Dissecting the sex-dependent muscle–brain axis: Hippocampal subfields mediate the association between grip strength and cognition in amnestic mild cognitive impairment
Wen-Juan Song, Guo-Hui Zhang, Pu Zhao, Jia-Jia Wu, Juan-Juan Lu, Jie Ma, Xu-Yun Hua, Jian-Guang XuBackground
Grip strength has been increasingly recognized as a potential indicator of cognitive decline and is closely associated with hippocampal structure. However, whether this muscle–brain relationship differs by sex among individuals with amnestic mild cognitive impairment (aMCI) remains unclear.
Objective
To explore sex-specific relationships among grip strength, hippocampal subfield volumes and cognitive function in aMCI.
Methods
This case-control study enrolled 144 aMCI patients and 84 healthy controls, demographic, neuropsychological, grip-strength data and 3.0 T MRI images were collected. Principal component analysis (PCA), multivariate regression, Pearson correlation and mediation analyses were performed.
Results
Significant differences were found in the volumes of 15 hippocampal subfields, education level, right grip strength and cognitive scores. A bilateral grip strength related factor extracted by PCA was significantly associated with global cognition, memory, language, executive function and emotional status. Sex-stratified analyses revealed sex-specific correlations between grip strength, cognitive scores and hippocampal subfield volumes. Right hippocampal fissure partially mediated (20.33%) the relationship between right grip strength and ACE-III scores in males.
Conclusions
Grip strength was correlated with hippocampal subfield integrity and cognitive function in a sex-specific manner. These observations illustrated an associative pathway linking muscular strength to cognitive vulnerability, with grip strength representing a potential observational marker for early-stage cognitive risk.