One of the few drugs that has been FDA-approved for patients with Alzheimer’s disease now identified as possibly increasing risk of a life-threatening condition of muscle breakdown

Many people with Alzheimer’s disease take the drug donepezil (brand name Aricept) to help ease symptoms for a time. But those on the drug should be aware of a rare but potentially life-threatening side effect. The drug can cause muscles to break down, leading to a condition called rhabdomyolysis that can lead to kidney damage and even death.

The risk of hospitalization for rhabdomyolysis was more than double that for those taking Aricept compared to other Alzheimer’s drugs, a new study reports.

Still, the condition is very rare, and anyone taking Aricept should not stop taking it. But because rhabdomyolysis is potentially very serious, patients should be aware of the problem and seek medical care should symptoms arise.

The main symptom of rhabdomyolysis, or rhabdo as it is commonly called, is intense muscle pain or weakness that does not go away. Urine can also turn dark. Emergency treatment is needed to manage the condition and may require a week or longer stay in the hospital.

For the study, Canadian researchers analyzed data on 220,353 men and women over age 65 who had gotten a prescription between 2002 and 2017 for one of three Alzheimer’s drugs: donepezil, rivastigmine (Execlon) or galantamine (Razadyne).

There were 88 hospitalizations for rhabdo among 152,300 patients taking donepezil (0.06 percent prevalence), compared to 16 cases among the 68,053 patients taking one of the other drugs (0.02 percent prevalence).

The authors note that doctors should rule out rhabdo if someone on an Alzheimer’s drug comes to the hospital because of constant muscle pain. Still, the condition remains very rare (about 25,000 per year in the U.S. from all causes), and most of the cases in the current study were not life-threatening.

Other medications may also trigger the condition, including antipsychotic medications, which are also often prescribed to people with Alzheimer’s disease to allay symptoms like agitation and aggression. Cholesterol-lowering statin drugs have also been tied to an increased risk of rhabdo. It is possible that Aricept cannot trigger rhabdo alone. Further studies will be required to determine what other cofactors might act with Aricept to trigger rhabdo.

The condition more commonly arises after intense physical exertion, often in people who have not been training regularly. The condition can arise in military recruits undergoing basic training, and in people beginning high-intensity workouts at the gym.

By, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Jamie L. Fleet, Eric McArthur, Aakil Patel, et al: “Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study.” CMAJ – Canadian Medical Association Journal, Sept. 16, 2019

A protein in skeletal muscles helps mice recover from sleep deprivation.



The protein Bmal1, which helps regulate the body’s internal clock, is found in especially high levels in the brain and in skeletal muscles. Mice completely deficient in Bmal1 were known to suffer from sleep impairments, but the specifics at play weren’t clear. At the University of California, Los Angeles, Ketema Paul and colleagues looked to these mice for clues about the role Bmal1 plays in sleep regulation.

When Paul’s team restored levels of the Bmal1 protein in the mice’s brains, their ability to rebound from a night of bad sleep remained poor. However, turning on production in skeletal muscles alone enabled mice to sleep longer and more deeply to recover after sleep loss.

For decades, scientists have thought sleep was controlled purely by the brain. But the new study indicates the ability to catch up on one’s sleep after a bout of sleeplessness is locked away in skeletal muscles, not the brain—at least for mice. “I think it’s a real paradigm shift for how we think about sleep,” says John Hogenesch, a chronobiologist at Cincinnati Children’s Hospital Medical Center who discovered the Bmal1 gene but was not involved in this study.

Paul’s group also found that having too much of the Bmal1 protein in their muscles not only made mice vigilant but also invulnerable to the effects of sleep loss, so that they remained alert even when sleep-deprived and slept fewer hours to regain lost sleep. “To me, that presents a potential target where you could treat sleep disorders,” says Paul, noting that an inability to recover from sleep loss can make us more susceptible to diseases.

The paper
J.C. Ehlen et al., “Bmal1 function in skeletal muscle regulates sleep,” eLife, 6:e26557, 2017.–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129