Plasma biomarkers predict deterioration in cognitively normal elderly adults

Plasma concentrations of the biomarkers amyloid-β (Aβ) 42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) could help predict deterioration in cognitively unimpaired (CU) elderly adults, a recent study has found.

In addition, employing these three biomarkers in clinical trials could help reduce the required sample size, making them more feasible and cost-effective to conduct.

The study included 435 CU adults followed a mean of 4.8±1.7 years, during which 28 converted to Alzheimer’s disease (AD) dementia and 39 to all-cause dementia. Almost half (46.2 percent) were plasma-positive for Aβ 42/40; 37.2 percent and 37.9 percent were P-tau-217- and NfL-positive, respectively.

Linear mixed-effects modelling showed that P-tau217 was most strongly associated with the longitudinal change in cognition, as measured by the Preclinical Alzheimer’s Cognitive Composite (PACC; β, –0.20 points per year per standard deviation [SD] increase in biomarker value; p<0.0001). This was followed by Aβ 42/40 then NfL.

However, combining all three biomarkers, along with basic demographic information, seemed to be the best approach, leading to a significant improvement in the prediction of cognitive decline as measured by PACC changes (R2, 0.14, 95 percent confidence interval [CI], 0.12–0.17; p<0.0001), as well as subsequent AD dementia (area under the curve, 0.82, 95 percent CI, 0.77–0.91; p<0.0001).

The researchers then conducted a simulated clinical trial to assess how the novel combination of biomarkers could impact scientific research.

They found that the three biomarkers together could cut the required sample size by 70 percent when cognition was set as an endpoint, and by 63 percent when AD dementia was set as the endpoint.

“Further work is needed to validate the optimal panel of biomarkers in an elderly CU population, although our preliminary results suggest that all three core plasma biomarkers could be useful,” the researchers said.