Alzheimer’s (AD) and other dementias are a global issue, but three recent views from New York are worth reading, each giving a nuanced perspective of how people are trying to deal with these devastating diagnoses.
The New York Times published an article (Oct 13) by noted author Robert Kolker, who has written books about difficult neuropsychiatric illnesses like familial schizophrenia. In the article titled Will We Ever Understand Dementia?, he provides an exploration of the intellectual history on how medical thinking in this area has evolved, and how the recent anti-amyloid dementia therapies were developed.
Kolker starts with a less frequent variant of dementia, Frontotemporal Dementia (FTD). It’s not unusual to develop medical ideas in variants, if the rarer condition can yield therapeutic ideas. For example, lessons learned in rare pediatric leukemia helped the beginning of chemotherapy, 70 years ago.
He mentions that dementia may involve proteins found in the autopsied brains of those afflicted. The most salient findings are abnormal accumulations of β-amyloid, along with abnormal distributions of the protein called tau, and more recently, TDP-43 and others. FTD may also show unusual shrinkage and atrophy of the frontal lobe; in AD atrophy may be more widespread.
Research groups tend to focus on one thing at a time, leading to expertise in either amyloid or tau or other proteinopathies. He revives a scalawag humorously calling the research groups the “Tau-ists” (Daoists) and the “β-aptists” (amyloid). There has been vigorous debate about the primacy of which protein is more important. It led to competition for research funds, and which proteinopathy should be targeted for therapy. It implies an almost religious fervor in the two camps.
He discusses how tau is now found in many other conditions, including CTE affecting football players and boxers. He was able to gather some striking quotes from clinicians, pointing out current skepticism about the primacy of β-amyloid; at one point he writes there is now a “collapse of the amyloid hypothesis.”
Kolker basically states that there are still problems in understanding all dementia, including AD, the β-amyloid predominant dementia, or the role of tau. He notes that amyloid seen on scans doesn’t always seem to match up well with an individual patient’s clinical condition, and that the effectiveness of current anti-amyloid therapy is still a bit of an issue. His new book, available soon, is said to explore a family with generations of FTD.
Dr. Gayatri Devi, a New York City neurologist and dementia author, wrote a JAMA Viewpoint piece (Oct 19), Testing for Alzheimer Disease in Asymptomatic Adults. She discusses new blood tests for abnormal protein levels associated with dementia. As the title suggests, it’s unclear what to do with positive results, since the results would not match the clinical condition of being “asymptomatic”. Even if a PET brain scan would be positive for an abnormal protein, the FDA labeling of the available products might limit their “on-label” usage to those with documented symptoms. She provides a well-considered front-line discussion.
Dr. Eric Larson, a noted Seattle dementia researcher, also wrote an article in the AMA J. Ethics about this dilemma: Should Slowing Senescence Be Regarded as a Legitimate Enterprise of Health Care? And this summer, Dr. S. Lyndon and Boston colleagues wrote a JAMA Viewpoint about current dementia workups, including blood tests: Alzheimer Disease Biomarkers and Assisted Dying/When Diagnosis Becomes a Deadline. It discusses how positive results might lead to more people requesting “physician assisted death (PAD)”.
On the other hand, Drs. S. Schindler and D. Wolk, St. Louis and Philadelphia, in an editorial, Predicting Risk of Cognitive Impairment With Alzheimer Disease Blood Biomarkers, are more sanguine about a study of the p-tau217 blood test. In their last paragraph, one must say that they are surprisingly optimistic, writing that preclinical trials “may soon demonstrate clinically meaningful benefit.” One is allowed latitude in editorials, of course, but some trial watchers have been hopeful for the demonstration of clinically meaningful substantial benefit for years.
Of course, Dr. Nancy Wexler, famous for laying the clinical and molecular foundation for the Huntington’s Disease blood test, also famously refused to take it herself, despite her mother’s affliction and her own known risk. She was once on a Presidential Ethics panel and discussed the issue in depth.
BTW, in cancer testing, a recently touted multi-cancer screening blood test failed in England (Galleri), but is evidently on its way to FDA approval in the US. (Europeans drug approvals/denials don’t always match up). The CA-125 test for ovarian cancer screening, CEA for colorectal cancer screening and AFP for liver cancer screening, once touted, have all become “not recommended.”
Back to the Big Apple, The New Yorker (Nov 9) has The Alzheimer Wars by Dr. Manvir Singh, an academician. He presents a more conventional view of the scientific debates about the pathophysiology of dementia. He also describes the debate between the β-aptists and Tau-ists research groups (who can resist? here’s my take, 2020). Even the AlzForum.com called it “The Feud”.
He provides other facets of the details on how dementia medical thinking evolved to its current state, not only the research on mechanisms, but importantly how the nature of research and medical culture, thought leaders, funding controls, and campaigns for awareness had an impact. He notes the interactions between academia, the government, and the pharmaceutical industry.
He gets quotes from the science officer at the Alzheimer’s Association, known for their advocacy of championing therapy, despite controversy. They were apparently involved in the FDA approval of aducanumab, the first anti-amyloid drug approved. It is documented that 10 of 11 members of an FDA expert committee members voted no, and the eleventh was uncertain. The FDA approved it anyway, using the rationale of β-amyloid scans as a “surrogate biomarker”, a bit of an unvetted criterion. He names probable influences in the process of approval.
His article then focuses on an informed patient’s personal decision-making process in getting therapy, even if the benefits and risks are a bit hazy. One is reminded of Pascal’s Wager, basically hoping for the best while acknowledging uncertainty.
Anyway, it’s interesting to see the different POV in thoughtful reportage about current dementia concepts, read the quotes about the uncertainties and dilemmas for patients and clinicians, along with a bit about perspectives, potential biases, advocacy and quality judgments in this arena, all trying to alleviate some human suffering.
Dementia in general may invoke the philosophical “mind-body” problem; these articles focus on the pragmatic medical framework and mechanisms of disease, “materialist” issues which, after a hundred years of research, are still debated. One group has recently written about the “mind”: Understanding Alzheimer Disease as a Disorder of Consciousness. Sorry if some links are paywalls.
P.S. About two more minutes of your time: Status Report to Insurance: Incontinent.
P.P.S. This blogger will try to do a second post, mainly citations for those interested, from interesting papers this year: the Cochrane meta-analysis review about “little or no difference” effected by current therapy, the ripples of this paper creating rebuttals, AAIC 2026, AlzForum, US Pointer/ADNI, etc.