PDF(Pubmed)
Abstract：
BACKGROUND: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults.
OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults.
METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer\'s disease.
RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase.
CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.
OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults.
METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer\'s disease.
RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase.
CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.
摘要：
背景：24小时休息-活动节律（RAR）与痴呆或轻度认知障碍（MCI）风险之间的关系仍然是一个越来越受关注的领域。以前的研究通常受到小样本量的限制，短期随访，年长的参与者。需要更多的研究来充分探索中老年人RAR受损与痴呆或MCI之间的联系。
目的：我们利用UKBiobank的数据来研究中老年人RAR紊乱与患痴呆和MCI的风险之间的关系。
方法：我们分析了91,517名年龄在43至79岁之间的UKBiobank参与者的数据。腕动记录用于得出非参数RAR指标，包括最活跃的10小时时段(M10)及其中点的活动水平，最不活跃的5小时(L5)的活动水平及其中点，24小时周期的相对振幅（RA）[RA=（M10-L5）/（M10L5）]，每日稳定，和每日变异性，以及24小时节律的振幅和顶相（余弦分析）。我们使用Cox比例风险模型来检查基线RAR与随后的痴呆或MCI发病率之间的关联，并根据人口统计学特征进行调整。合并症,生活方式因素，轮班状态,和阿尔茨海默病的遗传风险。
结果：在长达7.5年的随访中，555名参与者发展为MCI或痴呆。M10活性较低的患者痴呆或MCI风险增加（风险比[HR]1.28，95%CI1.14-1.44，每降低1-SD），L5活性较高（HR1.15，95%CI1.10-1.21，每1-SD增加），RA降低（HR1.23，95%CI1.16-1.29，每1-SD降低），较低的振幅（HR1.32，95%CI1.17-1.49，每1-SD降低），和更高的每日变异性（HR1.14，95％CI1.05-1.24，每1-SD增加）以及L5中点提前（HR0.92，95％CI0.85-0.99，每1-SD增加）。这些关联在<70岁和>70岁的人群中相似，在非轮班工人中，它们独立于遗传和心血管危险因素。M10中点未观察到显著关联，每日稳定，或者顶相。
结论：根据对中老年人进行客观RAR评估和近8年随访的大样本结果，我们认为,在痴呆或MCI发病之前,日常活动节律受到抑制和分散,可能是中年人和老年人临床前痴呆的风险生物标志物.
目的：我们利用UKBiobank的数据来研究中老年人RAR紊乱与患痴呆和MCI的风险之间的关系。
方法：我们分析了91,517名年龄在43至79岁之间的UKBiobank参与者的数据。腕动记录用于得出非参数RAR指标，包括最活跃的10小时时段(M10)及其中点的活动水平，最不活跃的5小时(L5)的活动水平及其中点，24小时周期的相对振幅（RA）[RA=（M10-L5）/（M10L5）]，每日稳定，和每日变异性，以及24小时节律的振幅和顶相（余弦分析）。我们使用Cox比例风险模型来检查基线RAR与随后的痴呆或MCI发病率之间的关联，并根据人口统计学特征进行调整。合并症,生活方式因素，轮班状态,和阿尔茨海默病的遗传风险。
结果：在长达7.5年的随访中，555名参与者发展为MCI或痴呆。M10活性较低的患者痴呆或MCI风险增加（风险比[HR]1.28，95%CI1.14-1.44，每降低1-SD），L5活性较高（HR1.15，95%CI1.10-1.21，每1-SD增加），RA降低（HR1.23，95%CI1.16-1.29，每1-SD降低），较低的振幅（HR1.32，95%CI1.17-1.49，每1-SD降低），和更高的每日变异性（HR1.14，95％CI1.05-1.24，每1-SD增加）以及L5中点提前（HR0.92，95％CI0.85-0.99，每1-SD增加）。这些关联在<70岁和>70岁的人群中相似，在非轮班工人中，它们独立于遗传和心血管危险因素。M10中点未观察到显著关联，每日稳定，或者顶相。
结论：根据对中老年人进行客观RAR评估和近8年随访的大样本结果，我们认为,在痴呆或MCI发病之前,日常活动节律受到抑制和分散,可能是中年人和老年人临床前痴呆的风险生物标志物.
