Contingency of Plasma Dementia Biomarkers on Cognitive Profiles for Prognosis of Incident Dementia: The ARIC Study.

Abstract

Plasma biomarkers such as phospho-tau species are increasingly used in clinical practice for the diagnosis of Alzheimer disease (AD). Phosphorylated-tau at threonine 181 (p-tau181) values also provide prognostic information about incident dementia. Cognitive status similarly conveys prognostic information, but the relationship between plasma biomarkers for AD and cognitive status requires clarification. Participants from the Atherosclerosis Risk in Communities (ARIC) study who were adjudicated as free of dementia in 2011-2013 had plasma samples analyzed for p-tau181 and other biomarkers. Participants were surveilled for incident dementia through December 31, 2022. Cumulative incidence curves, Cox models, and Fine-Gray models were used to evaluate the independent and combined discriminatory accuracy of cognitive status and plasma biomarkers for incident dementia. The sample comprised 1,577 ARIC participants (age 76.5 years, 60% women, 73% White, 27% Black). The risk of incident dementia was higher in persons with a baseline status of mild cognitive impairment (covariate-adjusted hazard ratio [HR] 2.94, 95% CI 2.61-3.33) compared with those who were cognitively unimpaired independent of biomarker status. The risk of dementia was also higher in persons with more abnormal concentrations of p-tau181 and other biomarkers independent of cognitive status. When age, cognitive status, and p-tau181 were included in the same models, the risk was attenuated relative to models where only cognitive status or plasma biomarkers were included. For continuous p-tau181 concentrations, the covariate-adjusted HR without cognitive status was 1.45 (95% CI 1.36-1.54), but when cognitive status was included, the HR decreased to 1.37 (95% CI 1.29-1.46). Models showed that when combined with age, p-tau181 alone, cognitive status alone, or the combination of p-tau181 and cognitive status had similar discriminatory accuracy. Cognitive status and plasma biomarker concentrations convey independent but overlapping information about the risk of incident dementia. Although cognitive status and plasma p-tau181 have similar discriminatory accuracies, the far lower incidence rate of dementia in persons who are initially cognitively unimpaired highlights the importance of an accurate clinical diagnosis.