The end of Alzheimer’s


Lisa Marshall is a freelance journalist who has been writing about health and medical science for 25 years. She is a mother of four and lives in Estes Park, CO.
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“Leese. It’s Dad. I need your help.”
My father’s calling me from the cafeteria at Denver’s Presbyterian/St. Luke’s Medical Center – the hospital where in 1967 he kicked off a prestigious career as a dashing, 6-foot-3 cardiologist. Dad tells me he’s been seeing patients. He just sat down to grab some lunch, but something’s wrong. He can’t remember where he parked the Jag.
“I think I may have had a little stroke or something.”
I do something that would have been unimaginable 6 months earlier. “Your car is in the shop Dad,” I lie. “I’ll come down in a bit and take you to get it.”
Dad sounds relieved. He tells me he has to get back to work, instructs me to page him if I need him, and hangs up.
Four minutes later, the phone rings.
“Leese. It’s Dad. I need your help.”
By the end of the day, my father has dialed my number 22 times. Each previous call evaporates from his mind as he grows more and more confused about his whereabouts.
Once, he thinks he’s at his mountain condo in Winter Park, CO, the place he taught me to ski fearlessly by day and play spirited games of chess by the fireplace at night. Another time, he’s at Johns Hopkins University in Baltimore, where he graduated from medical school near the top of his class.
When I can no longer bear to pick up his calls, the messages fill up my voicemail. After my work day ends, I wearily listen to each one, and delete.
At 8 p.m., as I sit wedged between my children on the sofa watching TV, Dad’s number pops up on the caller ID.
“Hi Leese. It’s been a while.”
As I say goodnight and hang up, I picture Dad in his new home, impeccably dressed in his customary sports coat, trousers, and brown loafers. His faded doctor’s badge perches on his left breast pocket, where he fastens it every day with pride.
Only Dad is not at work or relaxing at his ski condo. He is in his favorite brown recliner, in a tiny room with one small window, in a locked “memory care” unit. Next to him sits the phone.
Soon, he will forget how to dial it.
Inching Toward Treatments
Dr. Robert Marshall (aka Dr. Bob) was 72, traveling the world and enjoying retirement when, like a half-million people in the U.S. every year, he began the long and slow descent into the haze of Alzheimer’s disease.
I watched with aching grief as time erased my Dad bit by bit over the next 12 years.
As a science writer and a daughter, I was desperate for answers. So I took reams of notes. What exactly was going on in my father’s brain? Would it happen to me someday? And if it did, could anything fix it?
The answer to that last question — more than 115 years after Alois Alzheimer first reported a “peculiar severe disease process” in the brain — is still, heartbreakingly, no.
Alzheimer’s is the top cause of dementia. It can impair all the essential qualities that make a human unique: thinking, judgment, language, memory, emotions. Lifestyle changes can lower your chances of getting Alzheimer’s, and some medications can manage its symptoms. But nothing on the market today can do what my three siblings and I longed for — to stop the erosion of my father’s memory and even to restore it.
Yet, as we better grasp how memories are formed and why this intricate system goes haywire, some hopeful scientists say that day is drawing tantalizingly near.
Two recent medical advances hold the hope that memory loss, like heart disease, may someday soon be detected and treated early and affordably.
In June 2021, the FDA approved aducanumab (Aduhelm), the first new Alzheimer’s drug in 2 decades. It’s the first approved medication to target amyloid in people with mild cognitive decline or mild dementia. Amyloid is a sticky protein that is a hallmark of Alzheimer’s. Regulators took a hugely controversial path to fast-track Aduhelm based on its ability to remove brain plaques, even though it’s unproven that the drug actually slows cognitive decline.
The lack of convincing data, and concerns about brain swelling and bleeding in some patients, prompted an outside advisory committee to recommend against approving Aduhelm, which is given via a monthly IV injection. In January 2022, Medicare said it would not cover the whopping $2,300 per month price tag for Aduhelm except for those enrolled in a clinical trial. Despite the controversy, some experts hope that Aduhelm, a monoclonal antibody that mimics the body’s natural immune response to foreign invaders, will open the door to affordable, safer, new medications targeting early drivers of Alzheimer’s.
The year before Aduhelm’s debut, researchers at the University of Washington in Seattle unveiled the first clinically available blood test to detect possible Alzheimer’s. It’s not FDA approved or covered by insurance yet. But it, too, is viewed by some as the first of a new vanguard of inexpensive, noninvasive detection tools, akin to cholesterol tests for heart disease.
As for those already in the early grips of forgetfulness, scientists are testing everything from exercise and nutritional supplements to implantable brain stimulators to bring back lost function and to restore the cache of memories.
“I tend to be more hopeful than most,” says Nanthia Suthana, PhD, a neuroscientist and an assistant professor in residence at the David Geffen School of Medicine at UCLA. “But I’m optimistic that within our lifetime there could be a neural prosthesis that could benefit even severely memory-impaired individuals.”
Unlocking the Mysteries of Memory
Many people assume that memory is stored in a single place, much like money in a bank vault. Actually, you conjure the sights, sounds, smells, and feelings from the past when neurons fire in coordination across different regions of your brain.
Daydreaming about the blazing beach sunset from your last vacation? Your brain retrieves those vivid colors from its visual cortex located in the occipital lobe at the back of your head. Got a favorite song looped in your head? That emanates from the neural cells in your auditory cortex burrowed near your ears.

Researchers also recently discovered specialty cells that add context to your episodic memories, which are when you mentally relive a past experience. “Time cells” stamp your recollections in the right chronology, so you know that your daughter came to visit yesterday, not last month. “Place cells” act as geolocators, guiding you back to your parked car at the mall.
Electrical and chemical signals link these cells together through a complex architecture of synaptic connections. When you go to recall that memory, that original network crackles with life again.
“Your memory of last night’s dinner requires the activation of the same constellation of disparate neurons that perceived, paid attention to, and processed your initial experience of that meal,” says Lisa Genova, PhD, a neuroscientist and author of Remember: The Science of Memory and the Art of Forgetting.
Central to this process is a seahorse shaped region of the brain called the hippocampus. It first came to scientific light through Henry Molaison, widely known as H.M., perhaps the most famous patient in neuroscience. In an attempt to stop H.M.’s severe epileptic seizures, his surgeon in 1953 carved out chunks of the hippocampus from both sides of his brain.
When H.M., 27, woke up, his seizures were gone. But he was left with permanent amnesia. He forgot new events and facts almost instantly and was unable to make lasting memories. Every day, he said, “is alone in itself.” H.M.’s devastating fate kick-started the modern field of memory research.
The hippocampus is essential to convert what would otherwise be fleeting experiences into long-term memories stored in the regions that processed the initial experience via consolidation. As the home of the bulk of our place cells and time cells, the hippocampus lends temporal and spatial context to those memories.
It is, as Genova puts it, “the memory weaver.” And without his hippocampus, H.M. was caught in a sort of perpetual groundhog day.
As it turns out, Alzheimer’s hits the hippocampus first.
How Life Choices Affect Memory
My father was intellectually voracious. When he was in college, he learned Latin for fun. In his 30s, he taught himself to play piano. He treated patients at a leper colony in Nigeria. He devoured books by John Irving and Tom Wolf, loved art, and delighted in accompanying his grandkids to the theater.

Dr. Robert Marshall, aka Dr. Bob, dressed for work at Presbyterian Hospital in Denver in June 1967.
His inquisitive nature, I’m told, probably supplied him with a “cognitive reserve” that buffered him for a time from the ravages of Alzheimer’s. Each new lesson or experience strengthens our neural network and protects it from fraying.
“These neural connections are like train tracks that have been clicked together and are super easy to travel on,” Genova says. “If you only have 10, and some of them break, it can be hard to get around. But if you have 10,000 tracks you have options.”
Research has shown that people with deep cognitive reserves tend to deteriorate more slowly in the early years of Alzheimer’s. Or they are simply able to fake it better.
But for all of Dad’s cognitive stockpile, his brain had a lot of strikes against it.
He lit his first cigarette at 16 and smoked a pipe for decades. That likely damaged the blood vessels that ferry oxygen to his brain and inflamed his neural tissue.

Marshall with his then-wife, Yolanda, and daughters, Kari (left), and Marla, in 1964.
Dad ate meat, often processed, 7 days a week. The high sodium levels in his beloved bacon and roast beef probably contributed to his high blood pressure, another risk factor for Alzheimer’s. He also shunned leafy greens, whose nutrients are proven to protect against brain-cell-killing oxidative stress.
He retired in his 60s so he could travel the world. But ironically, people who retire early are significantly more prone to dementia. One study found that with diminished opportunities for cognitive and social stimulation, new retirees lose about 3 IQ points in the first 2 years.
Then, there was his chronic insomnia — a condition that I share.
This worries me for two reasons: During sleep, research shows, a cleansing channel of fluids passes through the spaces between our brain cells, providing a midnight wash cycle that ferries away the toxic plaques and tangles that can promote Alzheimer’s. Sleep is also the time when the hippocampus gets to work making memories last.
“If you don’t sleep,” Genova says, “your hippocampus doesn’t have time to finish the job.”
How Memory Is Lost
I first suspected something was wrong around 2007, when Dad told me he’d been out Jeeping on his favorite mountain pass and had gotten “really turned around.” Months later, a good Samaritan found Dad wandering in the dark in a parking lot after he dined out for dinner. The restaurant had closed more than an hour earlier. Dad was divorced and lived alone, so we finally convinced him to move into an assisted living center.
When my husband and I went to empty out his house, we found printed maps stashed everywhere, including one for the grocery store just a mile away. I peg this time as the beginning of his disease. But, in reality, it probably had been smoldering for years.

Research suggests that as many as 2 decades before symptoms arise, misfolded proteins called amyloid plaques begin to form between nerve cells, jamming up the network. Then come hairball-like clusters called tau aggregates, which emerge inside and around neurons, strangling them. As immune cells in the brain, called microglial cells, mount a response to what they see as an internal threat, the brain becomes inflamed, cells die, and the real damage begins.
The process tends to start in a region of the hippocampus called CA1, hitting those “time” and “place” cells hard. Regions where long-term, consolidated memories are already stored are affected much later. This is why Dad could not remember what he had for breakfast, but he could, when I had a minor heart problem, still scan my EKG and give me a spot-on diagnosis.
It would be a few years before doctors officially diagnosed Dad with Alzheimer’s, based on a battery of surprisingly low-tech cognitive exams. To truly know for sure, his doctor told us bluntly, we’d have to wait until he died and look at his brain.
Over a tear-filled dinner with my sister later, I was overcome with guilt.
“If only we could have caught it earlier somehow,” I said. “Maybe we could have done more to help him.”
Quest for Early Detection
When Dad was diagnosed, doctors were only beginning to use PET scans to look for amyloid plaque building up in the brain. The scan, which wasn’t covered by Medicare or Dad’s supplemental insurance, costs more than $5,000 and would have exposed him to radiation. His doctor advised against it.