The Association of Blood‐based biomarkers and Cognitive Change as Measured by Ecologically Sensitive Digital Biomarkers

Abstract

AbstractBackgroundThe Einstein Aging Study uses smartphones in an intensive burst design to digitally assess cognition up to 6 times daily for 2 weeks once a year. These burst assessments facilitate the estimation of novel cognitive markers including learning effects and asymptotic performance within bursts and over annual assessments. Here, we examine the influence of two blood‐based biomarkers, pTau‐181 and Neurofilament Light protein (NfL), on cognitive performance measured by digital cognitive markers at baseline and across 6 annual burst assessments.MethodParticipants were 293 older adults (Age = 77.4±4.9) free of dementia at baseline. Negative exponential models were used to examine two primary features of response time from the Symbol Search Test of processing speed: (1) learning rate across days within a burst and its change in rate of learning over annual follow‐up; and (2) asymptotic performance (i.e., fastest response time) at baseline and asymptotic change (the rate in which asymptotic performance changes across years). Asymptotic performance is thought to reflect best possible performance and to be relatively free of practice effects. The associations of pTau‐181 and NfL with these features at baseline and change over annual follow‐up were evaluated, adjusting for baseline age, sex, years of education and race/ethnicity.ResultPrimary model results are summarized in Table 1. The expected trajectory of symbol search response time across 16 study days within each of the six annual waves, for baseline levels of pTau‐181 and NfL is shown in Figures 1 and 2. Higher levels of both Tau‐181 and of NfL were associated with slower rates of learning in the baseline burst. Higher levels of these BBB at baseline were also associated with slower learning rates from burst to burst (over years) and with greater slowing in asymptotic performance over annual follow‐ups.ConclusionHigher levels of BBB of Tau and of neurodegeneration are associated with slower learning and with slower response times. These novel parameters derived from ambulatory cognitive testing show expected relationships with biomarkers supporting their validity. Future applications of ambulatory cognition could include the identification of subtle cognitive impairment and in measuring within person change in cognition in clinical trials or clinical practice.