0268 Life-Course Sleep Complaints and Long-Term Cognitive Trajectories in Adults Aged 45 to 90+ in the US and UK

Abstract Introduction Sleep disturbances have been linked to dementia risk, yet given the long prodromal period of neurodegeneration, it remains unclear whether they represent early markers or modifiable risk factors. A life course approach provides a unique opportunity to disentangle these roles: sleep problems earlier in life are more likely to precede neurodegenerative changes, whereas altered sleep in older adulthood may reflect early neurodegeneration processes already underway. We examined how sleep complaints across different life stages relate to cognitive trajectories over 10-20 years in >15,000 adults aged 45–90+ from the US and UK. Methods We analyzed data from the English Longitudinal Study of Aging (ELSA), Whitehall II (WII), and the Memory and Aging Project (MAP). Subjective sleep measures included sleep duration, difficulty falling asleep, difficulty staying asleep, nocturnal awakenings, and waking unrefreshed. Cognition was repeatedly assessed and standardized to cohort-specific Z-scores. Participants with baseline dementia were excluded. We used linear mixed-effects models to test sleep x baseline age x follow-up time interactions, adjusting for demographics and follow-up length. Results In ELSA (N = 9,473, age 66.0±9.65, follow-up 7.66±3.44 years), difficulty falling asleep showed a significant interaction with age and time (P=0.03). Among adults < 60 years, difficulty falling asleep ≥1 time/week showed an additional 0.97-unit decline in verbal fluency over 10 years (SE [standard error] = 0.04), whereas among adults ≥70 years it was associated with 0.11-unit less decline (SE = 0.05). Similar age-dependent patterns were observed in WII (N = 4,155; age 55.6±5.97, follow-up 15.4±5.05 years) and MAP (N = 1,831; age 79.5±7.67, follow-up 5.43±4.47 years), where insomnia symptoms and < 6-hour sleep were associated with slower cognitive decline at older ages across domains. Findings remained robust after additional adjustment for lifestyle factors, comorbidities, sleep medication use, and APOE ε4 status. Conclusion Sleep complaints earlier in life were associated with faster cognitive decline, supporting their role as risk factors. At older ages, shorter and disturbed sleep were linked to slower decline, consistent with degeneration of wake-promoting neuronal systems in prodromal dementia. These findings highlight that the cognitive implications of sleep disturbances vary markedly across the life course. Support (if any) NIA (R01AG083836)