The role of biofluid markers in predicting near‐term cognitive impairment

Abstract

AbstractBackgroundAlzheimer’s disease (AD) has been defined as a biological construct that can be determined using in vivo biomarkers. Recent studies confirmed the clinical value of the AT(N) framework when using Aß and tau positron emission tomography (PET) scans in predicting progression from cognitively unimpaired to MCI. Our study aims to investigate if plasma biomarkers can yield similar predictive performance to PET biomarkers, and to also compare against cerebrospinal fluid (CSF) biomarkersMethodIndividuals from the PREVENT‐AD cohort were included in the study. Participants had Aß and tau plasma measurements and at least one year of clinical follow‐up thereafter (n = 278). A subset of participants had CSF measurements (n = 102) and/or PET scans (n = 133) also with 1‐year clinical follow‐up. Participants were cognitively unimpaired at the time of all biomarker measurements. MCI diagnoses were made by clinical consensus among expert clinical and research staff blind to plasma, CSF, PET, MRI and APOE genotype. We established thresholds of plasma and CSF Aß and tau positivity based on >80% specificity in identifying individuals with significant levels of Aß‐PET (plasma Aß42/40 = 0.057; plasma pTau181 = 7.53 pg/mL; CSF Aß42 = 961.37; CSF pTau181 = 66.59 pg/mL). Aß ([18F]NAV4694) and tau ([18F]AV1451)PET thresholds were defined by the mean plus 2 standard deviations from young participants (Aß SUVR cut‐off = 1.17; tau SUVR cut‐off = 1.24).Result36.8% (7/19) of the A+T+ plasma group progressed to MCI, 50% (4/8) of the A+T+ CSF group progressed to MCI, and 46.6% (7/15) A+T+ PET group progressed to MCI (Fig. 1).We found differences in MCI progression status between the A+T+ group compared to the A‐T‐ and A+T‐ groups across all biomarkers’ measurements, with the A+T+ group always showing a higher rate of progression than the other two groups (post‐hoc chi‐square analyses; p<0.05).ConclusionAbnormal levels of Aß and tau plasma biomarkers can help predict near‐ term progression to MCI. When plasma thresholds are derived based on PET data, however, plasma biomarkers have a slightly lower specificity than PET and CSF biomarkers, and both plasma and CSF biomarkers are less sensitive than PET biomarkers.