By Dr. K. Nicole Mims, board-certified sleep physician
At a recent Mahjong for Memories Alzheimer's fundraiser event I was involved in, I gave a short talk on how sleep and Alzheimer’s intersect. It didn't get recorded, so I recorded it afterward. This isn't an overarching review. It's hyper-focused on one piece of the story: a class of sleep medications called DORAs.
And to be fair, the best talks at the event belonged to Jennifer and Tim, who spoke movingly about their spouses who developed early-onset Alzheimer's.
Sleep and Alzheimer's: a two-way street
Sleep and Alzheimer's disease affect each other in both directions. The Sleep Education website has a great graphic on this, and it's a good resource for lots of sleep questions.
One of the main things sleep does is clear waste from the brain, including beta-amyloid proteins. Beta-amyloid can clump together into plaques, which contribute to Alzheimer's disease. Those plaques can also cause inflammation in nerve cells, which can disrupt the sleep-wake system and make sleep harder. Worse sleep means less waste clearance, and the loop feeds itself.
What orexin does
To understand DORAs, we need to talk about orexin. Orexin is a neurotransmitter in the brain that tells us to wake up. The best way to understand it is to look at people who don't have enough of it: they can develop narcolepsy. Think Sleepy the Dwarf. They're very sleepy, they want to fall asleep all the time, and even after a refreshing nap, they're sleepy again a couple of hours later.
Some smart pharmaceutical scientists saw that loss of function and asked: what if we turned it into a tool for people who have trouble sleeping, by blocking the wake signal?
How DORAs work
DORA stands for dual orexin receptor antagonist. These medications block orexin's receptors, which quiets the brain's "stay awake" signal. Three are on the market in the U.S.: suvorexant, lemborexant, and daridorexant.
Orexin isn't just an on switch. It also helps regulate the sleep-wake cycle. That matters in Alzheimer's, because many patients experience sundowning and a flipped circadian rhythm, awake at night and asleep during the day. That can be very distressing for patients and their caregivers.
In a randomized trial of 285 people with probable Alzheimer's dementia and insomnia, suvorexant improved total sleep time measured in a sleep lab by about 28 minutes more than placebo after four weeks. Reviewers also describe DORAs as having a good tolerability profile without signs of rebound insomnia or dependence, compared with older drug classes like benzodiazepines and Z-drugs.
New research: DORAs and Alzheimer's
Here's why researchers are excited. A 2025 review in npj Biological Timing and Sleep (Ragsdale et al.) laid out the case that DORAs could ease Alzheimer's-related sleep problems and possibly support the brain's waste clearance during sleep. In mouse models, suvorexant reduced amyloid buildup and improved memory measures, and a small human study found it acutely lowered tau phosphorylation and amyloid in spinal fluid.
But be clear on where we are: there's no Alzheimer's indication for these drugs yet. The review notes that clinical evidence for an Alzheimer's-specific benefit is limited and long-term effects are still unknown. Trials, including a phase II study of lemborexant in cognitively normal older adults with amyloid, are under way.
Key takeaways
Sleep and Alzheimer's affect each other in both directions.
During sleep, the brain clears waste proteins like beta-amyloid.
Orexin keeps us awake and also regulates the sleep-wake cycle.
DORAs block orexin receptors and are being studied as a possible Alzheimer's therapy. No indication yet.
Talk to your doctor
This post is educational, not medical advice. If you or a loved one is struggling with sleep, especially alongside memory changes, talk to your doctor about what's right for you. If you're in Alabama or North Carolina, we'd be glad to help at Luminary Sleep.
References
Ragsdale SM, Radovich JM, Coiduras II, McCall WV, et al. Dual orexin receptor antagonists as promising therapeutics for Alzheimer's disease. npj Biological Timing and Sleep. 2025;2:11. doi:10.1038/s44323-025-00025-5
Herring WJ, et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial. Alzheimer's & Dementia. 2020. https://pmc.ncbi.nlm.nih.gov/articles/PMC7984350/
ClinicalTrials.gov. DORA and LP in Alzheimer's Disease Biomarkers (NCT06274528). https://clinicaltrials.gov/study/NCT06274528
Carvalho DZ, et al. Associations of Chronic Insomnia, Longitudinal Cognitive Outcomes, Amyloid-PET, and White Matter Changes in Cognitively Normal Older Adults. Neurology. 2025;105(7):e214155. doi:10.1212/WNL.0000000000214155
Sleep Foundation. Alzheimer's Disease and Sleep. https://www.sleepfoundation.org/physical-health/alzheimers-disease-and-sleep