ImportanceAn accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.ObjectiveTo clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset.Design, Setting, and ParticipantsParticipant data came from 4 prospective cohort studies: the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project, and the National Alzheimer Coordinating Center. Data were collected between 1997 and 2024 and were analyzed from July 2023 to August 2024. The settings were retirement communities, national-level surveys, and a multiclinic-based cohort. Included individuals were 60 years or older and without cognitive impairment at baseline. Included individuals also had data on age, sex, education level, and ethnicity and a frailty index score calculated at baseline.ExposureFrailty was the main exposure, with participants’ degrees of frailty quantified using retrospectively calculated frailty index scores.Main Outcomes and MeasuresIncident all-cause dementia ascertained through physician-derived diagnoses, self- and informant-report, and estimated classifications based on combinations of cognitive tests.ResultsThe participant number before exclusions was 87 737. After exclusions, data from 29 849 participants (mean [SD] age, 71.6 [7.7] years; 18 369 female [62%]; 257 963 person-years of follow-up; 3154 cases of incident dementia) were analyzed. Bayesian generalized linear mixed regression models revealed accelerations in frailty trajectories 4 to 9 years before incident dementia. Overall, frailty was positively associated with dementia risk (adjusted hazard ratios [aHRs] ranged from 1.18; 95% CI, 1.13-1.24 to 1.73; 95% CI, 1.57-1.92). This association held among participants whose time between frailty measurement and incident dementia exceeded the identified acceleration period (aHRs ranged from 1.18; 95% CI, 1.12-1.23 to 1.43; 95% CI, 1.14-1.80).Conclusions and RelevanceThese findings suggest that frailty measurements may be used to identify high-risk population groups for preferential enrolment into clinical trials for dementia prevention and treatment. Frailty itself may represent a useful upstream target for behavioral and societal approaches to dementia prevention.

中文翻译：

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美国和英国痴呆症之前的衰弱轨迹


重要性生物年龄和痴呆风险的可及标志物对于推进痴呆预防和治疗策略至关重要。虽然虚弱是该角色的候选者，但虚弱与痴呆之间关系的性质尚不清楚。目的通过调查痴呆发病前几年的衰弱轨迹，阐明虚弱与痴呆发生之间的时间关系。设计、设置和参与者参与者数据来自 4 项前瞻性队列研究：英国老龄化纵向研究、健康与退休研究、Rush Memory and Aging Project 和国家阿尔茨海默病协调中心。数据是在 1997 年至 2024 年间收集的，并在 2023 年 7 月至 2024 年 8 月期间进行了分析。这些设置是退休社区、国家级调查和基于多诊所的队列。纳入的个体年龄在 60 岁或以上，基线时没有认知障碍。纳入的个体还有年龄、性别、教育水平和种族的数据，以及基线时计算的衰弱指数评分。暴露虚弱是主要暴露，使用回顾性计算的虚弱指数评分量化参与者的虚弱程度。主要结局和措施通过医生衍生的诊断、自我和知情人报告以及基于认知测试组合的估计分类来确定事件全因痴呆。结果排除前的参与者人数为 87 737 人。排除后，分析了 29 849 名参与者 （平均 [SD] 年龄，71.6 [7.7] 岁;18 369 名女性 [62%];257 963 人年随访;3154 例痴呆病例）的数据。 贝叶斯广义线性混合回归模型揭示了痴呆前 4 至 9 年的虚弱轨迹加速。总体而言，虚弱与痴呆风险呈正相关（调整后的风险比 [aHRs] 范围为 1.18;95% CI，1.13-1.24 至 1.73;95% CI，1.57-1.92）。这种关联在虚弱测量和痴呆事件之间的时间超过确定的加速期的参与者中成立（aHR 范围为 1.18;95% CI，1.12-1.23 至 1.43;95% CI，1.14-1.80）。结论和相关性这些发现表明，虚弱测量可用于确定高危人群，以优先参加痴呆预防和治疗的临床试验。虚弱本身可能代表预防痴呆的行为和社会方法的有用上游目标。