Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Medical Biodynamics Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
Ann Neurol. 2023 Jun;93(6):1145-1157. doi: 10.1002/ana.26617. Epub 2023 Mar 3.
Delirium is a complex neurocognitive syndrome suspected to be bidirectionally linked to dementia. Circadian rhythm disturbances likely contribute to dementia pathogenesis, but whether these disturbances are related to delirium risk and progression to all-cause dementia is unknown.
We analyzed continuous actigraphy data from 53,417 middle-aged or older UK Biobank participants during a median 5 years of follow-up. Four measures were used to characterize the 24-hour daily rest-activity rhythms (RARs): normalized amplitude, acrophase representing the peak activity time, interdaily stability, and intradaily variability (IV) for fragmentation of the rhythm. Cox proportional hazards models examined whether RARs predicted incident delirium (n = 551) and progression to dementia (n = 61).
Suppressed 24-hour amplitude, lowest (Q1) versus highest (Q4) quartile (hazard ratio [HR] = 1.94, 95% confidence interval [CI] = 1.53-2.46, p < 0.001), and more fragmented (higher IV: HR = 1.49, 95% CI = 1.18-1.88, p < 0.001) rhythms predicted higher delirium risk, after adjusting for age, sex, education, cognitive performance, sleep duration/disturbances, and comorbidities. In those free from dementia, each hour of delayed acrophase was associated with delirium risk (HR = 1.13, 95% CI = 1.04-1.23, p = 0.003). Suppressed 24-hour amplitude was associated with increased risk of progression from delirium to new onset dementia (HR = 1.31, 95% CI = 1.03-1.67, p = 0.03 for each 1-standard deviation decrease).
Twenty-four-hour daily RAR suppression, fragmentation, and potentially delayed acrophase were associated with delirium risk. Subsequent progression to dementia was more likely in delirium cases with suppressed rhythms. The presence of RAR disturbances before delirium and prior to progression to dementia suggests that these disturbances may predict higher risk and be involved in early disease pathogenesis. ANN NEUROL 2023;93:1145-1157.
谵妄是一种复杂的神经认知综合征，据推测与痴呆症存在双向关联。昼夜节律紊乱可能有助于痴呆症的发病机制，但这些紊乱是否与谵妄风险以及发展为所有原因导致的痴呆症有关尚不清楚。
我们分析了英国生物库中 53417 名中老年参与者的连续活动数据，中位随访时间为 5 年。使用 4 个指标来描述 24 小时日常的休息-活动节律（RAR）：正常幅度、代表活动高峰时间的峰时、日间稳定性和节奏碎片化的日内可变性（IV）。Cox 比例风险模型检查了 RAR 是否预测了新发谵妄（n=551）和进展为痴呆症（n=61）。
24 小时幅度降低（Q1 与 Q4 四分位间距：HR=1.94，95%置信区间[CI]：1.53-2.46，p<0.001）和节律更为碎片化（IV 更高：HR=1.49，95%CI：1.18-1.88，p<0.001）提示谵妄风险更高，这是在调整了年龄、性别、教育程度、认知表现、睡眠时间/障碍和合并症之后的结果。在那些没有痴呆症的人中，每小时的峰值时间延迟与谵妄风险相关（HR=1.13，95%CI：1.04-1.23，p=0.003）。24 小时幅度降低与从谵妄进展为新发痴呆症的风险增加相关（每降低 1 个标准差的 HR=1.31，95%CI：1.03-1.67，p=0.03）。
24 小时日常 RAR 抑制、碎片化和潜在的峰值时间延迟与谵妄风险相关。在发生谵妄的病例中，随后进展为痴呆症的可能性更大。在谵妄和进展为痴呆症之前就存在 RAR 紊乱提示这些紊乱可能预示着更高的风险，并参与早期疾病的发病机制。
