Sexual dimorphism of frailty and cognitive impairment: Potential underlying mechanisms (Review).

The aim of the present study was to assess systematically gender differences in susceptibility to frailty and cognitive performance decline, and the underlying mechanisms. A systematic assessment was performed of the identified reviews of cohort, mechanistic and epidemiological studies. The selection criteria of the present study included: i) Sexual dimorphism of frailty, ii) sexual dimorphism of subjective memory decline (impairment) and atrophy of hippocampus during early life, iii) sexual dimorphism of late‑onset Alzheimer's disease and iv) sexual dimorphism mechanisms underlying frailty and cognitive impairment. Males exhibit a susceptibility to poor memory performance and a severe atrophy of the hippocampus during early life and females demonstrate a higher prevalence for frailty and late‑life dementia. The different alterations within the hypothalamic‑pituitary‑gonadal/adrenal axis, particularly with regard to gonadal hormones, cortisol and dehydroepiandrosterone/sulfate‑bound dehydroepiandrosterone prior to and following andropause in males and menopause in females, serve important roles in sexual dimorphism of frailty and cognitive impairment. These endocrine changes may accelerate immunosenescence, weaken neuroprotective and neurotrophic effects, and promote muscle catabolism. The present study suggested that these age‑associated endocrine alterations interact with gender‑specific genetic and epigenetic factors, together with immunosenescence and iron accumulation. Environment factors, including psychological factors, are additional potential causes of the sexual dimorphism of frailty and cognitive impairment.