THE ADAPTIVE POTENTIAL OF A MULTIDOMAIN SYSTEM: FUNCTIONAL, COGNITIVE AND PHYSIOLOGICAL INSIGHTS FROM AN INTERVENTION STUDY ON PRE-FRAIL OLDER ADULTS.

Background: Frailty and Intrinsic Capacity (IC) are often conceptualized as distinct constructs in ageing research, yet both likely emerge from interactions among cognitive, physiological, psychological, and functional domains. This thesis examined Frailty and IC as features of a dynamic, multi-domain system and tested whether a personalized dual-task exergame intervention could strengthen adaptive reserves in pre-frail older adults. Methods: PRAISE is a monocentric, randomized, two-arm pilot trial enrolling community-dwelling older adults in the pre-frailty range. Participants were randomized to a 12-month personalized dual-task exergame intervention or to a control group receiving good-practice advice. Assessments at baseline and follow-up included Frailty Index, IC composites, dual-task neuropsychological measures, actigraphy registration, and heart rate variability (HRV) measures. Correlation, clustering, and network analyses characterized system organization, while longitudinal mixed-effects models tested group × time effects. Results: Frailty and IC emerged as embedded nodes within a dynamic multi-domain architecture whose topology varied according to physiological and functional states. The intervention significantly reduced Frailty (primary outcome), improved global cognition and dual-task inhibitory control, and enhanced lower-limb function. Clustering and subject-level analyses on a restricted HRV sample further identified a distinct community linking cognitive and dual-task measures with ΔHRV reactivity parameters, which functioned as central bridging nodes. Greater gains in ΔLFnu were associated with poorer cognitive and dual-task performance. Inspection of spectral components demonstrated that this index reflected parasympathetic withdrawal rather than increased absolute low-frequency power. Expressed as a relative shift in high-frequency power (ΔHF%), this parameter may capture a “neurovegetative cost” of cognitive challenge, an autonomic analogue of dual-task cost, highlighting how adaptive resources are allocated under load. Conclusions: This work provides empirical evidence that a personalized dual-task intervention can induce coherent multi-domain improvements and offers a conceptual systems-based framework for ageing. Preserving independence in later life appears to depend not on isolated domains, but on strengthening adaptive interactions across cognitive, autonomic, and functional subsystems.