The Relationship Between Sleep, Cognition, and Dementia Risk in People With Focal Epilepsy.

BACKGROUND AND

OBJECTIVES

Sleep disruption and cognitive impairment are important comorbidities of focal epilepsy. However, the nature to which sleep affects cognition and long-term dementia risk in focal epilepsy, compared with other brain conditions, remains unclear. We examined the relationship between sleep, cognition, and dementia risk in patients with focal epilepsy compared with healthy controls and stroke patients.

METHODS

We conducted an analysis of the prospective UK Biobank cohort study, with baseline assessments performed between 2006 and 2010 and follow-up until 2021. Study groups were mutually exclusive participants with focal epilepsy and stroke at baseline assessment and healthy controls. Sleep characteristics included reports of sleep duration, obstructive sleep apnea, insomnia, napping, and dozing. Main outcomes were risk of incident all-cause dementia and Alzheimer disease from Cox proportional hazard modeling and comparison of executive function measures and brain total hippocampal and gray matter volumes using generalized linear modeling.

RESULTS

We examined a sample of 482,207 participants, aged between 38 and 72 years (mean [SD] 57.6 [8.1] years; 53.8% female), without dementia at baseline and a nested imaging subsample of 42,345 participants. Optimal sleep duration (6-8 hours) was associated with better executive function in control, focal epilepsy, and stroke groups. The impact of optimal sleep was significantly higher in individuals with focal epilepsy compared with controls (interaction term, p = 0.009), but not in the stroke group (interaction term, p = 0.574). Nonoptimal sleep was associated with worse executive function up to 8 years before the diagnosis of focal epilepsy. A 5-fold increased risk of developing dementia was seen in individuals with focal epilepsy and nonoptimal sleep (hazard ratio [HR] 5.15, 95% CI 3.77-7.04, p < 0.001) compared with healthy controls with optimal sleep. This was greater than in stroke individuals with poor sleep (HR 3.48, 95% CI 2.82-4.26, p < 0.001). Optimal sleep compared with nonoptimal sleep modified the dementia risk in in individuals focal epilepsy, with a significantly greater improvement compared with healthy controls (interaction term p = 0.017), while no significant difference was seen in the stroke group (interaction term p = 0.991).

DISCUSSION: Optimal sleep modified both cognitive performance and dementia risk in individuals with focal epilepsy compared with stroke patients and healthy controls. Based on self-reported sleep data, these findings suggest that improving sleep may be an impactful intervention to improve cognition and reduce dementia risk particularly in focal epilepsy.