Differential Roles of Neural Integrity, Physical Activity and Depression in Frailty: Sex-Related Differences

The frailty sex paradox has recently gained attention. At all ages, females are more likely to be frail and show a more severe phenotype but have a higher survival rate compared to males. The main aim was to test sex-specific differences in frailty syndrome using a multimodal evaluation from clinical and imaging data to deepen the understanding of different underlying mechanisms involved in the two sexes, and thus understand the association with different risk factors. Ninety-six community-dwelling older adults were characterized by clinical underpinnings (Fried's frailty indicators: comorbidity, depression, global cognitive level, physical activity, autonomy), and neural integrity (T1-weighted brain 3T MRI). The frailty x sex interaction in clinical and neural profiles was tested. Additionally, frailty risk factors were identified in the two sexes separately. Results showed that fragility was associated with an increment of depressive symptomatology in females, while a decrement in physical activity was observed already in the pre-frail stage in males. Finally, different risk factors were observed in the two groups: significant frailty predictors were neural integrity and physical activity in males, and age and depression in females. These data support the starting hypothesis of at least partially different mechanisms involved in the frailty phenotype between men and women.

Automated summary

The frailty sex paradox refers to the phenomenon that females are more likely to be frail and show a more severe phenotype but have a higher survival rate compared to males. This study aimed to test sex-specific differences in frailty syndrome using clinical and imaging data and identify different risk factors. The results showed that fragility was associated with depression in females, while physical activity decreased in males already in the pre-frail stage. Different risk factors were also observed, with neural integrity and physical activity being significant predictors in males and age and depression in females. These findings support the hypothesis of partially different mechanisms involved in the frailty phenotype between men and women.