Sex-specific associations of neurodegeneration and inflammatory biomarkers with intrinsic capacity in older adults: Findings from the 4-year longitudinal Multidomain Alzheimer's Prevention Trial (MAPT)

This four-year longitudinal study investigated whether the cross-sectional and longitudinal associations of inflammation-related and neurodegenerative-related blood biomarkers with intrinsic capacity differ according to sex. The sample comprised 1117 older adults (<70 years, 63.8 % females) from the Multidomain Alzheimer's Prevention Trial (MAPT). The domains of intrinsic capacity were operationalized as cognition (Mini-Mental State Examination), locomotion (Short Physical Performance Battery), vitality (Handgrip Strength), and psychological well-being (Geriatric Depression Scale), each scaled from 0 (worst intrinsic capacity possible) to 100 (best intrinsic capacity possible). Plasma biomarkers included interleukin 6 (picograms per milliliter), growth differentiation factor-15 (picograms per milliliter), tumor necrosis factor receptor 1 (picograms per milliliter), neurofilament light chain (picograms per milliliter), progranulin (nanograms per milliliter), and amyloid-beta ratio. Linear mixed models were analyzed to examine whether sex modified the cross-sectional and longitudinal association between biomarkers and intrinsic capacity. No significant interaction effect was observed at baseline. Longitudinal analyses revealed a significant interaction between sex and interleukin 6 (p = .005), such that higher levels of interleukin 6 tended to be associated with a faster decline in intrinsic capacity for males (B = −0.385; p = .055; 95 % CI = −0.778; 0.008) but not for females (B = 0.287; p = .041; 95 % CI = 0.011; 0.563). The other biomarkers had no sex-dependent associations with intrinsic capacity. A potential sex-dependent effect of the inflammatory status on intrinsic capacity must be further investigated.

Clinical trial registration with ClinicalTrials.gov NCT00672685.