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Objective: 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. Methods: 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). Results: Suppressed 24‐hour amplitude, lowest (Q1) versus highest (Q4) quartile (hazard ratio [HR]Q1 vs Q4 = 1.94, 95% confidence interval [CI] = 1.53–2.46, p < 0.001), and more fragmented (higher IV: HRQ4 vs Q1 = 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). Interpretation: 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 [ABSTRACT FROM AUTHOR]

Background: Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization.Methods: About 321 818 participants from the UK Biobank (mean age 58 ± 8 years [SD]; range 37-74 years) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype-a closely related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n = 4 775) was obtained from hospitalization records during a 12-year median follow-up. About 42 291 (mean age 64 ± 8 years; range 44-83 years) had repeat sleep assessment on average 8 years after their first.Results: In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores = 4-5) and severe (scores = 6-9) poor sleep burden groups were 18% (hazard ratio = 1.18 [95% confidence interval: 1.08-1.28], p < .001) and 57% (1.57 [1.38-1.80], p < .001), more likely to develop delirium, respectively. The latter risk magnitude is equivalent to 2 additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs no change) further increased the risk for delirium (1.79 [1.23-2.62], p = .002) independent of their baseline sleep score and time lag. The risk was highest in those younger than 65 years at baseline (p for interaction <.001).Conclusion: Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk. [ABSTRACT FROM AUTHOR]

Background: Many disease processes are influenced by circadian clocks and display ~24-hour rhythms. Whether disruptions to these rhythms increase stroke risk is unclear. We evaluated the association between 24-hour rest-activity rhythms, stroke risk, and major poststroke adverse outcomes., Methods and Results: We examined ~100 000 participants from the UK Biobank (aged 44-79 years; ~57% women) assessed with actigraphy (6-7 days) and 5-year median follow-up. We derived (1) most active 10-hour activity counts across the 24-hour cycle and the timing of its midpoint timing; (2) the least active 5-hour count and its midpoint; (3) relative amplitude; (4) interdaily stability; and (5) intradaily variability, for stability and fragmentation of the rhythm. Cox proportional hazard models were constructed for time to (1) incident stroke (n=1652) and (2) poststroke adverse outcomes (dementia, depression, disability, or death). Suppressed relative amplitude (lowest quartile [quartile 1] versus the top quartile [quartile 4]) was associated with stroke risk (hazard ratio [HR], 1.61 [95% CI, 1.35-1.92]; P <0.001) after adjusting for demographics. Later most active 10-hour activity count midpoint timing (14:00-15:26; HR, 1.26 [95% CI, 1.07-1.49]; P =0.007) also had higher stroke risk than earlier (12:17-13:10) participants. A fragmented rhythm (intradaily variability) was also associated with higher stroke risk (quartile 4 versus quartile 1; HR, 1.26 [95% CI, 1.06-1.49]; P =0.008). Suppressed relative amplitude was associated with risk for poststroke adverse outcomes (quartile 1 versus quartile 4; HR, 2.02 [95% CI, 1.46-2.48]; P <0.001). All associations were independent of age, sex, race, obesity, sleep disorders, cardiovascular diseases or risks, and other comorbidity burdens., Conclusions: Suppressed 24-hour rest-activity rhythm may be a risk factor for stroke and an early indicator of major poststroke adverse outcomes.

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., (©Shahab Haghayegh, Chenlu Gao, Elizabeth Sugg, Xi Zheng, Hui-Wen Yang, Richa Saxena, Martin K Rutter, Michael Weedon, Agustin Ibanez, David A Bennett, Peng Li, Lei Gao, Kun Hu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.05.2024.)

Background Spontaneous heart rate fluctuations contain rich information related to health and illness in terms of physiological complexity, an accepted indicator of plasticity and adaptability. However, it is challenging to make inferences on complexity from shorter, more practical epochs of data. Distribution entropy (DistEn) is a recently introduced complexity measure that is designed specifically for shorter duration heartbeat recordings. We hypothesized that reduced DistEn predicted increased mortality in a large population cohort. Method and Results The prognostic value of DistEn was examined in 7631 middle-older-aged UK Biobank participants who had 2-minute resting ECGs conducted (mean age, 59.5 years; 60.4% women). During a median follow-up period of 7.8 years, 451 (5.9%) participants died. In Cox proportional hazards models with adjustment for demographics, lifestyle factors, physical activity, cardiovascular risks, and comorbidities, for each 1-SD decrease in DistEn, the risk increased by 36%, 56%, and 73% for all-cause, cardiovascular, and respiratory disease-related mortality, respectively. These effect sizes were equivalent to the risk of death from being >5 years older, having been a former smoker, or having diabetes mellitus. Lower DistEn was most predictive of death in those <55 years with a prior myocardial infarction, representing an additional 56% risk for mortality compared with older participants without prior myocardial infarction. These observations remained after controlling for traditional mortality predictors, resting heart rate, and heart rate variability. Conclusions Resting heartbeat complexity from short, resting ECGs was independently associated with mortality in middle- to older-aged adults. These risks appear most pronounced in middle-aged participants with prior MI, and may uniquely contribute to mortality risk screening.