B27-03 Associations Between Circadian Rhythm and Cognitive Function in Older Adults Recovering From Critical Illness: Potential Roles of Sex, Chronotype, and Polypharmacy

Rationale Older adults surviving an intensive care unit (ICU) stay often experience circadian dysrhythmia from continuous/24-hour hospital care, which may contribute to cognitive dysfunction. This exploratory analysis examined associations between circadian rhythm and cognitive function, and potential effect modification by sex, chronotype, and psychoactive medication exposure during the early post-ICU transition. Methods We conducted secondary/exploratory analyses using baseline data from older adult ICU survivors enrolled in two ongoing clinical trials within 48 hours of ICU transfer to acute care. Circadian rhythm was characterized by mean amplitude of continuous body temperature over the first 24 hours of the observation period, measured by the iButton wearable sensor; lower amplitude indicated worse circadian dysrhythmia. Chronotype was categorized as morning/afternoon using the Composite Scale of Morningness. Psychoactive medication exposure (e.g., opioids, benzodiazepines, anti-psychotics/sedative-hypnotics, sleep aids, anti-depressants, anxiolytics) during the observation period was grouped into categories (e.g., 0, 1, 2+ medications). Working memory was assessed by Digit Span-Backward longest correct series (longer=better performance); executive function by Oral Trail Making Test-B completion time in seconds (shorter/faster time=better performance). Covariates included length of mechanical ventilation and PROMIS Depression T-score. Multiple regression explored associations between circadian rhythm and cognitive function; MANCOVA examined interactions with sex, chronotype, and psychoactive medications. Results For working memory, the regression model was significant (R2=0.419, p=.023); greater amplitude predicted better performance (β=.460, p=.03; n = 21). For executive function, the model was significant (R2=0.517, p=.007); higher depression scores predicted worse/slower times (β=.530, p=.01; n = 20). The sex × sleep medication interaction was significant for executive function (F(2,11)=11.49, p=.002, partial η²=.676). Performance among males remained stable across 0-2+ sleep medications, whereas performance among females was worse - especially those receiving 1+ medications - despite covariate adjustment. Moreover, the sex × opioid interaction was significant for working memory (F(2,10)=5.561, p=.024, partial η²=.527). Among those who received IV medications, male older adult ICU survivors outperformed their female counterparts. Moreover, females who received IV or PCA doses scored the worst overall. Finally the sex × chronotype × depression/anxiety medication interaction was significant for executive function (F(1,6)=16.941, p=.006, partial η²=.738). Afternoon-type females who received 2+ depression/anxiety medications performed worse when compared alongside their male counterparts. Conclusions Greater circadian rhythm amplitude was linked to better working memory. Female ICU survivors, especially afternoon chronotypes who received multiple psychoactive medications, showed the poorest cognitive performance. Although limited by small sample size, findings highlight subgroups potentially vulnerable to circadian dysrhythmia and polypharmacy during critical illness recovery.