Regular use of statins is associated with a reduced risk for Alzheimer's, according to a study published in the journal JAMA Neurology on Monday. Statins are a class of drugs used to reduce low-density lipoprotein, LDL cholesterol, within the body. The drug works by inhibiting the enzyme involved in the body's ability to produce LDL cholesterol.
The significance of this reduction seems to vary based on sex and ethnicity, said Julie Zissimopoulos, an assistant professor at the University of Southern California's Sol Price School of Public Policy and lead author of the study.
"We found risk reduction was slightly higher for women compared to men. So for women, the risk reduction and the onset of Alzheimer's was 15%. For men, it was 12%," Zissimopoulos said, adding that for Hispanic men in particular, the size of the reduction was much larger at 29%.
However, "it's important to know that this is not a study that establishes causality, because it's not an experiment," she said. "It's really important to put this study in the context of where we are in Alzheimer's disease treatment and prevention, and there's still no treatment that exists to delay or prevent Alzheimer's disease."
Alzheimer's disease, the most common cause of dementia among older adults, damages memory and thinking skills. It is the sixth leading cause of death in the United States, according to the National Institute on Aging. More than 5 million Americans are estimated to have the disease.
Surprising differences across statins
The new study involved Medicare data on 399,979 statin users 65 or older. They had no diagnosis of Alzheimer's disease and used statins between 2006 and 2008. Whether or not each statin user was diagnosed with Alzheimer's was tracked in data from 2009 to 2013.
After analyzing the data, Zissimopoulos and her colleagues found that those who were exposed to higher levels of statins -- such as from filling more prescriptions than others in a given year -- were 10% less likely to have an Alzheimer's disease diagnosis in each of the subsequent five years than those with lower statin exposure.
Specifically, the statin drug simvastatin (sold under the brand name Zocor) was associated with a lower risk for white women, Hispanic women, black women, white men and Hispanic men. Atorvastatin (Lipitor) was associated with reduced risk among white, black and Hispanic women and Hispanic men. Pravastatin (Pravachol) and rosuvastatin (Crestor) were associated with reduced risk for only white women.
For black men, the sample size within the data was too small to identify any statistically significant reductions for any statin drug, Zissimopoulos said.
"All of the statins seem to have some risk reduction, although the findings are much more consistent for simvastatin and atorvastatin, meaning they consistently reduce the risk of Alzheimer's disease across men and women and across most race and ethnic groups," she said.
Simvastatin and atorvastatin are lipophilic, which means they can cross the blood-brain barrier to enter the brain, possibly holding clues to why these statin types showed a consistent association with reduced risk in the study.
Pravastatin and rosuvastatin, which are hydrophilic and may not cross the blood-brain barrier, were not as consistent, but they still showed some reduction.
"So there is reason to believe that any statin could have an impact," Zissimopoulos said. "We need more study to understand the differences across these statins."
Statins, an Alzheimer's preventer?
The new study gives further support to the idea that there is no "one size fits all" approach to Alzheimer's prevention, said Dr. Richard Isaacson, associate professor of neurology and director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian. He was not involved in the study.
"This is an important study as it tries to decode the puzzle of which statin drugs may be beneficial in different populations," Isaacson said. "There is an urgent need to address Alzheimer's risk now and not wait until a blockbuster drug comes."
This isn't the first time researchers speculated about an association between statins and Alzheimer's disease. However, there has not been a consensus among researchers.
"It's been controversial in the literature as to whether statins actually reduce cognitive decline with aging and, in particular, Alzheimer's disease, or whether they can be harmful," said Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging, who was not involved in the new study.
In 2012, the Food and Drug Administration approved changing the safety labels on cholesterol-lowering statin drugs to indicate that they come with potential cognitive side effects, such as reversible memory loss and confusion.
Many separate studies -- such as a 2000 study published in the journal JAMA neurology -- have suggested that statins might help to prevent Alzheimer's disease. Others -- including a 2008 study published in the journal Neurology -- have suggested that statins may not be related to incidence of Alzheimer's disease.
The new study, however, serves as a "strong building block" in favor of the argument that statins are associated with a reduced risk for developing Alzheimer's disease, said Petersen, of the Mayo Clinic.
"If somebody asks, 'Should I be taking a statin to prevent Alzheimer's disease?' I would say, 'Well, there are some data that indicate that, but I would rather have you take your statin if your primary physician says you need it for vascular purposes,' " Petersen said.
"There's a fair amount of literature now indicating that hypertension, particularly in midlife; obesity, particularly in midlife; smoking (and) diabetes are all risk factors for dementia, as well as they are for vascular disease and heart disease," he said. "So, we've certainly tried to make a case that taking care of yourself from a vascular perspective may have spillover benefits for the likelihood of your developing dementia or particularly Alzheimer's disease."
The association between lowered cholesterol with statin use and a reduced Alzheimer's disease risk seems to support the notion that "what's good for the heart is good for the brain," said Dr. Rudolph Tanzi, director of the Genetics and Aging Research Unit in the MassGeneral Institute of Neurodegenerative Diseases at Massachusetts General Hospital.
Hydrophilic statins, which don't cross the blood-brain barrier, still showed an association with reduced risk in the new study, which seems to suggest that a reduced risk may not stem solely from cholesterol levels in the brain but in the body as a whole. Statins may decrease not only cholesterol but also oxidative stress and inflammation.
"By just having a healthier heart and a healthier cardiovascular system -- meaning not just statins but exercise and diet and the like -- the message is the same, what's good for the heart is good for the brain, and I think this reinforces that," Tanzi said.
"I think this also relates to earlier findings this year that showed that Alzheimer's incidence has started to go down," he said. "We're getting older, so prevalence is going to go up. In other words, the number of cases is going to go up, because we're growing older ... but the fact that incidence, the percent of people getting it, is going down suggests that that's because we're living in a healthier way."