Brain Functional Alterations Associated With Postural Stability Across the Frailty Continuum: A Resting-State fMRI...

Frailty is a common geriatric syndrome characterized by a progressive decline in physical function and an increased susceptibility to adverse outcomes, including falls. Although diminished postural stability is a hallmark of frailty, the neural correlates associated with balance impairments throughout the progression of the syndrome remain unclear. This study aims to elucidate the brain functional activity of older adults with varying degrees of frailty during a resting state, as well as the relationship between this activity and postural stability.

Sixty-eight older adults were divided into non-frail (n = 23), pre-frail (n = 30), and frail (n = 15) groups based on the Fried frailty phenotype. Postural stability was assessed using the Huber®360 neuromuscular control training and assessment system. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired on a 3.0 T scanner, and the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were utilized as indicators of brain functional activity. Spearman correlation analysis was employed to examine the correlations between the brain functional activity and the postural stability.

Compared to the non-frail group, the frail and pre-frail groups were significantly older and exhibited poorer performance in grip strength, Short Physical Performance Battery (SPPB) scores, and Timed Up and Go Test (TUGT) results, as well as a greater burden of comorbidities-such as depressive symptoms and sleep disturbances (all p < 0.05). Significant inter-group differences were observed across all postural stability parameters. Relative to the non-frail group, the pre-frail group exhibited significantly decreased ALFF in the left inferior frontal gyrus (pars opercularis) extending to the insula, while the frail group demonstrated reduced ALFF in bilateral posterior cerebellum; additionally, the frail group showed decreased ReHo in the left posterior cerebellum/pons and increased ReHo in the right middle temporal/occipital gyrus. ALFF was significantly correlated with right single-leg sway area, the limits of stability, SPPB score, and TUGT completion time, whereas ReHo was significantly correlated only with SPPB score and TUGT completion time (all p < 0.05).

Resting-state brain function exhibits significant differences among older adults in varying states of frailty, primarily involving spontaneous activity and local synchronization within the cerebellum-pons circuitry and cognition-related brain regions. These functional brain abnormalities are closely associated with diminished postural stability, suggesting that alterations in central nervous system function may represent a significant neural correlate of impaired balance in frail older adults. This study provides neuroimaging evidence to support the early screening of frailty and balance-related interventions in older adults, while also laying a foundation for future longitudinal and multimodal investigations.