Munich, Medizinische Hochschule Hannover, Leipzig University, University Medical Center Hamburg-Eppendorf, University of Science and Technology of China, Sahlgrenska University Hospital, Sorbonne Université, Institut des Sciences Moléculaires, Pitié-Salpêtrière Hospital, Institut du Cerveau, University of Gothenburg, University of Wisconsin–Madison, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,000
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Desert Research Institute, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, National Institute for Health and Care Research, University College London, European Commission, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Hjärnfonden, Vetenskapsrådet, Fondation pour la Recherche sur Alzheimer, HORIZON EUROPE Framework Programme
Awards: G1057200632, G1088883541, G1135383168, G1222782219, G1253720191, G1311708188, The Alzheimer’s Association quality control (QC) program for CSF and plasma biomarkers - Continuation, G150733400, G1551449788, G1588116593, G1771944843, G1802301745, G1833008592, Understanding Alzheimer Blood Biomarkers for Tau Pathology, G201353144, G2057385626, G2108271864, PREADAPT - Identifizierung personalisierter Entzündungsprofile des Alterns und ihre Auswirkungen auf die Demenzentwicklung - Teilprojekt: Definition eines altersbedingten SASP-Scores, welcher den kognitiven Abbau moduliert und Identifizierung der zugrundeliegenden genetischen Faktoren, G237833635, G2385484910, G2501682398, G2799940023, The Alzheimer biomarker toolbox – use in pathogenic studies, diagnostics and theragnostics, G2841269746, G2879339865, G292763017, G3027168043, DESCARTES - Ein blutbasierter diagnostischer und prognostischer Test der Alzheimererkrankung - Messung und Analyse von Protein-Blutbiomarkern in verschiedenen Kohorten und Projektkoordination, G308275008, G313301595, G3241251457, Fluid biomarkers for neurodegenerative dementias, DESCARTES - Ein blutbasierter diagnostischer und prognostischer Test der Alzheimererkrankung - Entwicklung und Validierung des Tests zur Vorhersage der Krankheitsprogression, G3903502641, G3914690605, G4181470480, G4234328627, G4260843567, G432431387, G434337789, G4377393254, G4404751248, G4549622993, G5040492720, G506008078, G516766298, Tau pathology in Alzheimer´s - understanding pathophysiology through biomarkers in blood and CSF, Fluid biomarkers for neurodegenerative dementias, G5619554209, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6142763750, G6158734006, G6168044258, G6289970089, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6745400708, G691317373, G7143958211, G7748812462, G791739130
OpenAlex ID: W4401637322