Sleep Impairment as a Modifiable Dementia Driver, With Bryce Mander, PhD

Sleep disorders like obstructive sleep apnea and chronic insomnia are established risk factors for Alzheimer's disease (AD), and emerging neuroimaging and biomarker data suggest sleep physiology is directly tied to the accumulation of AD pathology.

At SLEEP 2026 in Baltimore, Maryland, Bryce Mander, PhD, led a session titled “Sleep Impairment as a Modifiable Driver of Dementia: Neural, Glymphatic, and Clinical Pathways,” highlighting evidence extending beyond epidemiologic association. Disrupted sleep in at-risk individuals appears to amplify the cognitive consequences of underlying AD pathology, making sleep disturbance both a risk marker and a potential intervention target earlier in the disease course.

Sleep disorders are prevalent, underscreened, and often managed in isolation from cognitive risk. Mander's session reframes both as part of a shared neurodegenerative trajectory warranting integrated assessment.

Sleep Physiology, AD Biomarkers and Cognitive Effects in At-Risk Populations

Mander referenced data linking the brain's expression of sleep physiology to multiple pathophysiological features of AD. Neuroinflammatory markers, amyloid and tau protein accumulation, and synaptic integrity markers all show associations with how the brain generates and regulates sleep.¹ These relationships suggest sleep disruption is not simply a downstream symptom of neurodegeneration but may reflect and contribute to the underlying disease process.

"Sleep disorders like sleep apnea and chronic insomnia are known risk factors for Alzheimer's disease," Mander told Patient Care Online. "The people who are most vulnerable to the consequences of these sleep disorders are the people at risk for dementia."

The cognitive effects of sleep disorders appear more severe in individuals with elevated AD biomarkers. Patients with higher amyloid or tau burden experience greater cognitive impairment from the same degree of sleep disruption compared with those without elevated biomarker profiles. This interaction has direct implications for screening: a patient with new or worsening sleep complaints and a family history of AD or other risk factors may warrant closer cognitive surveillance than the sleep complaint alone would suggest.

Evidence for Sleep Disorder Treatment and AD Biomarker Modification

Whether treating sleep disorders can meaningfully reduce AD risk remains an open question, but early data provide a basis for cautious optimism. Small proof-of-concept studies have shown patients treated with continuous positive airway pressure (CPAP) for 2 years show cerebrospinal fluid (CSF) AD biomarker profiles more consistent with controls than with at-risk individuals, while untreated patients over the same period show biomarker trajectories consistent with disease progression.¹ Case-level data have also documented biomarker improvement following a year of CPAP initiation in patients with at-risk CSF profiles at baseline.

Mander called attention to the limitations of this evidence base, noting that large-scale phase 3 trials have not been completed, and existing data come from small studies without the statistical power to establish causation. Designing adequately powered trials presents a structural challenge: withholding treatment for sleep apnea in a symptomatic control arm is not ethically feasible, complicating placebo-controlled trial design.

"The big phase 3 trials haven't been done yet, and that's an important caveat," Mander said. "But we can see some of those effects can be reversed in smaller studies."

As such, Mander encourages clinicians to treat sleep disorders on their own clinical merits while recognizing their potential contribution to cognitive trajectory. His framing positions sleep health as a modifiable variable in a population where few such targets currently exist.²

Editors’ note: Mander reports relevant disclosures with Eisai Co and AstronauTx.

References

1. Mander B. Sleep impairment as a modifiable driver of dementia: neural, glymphatic, and clinical pathways. Presented at: SLEEP 2026; June 2026.

2. Lucey BP, Bateman RJ. Amyloid-β diurnal pattern: possible role of sleep in Alzheimer's disease pathogenesis. Neurobiol Aging. 2014;35(suppl 2):S29-S34. doi:10.1016/j.neurobiolaging.2014.03.035