Circadian Rest–Activity Rhythms, Delirium Risk, and Progression to Dementia

🥈 Top 2% JournalFeb 22, 2023Annals of neurology

Daily Activity Patterns, Risk of Delirium, and Development of Dementia

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Abstract

Suppressed 24-hour amplitude of daily rest-activity rhythms is associated with a 1.94-fold higher risk of .

Lower amplitude in daily rest-activity rhythms is linked to increased delirium risk among participants.
More fragmented daily rhythms are associated with a 1.49-fold higher risk of delirium.
Each hour of delayed peak activity time (acrophase) correlates with a 1.13-fold increase in delirium risk in those without .
Suppressed daily rhythms are also associated with a 1.31-fold higher risk of progressing from delirium to new onset dementia.
These findings suggest that disturbances in daily rest-activity rhythms may indicate higher risk and contribute to early disease progression.

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OBJECTIVE: is a complex neurocognitive syndrome suspected to be bidirectionally linked to . 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]= 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). Q1 vs Q4Q4 vs Q1

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.

Key numbers

1.94

Higher Risk

Hazard ratio comparing lowest vs. highest amplitude quartiles.

1.31

Progression to Risk

Hazard ratio for progression to after .

1.49

Increased Fragmentation Risk

Hazard ratio for higher variability in daily rhythms.

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Abstract

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