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The search for drugs to prevent or delay Alzheimer’s disease has been a decades-long exercise in frustration, with promising candidate after promising candidate coming up short. A drug we already have on hand that’s highly effective at something else may stop Alzheimer’s — but we are nowhere close to getting it tested for that purpose and into the hands of patients.

From drugs aimed at clearing away brain deposits of an Alzheimer’s-linked protein called beta-amyloid to those targeting tau, another Alzheimer’s-linked protein, or easing inflammation or blocking certain neuroreceptors, billions of dollars have been spent in search of a blockbuster therapy, with disappointing results so far.


Meanwhile, many people who use cholesterol-lowering statins to fight heart disease seem to be on a slower track for developing Alzheimer’s than the rest of the population. Yet multiple hurdles make it difficult for researchers to undertake the definitive studies to determine whether and how to use these safe and inexpensive drugs to prevent Alzheimer’s.

Some trials testing whether statins could reverse Alzheimer’s failed to produce conclusive evidence. But they did not address whether taking statins decades before Alzheimer’s symptoms arise might prevent the disease.

Pharmaceutical companies lack the incentive to pay for expensive clinical trials to get older drugs approved for new uses. Why? Because many of them, like statins, are already off-patent, meaning they are sold at a low price.


We need to wake up to what is at stake.

With the status quo, the number of Americans over age 70 with Alzheimer’s will jump from 3.6 million to 9.1 million by 2050, according to research two colleagues and I have done using what’s called the Future Elderly Model. We predicted that annual costs for treating people with Alzheimer’s will top $1.5 trillion in 2050, which would devour the Medicare and Medicaid budgets.

A delay of Alzheimer’s onset by just one year would shrink the number of Americans with the disease by 1.3 million and save $219 billion annually.

Researchers have suspected for some time that a high level of cholesterol in the bloodstream might be linked to the accumulation of beta-amyloid plaques in the brain, one signature of Alzheimer’s. If statins can successfully reduce cholesterol levels and prevent heart disease, so the thinking goes, they could also influence the advent and advancement of Alzheimer’s.

To find out if that’s so, two other colleagues and I from the University of Southern California Schaeffer Center for Health Policy and Economics looked at the Medicare claims of 400,000 men and women who used a statin but who did not have Alzheimer’s before 2009. We followed them through 2013 to see which ones developed the disease.

Women with high statin use were 15 percent less likely, and men 12 percent less likely, to have been diagnosed with Alzheimer’s each year compared to individuals with little or no use of a statin.

The study, which was published in the December issue of JAMA Neurology, showed that some statins may be more effective at preventing or delaying Alzheimer’s disease than others. It also suggested that the effects of statins may depend on race and gender.

An important caveat: Because the study was not a randomized clinical trial, it does not provide the kind of cause-and-effect evidence about statins and Alzheimer’s disease the FDA needs to approve a new use for statins. Instead, we need randomized clinical trials to determine if statins truly do prevent or delay Alzheimer’s disease and, if so, which statin is most effective for which group(s) of patients, the optimum dosing levels, and at what age individuals need to start taking a statin to ward off Alzheimer’s.

Such trials should independently clarify the preventive and therapeutic effects of statins on the risk and progression of Alzheimer’s disease. Trials that use brain imaging, for example, may help identify how statins work in the brain and whether other therapeutic treatments may be needed after the onset of disease symptoms.

Some people with a family history of Alzheimer’s might be tempted to ask their doctors to prescribe a statin now on the basis of preclinical trial evidence. But that is mostly a nonstarter. Many physicians are rightly reluctant to prescribe drugs for off-label, unapproved indications, and insurance companies often refuse to cover the use of drugs for them.

The National Institutes of Health, other publicly funded entities, and public and private partners should take up the cause of new clinical trials for statins. And given the stakes for both Americans’ health and the federal budget, Congress should ensure that adequate funding is available for such trials.

At the same time, the FDA should take a new look at the powerful evidence available in so-called real world studies, such as the Schaeffer Center-led look at statins. Troves of data in the form of electronic medical records and insurance claims now exist for drugs that have been in use for many years. The recently passed 21st Century Cures Act took a step in this direction, requiring the FDA to establish a program for evaluating real world evidence to support the approval of existing drugs for new uses. Such a program could potentially reduce the costs associated with approval for such expanded use.

Alzheimer’s devastates millions of lives each year and threatens the foundations of our health care system. We should seize every opportunity to put speed bumps in its path.

Julie Zissimopolous, PhD, is associate director of the Leonard D. Schaeffer Center for Health Policy & Economics and vice dean of academic affairs at the Price School of Public Policy at the University of Southern California.

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