LAUSR

Disrupted nighttime sleep (DNS) is common in narcolepsy type 1 (NT1), yet its impact on cognitive function is unknown. Given known associations between sleep-dependent memory consolidation and N2 sleep spindles, we hypothesized that NT1 impairs memory consolidation, due to fragmented N2 sleep and altered N2 sleep spindles in the NT1 group. In this case-control study, we trained n=23 NT1 participants [mean age 15.8 years (3.2)] and n=28 healthy control (HC) patients [13.6 years (3.7)] to criterion on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. NT1 participants could take SSRI/SNRI medication for cataplexy but were weaned off wake-promoting medications and excluded if on an oxybate. We extracted wake and sleep stage bout numbers from sleep and N2 spindle characteristics from the polysomnogram and conducted linear regression with memory consolidation results across groups. Adjusting for age, NT1 participants had longer sleep duration than HC, more N1%, lower N3%, higher Wake/N1 Index, as well as more bouts per hour of Wake, N1, N2, REM than controls (p’s < 0.04). Compared to HC, NT1 subjects had similar N2 spindle density, amplitude, and sigma power, but shorter duration of N2 spindles (p=0.009). More NT1 participants could not meet performance criterion on the initial learning task and required an easier memory task vs. HC (p=0.02) despite being older than HC. NT1 participants showed a trend for impaired memory consolidation vs. HC across a night of sleep after adjusting for age, gender, and total sleep time (p=0.07). Across groups, shorter N2 spindle duration (p=0.02) but not increased N2 bout number was associated with worse sleep-dependent memory consolidation. Compared to controls, NT1 participants showed encoding difficulties but only a trend difference in memory consolidation despite greater sleep fragmentation. NT1 participants had briefer N2 sleep spindles and overall, these shorter N2 spindles were associated with greater memory consolidation deficits. Future sleep therapeutic studies are needed to determine if sleep-dependent memory consolidation can be improved to address daytime cognitive problems in NT1 patients. Jazz Pharmaceuticals and National Institutes of Health grant 5K23NS104267-2