Background: Cognitive frailty (CF) is defined as the simultaneous presence of physical frailty and cognitive impairment among older adults without dementia. Previous studies have revealed that neuropathological changes may contribute to the degeneration of subcortical nuclei in the process of cognitive impairment. However, it is unclear in CF. The aim of this study is to investigate the changes in subcortical nuclei in older adults with CF and their relationship with cognitive decline and physical frailty. Methods: A total of 26 older adults with CF and 26 matched healthy subjects were enrolled. Cognitive function and physical frailty were assessed with the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and the Chinese version of the Edmonton Frailty Scale (EFS). Volumetric and diffusion tensor imaging (DTI) parameters of subcortical nuclei were measured with structural and DTI brain magnetic resonance imaging (MRI) and compared between groups. Partial correlation analysis was conducted between subcortical nuclei volumes, MoCA scores, and physical frailty indexes. Results: Significant volume reductions were found in five subcortical nuclei, including the bilateral thalami, left caudate, right pallidum, and accumbens area, in older adults with CF (P < 0.05), and the bilateral thalami was most obvious. Decreased fractional anisotropy and relative anisotropy values were observed only in the left thalamus in the CF group (P < 0.05). No group differences were found in apparent diffusion coefficient (ADC) values. The MoCA scores were positively correlated with the volumes of the bilateral thalami, right pallidum, and accumbens area (P < 0.05). Negative correlations were found between the physical frailty index and the volumes of the bilateral thalami, caudate, pallidum, and right accumbens area (P < 0.05). Conclusion: Microstructural changes occur in the subcortical nuclei of older adults with CF, and these changes are correlated with cognitive decline and physical frailty. Therefore, microstructural atrophy of the subcortical nuclei may be involved in the pathological progression of CF.

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