Altered resting-state functional connectivity in individuals at risk for Alzheimer’s disease: a longitudinal study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Resting-state functional connectivity magnetic resonance imaging (rs-fMRI) is a sensitive tool for detecting early brain changes associated with Alzheimer's disease, even in its preclinical stages. Amnestic mild cognitive impairment (aMCI) and late-life depression (LLD) are two prevalent conditions in older adults that significantly elevate the risk of cognitive decline and dementia. This study aimed to elucidate the underlying neurobiological substrates by longitudinally identifying and comparing distinct connectivity patterns in aMCI subjects and LLD patients, and by examining the associations between these patterns and clinical measures of cognitive and mood impairments. Methods: The study included three groups: 26 healthy controls (HCs), 15 individuals with aMCI, and 21 patients with LLD. All participants underwent rs-fMRI and neuropsychological assessments at baseline and at a 2-year follow-up. Functional connectivity was analyzed using a group Independent Component Analysis (ICA) model to investigate both group differences and longitudinal changes over time. Results: At baseline, individuals with aMCI exhibited reduced functional connectivity in the precuneus, whereas LLD patients showed decreased connectivity in frontal, insular, and postcentral regions alongside increased connectivity in posterior parietal and cuneal cortices. Correlation analyses revealed that lower baseline insular connectivity predicted higher depressive symptoms at follow-up in aMCI subjects. In LLD, reduced baseline precuneus connectivity was associated with better two-year outcomes in global cognition and long-term memory. Conclusions: This study provides evidence of distinct alterations in resting-state functional connectivity in individuals with aMCI and LLD, underscoring region-specific vulnerabilities that may contribute to cognitive decline and depressive symptomatology in older adults.
Institutions: Instituto de Salud Carlos III, Institut d'Investigació Biomédica de Bellvitge, Centro de Investigación Biomédica en Red de Salud Mental, Universitat de Barcelona, Universidad Mayor, Bellvitge University Hospital, Universidad Católica de Murcia, Biomedical Research Networking Center on Neurodegenerative Diseases, Universitat Autònoma de Barcelona, Corporació Sanitària Parc Taulí, Institute of Research and Innovation Parc Tauli
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,970
Funders: Centres de Recerca de Catalunya, Generalitat de Catalunya, Federación Española de Enfermedades Raras, Ministerio de Ciencia e Innovación, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund, Departament de Salut, Generalitat de Catalunya
OpenAlex ID: W4411036116