Longitudinal Associations of Multimodal Core 1 Alzheimer Disease Biomarkers With Cognition in Aging and Preclinical Alzheimer Disease
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND OBJECTIVES: Addressing the association between early-changing Alzheimer disease (AD) biomarkers and cognition is essential for characterizing preclinical AD. However, few studies have explored this relationship longitudinally, especially across multiple biomarker modalities. The aim of this study was to evaluate longitudinal associations of multimodal core 1 AD biomarkers with cognition in a cognitively unimpaired (CU) population at increased risk of AD dementia. METHODS: profiles) and longitudinal neuropsychological assessments (2 time points, 3-year follow-up). The primary study outcome was the modified Preclinical Alzheimer's Cognitive Composite (mPACC) score. Study measurements included plasma phosphorylated tau (p-tau) 217, CSF p-tau181/β-amyloid (Aβ) 42, and Aβ PET ([¹⁸F]flutemetamol). Mixed-effects models were used to evaluate the longitudinal associations between fluid biomarkers and mPACC score; voxel-wise models were used to evaluate the longitudinal association between neuroimaging and mPACC score. Sensitivity analyses evaluated these associations stratifying by Aβ status. RESULTS: = 0.024) and Aβ PET load in frontoparietal regions were associated with mPACC decline. DISCUSSION: This study demonstrated significant longitudinal associations between multimodal core 1 AD biomarkers and cognitive function over 3 years in CU individuals, including those at the Aβ-negative stage. Distinct biomarker modalities provided complementary insights, emphasizing the potential of blood-based biomarkers for tracking subtle cognitive decline and neuroimaging for delineating vulnerable brain regions in aging and preclinical AD. These findings are crucial for identifying and monitoring high-risk CU individuals, further informing preventive intervention strategies for AD.
Source: Neurology
Authors: David López-Martos, Marc Suárez-Calvet, Marta Milà-Alomà, Juan Domingo Gispert, Gemma Salvadó, Anna Brugulat-Serrat, Mahnaz Shekari, Carolina Minguillon, Henrik Zetterberg, Kaj Blennow, Oriol Grau-Rivera, Gonzalo Sánchez-Benavides, for the ALFA study, Federica Anastasi, Annabella Beteta, Raffaele Cacciaglia, Irene Cumplido Mayoral, Alba Cañas, Marta del Campo, Carme Deulofeu, Ruth Dominguez, Maria Emilio, Sherezade Fuentes, Patricia Genius, Armand González Escalante, Laura Hernández, Jordi Huguet, Paula Marne, Tania Menchón, Paula Ortiz, Wiesje Pelkmans, Albina Polo, Sandra Pradas, Blanca Rodríguez Fernández, Núria Tort-Colet, Iman Sadeghi, Anna Soteras, Marc Vilanova, Natalia Vilor Tejedor
Institutions: Pasqual Maragall Foundation, Barcelonaβeta Brain Research Center, Hospital del Mar Research Institute, Instituto de Salud Carlos III, Hospital Del Mar, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, San Francisco VA Medical Center, University of California, San Francisco, Northern California Institute for Research and Education, Lund University, Global Brain Health Institute, University of Wisconsin–Madison, Sahlgrenska University Hospital, Sorbonne Université, Pitié-Salpêtrière Hospital, UK Dementia Research Institute, Institut du Cerveau, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg, University of Science and Technology of China
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4415333252