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The FDA fast-tracked its approval of Biogen’s Aduhelm earlier this summer. (Dreamstime/TNS)

The approval of a controversial new drug for Alzheimer’s disease, Aduhelm, is shining a spotlight on mild cognitive impairment (MCI) — problems with memory, attention, language or other cognitive tasks that exceed changes expected with normal aging.

After initially indicating that Aduhelm could be prescribed to anyone with dementia, the Food and Drug Administration now specifies that the prescription drug be given to individuals with MCI or early-stage Alzheimer’s, the groups in which the medication was studied.

Yet this narrower recommendation raises questions: What does a diagnosis of MCI mean? Is Aduhelm appropriate for all people with MCI, or only some? And who should decide which patients qualify for treatment — dementia specialists or primary care physicians?

Debate surrounds Aduhelm because its effectiveness has not been proven, its cost is high (an estimated $56,000 a year, not including expenses for imaging and monthly infusions), and its potential side effects are significant (41 percent of patients in the drug’s clinical trials experienced brain swelling and bleeding).

Furthermore, an FDA advisory committee strongly recommended against Aduhelm’s approval, and Congress is investigating the process leading to the FDA’s decision. Medicare is studying whether it should cover the medication, and Veterans Affairs has declined to do so under most circumstances.

Clinical trials for Aduhelm, developed by Biogen, based in Cambridge, Mass., excluded adults over 85, people taking blood thinners, people who had experienced a stroke, and those with cardiovascular disease or impaired kidney or liver function, among other conditions. If those criteria were broadly applied, 85 percent of people with MCI would not qualify for the drug, according to a research letter in the Journal of the American Medical Association.

Given these considerations, carefully selecting patients with mild cognitive impairment who might respond to Aduhelm is “becoming a priority,” said Kenneth Langa, a professor of medicine, health management and policy at the University of Michigan.

Ronald Petersen, who directs the Mayo Clinic’s Alzheimer’s Disease Research Center, said, “One of the biggest issues we’re dealing with since Aduhelm’s approval is, ‘Are appropriate patients going to be given this drug?’”

Here’s what people should know about MCI based on a review of research studies and conversations with leading experts:

Basics

Mild cognitive impairment is often referred to as a borderline state between normal cognition and dementia. But this can be misleading. Although a significant number of people with mild cognitive impairment eventually develop dementia — usually Alzheimer’s disease — many do not.

Cognitive symptoms — for instance, difficulties with short-term memory or planning — are often subtle, but they persist and represent a decline from previous functioning. Yet a person with the condition may still be working or driving and appear entirely normal. By definition, mild cognitive impairment leaves intact a person’s ability to perform daily activities independently.

According to an American Academy of Neurology review of dozens of studies, published in 2018, mild cognitive impairment affects nearly 7 percent of people 60 to 64, 10 percent of those 70 to 74 and 25 percent of those 80 to 84.

Causes

Mild cognitive impairment can be caused by biological processes (the accumulation of amyloid beta and tau proteins and changes in the brain’s structure) linked to Alzheimer’s disease. Between 40 percent and 60 percent of people with mild cognitive impairment have evidence of Alzheimer’s-related brain pathology, according to a 2019 review.

But cognitive symptoms can also be caused by other factors, including small strokes; poorly managed illnesses such as diabetes, depression and sleep apnea; responses to medications; thyroid disease; and unrecognized hearing loss. When these issues are treated, normal cognition may be restored or further decline forestalled.

Diagnosis

Usually, this process begins when older adults tell their doctors that “something isn’t right with my memory or my thinking” — a “subjective cognitive complaint.”

Short cognitive tests can confirm whether objective evidence of impairment exists. Other tests can determine whether a person is still able to perform daily activities successfully.

More sophisticated neuropsychological tests can be helpful if there is uncertainty about findings or a need to better assess the extent of impairment. But “there is a shortage of physicians with expertise in dementia — neurologists, geriatricians, geriatric psychiatrists” — who can undertake comprehensive evaluations, said Kathryn Phillips, director of health services research and health economics at the University of California at San Francisco’s School of Pharmacy.

The most important step is taking a careful medical history that documents whether a decline in functioning from an individual’s baseline has occurred and investigating possible causes such as sleep patterns, mental health concerns and inadequate management of chronic conditions that need attention.

Progression

Mild cognitive impairment doesn’t always progress to dementia, nor does it usually do so quickly. But this isn’t well understood. And estimates of progression vary, based on whether patients are seen in specialty dementia clinics or in community medical clinics and how long patients are followed.

One review of 41 studies found that 5 percent of patients treated in community settings each year went on to develop dementia. For those seen in dementia clinics — typically, patients with more serious symptoms — the rate was 10 percent. The American Academy of Neurology’s review found that, after two years, 15 percent of patients were observed to have dementia.

Progression to dementia isn’t the only path people follow.

A sizable portion of patients with mild cognitive impairment — from 14 to 38 percent — are discovered to have normal cognition upon further testing.

Only people with MCI associated with Alzheimer’s should be considered for treatment with Aduhelm, experts agreed.

“I think, for the early rollout of a complex drug like this, treatment should be overseen by specialists, at least initially,” the Mayo Clinic’s Petersen said.

This report is a product of Kaiser Health News, a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.