Chronic Ankle Instability Is Associated With Smaller Sensorimotor Deficits and Greater Integrity of the Superior Cerebellar Peduncles With Aging

BACKGROUND: Chronic ankle instability is associated with balance deficits and maladaptive cerebellar neuroplasticity across age groups. However, it remains unclear how aging and chronic ankle instability interact to influence these abnormalities, particularly in cerebellar structures that are essential for proprioception and motor coordination. This gap in understanding limits the development of age-specific rehabilitation strategies. QUESTIONS/PURPOSES: This study aimed to: (1) determine the interaction effect of chronic ankle instability and aging on sensorimotor deficits, (2) assess whether this interaction is reflected in superior and inferior cerebellar peduncle microstructure changes, and (3) evaluate the correlation between altered cerebellar peduncle integrity and balance performance in patients with chronic ankle instability and a control cohort. METHODS: Between August 2022 and January 2024, we screened 134 individuals for participation. Of these, 61% (82 of 134) were considered potentially eligible based on the inclusion criteria. One patient in the control group was excluded because of poor imaging quality. Ultimately, 60% (81 of 134) of participants were included in the final analysis, consisting of 51% (41 of 81) in the chronic ankle instability group (18 females, age 30 ± 6 years) and 49% (40 of 81) in the control group (17 females, age 29 ± 8 years). We collected participants' demographic information, clinical history, as well as clinical data, including Cumberland Ankle Instability Tool scores for self-reported instability and Tegner activity scores. All participants underwent the Y-balance test to evaluate sensorimotor deficits and diffusion-weighted imaging to assess the structure of the central nervous system. We focused on the superior and inferior cerebellar peduncles as regions of interest and performed both traditional diffusion tensor imaging and advanced neurite orientation dispersion and density imaging to evaluate the cerebellar white matter microstructure. Multivariable linear regressions with interaction terms were conducted to examine the interaction effects of chronic ankle instability and age on primary clinical outcomes (Y-balance test scores and diffusion tensor imaging/neurite orientation dispersion and density imaging outcomes). Correlation analyses between posteromedial reach distances on the Y-balance test and significant diffusion tensor imaging/neurite orientation dispersion and density imaging outcomes were performed within the chronic ankle instability and the control groups, respectively. In particular, we calculated a standardized beta coefficient (β*) for each regression model to facilitate comparison of effect sizes across variables to more easily judge which predictors contributed more substantially to the outcomes. RESULTS: After controlling for potential confounding factors including sex, BMI, and Tegner activity scores, we found that although participants with chronic ankle instability generally had poorer dynamic balance, the group differences in anterior (β = 0.58 × 10 -2 [95% CI 0.09 × 10 -2 to 1.07 × 10 -2 ]; β* = 1.11; p = 0.02), posteromedial (β = 0.74 × 10 -2 [95% CI 0.10 × 10 -2 to 1.38 × 10 -2 ]; β* = 1.15; p = 0.03), and average Y-balance test scores (β = 0.56 × 10 -2 [95% CI 0.02 × 10 -2 to 1.10 × 10 -2 ]; β* = 1.01; p = 0.046) were smaller in older participants. Similarly, we found that compared with controls, participants with chronic ankle instability generally had impaired nerve pathways in superior cerebellar peduncles, characterized by lower fractional anisotropy values and higher orientation dispersion index values. However, these structural differences were smaller among patients with older age, in fractional anisotropy (β = 1.96 × 10 -3 [95% CI 0.09 × 10 -3 to 3.82 × 10 -3 ]; β* = 0.93; p = 0.04), and orientation dispersion index values (β = -1.41 × 10 -3 [95% CI -2.49 × 10 -3 to -0.33 × 10 -3 ]; β* = -1.16; p = 0.01) compared with age-matched controls. In the superior cerebellar peduncles of the control group, participants with higher fractional anisotropy values had slightly greater posteromedial reach distances on the Y-balance test (r = 0.39; p = 0.01), suggesting better dynamic balance. In contrast, participants with higher orientation dispersion index values had slightly shorter posteromedial reach distances (r = -0.32; p = 0.04), suggesting poorer dynamic balance. CONCLUSION: We found that the combination of older age and chronic ankle instability correlates with improved sensorimotor testing and potentially adaptive structural white matter changes in the cerebellum, particularly in the superior cerebellar peduncles. These findings suggest a possible age-related neural adaptation and highlight the need for future longitudinal and interventional studies to clarify these associations and explore whether age-specific rehabilitation strategies could be beneficial. LEVEL OF EVIDENCE: Level III, prognostic study.