Plasma biomarkers of alzheimer's disease and related dementias are associated with cognitive change in community-dwelling older individuals in Australia and the US.

Plasma biomarkers of Alzheimer's disease and related dementias (ADRD) are associated with the risk of dementia. However, the extent to which they could reflect cognitive ageing, and whether this is consistent across factors known to influence biomarkers (e.g. sex and chronic kidney disease) and in different populations, is unknown. Data were from a diverse community-dwelling cohort of older individuals without dementia in Australia (n = 11,930) and the US (n = 1,181). Global cognition, verbal fluency, episodic memory and psychomotor speed were assessed repeatedly over more than a decade. Plasma phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and amyloid beta (Aβ) 42 and 40 were measured using Simoa technology. Higher levels of p-tau181 (β: -0.001 to -0.212), GFAP (β: -0.022 to -0.300) and NfL (β: -0.022 to -0.219), and lower levels of Aβ42/40 ratio (β: 0.015 to 0.126) were associated with greater cognitive decline over time. Associations were strongest for global cognition, episodic memory, and psychomotor speed, and weaker/non-significant for verbal fluency. All associations were consistent across countries. Furthermore, in stratified analyses, the results did not differ by sex or depending on the presence of chronic kidney disease. We found robust associations between plasma ADRD biomarkers and cognitive change in initially healthy older individuals in both Australia and the US, and across both sexes. Despite chronic kidney disease influencing biomarker levels, associations were consistent among individuals with and without chronic kidney disease. This indicates the potential broad utility of these biomarkers.