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Associations Between Blood-Based Biomarkers and Cognitive and Functional Trajectories Among Participants of the
Leslie Grasset1, Vincent Bouteloup1, Federica Cacciamani1
1From the UMR 1219 (L.G., V.B., F.C., G.C., C.D.), Bordeaux Population Health Center, University of Bordeaux, Inserm; CIC 1401-EC (L.G., V.B., F.C., G.C., C.D.), Inserm, University of Bordeaux, CHU de Bordeaux; Centre Hospitalier Universitaire (CHU) de Bordeaux (V.B., G.C., C.D.), Pole de sante publique; ARAMISLab (F.C.), Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, CNRS, Inria, Inserm, AP-HP, Hôpital de la Pitié Salpêtrière; Qairnel SAS (F.C.), Paris; Laboratory of Immunology and Immunogenetics (I.P.), Resources Biological Center (CRB), CHU Bordeaux; Univ. Bordeaux (I.P.), CNRS, ImmunoConcEpT, UMR 5164; and Univ. Bordeaux (V.P.), CNRS UMR 5293, Institut des Maladies Neurodégénératives, Centre Mémoire de Ressources et de Recherches, Pôle de Neurosciences Cliniques, CHU de Bordeaux, France.
Background And Objectives:
Elevated levels of Alzheimer disease (AD) blood-based biomarkers are associated with accelerated cognitive decline. However, their distinct relationships with specific cognitive and functional domains require further investigation. We aimed at estimating the associations between AD blood-based biomarkers and the trajectories of distinct cognitive and functional domains over a 5-year follow-up period.
Methods:
We conducted a clinic-based prospective study using data from the MEMENTO study, a nationwide French cohort. We selected dementia-free individuals at baseline aged 60 years or older. Baseline measurements of β-amyloid (Aβ) 40 and 42, phosphorylated tau (p-tau181), and neurofilament light chain (NfL) concentrations were obtained using the Simoa HD-X analyzer. Mini-Mental State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT), animal fluency, Trail Making Tests A and B, Short Physical Performance Battery (SPPB), and Instrumental Activities of Daily Living were administered annually for up to 5 years. We used linear mixed models, adjusted for potential confounders, to model AD biomarkers' relation with cognitive and functional decline.
Results:
A total of 1,938 participants were included in this study, with a mean (SD) baseline age of 72.8 (6.6) years, and 62% were women. Higher baseline p-tau181 and NfL were associated with significantly faster decline in most cognitive, physical, and functional outcomes (+1 SD p-tau181: βMMSE = -0.055, 95% CI -0.067 to -0.043, βFCSRT = -0.034, 95% CI -0.043 to -0.025, βfluency = -0.029, 95% CI -0.038 to -0.020, βSPPB = -0.040, 95% CI -0.057 to -0.022, and β4IADL = -0.115, 95% CI 0.091-0.140. +1 SD NfL: βMMSE = -0.039, 95% CI -0.053 to -0.025, βFCSRT = -0.022, 95% CI -0.032 to -0.012, βfluency = -0.014, 95% CI -0.024 to -0.004, and β4IADL = 0.077, 95% CI 0.048-0.105). A multiplicative association of p-tau181 and NfL with worsening cognitive and functional trajectories was evidenced. Lower Aβ42/40 ratio was only associated with slightly faster cognitive decline in FCSRT and semantic fluency (+1 SD: β = 0.011, 95% CI 0.002-0.020, and β = 0.011, 95% CI 0.003-0.020, respectively). These associations were not modified by APOE ε4, sex, nor education level.
Discussion:
In a memory clinic sample, p-tau181 and NfL, both independently and jointly, are linked to more pronounced cognitive, physical and functional declines. Blood-based biomarker measurement in AD research may provide useful insights regarding biological processes underlying cognitive, physical, and functional declines in at-risk individuals.
