Association of plasma growth differentiation factor 15 with wake after sleep onset in mild cognitive impairment.

OBJECTIVES: Circulating growth differentiation factor 15 (GDF-15) concentrations increase with age and are elevated in chronic diseases, but evidence regarding habitual wake after sleep onset (WASO) and circulating GDF-15 remains limited. We therefore examined the cross-sectional association between plasma GDF-15 and wearable-estimated WASO in older adults with mild cognitive impairment (MCI). DESIGN: Cross-sectional biomarker analysis of first-year data from a prospective community-based cohort. SETTING: USUKI study, Usuki, Oita, Japan. PARTICIPANTS: 118 community-dwelling adults aged ≥65 years with MCI. INTERVENTION: None. MEASUREMENTS: We measured plasma GDF-15 concentrations using an enzyme-linked immunosorbent assay. We averaged wearable sleep data across repeated assessments. WASO was the primary measure of sleep continuity; total sleep time (TST) was examined as a measure of sleep quantity; and amyloid burden was assessed using 11C-Pittsburgh compound B PET (PiB-PET) global standardized uptake value ratio (SUVR) and PiB positivity. RESULTS: The median plasma GDF-15 concentration was 1,230.8 pg/mL (IQR, 956.6-1,590.5), and the median WASO was 18.4 min (IQR, 11.6-27.5). After adjustment for age, sex, education, diabetes mellitus, and estimated glomerular filtration rate, each 10-min increment in WASO was associated with a 10.6% higher GDF-15 concentration (95% CI, 4.8%-16.8%; p < 0.001). TST and PiB-PET global SUVR were not significantly associated with GDF-15, and the proportion of PiB-positive participants did not differ across GDF-15 tertiles. CONCLUSION: In older adults with MCI, poorer habitual nocturnal sleep continuity, as reflected by greater wearable-estimated WASO, was associated with higher plasma GDF-15 concentrations after multivariable adjustment.