Sleeping Pill Lowers Alzheimer's Proteins in New Study

Disruptions in sleep patterns often serve as an initial indicator of Alzheimer's disease. Individuals who are later diagnosed with this condition frequently encounter challenges in initiating and maintaining sleep well before the onset of cognitive deficits like memory impairment and disorientation.

Disruptions in sleep patterns often serve as an initial indicator of Alzheimer's disease. Individuals who are later diagnosed with this condition frequently encounter challenges in initiating and maintaining sleep well before the onset of cognitive deficits like memory impairment and disorientation. This creates a harmful feedback loop: the neurological alterations caused by Alzheimer's interfere with normal sleep cycles, while inadequate rest exacerbates detrimental brain modifications.

Scientists from Washington University School of Medicine in St. Louis have discovered a promising method to interrupt this damaging cycle. In a compact two-night clinical trial, participants who consumed a sleeping pill prior to bedtime showed notable reductions in concentrations of critical Alzheimer's-associated proteins. This outcome is positive because elevated levels of these proteins correlate strongly with disease progression. The trial utilized suvorexant, a sleep aid already authorized by the Food and Drug Administration for treating insomnia, suggesting that such medications might help decelerate or even halt Alzheimer's advancement. Nevertheless, extensive additional research is essential to validate this strategy's effectiveness.

The findings appear in the April 20 edition of Annals of Neurology.

'This represents a preliminary proof-of-concept investigation. It would be unwise for those concerned about Alzheimer's risk to view these results as justification for nightly suvorexant use,' explained lead researcher Brendan Lucey, MD, an associate professor of neurology and head of Washington University's Sleep Medicine Center. 'We lack data on whether prolonged administration prevents cognitive deterioration, including optimal dosing and suitable patient profiles. That said, these preliminary outcomes are highly promising. The medication is readily accessible, established as safe, and now demonstrated to influence proteins pivotal to Alzheimer's pathology.'

Suvorexant is categorized among dual orexin receptor antagonists, a group of drugs designed for insomnia treatment. Orexin, a naturally occurring molecule, stimulates alertness. Inhibiting orexin facilitates sleep onset. Currently, the FDA has greenlit three such inhibitors, with others under development.

The pathological process of Alzheimer's initiates with the aggregation of amyloid beta protein plaques within brain tissue. Following extended amyloid buildup, another protein called tau forms neurotoxic tangles. Cognitive manifestations, including forgetfulness, typically arise concurrently with detectable tau tangles.

Lucey and his team were pioneers in demonstrating, in human subjects, that suboptimal sleep correlates with increased amyloid and tau in the brain. Whether enhanced sleep quality conversely diminishes these proteins—potentially slowing, stopping, or reversing Alzheimer's trajectory—remains under investigation. However, experiments in rodents using orexin blockers have yielded optimistic results.

To evaluate orexin inhibitors' impact in humans, Lucey and collaborators enrolled 38 cognitively intact individuals aged 45 to 65 for a two-night sleep assessment. At 9 p.m., participants received either a 10 mg dose of suvorexant (13 subjects), a 20 mg dose (12 subjects), or a placebo (13 subjects), then retired in a specialized clinical facility at Washington University. Investigators collected cerebrospinal fluid samples via lumbar puncture every two hours over 36 hours, commencing one hour prior to drug or placebo administration, to track fluctuations in amyloid and tau concentrations throughout the ensuing day and a half.

In those administered the higher 20 mg dose of suvorexant, cerebrospinal fluid amyloid levels decreased by 10% to 20% relative to the placebo cohort. Similarly, levels of hyperphosphorylated tau—a particularly harmful variant—declined by 10% to 15% compared to placebo recipients. These reductions achieved statistical significance. No meaningful disparities emerged between the low-dose suvorexant group and the placebo group.

Twenty-four hours post-initial dose, hyperphosphorylated tau concentrations in the high-dose cohort had rebounded, though amyloid remained suppressed versus placebo. Administering a second suvorexant dose on the subsequent night again lowered both protein levels in the high-dose participants.

'Consistent daily reductions in amyloid could gradually diminish plaque buildup in the brain,' Lucey noted. 'Hyperphosphorylated tau plays a crucial role in Alzheimer's etiology, as it contributes to tangle formation that destroys neurons. Mitigating tau phosphorylation might curtail tangle development and subsequent neuron loss.'

Given its limited scope—examining just two doses in a modest sample—this research is exploratory. Lucey is now conducting trials to probe extended orexin inhibitor effects in dementia-prone populations.

'Upcoming research must involve months-long drug regimens, monitoring amyloid and tau dynamics longitudinally,' Lucey emphasized. 'We plan to include older adults who are cognitively intact yet harbor amyloid plaques. Our current trial featured healthy midlife participants; outcomes could vary in seniors.'

'I remain optimistic about harnessing the sleep-Alzheimer's connection to avert cognitive decline with targeted therapies,' he added. 'We're not at that stage yet. For now, my recommendation is prioritizing quality sleep; if issues persist, consult a sleep specialist for tailored interventions.'