This month, the Food and Drug Administration changed the label for the recently approved Alzheimer’s treatment aducanumab — sold under the brand name “Aduhelm” — to specify that the controversial drug made by U.S. biotech company Biogen should be used only by patients with mild dementia or mild cognitive impairment. This should be no bar to widespread use, however, as recent efforts indicate that Biogen may be trying to persuade adults who occasionally misplace their keys that they not only have Mild Cognitive Impairment (MCI), but that MCI is an early form of Alzheimer’s disease.
“It’s Time We Know,” a purportedly educational website on MCI, was launched by Biogen and Japanese drugmaker Eisai, which co-promotes aducanumab, in early May, about a month before the drug was approved. This website states that 1 in 12 Americans aged 50 years and older have noticeable symptoms of MCI and that MCI is most commonly due to Alzheimer’s disease.
A review of medical literature suggests neither statement is true, and Biogen failed to provide any supporting information when we asked for it. In fact, there is no standardization in diagnosing MCI, and estimates of prevalence among people over 65 range from 3% to 22%. MCI is a risk factor for Alzheimer’s, but it is not necessarily Alzheimer’s, and it does not usually lead to Alzheimer’s. It is has many causes, including: medications, fatigue, depression, hypothyroidism, vitamin B12 deficiency and sleep apnea. Besides, MCI often remains stable or disappears.
We dare you to try to pass Biogen’s “Symptoms Quiz.” All 10 people we gave the test to (seven of whom were in their 20s), were advised to see their physician for memory testing after taking it. The survey asks how often certain conditions affect the reader or someone they care about, then lists, among other things:
“Losing train of thought or the thread of conversations, books, or movies”;
“Feeling depressed, irritable, impulsive, or anxious — mood changes that aren’t typical for you”;
And “becoming increasingly overwhelmed when making decisions, accomplishing tasks, or understanding instructions, including following a recipe or keeping track of monthly bills.”
From our observations, anyone experiencing even one of these common events once a week is given this recommendation: “If these symptoms concern you, then you may want to make an appointment with your doctor to discuss them and see if cognitive screening may be right for you.”
The site then asks for a ZIP code and directs people to several neurologists in their area. On the same page, one can also view local PET scanners and lumbar puncture testing centers. PET Scans and lumbar punctures are used to test for beta-amyloid plaques. Are Biogen and Eisai trying to expand the definition of MCI, encourage testing for plaque, and then sell the MCI plus plaque combo as an indication of Alzheimer’s? If so, that’s brilliant marketing, but it’s not based on any science we are aware of.
Plaque — essentially sticky bits in the brain — is more common in people with Alzheimer’s, but it is also common in people without Alzheimer’s. Many elderly people have plaque and no symptoms. Also, the amount of plaque doesn’t correlate with symptoms. Up to 50% of cognitively normal elderly people have typical signs of Alzheimer’s on autopsy. While this has been termed asymptomatic Alzheimer’s, no one who is (or was) cognitively normal should be given an Alzheimer’s diagnosis.
Given that the link between Alzheimer’s and plaque is unclear, it’s no surprise that none of the 25 trials of drugs that reduces plaque in Alzheimer’s patients has been successful in treating the disease. Aduhelm was approved on the basis of reducing plaque, but it has not been shown to improve cognition. It had a small effect of reducing clinical decline, possibly due to chance, in one of two large trials; the second showed no effect. Plaque doesn’t indicate future decline, either. In a study that followed people for up to 16 years, normal elderly people with plaque and pathologic brain changes typical of Alzheimer’s had the same risk of cognitive decline as those with no brain changes.
Although Aduhelm has not been approved for preventing Alzheimer’s, or to treat non-Alzheimer’s-related MCI, Biogen and Eisai’s “It’s Time We Know” website appears designed to ratchet up anxiety in anyone juggling multiple responsibilities or who gets distracted during small talk. Convincing perfectly normal people they should see a specialist, be tested for amyloid plaque and, if present, assume they have early Alzheimer’s is a great strategy for increasing Aduhelm prescriptions; the worried well outnumber the actual sick, and younger patients can potentially use the drug for decades. Luring people into testing for amyloid and then convincing them that MCI plus plaque equals early Alzheimer’s disease could lead to millions of prescriptions — and billions of dollars in profit — for an ineffective and expensive drug.
Patricia Bencivenga is a graduate student in Georgetown University’s program in Health and the Public Interest. Adriane Fugh-Berman is a professor in the departments of Pharmacology and Physiology and in the Department of Family Medicine at Georgetown University Medical Center, where she’s also the director of PharmedOut, a research and education project that promotes evidence-based prescribing.