Association of tau burden with sleep disordered breathing in adults with Down syndrome
Anna C. Smith, Sigan Hartley, David T. Plante, Aubrey S. Johnson, Diana S. Guzmán, Amarachukwu Okafor, Samantha Rossano, Dana Tudorascu, Adam M. Brickman, Bradley T. Christian, Ozioma Okonkwo, Beau Ances, Annie Cohen, Benjamin L. Handen, Patrick J. Lao- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Adults with Down syndrome (DS) overproduce the amyloid precursor protein and nearly all evidence clinical symptoms of Alzheimer’s Disease (AD) dementia in later life. Sleep disordered breathing, and specifically, obstructive sleep apnea (OSA), is common in adults with DS. OSA has been associated with risk of AD in adults without DS, and sleep disturbances may have a bidirectional relationship with AD pathology. We hypothesized that greater tau burden is associated with subsequent sleep disordered breathing in a time‐lagged design.
Methods
Eighty young adults with DS (37±8 yrs, 49% women, 94% cognitively‐stable/6% MCI‐DS) from the ABC‐DS study underwent tau PET ([18F]‐AV1451, Braak stage SUVRs) and were assessed 4±0.7 years after PET using WatchPAT home sleep testing. Sleep variables included oxygen desaturation index (ODI) and apnea‐hypopnea index (AHI). General linear models assessed tau burden on later sleep impairments. Models were run in the whole group and the cognitively‐stable group alone, with and without age adjustment. Analyses were run using overall sleep measures and those in REM and non‐REM (NREM) sleep separately.
Results
In unadjusted models, greater tau in early, middle, and late Braak stages were associated with a higher ODI, while greater tau in middle Braak stages was associated with a higher AHI. In the cognitively‐stable group alone, greater tau in early and middle, but not late, Braak stages were associated with a higher ODI, while greater tau in middle Braak stages was associated with a higher AHI. Adjusting for age, greater tau in late Braak stages was associated with ODI in the whole group and the cognitively‐stable group alone. Associations for overall sleep measures were driven by NREM measures (Table 1).
Conclusion
In adults with DS with a high prevalence of OSA, tau burden was associated with subsequent intermittent nocturnal hypoxemia as measured by the ODI during NREM sleep. These findings align with those in adults without DS, linking AD pathology, disturbed sleep, witnessed apneas, and nocturnal hypoxemia. Both longitudinal and randomized studies are required to clarify cause‐effect relationships, including the presence of mediating and/or moderating variables such as reduction in sleep depth or continuity.