The Association Between Levels of Plasma Biomarkers and Cognitive Performance in the Oldest Old

Abstract

AbstractBackgroundLower cognitive performance in Alzheimer’s Disease (AD) patients has been correlated with changes in blood‐based biomarkers Amyloid‐βeta‐40 (Aβ40), Amyloid‐βeta‐42 (Aβ42), phosphorylated Tau (pTau), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). However, it is still unclear whether there is an association between cognitive performance and plasma biomarkers in the oldest old. Here we investigate I) The association of plasma biomarkers with age across a wide age‐continuum until extreme age (≥100 years); II) To what extent plasma biomarkers associate with cognitive performance ≥100 years.MethodThe Dutch 100‐plus study cohort comprises of self‐reported cognitively healthy centenarians. Biomarkers were measured in 202 centenarians (137 females) on the Simoa platform. We also included centenarian siblings, offspring and their respective partners (N = 318), who were cognitively healthy. I) To investigate the relationship between age and biomarkers, we standardized all biomarkers and performed linear regression analyses. II) Cognitive performance in centenarians was determined using a comprehensive neuropsychological test battery assessing several cognitive domains. Biomarker concentrations were divided into tertiles. Cognitive performance was assessed adjusting for age, sex and education.ResultI) We observed an age‐related increase Aβ40 (rs = 0.70; range 46.5‐286.5 pg/mL), Aβ42 (rs = 0.53; range 1.4‐17.7 pg/mL), pTau‐181(rs = 0.68; range 0.5‐12.8 pg/mL), NfL (rs = 0.81; range 4.5‐378.7 pg/mL) and GFAP (rs = 0.76; range 24.4‐1085.1 pg/mL), or decrease in Aβ42/40 (rs = ‐0.43; range 0.01–0.10 pg/mL; P<0.001 for all biomarkers, Figure 1). II) Lower Aβ42/40 was associated with lower cognitive performance on global cognition (based on composite z‐score of all tests) β(95%CI) 0.26(0.00–0.51), P = 0.002) and domain executive functioning β(95%CI) 0.16(‐0.07–0.40), P = 0.039), but not with the Mini‐Mental State Examination (MMSE) or the other cognitive domains. Higher concentrations of NfL were associated with lower cognitive performance on MMSE β(95%CI) ‐0.22(‐1.48–1.04), P = 0.005), but not with the separate cognitive domains tested.ConclusionLevels of plasma biomarkers rise with age, also in cognitively healthy individuals. However, correlation with cognitive performance varies across biomarkers and cognitive tests, and deserves further evaluation.