社会孤立对阿尔茨海默病影响的研究进展

Research Progress on the Impact of Social Isolation on Alzheimer’s Disease

阿尔茨海默病(Alzheimer disease, AD)是一种不可逆的神经退行性疾病。其病程长,目前没有药物能够有效治疗AD。目前有证据指出,孤独是AD和其他相关失智症发展的可变危险因素,与社会隔绝的人患失智症的风险往往比远离社会孤立的人患失智症风险高。感知到的社会孤立或孤独会促进并加剧大脑中的β-淀粉样蛋白斑块(amyloid-protein, Aβ)的沉积和tau蛋白过度磷酸化,而社会孤立和AD的不同阶段大脑区域都会受到影响表现出功能障碍,例如前额叶皮层、杏仁核或海马体。同时,社会孤立和感知孤独感会促进早期AD患者大脑中Aβ的产生和tau蛋白过度磷酸化,来自社会隔离和孤独的压力也会影响Aβ的积累和tau蛋白的过度磷酸化。此外,应激引起的糖皮质激素水平升高会导致Aβ和tau蛋白病变的加剧,从而加速神经纤维缠结的发展。社交孤立也可能通过增加氧化应激加重AD病理。感觉到被孤立和拥有孤独的经历都会对心理和身体健康产生不利影响。随着我国人口老龄化,再加上新型冠状病毒COVID-19的出现以及由此产生的隔离阻碍了社交,疫情隔离使人们减少了社交,会出现社会孤立这一现象,同时也会加剧AD病情发展。有研究指出,晚年远离社会隔离会降低患失智症风险4%,对此早期积极预防社会孤立尤其重要,远离社会孤立,应多出门走动与同伴交流,提高认知储备(Cognitive reserve, CR)水平及多认识新事物是积极预防AD的重要方法。

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease. The course of disease is long, and no drugs can effectively treat AD. Evidence now points to loneliness as a modifiable risk factor for the development of AD and other related dementia. People who are socially isolated tend to have a higher risk of developing dementia than people who are socially isolated. Perceived social isolation or loneliness promotes and intensifies Aβ deposition and tau hyperphosphorylation in the brain. Both social isolation and different stages of AD affect brain regions that show dysfunction, such as the prefrontal cortex, amygdala, or hippocampus. At the same time, social isolation and perceived loneliness promote Aβ production and tau hyperphosphorylation in the brain of early AD patients. Stress from social isolation and loneliness also affects Aβ accumulation and tau hyperphosphorylation. The increase in glucocorticoid levels caused by stress leads to the exacerbation of Aβ and tau protein lesions, thereby accelerating the development of neurofibrillary tangles. Social isolation may also exacerbate AD pathology by increasing oxidative stress. Feeling isolated and having experiences of loneliness can both have adverse effects on mental and physical health. With the aging population in our country, the emergence of COVID-19 and the resulting isolation has hindered social interaction, which makes people reduce social interaction, resulting in social isolation and aggravating the development of Alzheimer’s disease. Studies have pointed out that staying away from social isolation in later life can reduce the risk of dementia by 4%. Therefore, it is particularly important to actively prevent social isolation in the early stage. To stay away from social isolation, we should go out and communicate with peers more, improve cognitive reserve (CR) level and learn more about new things are important ways to actively prevent AD.