Concurrent trajectories of physical frailty and cognitive impairment among nursing home residents and community-dwelling older adults

以生理储备下降和对压力源的易感性为特征的身体虚弱，以及从轻度损伤到痴呆的认知障碍，往往同时发生在老年人身上。这两种疾病都与严重的不良健康结果、高昂的医疗费用和沉重的照顾者负担有关，并且在美国社区居住的老年人中非常普遍。然而，对于在养老院接受长期护理的老年人，关于这两种情况在他们住院期间的患病率的数据很少。以社区为基础的研究表明，身体虚弱的临床表现不同，这可能对其管理有影响。目前尚不清楚这种异质性在老年养老院居民中是否相似，以及是否受到认知障碍的影响。此外，身体虚弱和认知障碍具有共同的风险因素，并预测彼此的未来发病，但这种复杂相互作用的机制尚不清楚。最后，抑郁症与这两种情况密切相关，但关于抗抑郁药对身体虚弱和认知障碍进展的影响的研究结果并不一致。拟议的F99/K00项目力求通过人口纵向数据和先进统计方法的两个具体目标来解决这些差距。目的1（论文研究）侧重于老年养老院居民，并将描述身体虚弱和认知障碍的患病率；确定身体虚弱的亚组，并根据认知障碍水平检查亚组的变化；描述身体虚弱和认知障碍的发展轨迹，并检查轨迹之间的相关性。目标2（博士后研究）扩展到社区中的老年人，并将评估身体虚弱和认知障碍之间的相互关联；量化累积接触抗抑郁药对身体虚弱、认知障碍和抑郁症状轨迹的影响；并通过因果中介分析检验抑郁症状作为身体虚弱对认知障碍的中介作用。方法上的创新包括使用潜在类别分析、基于群体的轨迹模型、结构方程模型（自回归交叉滞后面板分析、自回归潜在轨迹模型）和因果中介。该提案与美国日益增长的老龄化人口直接相关，包括那些居住在养老院和那些生活在社区的人，因为它使用了国家养老院数据库最小数据集3.0（目标1）和与医疗保险D部分药物事件文件和协调认知评估协议（目标2）相关的全国代表性健康和退休研究。该项目将阐明与年龄相关的身体和认知状况的同步进展。研究结果将为未来开发诊断工具和预测模型提供信息，以促进及时识别有加速功能衰退风险的老年人，并根据老年人的需要实施量身定制的护理，有效延缓负面健康结果的发生，提高生活质量，促进健康长寿。

Physical frailty, characterized by decreased physiologic reserve and increased vulnerability to stressors, and cognitive impairment, ranging from mild impairment to dementia, often co-occur in older adults. Both are associated with considerable adverse health outcomes, high healthcare costs, and substantial caregiver burden, and highly prevalent in U.S. community-dwelling older adults. However, for older adults receiving long-term care in nursing homes, data is scarce on the prevalence of the two conditions over their stay. Community-based studies suggest heterogeneous clinical presentation of physical frailty, which may have implications for its management. It is unknown if such heterogeneity is similar in older nursing home residents and if it is influenced by cognitive impairment. Further, physical frailty and cognitive impairment share risk factors and predict future onset of one another but the mechanism of this complex interplay remains unclear. Lastly, depression is strongly correlated with both conditions, yet findings regarding the impact of antidepressants on the progression of physical frailty and cognitive impairment are inconsistent. This proposed F99/K00 project seeks to address these gaps by two specific aims with population longitudinal data and advanced statistical methods. Aim 1 (dissertation research) focuses on older nursing home residents and will describe the prevalence of physical frailty and cognitive impairment; identify subgroups of physical frailty and examine the variation of subgroups by cognitive impairment levels; and delineate the developmental trajectories of physical frailty and cognitive impairment and examine the correlations between trajectories. Aim 2 (post-doctoral research) expands to older adults in the community and will assess the reciprocal association between physical frailty and cognitive impairment; quantify the impact of cumulative exposure to antidepressants on trajectories of physical frailty, cognitive impairment and depressive symptoms; and examine the effect of depressive symptoms as a mediator of physical frailty on cognitive impairment with causal mediation analysis. Methodological innovations include the use of latent class analysis, group-based trajectory models, structural equation models (autoregressive cross-lagged panel analysis; autoregressive latent trajectory model), and causal mediation. This proposal is directly relevant to the growing aging population in the U.S., including those residing in the nursing homes and those living in the community, since it uses the national nursing home database Minimum Data Set 3.0 (Aim 1) and the nationally-representative Health and Retirement Study linked to Medicare Part D Drug Event Files and the Harmonized Cognitive Assessment Protocol (Aim 2). This project will shed light on the concurrent progression of age-related physical and cognitive conditions. Results will inform future work to develop diagnostic tools and prediction models to facilitate timely identification of older adults at risk for accelerated functional decline, and implement care tailored to older adults’ needs to effectively delay the onset of negative health outcomes, enhance quality of life, and foster a healthy longevity.