Eugenia Zukerman, flute virtuoso, author and television music reporter, has clinical Alzheimer’s disease (AD). She has openly discussed her condition with the media, and wrote about it in her latest book, “Like Falling Through a Cloud: A Lyrical Memoir,” published late last year.
Her sister, Dr. Julie Ingelfinger, recently wrote a moving NEJM Perspective about Eugenia and their mother, who also developed dementia. She quotes Eugenia’s writing, about the stigma of an Alzheimer’s diagnosis: “When I was a kid, the dark cloud no one dared mention was cancer … the ultimate exclusion from a social life. I hope that someday soon, ‘I have Alzheimer’s’ will be said with a strong voice and clear determination to eliminate it.”
This eloquently personalizes three current dilemmas: 1) there is a social awkwardness attached to the clinical diagnosis; 2) there is currently no way to eliminate the cognitive effects of dementia; and 3) there is a stark contrast in the development of dementia therapies compared to current cancer therapies.
[photo: Vaughn Nelson, cropped, CC BY-NC-SA 2.0 from flickr.com]
Dr. Ingelfinger, an academic physician at Harvard, calls for adult cognitive screening, a “kinder, gentler” approach to care, and points out the lack of disease-modifying therapy for her sister or anyone else with dementia.
To her point on adult cognitive screening, just months ago the US Preventive Services Task Force could not recommend screening, writing “the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment in older adults.” JAMA published the results of their comprehensive meta-analysis.
What might be the harms of screening? For working adults, and those needing on-going health insurance here, the harms might be economic. Then, as Zukerman points out, there might be an issue with social awkwardness. There may be significant depression and suicidal ideation in screening for terrible diseases with no current therapy, like Huntington’s disease.
[Parenthetically, Dr. Nancy Wexler, who helped develop the Huntington’s genetic test, made a determined, thoughtful choice to abstain from her own test for decades. Without a therapy, she said she didn’t think she would be significantly happier if results showed she wouldn’t develop the disease, implying she might be quite sad with a result showing she would. That recently changed, when she developed movement problems, with a promising credible therapy on the horizon.]
Ingelfinger also notes the projected needs of burgeoning numbers of people living with dementia, even without screening already estimated at over 5 million in the US. On an individual level, she cites the work of Dr. Tia Powell, an academic psychiatrist who writes of focusing on an AD person’s abilities and adaptations as an approach to care. In the UK, a Lancet review encourages the early involvement of a palliative care approach.
Although Ingelfinger notes that there is no cure, she mentions on-going studies in genetics and neuroscience. She does state: “The National Academy of Medicine suggests that sufficient evidence supports physical exercise, keeping an active mind, controlling other health issues, and optimizing nutrition to delay or prevent dementia onset.”
The National Academy of Medicine (NAM) happened to be the subject of a NEJM Perspective piece the very next week, written by Fauci and Lane. The authors describe the impact of NAM scientific strategy and leadership in the amazing progress against HIV/AIDS, once rapidly fatal, and for the development of current life-prolonging and preventative therapies.
So why hasn’t clinical therapy in AD or related dementias advanced at all, given the contemporary progress and success in AIDS and cancer?
Of course, the brain remains a tantalizing “black box” which has never yielded easily. Many neurologic conditions, including brain infections, brain trauma and brain tumors seem different than similar problems in other parts of the body. Is the black box really intractable?
Could funding for research be part of the issue? At the NIH, AD only achieved the $2B level in 2018 (combining the National Institute of Aging (NIA) and others), while the National Cancer Institute (NCI) budget was about $6B. Both emphasize basic research, as one would properly expect, but both are critical funding sources for the clinical end of research.
Here the differences are perhaps more telling. In budget statements to Congress, the NIA describes the need to fund a patient recruitment initiative, whereas the NCI touts already recruiting well over 30,000 patients in clinical trials.
Cancer has its “moonshot” funding, but Alzheimer’s has a goal with a deadline: effective therapy by 2025. Smart people have been working on it: The National Plan to Address Alzheimer’s was updated in October 2019, and the National Alzheimer’s Project Act Advisory Council does meet, each apparently maintained since 2012. But is that approach effective enough?
What may be missing is a specific therapeutic strategy, from recruiting patients like oncologists do, to comprehensively and aggressively testing repurposed drugs, to pushing the pedal to the metal on the Accelerated Medicines Partnership. As Fauci and Lane point out in AIDS, a publicized strategy and accountable leadership seem fundamental for successful therapy development. Musicians and non-musicians, people living with dementia and their families, are waiting.
by Ron Louie, MD
Clinical Prof. Pediatrics (Heme-Onc)
University of Washington, Seattle