Worse Performance of Complex Daily Activities is associated with Plasma Neurofilament Light

Abstract

AbstractBackgroundThe preclinical stage of Alzheimer disease (AD) is a clinically silent period that is detectable through neuroimaging and biofluid biomarkers of amyloid, tau, and neurodegeneration. We evaluated whether performance of cognitively‐focused complex daily activities is associated with plasma biomarkers of brain amyloidosis or neuroaxonal injury in cognitively normal (CN) older adults.MethodIn this cross‐sectional analysis of an ongoing longitudinal cohort study, CN older adults performed three cognitively‐focused complex daily activtites (shopping, checkbook balancing, and medication management) from the Performance Assessment of Self‐Care Skills (PASS) in their home. PASS tasks were scored for independence of performance, with more assistance required indicating worse performance. Participants also had a plasma sample obtained within two years of completing the PASS. Plasma amyloid (Aβ42 and Aβ40) were evaluated by high precision immunoprecipitation mass spectrometry assays and neurofilament light (NfL), a marker of neuroaxonal injury, was measured with single molecule array (Simoa) assays. Amyloid Probability Score (APS) was calculated from a combination of plasma Aβ42/Aβ40, APOE status, and age and reflects the likelihood that an individual will be amyloid positive on an amyloid positron emission tomography (PET) scan. Nonparametric partial correlations were used to examine the associations between PASS performance and biomarkers of AD (plasma Aβ42/Aβ40, APS, and plasma NfL), controlling for age and sex.Result105 CN participants (mean age 74.7 years, 55% female, 88% white) were included. After controlling for age and sex, worse performance of complex daily tasks (more assistance required) was associated with increased plasma NfL (Spearman’s ρ: 0.234, p = 0.04) but not plasma Aβ42/Aβ40 or APS.ConclusionThis study suggests that worse performance of complex daily activities in CN older adults may be associated with increased plasma NfL, a marker of neuroaxonal injury, but not with other plasma biomarkers of brain amyloidosis (plasma Aβ42/Aβ40 or APS). These findings could lead to a better understanding of functional changes that may associate with neuroaxonal injury prior to the onset of noticeable memory symptoms in AD or related dementias.