Relationship of ADRD plasma biomarkers with mobility in cognitively unimpaired older adults

Abstract

BACKGROUND Temporal relationships between physical and cognitive decline with aging are poorly understood, and little is known about the underlying mechanisms linking these conditions. We hypothesized that plasma biomarkers of Alzheimer’s disease and related dementias (ADRD) may be associated with mobility performance in older adults who are cognitively unimpaired. METHODS We constructed separate linear mixed models to examine the cross-sectional associations of 5 plasma ADRD and aging-related biomarkers with 4 measures of mobility in a cohort of 192 cognitively unimpaired older adults. We secondarily described the association of the same biomarkers with 4 cognitive domain scores. RESULTS Higher phorphorylated-tau181 was associated with worse performance on the expanded short physical performance battery (eSPPB), slower 4m gait speed, and shorter balance time. Higher neurofilament light (NfL) was associated with worse eSPPB, slower 4m gait speed and slower 400m gait speed in adjusted models. However, there was no association of Aβ42/Aβ40, p-tau217, or glial fibrillary acidic protein with mobility. Only p-tau217 was associated with global and processing speed cognitive domain scores in multivariable models, but not after adjusting for multiple comparisons. CONCLUSIONS These data suggest that p-tau181 and NfL are potential markers of mobility performance in cognitively normal older adults, even when they are not associated with cognitive performance. Future studies should examine how such markers predict change over time in mobility and cognitive function and whether they may indicate pathways that could be targeted for preventive management.