Abstract

Abstract

Friday, August 10, 2018

Sequential steps


On the first Sunday in February 2018, I was involved with a “dementia-friendly” training session. The venue was at my church, St. James’s, which serves both Cambridge and Somerville. A few of people who came had some form of dementia themselves. Immediately after my diagnosis in 2015, my minister, Holly Lyman Antolino, took an interest in my disease. Another key part was filled by Beth Soltzberg, who works at Jewish Families & Children’s Services in Waltham. We were among volunteers in overseeing a volunteers’ training session for people interested in being “Dementia Friends.”
What does this term mean? Volunteers are trained to detect dementia and take appropriate steps. In a ten-page packet that was passed out that February Sunday, the header on the left read “Normal Aging,” and on the right, “10 Early Signs and Symptoms.” Some are subtle. They include, “Confused about the day [of the week] but recalled it later.” On the other side of the ledger are such things as, “Difficulty completing familiar tasks at home, at work or at leisure.” Another warning is “Confusion with time or place.” This is a significant one. And, one cell down on the chart is “Trouble understanding visual images and spatial relationships.” People who have this trouble may want to be screened for postcortical atrophy [PSA], a form of dementia that affects visual processing.
The two most alarming signs are the last two on the list: “Withdrawal from work or social activities”; and, more ominous, “Changes in mood and personality.” I am no expert, but I would be alarmed if a loved one of mine were showing these signs.
Another exercise, called “Bookcase Story,” showed how certain skills and forms of memory are more durable than others: “Imagine that each of has a bookcase that we’ve been filling up throughout our lives. Each book represents our skills or memories.” A picture accompanying the exercise shows a bookcase that is missing most of the books in the upper shelves, but still has many books on the bottom two shelves. Emotions are much more durable than thoughts, and short-term thoughts often dart away like swallows—frustratingly for those of us who are living with dementia. The lower depths of the brain are where the emotions reside. This is the domain of emotions, which typically endure long after the higher levels of thinking have been banished.
In another part of the session, participants were asked to write out a step-by-step process for something you know how to do. I chose to list the steps I take to make a sockeye salmon sandwich. First, I found a can opener in one of our kitchen drawers. But I didn’t open the salmon immediately. That would have caught the attention of one of our two cats, Rusty. Our other cat is skittish, and only eats dry food, so we don’t have to worry about her getting in the way. But Rusty is eternally voracious, and aims to push the envelope. Only occasionally does Rusty get up on the wooden railing on our back porch and plop down on the flashing. But when he does, it’s unnerving. When we were renting in Somerville, we had a large cat, even bigger than Rusty, and that cat did fall off our deck. We were surprised that he wasn’t seriously injured. All he did when he got back into the house was to hiss at his sibling.
I have digressed. I had to make sure one of our two cats, Rusty, didn’t rush into our kitchen as soon I opened the can. And it was a hot day, so I wanted to eat on our deck. But I still wasn’t certain that Rusty wouldn’t escape onto our deck. A couple of months earlier, Rusty did escape. I understand that cats tend to have excellent balance, but Paula and I were acutely aware that he could break a bone or worse. We had to entice him with wet food to get close to him so we could snatch him.
But back to the kitchen, with the aim of constructing my salmon sandwich. First, I found a small stainless steel bowl, large enough for three servings. Then, I grabbed two slices of multigrain bread from a local bakery that I have been patronizing for more than fifteen years. I mixed the olive oil and the balsamic vinegar, along with chopped celery and onions, in the mixing bowl. I also sprinkled some fresh-ground black pepper, before mixing everything together. Finally, I opened the can of “Red” salmon, more familiar to me as “sockeye” salmon. Before I finally opened the can, I made sure that Rusty was sleeping. Fortunately, he was. Then I quickly mixed up the contents. And, fortunately, Rusty doesn’t like my home-made dressing. He’d rather have his meaty cat food.


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.

Saturday, June 23, 2018

Anxiety


My plan this week was to write about the corrosive effect of anxiety among people with dementia. That is still my aim, but not quite the way I expected. As a prologue, I must confess that I lost most of my first draft of this blogpost. I thought I was immune to this kind of mistake. I always back up my drafts, off-site. Where the vulnerability was exposed was in the name of the file. The two files were almost identical: only one or two key strokes were different. I was left with a rump end. From time to time, I aim to hit a lyrical vein, or even a stream-of-consciousness flow—if the piece had survived. My writing was flowing. I felt this would be one of my better blogposts. But the next day I had almost no recollection of what I had written the day before. That speaks volumes about this insidious disease.
The file should have been in the trash-can icon, from which I could easily have retrieved it to my desktop. I was pleased with my first draft. And when I realized I was having trouble finding it, I didn’t panic. I assumed that there was a way to bring forth my missing file. But the other file, the shorter one, was overwritten. One file held the entire draft. The other one held a fragment, about one-third of my full draft. Unknowingly, I had wiped out a large portion of my blogpost. And as any writer can tell you, rewriting what you’ve lost can be profoundly challenging—especially if you have dementia. I could remember almost nothing from the brunt of my lost first draft.
This, of course, was profoundly frustrating. I knew that I was writing well, but I was unable to transfer the information to my long-term memory. Anxiety runs on one side of my family, so it’s no surprise that I would have anxiety problems once I developed Alzheimer’s. But it wasn’t until I developed Alzheimer’s did my anxiety became a problem for me.
What he did struggle with was anxiety. It’s one reason why he didn’t do as well as he might have in his dual careers, in teaching and commercial fishing. How is this connected with dementia?  Because anxiety on its own can be terribly corrosive. To introduce a metaphor from the drug culture, fentanyl, used to speed up the high from opiates, is like adding anxiety to people who already have Alzheimer’s disease. The less stress you have on your shoulders, the better.

Friday, June 8, 2018

Why we sleep


This book by Matthew Walker is a revelation. Most people rarely think deeply about sleep, unless they are running a sleep deficit, or worse. Occasionally, in my twenties, I would have a severe bout of insomnia. The worst was in Berlin, about six months after the Wall came down. I felt like a husk of myself. As dawn was rising, saliva was pooling in my mouth. But since that lonely dawn more than a quarter-century ago, I’ve only rarely had pronounced sleep problems. These days, Paula is the one who isn’t sleeping very well, thanks in part to my penchant for tossing and turning in my sleep.
Aptly, Walker devoted a section of his book to Alzheimer’s disease. Most people recall learning about REM [rapid eye movements] in high school biology classes. But I had not heard of, or long forgotten, NREM [non-dreaming] sleep. As Walker noted, people have less of the deep NREM sleep as they age. But those with Alzheimer’s suffer this symptom much more acutely: “Sleep disturbance precedes the onset of Alzheimer’s disease by several years, suggesting that it may be an early warning sign of the condition, or even a contributor to it.”
Walker continued, “What struck me was the location in the brain where amyloid accumulates early in the course of Alzheimer’s disease, and most severely in the late stages of the disease. That area is in the middle part of the frontal lobe...the same brain region essential for the electrical generation of deep NREM sleep in healthy young individuals.”
Walker collaborated for several years with Dr. William Jagust at the University of California, Berkeley. The research teams developed a hypothesis: “The more amyloid deposits there were in the middle regions of the frontal lobe, the more impaired the deep-sleep quality was.” Walker stated that their research added “a key piece in the jigsaw puzzle of Alzheimer’s disease,” namely  “a new pathway through which amyloid plaques may contribute to memory decline later in life.” He goes on to explain: “Despite Alzheimer’s being typified by memory loss, the hippocampus—that key memory reservoir in the brain—is mysteriously unaffected by amyloid protein,” which is usually regarded as the most prominent feature in Alzheimer’s disease, with its canary-in-the-coal-mine feature.
Walker believed sleep disruption could be “the missing intermediary factor—one that was transacting the influence of amyloid in one part of the brain on memory, which depended on a different region of the brain.”
In a clinical study to test this theory, elderly patients with varying amounts of amyloid plaque were asked to learn a new set of facts. “We discovered a chain-reaction effect,” Walker wrote. “Those individuals with the highest levels of amyloid deposits in the frontal regions of the brain had the most severe loss of deep sleep and ... [thus] failed to successfully consolidate those new memories. Overnight forgetting, rather than remembering, had taken place. The disruption of deep NREM sleep was therefore a hidden middleman brokering the bad deal between amyloid and memory impairment in Alzheimer’s disease.” The distinction, according to Walker, was that this was not just “normal aging”; it was “a departure from what otherwise is the signature of sleep decline as we get older.”
While Walker was doing his research, he became acquainted with Maiken Nedergaard. The Dutch researcher “found a kind of sewage network called the glymphatic system within the brain. Its name is derived from the body’s equivalent lymphatic system.” (Named from the Greek root word for “glue.”) There was a second major breakthrough, according to Walker: “Think of the buildings of a large metropolitan city physically shrinking at night, allowing municipal cleaning crews easy access to pick up garbage . . . , followed by a good pressure-jet treatment of every nook and cranny. When we wake each morning, our brains can once again function efficiently thanks to this deep cleaning.”
Walker asked rhetorically, “So what does this have to do with Alzheimer’s disease? One piece of toxic debris evacuated by the glymphatic system during sleep is amyloid protein—the poisonous element associated with Alzheimer’s.” Walker went on to suggest, coyly, that “wakefulness is low-level brain damage.” And, in a more serious vein, Walker observed, “Can we begin supplementing the declining deep sleep of vulnerable members of our society during midlife?” That is a laudable goal. But I have two comments. The first is that, within a week to 10 days after leaving my job, I was sleeping well after many years of difficulty sleeping. And that wasn’t just a flash in the pan. It’s been three years since my diagnosis, and I usually go to bed around 11:30 and wake up around 7:30. But something tells me that sooner or later, I will not be sleeping soundly. More than six years since my first symptoms, I am cherishing my sleep.

Saturday, May 26, 2018

A sad end to an honorable man


The day after New Year’s Day 2018, the Boston Globe published a thorough exposé, one that involved people who Paula and I knew from the Alzheimer’s Association, Judy and her husband Steve. As the Globe noted, “People with Alzheimer’s and other forms of dementia frequently need hospital care, yet few hospitals are prepared for them.” In a memorable comment about how hospital staff treated Steve, who had early-onset Alzheimer’s, Judy noted, “I felt like we were aliens that had just landed in a place that had no idea of the language we spoke and no concept of the disease my husband had.”
The consequences were awful. The Globe made clear that Steve was much worse off than before he was admitted, including losing the ability to walk, violating the Hippocratic oath. By early April, he died at age 65. Since then, Judy has made a point of keeping Steve in her memory. It’s helpful, of course, to have an extended family as a form of support. In addition to two grown adult children, she has three grandchildren.
About 10 years ago, Steve built a townhouse adjacent to their main home. The family also maintains a home in coastal Maine. “He just loved life and being with his family and he loved to work on his projects. I think that speaks to what a patient man he was. He even build an in-ground swimming pool”—a task that most people who are handy would eschew. And Judy recalls having animated discussions with Steve on Eastern poetry and philosophy. One of Steve’s favorite poems was a short work by Edwin Markham; Judy relates it to Steve’s desire to participate in clinical trials and ultimately to donate his brain for research. He knew the research into this terrible disease wouldn’t help him, but would help others. Markham’s poem is:

He drew a circle that shut me out
—Heretic, rebel, a thing to flout.
But love and I had the wit to win:
We drew a circle that took him in!

            According to Judy, Steve’s first symptoms appeared 12 or 13 years ago, reflecting how long he was living with the disease. At that time, Judy and Steve were vacationing in the Mediterranean, in Barcelona and other cities. “Steve was an organized man. He carried a messenger bag, and had a pocket for everything,” Judy said. “We had that with us on our trip: The passports in one place, our bathing suits in another, dry socks in another. But whenever we arrived at a new place, he would empty out the whole bag. And I wondered, ‘Now why did he do that?’” On that trip, Judy first noticed that mornings were becoming more challenging.
            And then, seven years ago, Steve had redone the living room and repainted it. A day or so after finishing, he took an afternoon nap, and when he awoke, he asked, “Hey, who moved the furniture?”
“There were times when Steve would send me a message [from work],” Judy recalled. In one case, the topic was that Steve couldn’t find his car keys. When Judy arrived at Northeastern where he worked, it turned out that Steve had had the keys in his pocket the entire time. Another time, Steve delivered an important financial report to his boss, but the report was identical to the one Steve had turned in earlier. This was in May 2011. At that time, Steve began to say, “I can’t go to work today.” According to Judy, Steve “had never missed a day in his life, unless he was truly sick.” This was when the diagnosis process began.
Five months later, a neuropsychologist concluded that Steve had mild cognitive impairment, sometimes considered as a forerunner to Alzheimer’s. Later, another doctor arranged a lumbar puncture, a diagnostic test with high accuracy for diagnosing Alzheimer’s. In late September, Northeastern offered Steve an assistant to compensate for his cognitive decline. Originally, Judy wanted Steve to keep working. But one of his doctors noted that anxiety can accelerate the progress of Alzheimer’s. “If you want to make this disease go faster, expose yourself to stress,” the doctor said. After discussing what to do, the couple agreed that Steve should retire. Steve began to work with Judy at her family daycare center in their home.
Judy recalls this as pleasant period. In nice weather, Steve and Judy would hang out in a park with the daycare children. Some of the kids called Steve “Gramps.” This arrangement worked quite well, especially early on. But then came a time when Steve’s condition further eroded.
Had there been a chance for Steve? By the time I met him in late 2015 or early 2016, he was no longer speaking. Of course, spouses have many ways to communicate beyond speech. When he could still talk, Steve often said, “I want to go home,” even though they were at home. Judy said, “I knew he meant he wanted to go back to how things used to be.” Steve also often said, “My head is firing!” when having difficulty. Much later, when he was nonverbal, Judy described him as sometimes vigorously rubbing the sides of his head. She interpreted this not as a sign of a physical problem, but as his effort to communicate to her, “My head is firing!”
And I honor Steve, in his past agony of his Alzheimer’s, for coining a new term: My head is firing! At some point, I, too, may experience what Steve discovered first.