Sexual dimorphism of frailty and cognitive impairment: Potential underlying mechanisms

Abstract

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.

Prevalence and Risk Factors for Cognitive Frailty in Aging Hypertensive Patients in China

“…Depression can lead to the upregulation of tumor necrosis factor (TNF) and interleukin (IL)-6. Inflammatory cytokines can penetrate the blood-brain barrier, act on skeletal muscle, accelerate the occurrence of sarcopenia and cognitive dysfunction, and eventually lead to CF [49]. Depression in the aging population is characterized by less verbalization, less movement, mental fatigue, unwillingness to communicate with others, and the continuous lack of physical activity and interpersonal communication, leading to cognitive decline and physical frailty [49].…”

Manual dexterity in young and healthy older adults. 1. Age‐ and gender‐related differences in unimanual and bimanual performance

“…Recent research has shown that females are more vulnerable than males to substantial loss of muscle (Cruz-Jentoft et al, 2010) and that the prevalence of frailty is higher among females (Ruan et al, 2017). Recent research has shown that females are more vulnerable than males to substantial loss of muscle (Cruz-Jentoft et al, 2010) and that the prevalence of frailty is higher among females (Ruan et al, 2017).…”

“…The second biological mechanism that is relevant to explain gender differences in dexterity decline is age-related reduction in muscle mass and strength. Recent research has shown that females are more vulnerable than males to substantial loss of muscle (Cruz-Jentoft et al, 2010) and that the prevalence of frailty is higher among females (Ruan et al, 2017). Therefore, females may experience an earlier decline in hand strength and function than males.…”

The Effects of Elaeagnus angustifolia L. on the Thyroid-Stimulating Hormone, Dehydroepiandrosterone-Sulfate, Prolactin and Cortisol Levels in Post-Menopausal Women: A Double-Blind, Randomized, and Placebo-Controlled Study

“…DHEA is a precursor to androgens and estrogen and its conversion into estrone is the major source of estrogen in postmenopausal women (Rodwell et al, 2018). DHEA-S is the most abundant steroid hormone in serum (Ruan et al, 2017) and can modulate lipid and glucose metabolism (Yen and Laughlin, 1998). As DHEA-S levels decrease, pain threshold and tolerance decrease (De Abreu Freitas., 2012).…”