Associations Between Blood-Based Biomarkers and Cognitive and Functional Trajectories Among Participants of the MEMENTO Cohort
Neurology. 2024-05-14; 102(9):
DOI: 10.1212/wnl.0000000000209307
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1. Neurology. 2024 May;102(9):e209307. doi: 10.1212/WNL.0000000000209307. Epub
2024 Apr 16.
Associations Between Blood-Based Biomarkers and Cognitive and Functional
Trajectories Among Participants of the MEMENTO Cohort.
Grasset L(1), Bouteloup V(1), Cacciamani F(1), Pellegrin I(1), Planche V(1),
Chêne G(1), Dufouil C(1); MEMENTO study group(1).
Author information:
(1)From 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.
DOI: 10.1212/WNL.0000000000209307
PMID: 38626384 [Indexed for MEDLINE]