Hope is the thing with feathers

I have been grappling with where I land on whether the hope that lecanemab offers outweighs its risks since it received full approval from the Food & Drug Administration (FDA) in 2023. It is a member of the class of monoclonal antibodies (mAbs) directed against amyloid for Alzheimer's disease (AD). I do not think that Emily Dickinson had medical decision-making in mind when she penned "Hope" is the thing with feathers,1 but for me, the poem captures how much hope colors my perceptions when discussing complex treatment options with clinicians. I am writing this as a potential patient, experienced care partner, and current CEO of the American Geriatrics Society (AGS), an organization dedicated to improving the health of all of us as we age. The story that I tell here is from my earliest days as a care partner—working at a major academic health center but lost in the wilderness of navigating healthcare with a person with complicated needs, my late aunt. In the 1990s, hope had me wheeling my aunt into a neurologist's office in search of both an answer to and a cure for what ailed her. I have a memory of learning that the symptoms that bedeviled my aunt, among them dementia with delusions of little people living in her ceiling, were likely due to scarring from her participation in a clinical trial with radiation to the brain to prevent further spread of her lung cancer. Hope for a cure flew away on that day and over the subsequent months and years as she declined cognitively and physically to the point where she needed skilled nursing. At the same time, I progressed from writing checks to making complex medical decisions, and, ultimately, making sure her death was as peaceful as possible by respecting her wishes.2 With lecanemab, hope is the thing that would push me to a yes because it is being positioned as a treatment that will potentially alter the trajectory of the cognitive decline that comes with an AD diagnosis. "I would not give you false hope," a lyric from Paul Simon's Mother and Child Reunion, perfectly captures how much the hope we humans carry for how medicines can alter our own disease trajectories is influenced by how the science for new treatments is rolled out to the public. In healthcare, false hope happens when experts and trusted organizations gloss over the negatives, risks, and unknowns when describing a course of treatment. It can happen when a conversation about a treatment plan or obtaining informed consent does not start with a discussion of "What matters to you." In the case of lecanemab, false hope comes about when trusted organizations state that they are expanding research criteria for diagnosing AD into a recommendation that these criteria are ready for use in clinical practice. The rationale they cite? We have a disease-altering therapy for this disease.3 It happens when the message from these same trusted organizations is that "[we have a drug that reduces] clinical decline by 27%" without explaining that it's not really the decline in your cognition that is being reduced.4 Rather, it is how well you perform or don't perform on a scale that rates the decline in your cognition due to AD. Without the context of how weak the evidence is,5 the omission of any framing around the slowing of decline being on a rating scale means that these trusted organizations are fanning those tiny hopeful feathers that have us searching for the cure for what ails us or our loved ones. Recently, I laid out eight questions I would ask if I was considering lecanemab for myself or for a loved one in a column I write for the quarterly AGS newsletter.6 If I were to sum those questions up, shared clinical decision-making should be framed by what matters to me and clinicians should be candid about what is known and unknown about my condition and about the potential ways that it could be treated. Would that every conversation about health care decisions that I need to make be as pragmatic as the discussions about surgery on my arthritic toe back in 2013. We talked about the risks and about the things that mattered to me—balancing long walks without pain against giving up cute little boots with kitten heels. Giving up the boots was well worth gaining back the long walks. If I were in the early stages of AD with capacity to participate in shared decision-making about lecanemab, I would hope that my clinician is well-versed in the trial data and what that data might mean for me. I would want them to tell me whether people like me had been included or excluded in trials; to be honest about the potential benefits and risks and the limits as to what is known about both; clear about the treatment costs; and clear about how receiving this treatment might impact my care needs and partners. Most importantly, I would want to know whether we have data that being treated with lecanemab would extend the time I have to live the life that I want to live in a meaningful way. At this juncture, that is a tall order for clinicians given that the Clarity AD trial enrolled mostly healthy people, and was under powered in terms of under-represented, minoritized individuals and older adults.7 This is why, as a patient advocate, I think it is critically important that we collect real-world data on mAbs as the Centers for Medicare & Medicaid Services (CMS) is requiring.8 The reality is that we do not currently have evidence that the slowing of the decline on a dementia rating scale results in an outcome that matters most to someone living with AD. One thing that I learned from that formative caregiving experience with my aunt is that sometimes the cure (an experimental lung cancer protocol) can save you from dying while leaving you with a passel of symptoms that prevent you from living the life that you thought you would live. Following that long ago visit to a neurologist, I took my aunt to see a geriatrician given her symptoms also included unsteadiness on her feet and urinary incontinence. That geriatrician and the team she pulled together focused on how best to support my aunt given the complexity of her symptoms and our family's desire for her to live in her apartment for as long as possible. As a result, we were able to give her more time with access to her own personal stash of Cool Whip than she might have had otherwise. That care team introduced me to a new way of thinking about health and aging long before I knew that AGS existed. As a caregiver, I have benefitted from the geriatrics whole-person approach with a focus on maintaining independence and function for us all as we age. This has given me hope that I will be equipped to make the right decisions, at the right time, and in the right place when it comes to my own health. So, what advice would I give to my future self on lecanemab? Despite my innate desire to leave some wiggle room for a "yes," my advice to her is that it should be a hard no on lecanemab—too much risk at too high of a cost, with too little meaningful benefit. Hope is perched in my soul telling me that this first generation of mAbs for AD is the precursor to drugs that will offer real therapeutic benefit for people living with AD and other dementias. Hope is in my heart that future clinicians across all specialties and disciplines will know that sometimes letting go of hope is the thing we may need to do to live our best lives possible in the time that we have left to live. The author is responsible for the opinions expressed in this commentary. The author wishes to thank G. Michael Harper, MD, Elvy Ickowicz, MPH, Paul Tatum, MD, MSPH, CMD, Heather Whitson, MD, MHS, and Eric A. Widera, MD for their critical review of the manuscript. The author also wishes to thank Aimee Cegelka, MA, and Anna Kim, LMSW for their assistance with manuscript preparation. The author has no conflicts of interest to disclose. None.