Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline.

Introduction: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum.
Methods: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid.
Results: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline.
Discussion: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.
Competing Interests: S.J.T. participated in scientific advisory boards of Roche Pharma AG, Biogen, Grifols, and MSD, and received lecture fees from Roche and MSD. M.T.H. serves as a scientific board member of IFM Therapeutics, Novo Nordisk, and Alector and has received lecture honoraria from NovoNordisk. The other authors state no competing interests. Author disclosures are available in the supporting information.
(© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)