Associations between blood‐based biomarkers and cognitive decline among participants at risk of Alzheimer’s disease: the Memento cohort

Abstract

AbstractBackgroundBlood‐based biomarkers for Alzheimer’s disease (AD) pathology and neurodegeneration are promising biomarkers due to their lower cost, accessibility, and minimally invasive nature. Higher levels of AD blood‐based biomarkers have been shown to be associated with the risk of AD and cognitive decline. Yet, the specific cognitive domains involved need to be further investigated. We thus aimed at estimating the association between levels of baseline AD blood‐based biomarkers with cognitive trajectories over 5 years of follow‐up across different domains in a large clinical based cohort.MethodWe selected the 2060 dementia‐free individuals aged 60 years and older included in the Memento study, a French nationwide cohort, following patients from 28 memory clinics with either isolated cognitive complaints or mild cognitive impairment. Amyloid‐β 40 and 42, P‐tau181, and Neurofilament Light Chain (NfL) concentrations were measured at baseline using Simoa HD‐X analyzer. Global cognition, episodic memory, semantic memory, and executive functioning were assessed every year up to 5 years using the Mini Mental State Examination, the Free and Cued Reminding test, the Animal fluency test, and the Trail Making Test B respectively. Linear mixed models adjusted for sex, education level, APOE‐ε4 status, and practice effect, with age as time scale and quadratic slopes were performed to examine how AD blood‐based biomarkers relate to longitudinal cognitive trajectories by domain.ResultMean age was 72.8 years, 62% were women, 28% were APOE‐ε4 carriers, and 58% had a Clinical Dementia Rating score of 0.5. Higher baseline plasma P‐tau181 was associated with significantly faster nonlinear cognitive decline in all four cognitive domains (p<0.001). On the opposite, baseline plasma Aβ42/40 ratio and NfL were not associated with cognitive decline whatever the domain. Associations between AD blood‐based biomarkers and faster cognitive decline were not modified by APOE‐ε4, sex, nor education level (p value for interaction > 0.05).ConclusionIn a memory clinic population, plasma P‐tau181 is a marker of future cognitive decline. This marker is a good candidate for additional studies assessing biomarkers relevant for the identification of individuals who may benefit from treatment early in the disease course.