Ren Ziyang, Luo Yanan, Liu Yunduo, Gao Jiatong, Liu Jufen, Zheng Xiaoying
Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Department of Global Health, School of Public Health, Peking University, Beijing, China.
J Affect Disord. 2025 Jun 1;378:254-262. doi: 10.1016/j.jad.2025.03.001. Epub 2025 Mar 5.
Loneliness is prevalent currently and could result in increased dementia risks, whereas the associations of prolonged loneliness and its changes with cognitive decline and dementia remain less investigated.
Data were from the English Longitudinal Study of Ageing (ELSA) and Health and Retirement Study (HRS). Loneliness was assessed using the Revised UCLA Loneliness Scale. Health risk factors for dementia included unhealthy lifestyles, depressive symptoms, chronic diseases, and functional limitations. Cognitive function was assessed using validated tests in both cohorts, with cognitive decline defined as cognitive z-scores < -1.5. Dementia was identified through self- or proxy-reported physician diagnoses. The Cox proportional hazard regression and Aalen's additive hazard regression were performed to calculate the relative and absolute risk for cognitive decline and dementia, respectively. Covariates including socio-demographic characteristics, social networks, and polygenic scores were adjusted.
Of 6721 ELSA and 10,195 HRS participants aged ≥50y, 2129 (13.7 %) and 612 (3.6 %) developed incident cognitive decline and dementia in about 10 years, respectively. Participants with severe (versus no) cumulative loneliness had 42 % and 98 % higher cognitive decline and dementia risks after pooling, corresponding to 791.6 (477.4-1105.8) and 372.8 (223.6-522.0) excess incidence densities (/10 person-years). Additionally, those who recovered from frequent loneliness (versus persistent frequent) were 9 %-31 % less likely to develop unhealthy lifestyles, depressive symptoms, chronic diseases, and functional limitations, and were at 33 % lower risks of dementia, corresponding to -248.6 (-446.0 ~ -51.2) excess incidence density.
Prolonged loneliness could increase the risks of incident cognitive decline and ADRD, while alleviating loneliness may help.
孤独在当下很普遍，且可能导致痴呆风险增加，然而长期孤独及其变化与认知衰退和痴呆之间的关联仍较少被研究。
数据来自英国老龄化纵向研究（ELSA）和健康与退休研究（HRS）。使用修订版的加州大学洛杉矶分校孤独量表评估孤独感。痴呆的健康风险因素包括不健康的生活方式、抑郁症状、慢性疾病和功能受限。在两个队列中均使用经过验证的测试评估认知功能，认知衰退定义为认知z分数＜-1.5。通过自我或代理报告的医生诊断来确定痴呆。进行Cox比例风险回归和阿伦累加风险回归，分别计算认知衰退和痴呆的相对风险与绝对风险。对包括社会人口学特征、社交网络和多基因分数在内的协变量进行了调整。
在6721名年龄≥50岁的ELSA参与者和10195名HRS参与者中，分别有2129名（13.7%）和612名（3.6%）在约10年中出现了新发认知衰退和痴呆。合并后，有严重（相对于无）累积孤独感的参与者出现认知衰退和痴呆的风险分别高出42%和98%，对应的超额发病率密度分别为791.6（477.4 - 1105.8）和372.8（223.6 - 522.0）/10人年。此外，那些从频繁孤独中恢复过来（相对于持续频繁孤独）的人，出现不健康生活方式、抑郁症状、慢性疾病和功能受限的可能性降低了9% - 31%，患痴呆的风险降低了33%，对应的超额发病率密度为-248.6（-446.0 ~ -51.2）。
长期孤独可能会增加新发认知衰退和ADRD的风险，而减轻孤独感可能会有所帮助。
