Study Finds Plasma Neurodegeneration Biomarkers Provide Limited Prediction of Short-Term Physical Decline in Older Adults

A prospective analysis published in Geroscience reports that baseline levels of plasma neurodegeneration biomarkers do not predict short-term physical decline in older adults, though longitudinal changes in the NT1 biomarker correlate with changes in grip strength.

Researchers investigated the association between circulating neurodegeneration biomarkers (NT1, NfL, oAβ, and pTau217) and physical performance measures (walking speed, grip strength, and the Short Physical Performance Battery) in 506 older adults from the COSMOS Clinic substudy.

The primary analysis adjusted for demographics, cardiovascular risk factors, and body mass index showed no statistically significant associations between baseline levels of NT1, NfL, or oAβ and subsequent two-year changes in physical performance.

In secondary analyses, a longitudinal two-year change in the NT1 biomarker was statistically significantly associated with a concurrent change in grip strength (beta = 1.408, p = 0.01).

No other significant longitudinal associations were identified, leading researchers to conclude that these biomarkers provide limited predictive information regarding short-term physical performance decline in this demographic.

Identifying blood-based biomarkers of aging and functional decline is crucial for establishing reliable clinical trial endpoints, yet these findings suggest that circulating markers of neurodegeneration may not serve as early indicators of short-term physical decline.

The specific correlation between changes in the NT1 biomarker and grip strength suggests that further longitudinal research may be required to dissect the biological links between neuromuscular aging and N-terminal tau fragments.

Developers of neurodegenerative and longevity therapies targeting tau or general aging mechanisms may face challenges using short-term physical performance metrics as secondary clinical endpoints, as circulating neurodegeneration biomarkers do not appear to predict physical functional changes over a two-year window.

The lack of predictive value over two years suggests that therapeutic trials aiming to improve physical health may require longer clinical trial durations or alternative physiological biomarkers to demonstrate efficacy.

Further clinical studies evaluating these biomarkers over longer observational windows to see if associations with physical performance emerge past the two-year mark.