Exercise and nutritional support reduce mobility disability in frail older adults
1. In 1,199 older adults with frailty, sarcopenia, and multimorbidity from the SPRINTT trial, a multicomponent lifestyle program reduced the risk of mobility disability or death compared with health education (HR 0.78), extending event-free time by 2.09 months over 36 months.
2. Benefit appeared clearest in psychiatric and unspecific multimorbidity patterns and uncertain in cardiometabolic and respiratory patterns, but these post hoc subgroup findings are hypothesis-generating.
A Nature Aging analysis post hoc analysis published August 31st examined whether the effect of the SPRINTT multicomponent intervention varied by multimorbidity pattern. The analysis included 1,199 of the trial’s 1,519 randomized participants (median age 79 years; 71% women; median 6 chronic conditions), all with physical frailty, sarcopenia, and at least two chronic conditions. The intervention combined individually tailored aerobic, resistance, flexibility, and balance training (supervised center-based sessions up to four times per week plus home exercise), nutritional counseling focused on protein and energy intake, and thigh-worn activity monitoring, while the control group received health education sessions followed by simple stretching, for up to 36 months. The primary endpoint was mobility disability, defined by inability to complete a 400-m walk, or death. Overall, the intervention reduced risk of the endpoint (HR 0.78) and increased event-free probability by 5.3% at 12 months, 7.5% at 24 months, and 8.2% at 36 months. Latent class analysis identified four multimorbidity patterns: unspecific (55%), psychiatric (24%), cardiometabolic (13%), and respiratory (7%). The clearest benefit appeared in the psychiatric pattern (HR 0.65), where event-free probability rose by 13.1% at 36 months. Bayesian partial pooling also supported benefit in the unspecific pattern (HR 0.80), whereas estimates for the cardiometabolic and respiratory patterns were imprecise and close to zero in absolute terms.
The subgroup findings should be interpreted cautiously. The interaction between treatment and multimorbidity pattern was not statistically significant (P = 0.870), the cardiometabolic (n = 161) and respiratory (n = 88) subgroups were small, and the authors’ simulation suggested that detecting an interaction of the observed size would require roughly 6,000 to 7,000 participants. The absence of a clear benefit in those groups is therefore not evidence that the intervention does not work for them. Patterns were also derived from diagnostic data with limited coding granularity, no biomarkers were available to test whether the patterns reflect distinct biology, and the population was restricted to older adults meeting SPRINTT’s frailty and sarcopenia criteria. The authors propose that milder or psychiatric clusters may retain more physiological reserve, while cardiometabolic and respiratory clusters involve greater inflammation and multisystem impairment, but this remains a hypothesis. For clinicians, the immediate implication is that multimorbidity, including a high chronic disease burden, should not exclude frail older adults from structured exercise and nutritional support, since the overall effect was favorable in a population already living with frailty, sarcopenia, and a median of six conditions. In practice, this supports assessing mobility with measures such as gait speed or the 400-m walk, offering supervised multicomponent programs aligned with guidance on aerobic, strength, balance, and functional training, and closely monitoring patients with cardiometabolic or respiratory disease, whose response is less certain.
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