Controversy surrounds Aduhelm because its effectiveness hasn’t been proved, its cost is high – an estimated US$56,000 a year, not including expenses for imaging and monthly infusions – and its potential side effects are significant (41 per cent of patients in the drug’s clinical trials experienced brain swelling and bleeding).

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

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Here’s what people should know about mild cognitive impairment based on a review of research studies and conversations with leading experts.

The 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 per cent of people ages 60 to 64, 10 per cent of those 70 to 74 and 25 per cent of 80- to 84-year-olds.

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 per cent and 60 per cent of people with mild cognitive impairment have evidence of Alzheimer’s-related brain pathology, according to a 2019 review.

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Subtypes

During the past decade, experts have identified four subtypes of mild cognitive impairment. Each subtype appears to carry a different risk of progressing to Alzheimer’s disease, but precise estimates haven’t been established.

People with memory problems and medical issues who are found to have changes in their brain through imaging tests are thought to be at greatest risk.

“If biomarker tests converge and show abnormalities in amyloid, tau and neurodegeneration, you can be pretty certain a person with MCI has the beginnings of Alzheimer’s in their brain and that disease will continue to evolve,” said Dr Howard Chertkow, chairman for cognitive neurology and innovation at Baycrest, an academic health sciences centre in Toronto, Canada, that specialises in care for older adults.

Diagnosis

Usually, this process begins when older adults tell their doctors that “something isn’t right with my memory or my thinking” – known as 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.

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.

Mild cognitive impairment “isn’t necessarily straightforward to recognise, because people’s thinking and memory changes over time [with advancing age] and the question becomes ‘Is this something more than that?’” said Dr Zoe Arvanitakis, a neurologist and director of Rush University’s Rush Memory Clinic in Chicago.

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Progression

Mild cognitive impairment doesn’t always progress to dementia, nor does it usually do so quickly. But this isn’t well understood.

Progression to dementia isn’t the only path people follow. A sizeable proportion of patients with mild cognitive impairment – from 14 per cent to 38 per cent – are discovered to have normal cognition after further testing.

Another group remains stable over time. (In both cases, this may be because underlying risk factors – poor sleep, for instance, or poorly controlled diabetes or thyroid disease – have been addressed.)

Still another group of patients fluctuate, sometimes improving and sometimes declining, with periods of stability in between.

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“You really need to follow people over time – up to 10 years – to have an idea of what is going on with them,” said Dr Oscar Lopez, director of the Alzheimer’s Disease Research Centre at the University of Pittsburgh.

Specialists versus generalists Only people with mild cognitive impairment associated with Alzheimer’s should be considered for treatment with Aduhelm, experts agreed. “The question you want to ask your doctor is, ‘Do I have MCI [mild cognitive impairment] due to Alzheimer’s disease?’” Chertkow said.

Because this medication targets amyloid, a sticky protein that is a hallmark of Alzheimer’s, confirmation of amyloid accumulation through a PET scan or spinal tap should be a prerequisite. But the presence of amyloid isn’t determinative: one-third of older adults with normal cognition have been found to have amyloid deposits in their brains.