Association Between Fatigue and Intrinsic Capacity Among People Aged 20 to Over 100 Years Old from the INSPIRE-T Cohort

This study aimed to investigate the cross-sectional association of fatigue, including SF and MF, with IC in adults.

Data were collected from 888 participants (62.0% women) aged 20–100 years, as part of the observational INSPIRE-T study. SF was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue questionnaire, which evaluates self-perceived fatigue levels. MF was measured through knee extension exercises by recording the number of contractions that participants could perform until they could no longer sustain 50% of their maximal voluntary contraction using A Biodex System 3 dynamometer. IC was assessed across five domains: cognition (Mini-Mental State Examination), locomotion (Short Physical Performance Battery), psychology (the nine-item Patient Health Questionnaire for depression), vitality (Handgrip strength), and sensory function (WHO simple eye chart and whisper test), with each domain rescaled to a 0-to 100-point scale. A composite IC score was derived as the mean of the five domains. Multiple linear regression analyses were conducted to explore the associations between SF, MF, and IC. The adjusted model considered covariates including age, sex, education level, chronic conditions measured by a modified Charlson comorbidity index, the number of medicines, and BMI.

Participants with high SF levels had significantly lower scores in all IC domains and composite IC scores than those with low SF levels (p 0.01). Multiple linear regression analysis indicated that SF was negatively associated with all IC domains except cognition and significantly associated with the composite IC score (p 0.01). Conversely, MF showed no significant association with any IC domain. When both SF and MF were included in the regression model, SF remained significantly negatively associated with IC scores, whereas MF did not show any significant association.

This study demonstrated a significant negative association between SF and each IC domain, as well as the composite IC score. In contrast, MF, as measured by knee extension tasks, did not appear to influence IC. These findings suggest that subjective perceptions of fatigue may have a stronger association on overall capacity than objective measures of muscle performance.

SF management can help maintain and improve IC. Future studies should explore targeted interventions to mitigate SF and further investigate the mechanisms linking SF to IC.