Department of Neurology, Oregon Health & Science University, Portland, OR, United States of America.
Oregon Center for Aging & Technology (ORCATECH), Portland, OR, United States of America.
PLoS One. 2023 Jun 8;18(6):e0286812. doi: 10.1371/journal.pone.0286812. eCollection 2023.
Outcome measures available for use in Alzheimer's disease (AD) clinical trials are limited in ability to detect gradual changes. Measures of everyday function and cognition assessed unobtrusively at home using embedded sensing and computing generated "digital biomarkers" (DBs) have been shown to be ecologically valid and to improve efficiency of clinical trials. However, DBs have not been assessed for their relationship to AD neuropathology.
The goal of the current study is to perform an exploratory examination of possible associations between DBs and AD neuropathology in an initially cognitively intact community-based cohort.
Participants included in this study were ≥65 years of age, living independently, of average health for age, and followed until death. Algorithms, run on the continuously-collected passive sensor data, generated daily metrics for each DB: cognitive function, mobility, socialization, and sleep. Fixed postmortem brains were evaluated for neurofibrillary tangles (NFTs) and neuritic plaque (NP) pathology and staged by Braak and CERAD systems in the context of the "ABC" assessment of AD-associated changes.
The analysis included a total of 41 participants (M±SD age at death = 92.2±5.1 years). The four DBs showed consistent patterns relative to both Braak stage and NP score severity. Greater NP severity was correlated with the DB composite and reduced walking speed. Braak stage was associated with reduced computer use time and increased total time in bed.
This study provides the first data showing correlations between DBs and neuropathological markers in an aging cohort. The findings suggest continuous, home-based DBs may hold potential to serve as behavioral proxies that index neurodegenerative processes.
可用于阿尔茨海默病（AD）临床试验的结局测量在检测逐渐变化的能力方面存在局限性。使用嵌入式传感和计算生成的“数字生物标志物”（DB）在家中进行非侵入性评估的日常功能和认知测量，已被证明具有生态有效性，并提高临床试验的效率。然而，尚未评估 DB 与 AD 神经病理学之间的关系。
本研究的目的是在最初认知正常的基于社区的队列中，对 DB 与 AD 神经病理学之间的可能关联进行探索性检查。
本研究纳入的参与者年龄≥65 岁，独立生活，年龄健康状况良好，并持续随访至死亡。算法在持续收集的被动传感器数据上运行，为每个 DB 生成日常指标：认知功能、移动性、社交和睡眠。对固定的死后大脑进行神经原纤维缠结（NFT）和神经原纤维缠结（NP）病理学评估，并在 AD 相关变化的“ABC”评估背景下按照 Braak 和 CERAD 系统进行分期。
该分析共纳入 41 名参与者（死亡时的平均年龄±SD=92.2±5.1 岁）。四个 DB 与 Braak 分期和 NP 评分严重程度均表现出一致的模式。NP 严重程度与 DB 综合评分和步行速度降低相关。Braak 分期与计算机使用时间减少和总卧床时间增加相关。
本研究首次提供了在老年队列中 DB 与神经病理学标志物之间存在相关性的证据。研究结果表明，基于家庭的连续 DB 可能具有作为神经退行性过程的行为替代物的潜力。
