Associations of Chronic Insomnia, Longitudinal Cognitive Outcomes, Amyloid-PET, and White Matter Changes in Cognitively Normal Older Adults

BACKGROUND AND OBJECTIVES: The relationship between insomnia and cognitive decline is poorly understood. We investigated associations between chronic insomnia, longitudinal cognitive outcomes, and brain health in older adults. METHODS: From the population-based Mayo Clinic Study of Aging, we identified cognitively unimpaired older adults with or without a diagnosis of chronic insomnia who underwent annual neuropsychological assessments (z-scored global cognitive scores and cognitive status) and had quantified serial imaging outcomes (amyloid-PET burden [centiloid] and white matter hyperintensities from MRI [WMH, % of intracranial volume]). We used mixed-effects models to examine associations between baseline insomnia (independently or with interaction with self-reported changes in habitual sleep duration) and longitudinal cognitive z-scores, log-transformed WMH, and amyloid-PET levels while adjusting for multiple confounders, including sleep apnea diagnosis. The risk of incident cognitive impairment (CI) was estimated using the Cox proportional hazards model. RESULTS: We included 2,750 participants (mean 70.3 ± 9.7 years old, 49.2% female) in global cognition models and 2,814 in Cox models with median follow-up of 5.6 years. A total of 1,027 and 561 participants were included in WMH and amyloid-PET models, respectively. Insomnia was associated with a 0.011 per year (95% CI -0.020 to -0.001, p-interaction = 0.028) faster decline in global cognitive scores and 40% increased risk of CI (hazard ratio [HR] 1.4, 95% CI 1.07-1.85, p = 0.015). Insomnia with reduced sleep was associated with baseline cognitive performance (β = -0.211, 95% CI -0.376 to -0.046, p-interaction = 0.012), WMH (β = 0.147, 95% CI 0.044-0.249, p-interaction = 0.005), and amyloid-PET (β = 10.5, 95% CI 0.5-20.6, p-interaction = 0.039) burden. Insomnia participants sleeping more than usual (potentially indicating remission of symptoms) had lower baseline WMH burden (β = -0.142, 95% CI -0.268 to -0.016, p-interaction = 0.028). Insomnia was not associated with the rate of WMH or amyloid accumulation over time. In participants with insomnia, hypnotic use was not associated with cognitive scores (β = 0.016, 95% CI -0.201 to 0.233, p = 0.888) or incident CI (HR 0.94, 95% CI 0.5-1.6, p = 0.832). DISCUSSION: We found an association between insomnia, cognitive decline, and increased risk for CI. Insomnia with reduced sleep was associated with worse cognitive performance and poorer brain health (WMH and amyloid burden) at baseline. Sleeping more than usual was associated with lower WMH burden.