Abstract

Abstract

Friday, July 27, 2018

The preclinical phase


With Boston’s world-class constellations of hospitals and research institutions, it’s hard to have a consensus on who is the most prominent figure in Alzheimer’s research. But the name of Reisa Sperling often comes up. In a well-researched Boston Globe magazine article by Joshua Kendall, the author makes the case that “preclinical medicine” could be the way to counter Alzheimer’s. The most important syllable in this phrase is pre: The gestation period of 10 to 15 years, before Alzheimer’s flowers. By the time people are showing signs of the disease, the die has been cast. And this incubation period typically lasts from ten to fifteen years. “It used to be that you could diagnose Alzheimer’s only upon autopsy,” Sperling noted.
Back in 2011, Sperling was the primary researcher who “proved that the telltale signs of Alzheimer’s long before the patients began to exhibit symptoms.” Following through, Sperling was the primary writer of what became more than twenty writers who contributed to the project. “Sperling proposed using the preclinical phase to change the very definition of the disease, arguing that it should now be based solely on the presence of amyloid and tau,” the two primary symptoms of Alzheimer’s.
In a dark turn, Sperling’s father, also a noted Alzheimer’s researcher, was showing signs of dementia himself. During that year’s Thanksgiving break, Sperling encountered sardine cans all over his office, some of which had been opened. “Her father’s decline was swift, and Leslie died of Alzheimer’s in 2016.  As Kendall observed,  “Research on Alzheimer’s, which accounts for 60 to 80 percent of all cases, urgently needs a reboot.” For the most part, specialists agree that  Alzheimer’s arises from what Kendall describes as “the complex interplay between genetic and environmental risk factors.” I myself, over the last three years  since my diagnosis, have struggled to explain how I ended up with Alzheimer’s. I am now agnostic. The article goes on to record the miserable failures of drugs for Alzheimer’s disease. I am intimately aware of the biotechnology  industry’s failures. Back in late 2016 or early 2017, there was a time when optimism was rising. But one of my cohorts was taking part in the trial. The hope was rather modest: to slow Alzheimer’s progress. It was hard not to be optimistic. But it didn’t pan 0ut.  And even Reisa Sperling couldn’t change that. For many of  my generation of people with early-onset Alzheimer’s, the sand is slipping through the hourglass.
Note: This blogpost was written before Biogen announced its breakthrough in early July. And there is no certainty that Biogen will past muster in clinical trials, however convenient that would be.

Friday, July 13, 2018

A breakthrough


Back on October 21, 2016, my blogpost topic was titled “A means to slow Alzheimer’s?” Some days earlier, I had seen an article by Damian Garde, who writes for the STAT news service, which covers
Alzheimer’s and 0ther neurological disorders. I was a bit tardy to understand the implications. As Garde noted at the time, a “secondary analysis of pooled data showed a 34 percent reduction in the patients’ cognitive decline.” But things didn’t go to fruition. And for the next couple of years, little progress was made in detecting  maddening Alzheimer’s secrets. My next sentence was an understatement: “This finding could be significant”—a sign that in 2016 my understanding of my disease was still rather shallow.
And then the breakthrough was revealed: Alzheimer’s gave up one of its cherished secrets. And it was Biogen, in Cambridge, which performed the alchemy, just after the 4th of July.
What does this mean for me and my cohorts? It’s complicated. My six-plus years of living with early-onset Alzheimer’s has brought me to the end of the first phase of the disease, and into the early-middle stage. In a statement, the company stated, “Biogen is declaring success with a once-failed treatment with for Alzheimer’s disease, pointing to positive secondary results in hopes of saving a drug that many had written off entirely.”
For those of us who are living with the disease, there are still Just organizing the far-flung clinical trials will be a vast organizing project. And, sadly, vast legions of people with Alzheimer’s too far down the Alzheimer’s path to qualify for the clinical trials. I myself am in good physical health, as I approach my 57th birthday. But I have a different concern: I may not be able to withstand the dosage to break up the amyloid plaque, which in recent years has emerged as the key aspect of Alzheimer’s disease.
As a high school football player and wrestler, I had a reputation for my toughness. The difference here is that I would be the passive object, worried that I wouldn’t be able to absorb the full strength of the dosage. Am I being irrational? It’s not like we are starting the clinical trials immediately. But in a-worst-case scenario, I could end up with brain inflammation, and leave me much more worse than I am now. Should I trust the odds? First of all, I want to know the odds.
The clinical trials are expected to last for two years on multiple continents. I invite my readers to contact me on this topic, at mitch.evich@gmail.com

Friday, July 6, 2018

Ups and downs


I never met Ralph Hergert, but I did attend his funeral. In his two professions, as a minister and a social worker, he was widely known in Somerville and Cambridge. His wife, Leslie F. Hergert, has written a quirky and insightful memoir of her late husband. The quirkiness is in the book’s structure. Rather than employing a conventional narrative, Hergert chose the primer mode, titled Alzheimer’s Through the Alphabet: One Journey of Ups and Downs. I would advise readers to read Hergert’s introduction, as it provides some important context. Significantly, Hergert states, “This narrative provides little, if any, advice.” In other words, readers are largely left to their own interpretations.
Some of the juxtapositions are inspired. On the left page, for the letter A, the topic is “Annoying Period.” As Hergert put it, “most of us don’t admit when talking about Alzheimer’s: Our loved ones with Alzheimer’s do lots of annoying things,” like repeating questions and, in more extreme situations, putting the keys in the freezer. On the opposite page, the title is “Becoming a Better Person.” This full passage is difficult to summarize, in part because Hergert is such an accomplished prose stylist. Here’s an extended example, under the header, “Mixed Messages.”
“As should be clear by now,” Hergert wrote, “the messages I have to convey are very mixed. I am never quite sure whether to say how terrible this disease is or how manageable it is. Is it a devastating disease that takes a painful toll on loved ones? Is it something you can deal with if you change your expectations and ways of doing things? ... Do I want legislators and businesspeople and the public to understand the difficulties of this expensive, long-lasting disease and its changing support needs? Or do I want to provide encouragement to people with the disease and their caregivers? Is it manipulative to change messages with audiences? I worry about that, but both messages are true and need to be heard.”
One of my favorite entries in this book is “Hope.” This is not the hope of traditional Christianity. To me, it sounds like the “faith” of the twentieth-century, embodied in existentialism. Hergert writes: “I live without hope.” Rejecting the notion of hope (along with two strange metaphors from Emily Dickinson, “Hope is a strange invention,” and more strangely, “Hope is the thing with feathers”), Hergert then moves to one of her key points: “I have found that living without hope frees me to live in the present and experience the moments—whether sad or happy or funny or difficult—as they come.”
The letter G hosted two near-antonyms: gratitude and grief. I chose to focus on grief. Hergert went into the etymology of the word, distinguishing grief from other synonyms. She commented, “Early on, I felt sad from time to time but was less aware of the ongoing grief. Now it seems to have moved in as a constant presence, a feeling behind my eyes, a weight that tires me, a cloud or shadow over the brightest of days.” May I suggest that this is a kind of dark poetry?
Under the header “Incontinence,” Hergert writes, “Somehow, body fluids never bothered me.” She makes an exception for snot, which did gross her out when her daughter was little. But, “when people in our support group started sharing stories of their husbands pooping on the floor or peeing into an open suitcase, I said that would be the signal that Ralph needed to go to a nursing home. But I had forgotten that excrement didn’t bother me except as a problem and an inconvenience.”
Under J (for “Joy”) is a charming vignette. At that time, Ralph and Leslie were living in Chicago. It was winter. “The alley was a minefield of dog poop. I thought it was disgusting and was just about to complain about it when Ralph said, ‘You know what’s great about winter? All the dog poop is frozen.’”
And under “Losses” is what Hergert termed “the Ossie Davis moment.” (Davis was an African-American actor and civil rights pioneer.) The gist of the matter was that Ralph and Leslie heard on the news one morning that Davis was dead, and discussed him and his death for several minutes. “Then Ralph went downstairs to get the newspaper. When he returned, he said, ‘Hey! Ossie Davis died.’”
The first time I read this passage, I focused on the humor. It wasn’t until a day or two later that I grasped the pathos of the situation: Even in 2005, roughly a decade before Ralph’s death, his short-term memory was severely impaired.
It was many years later when Ralph got lost, in June 2013. As Leslie put it, “Ralph was a walker. He loved to walk around the city. It was something he could do as his disease progressed, and it was something friends could do with him.” Walking was very important to him. He was not a “wanderer,” a person who goes AWOL from an institution; he left the house unannounced while Leslie was in the apartment downstairs helping her mother. Massachusetts has a “Silver Alert” law, which allows police to look for a lost person with dementia immediately, instead of waiting 48 hours before searching for a missing adult. There was a beer festival in Davis Square that night, and Leslie thought it seemed plausible that Ralph was having a beer at the festival. But Ralph was not there. The next day was even more intense. Things ended safely, after 28 hours of searching. And Massachusetts’ Silver Alert system had shown its worth.