Clinical practice in the Alzheimer’s biomarker era: drugs for the brain and care for the mind

Alzheimer’s disease, unlike conditions like hypertension, must speak to be diagnosed. For much of the 20^th century, diagnosis required a person to recount a story of their own or their loved one’s disabling cognitive impairments, or dementia. The 21^st century discovery of mild cognitive impairment relaxed the need for disability. Persons experiencing simple inefficiencies in performing their usual and everyday activities could be diagnosed with Alzheimer’s disease. Spectacular advances in biomarker technologies measuring beta-amyloid and hyperphosphorylated tau proteins – together with neurodegeneration, the two pathological hallmarks of the disease – promise that someday, perhaps quite soon, persons who do not have any measurable cognitive impairments could be diagnosed with Alzheimer’s disease. In this issue of JAMA Network Open, the European Amyloid Imaging to Prevent Alzheimer’s Disease initiative, known as AMYPAD, reports its efforts to explain what this novel clinical practice might be like.¹

The authors report that telling a person with subjective cognitive decline that their brain has elevated levels of beta-amyloid does not cause notable increases in measures of anxiety or depression. “Subjective cognitive decline” describes a kind of liminal existence; a person is neither healthy nor impaired. Definitions vary, unfortunately, but this study described a person with at least five years of bothersome cognitive problems whose metric assessments of cognition showed no impairments.

Knowledge of elevated amyloid wasn’t benign, however. It precipitated increases on the Impact of Events Scale, a measure of the distress precipitated by witnessing a traumatic event. Persons endorsed a host of behaviors and moods such as feeling preoccupied or distracted with the information and seeking to avoid the topic. This finding recapitulates similar studies of beta-amyloid disclosure.²

Persons who learned a “not elevated” result have none of these experiences.³ They uniformly describe one feeling: “relief.” Their mind at ease, they reinterpret their cognitive problems as “normal aging.” The event fades and is soon forgotten.

In contrast, persons with an elevated amyloid experience a change of mind. They report an increase in their estimated lifetime risk of developing dementia. They want metric data, not just a report of “elevated amyloid.”⁴ Some develop a preoccupation with their future.⁵ They think over plans for retirement, leisure, and living arrangements with attention to proximity to friends and family. Concerns of stigma and discrimination cause them to discern with whom they may share the result.

AMYPAD recruited persons with a positive biomarker test for drug studies seeking an intervention to prevent or delay the onset of cognitive impairments caused by neurodegenerative diseases. Prevention is inspiring. This is goal No. 1 of the U.S. national Alzheimer’s plan, after all: to discover treatments that will effectively prevent these diseases.

Should one of these clinical trials succeed, disclosing Alzheimer’s disease biomarker results to persons with subjective cognitive decline will move from clinical research into clinical practice. A drug that reduces the risk of dementia ought to palliate the adverse feelings associated with learning one is at risk of dementia, but short of a cure for each and every disease of the aging brain, people will need to live with their risk of transitioning from subjective to objective cognitive impairments.

They’re going to need care. But what should it look like?

Studies of the impact of learning Alzheimer’s biomarker information describe the features of this care. The participants in the AMYPAD study received care at a memory center where they received expert education about Alzheimer’s disease and amyloid. They underwent an assessment of their mood and well-being. The test result was disclosed in the context of a relationship with a clinician with expectations of follow-up. I presume persons whose Impact of Events score was sufficiently elevated received additional follow-up.

Often, another person – a friend or family member – was present at these visits. In Alzheimer’s disease research, this person is called a study partner. In Alzheimer’s clinical practice, they’re typically called a caregiver or care partner. For persons with subjective cognitive decline, nomenclature is a work in progress. They’re sometimes called “pre-caregivers,” but that term is at least odd.⁶ “Supporter” gets closer to the mark. Whatever the name, a person who knows they are at risk of developing dementia ought to have others involved in their life. These people will monitor them and help them plan how to manage problems performing activities of daily living.

Notably, the AMYPAD investigators report Impact of Event scores were higher in persons who had a study partner present. This result makes sense. Knowledge of a biomarker that increases one’s lifetime risk of developing disabling cognitive impairments is an important event not only for the person with beta-amyloid but the people who might be expected to care for that person.⁷ They experience the event much like the person who has elevated beta-amyloid. I can imagine these people talking about and even struggling with the information. Alzheimer’s disease affects one brain and at least two minds, the patient and their caregiver.

To help these minds make sense of and live with this life event, they’ll all need care. It should begin with having sufficient space and chairs in the exam room for at least two people. There, they should meet with a variety of clinicians, such as social workers, skilled in talking about the things that make a life well lived. These conversations could guide them to think about who to share results with and how to plan for their futures. In the months to follow, if they feel a sense of direction and purpose in their lives, if they enjoy making plans and working to make them a reality, we can conclude they’ve received quality care.