Plasma biomarkers of neurodegeneration and physical performance in older adults

Physical performance declines with age, but its association with circulating neurodegeneration biomarkers remains unclear. Blood biomarkers including NT1, NfL, oAβ, and pTau217 may reflect early neurodegenerative changes linked to physical performance decline. Evidence linking these biomarkers to physical performance is limited. We analyzed older adults in the COSMOS Clinic substudy with baseline and two-year follow-up assessments of plasma NT1, NfL, and oAβ and a single assessment of pTau217. Physical performance was assessed using walking speed, grip strength, and the Short Physical Performance Battery (SPPB). The primary analysis examined associations between baseline biomarker levels and two-year changes in physical performance. Secondary analyses examined longitudinal associations between two-year changes in biomarkers and concurrent changes in physical performance. Models were adjusted for demographics, cardiovascular risk profile, body mass index, and the baseline value of the physical performance measures, and we considered all biomarkers jointly. We included 506 participants; the mean age was 69.7 years, and 49.3% were women. In the primary analysis, we found no statistically significant associations between baseline NT1, NfL, or oAβ and two-year changes in physical performance. In fully adjusted models, baseline NfL was not associated with 2-year changes in physical performance, with estimates ranging from β = -0.046 (p = 0.69) for SPPB to β = 0.350 (p = 0.48) for grip strength. Similarly, estimates for NT1 ranged from β = -0.097 (p = 0.50) for SPPB to β = 0.267 (p = 0.67) for grip strength, and those for oAβ ranged from β = -0.124 (p = 0.39) for grip strength to β = 0.008 (p = 0.25) for fast walking speed. In the secondary longitudinal analysis, two-year change in NT1 was statistically significantly associated with change in grip strength (β = 1.408, p = 0.01). No other significant associations were observed. Baseline NT1, NfL, or oAβ were not associated with changes in physical performance measures over two years. Changes in NT1 were associated with changes in grip strength. Overall, these biomarkers provided limited information on short-term physical performance decline.