The Association of Plasma Biomarkers and Survival in the Oldest Old

Abstract

AbstractBackgroundPrevious research showed that plasma NfL (neurofilament light chain) associated with survival. Here we perform exploratory analyses to associate a broader range of plasma biomarkers Amyloid‐βeta‐40 (Aβ40), Amyloid‐βeta‐42 (Aβ42), phosphorylated Tau‐181 (pTau‐181), NfL and glial fibrillary acidic protein (GFAP), with survival after reaching 100 years.MethodThe longitudinal Dutch 100‐plus study cohort comprises of self‐reported cognitively healthy centenarians. Biomarkers were measured in 202 centenarians (137 females, ISCED education level median [IQR] 3 [2–4]) on the Simoa platform. Information on survival was obtained via family report until January 2023. Centenarians who were alive were censored at date of last visit or date last confirmed alive. We investigated the relationship between biomarkers and survival by cox regression analyses, adjusting for age at blood draw, sex and cognitive functioning. We performed maximally selected log‐rank statistics between all plasma biomarkers and survival rate to find an optimal cut‐off, and constructed Kaplan‐Meier survival curves.ResultOf 202 centenarians (median age [IQR] at blood draw 101.4 [100.4‐102.9]), 173 (85.6%) were deceased (median age [IQR] at death 103.2 [102.0‐104.3]). The median (IQR) survival time after blood draw was 14.4 (5.5‐25.1) months. All biomarkers Aβ40, Aβ42, pTau‐181, NfL and GFAP intercorrelated (rs = 0.17–0.79; all P‐values<0.05). Cox regression analyses showed that for each standard deviation increase in NfL, adjusted for age, sex, and MMSE score, the risk of mortality increased by 28% (HR 1.28; 95% CI, 1.11–1.47; P<0.001), Table 1. Maximally selected log‐rank statistics split up NfL into survival groups high and low (cut‐off 70.34 pg/mL, M = 3.803, P = 0.003, Figure 1). The median (IQR) shorter survival time of high versus low NfL was 7.8 (5.38‐9.27) months. No statistically significant cut‐off values were identified for the remaining biomarkers.ConclusionOur results indicate that elevated levels of NfL, but not Aβ40, Aβ42, pTau‐181 and GFAP, associate with lower survival. Furthermore, we were able to find an optimal cut‐off for NfL at which survival in centenarians could be split twofold.