Circadian Rest-Activity Rhythms, Delirium Risk, and Progression to Dementia.

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.

Daily rhythm of dynamic cerebral autoregulation in patients after stroke.

Dynamic cerebral autoregulation (dCA) in healthy young adults displays a daily variation. Whether the rhythm exists in patients with stroke is unknown. We studied 28 stroke patients (age: 26-83 years, 7 females) within 48 hours after thrombolysis. dCA was assessed 54 times in these patients during supine rest (twice in 26 and once in 2 patients): 9 assessments between 0-9AM, 12 between 9AM-2PM, 20 between 2-7PM, and 13 between 7PM-12AM. To estimate dCA, phase shifts between spontaneous oscillations of cerebral blood flow velocity (CBFV) in the middle cerebral artery and arterial blood pressure (BP) were obtained in four frequency bands: <0.05 Hz, 0.05-0.1 Hz, 0.1-0.2 Hz, and >0.2 Hz. CBFV-BP phase shifts at <0.05 Hz were significantly larger between 2-7PM, suggesting better dCA, than those at other times (p < 0.0001), and the daily rhythm was consistent for stroke and non-stroke sides. No significant rhythms were observed at higher frequencies (all p > 0.2). All results were independent of age, sex, stroke type and severity, and other cardiovascular conditions. dCA after stroke showed a daily rhythm, leading to a better regulation of CBFV at <0.05 Hz during the afternoon. The finding may have implications for daily activity management of stroke patients.