The results of a large-scale screening study could be used to develop blood tests to diagnose diseases such as Alzheimer’s before symptoms take hold.
“An analysis of around 1,500 blood proteins has identified biomarkers that can be used to predict the risk of developing dementia up to 15 years before diagnosis.
The findings, reported today in Nature Aging1, are a step towards a tool that scientists have been in search of for decades: blood tests that can detect Alzheimer’s disease and other forms of dementia at a very early, pre-symptomatic stage.
Researchers screened blood samples from more than 50,000 healthy adults in the UK Biobank, 1,417 of whom developed dementia in a 14-year period.
They found that high blood levels of four proteins — GFAP, NEFL, GDF15 and LTBP2 — were strongly associated with dementia.”
A computed-tomography scan of a brain affected by Alzheimer’s disease, the most common cause of dementia. Credit: Vsevolod Zviryk/Science Photo Library
“Get ready to focus on your brain, because according to the AAN, the era of preventive neurology has arrived. In fact, the academy is hoping that all Americans will be on the healthy brain train by 2050.
“It’s a brain health revolution,” Rost said. “We want to help the public understand that a lifetime of health begins with brain health.”
Latozinemab is an investigational human monoclonal antibody.
The drug is currently being examined in a phase 3 clinical trial.
The FDA has granted breakthrough therapy designation to latozinemab, an investigational therapeutic designed to block sortilin and elevate progranulin to treat frontotemporal dementia with a progranulin gene mutation.
According to a press release from Alector Inc., the breakthrough designation was approved based on data from the phase 2 INFRONT-2 clinical trial of latozinemab in patients with the condition.
“Millions of Americans are thought to have M.C.I., though exact numbers are hard to pin down because experts say the condition is underdiagnosed. There are likely several reasons for that: M.C.I. can be tricky to identify during a primary care visit, when physicians typically only have 15 minutes or so with a patient. People may also be scared to disclose their concerns to a doctor, or might not even realize that they have a problem.”
Across the United States, millions of families are confronting a seemingly impossible question: When dementia changes a relative, how much should they accommodate their new personality and desires?
Katie Engelhart, a writer for The New York Times Magazine, tells the story of one family’s experience.
“I talk to our dog; I talk to our cats. Mind you that these are not deep conversations, such as the ones I have with my wife. It turns out, however, that the presence of pets in the house can have profound effects on slowing the verbal cognitive decline in older individuals. There is one catch: you have to be living alone.”
“I believe this study underscores something that is all too real about disconnectedness in our modern culture. Loneliness and isolation are significant threats to physical and mental health. Recently, the US Surgeon General issued an advisory on the public health crisis of loneliness, isolation, and lack of connection in our country.1 Primary care clinicians need to be aware of this and ask patients specifically about their social networks and feelings of loneliness.”
Ollie and Maxine
“Reaching out to, and building connections with family, friends, and — importantly — others in our communities who are disconnected, is vitally important to health and well-being. And, in some cases, a household pet can be a big benefit. I tell this to my dog and cats all the time.”
GLP-1 agents such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are game-changers. In addition to weight loss, they may reduce neurodegenerative diseases, such as Parkinson’s and Alzheimers dementia, due to a reduction in metabolic syndrome, reduction in vascular events and neuroprotective effects.
“GLP-1 plays important role in augmenting insulin signalling inside the brain. GLP-1 receptors, present inside the brain, are also involved in cognition, synaptic transmission in hippocampal neurons, and cell apoptosis. Overexpression of this receptor is responsible for cognition enhancement and neuroprotection, while deficiency increases the chances of seizure and neurodegeneration (81, 82). Therefore, GLP-1 receptors are considered as validated target for exploring candidates with better neuroprotection and cognition enhancing abilities (83).”
Want to slow memory loss after 60? A multivitamin may be the answer.
A group taking a multivitamin was two years younger in memory function than a group taking a placebo, research shows
It is the third in a series of studies assessing the cognitive effects of a daily multivitamin on older adults. And a systematic review, or meta-analysis, of the three studies accompanying the most recent paper said their cumulative results were similar: The group taking a multivitamin was two years younger in memory function compared with the group taking a placebo.
And don’t forget exercising and keeping your mind busy by reading and doing puzzles. If you are retired and watching cable TV and Fox News all day, doubt balanced meals or vitamins are going to help.
“Persistent cognitive deficits even in those without clinical neurological complications. When compared to normative age-matched data, these deficits were equivalent in magnitude to ageing from 50 to 70 years of age (1). This study indicated cognitive deficits were associated with the severity of the initial infective insult, post-acute mental health status, and a history of #COVID-19 associated #Encephalopathy, with strong concordance between subjective and objective deficits.”
Revolutionary new treatments to slow cognitive decline will require doctors and patients to think about quality of life in new ways.
A patient I’ll call Robert began a recent visit to the Penn Memory Center with a pithy, direct request: “As soon as possible, I want to start one of those Alzheimer’s disease treatments.”
In 20-plus years of practice, I’d never had a visit begin with these words. When I first diagnosed Robert with Alzheimer’s disease a year ago, our conversation about treatment was limited to drugs that might enhance his cognitive and day-to-day functional abilities. Their risks were minimal, but so were their benefits. But on July 6, the FDA approved lecanemab, sold by Eisai and Biogen under the brand name Leqembi, for the treatment of Alzheimer’s disease. By year’s end it’s on track to approve another drug, donanemab, being developed by Eli Lilly.
As I explained to Robert and his wife, these new drugs are quite different. In tests involving patients in the two early stages of Alzheimer’s—mild cognitive impairment and mild stage dementia—both medicines reduced beta-amyloid build-up in the brain, one of the pathologies that cause the disease, and slowed the pace of decline in cognitive and functional abilities. The new drugs can’t cure Alzheimer’s, but they could offer patients more time in these stages before they transition to moderate stage dementia.
Robert is currently in the mild cognitive impairment stage. He has subtle but noticeable problems that cause inefficiencies in life’s daily activities. Right now, for instance, he struggles to work through financial matters and makes a few mistakes along the way, but he’s able to catch them. When his cognitive impairments get worse and his wife has to take over activities he once performed, his diagnosis will change to mild stage dementia.
A year and a half of treatment with the new Alzheimer’s drugs has been shown to reduce the chance of progression to mild stage dementia by about 10%. This benefit comes with notable risks, including small patches of brain bleeding and swelling, which can cause falls and confusion and may require stopping the drug. And there are other barriers. The new Alzheimer’s therapies are very expensive—one year of lecanemab therapy is priced at $26,500. They are difficult to deliver, require an extensive work-up to determine eligibility and involve intensive monitoring for side effects. As many as 8 million Americans are estimated to be living with mild cognitive impairment, but only about 8% to 17.4% will meet all the criteria to take one of these drugs, according to a study published last month in the journal Neurology.
As Robert, his wife and I talked about these medicines, something very interesting happened. After objectively weighing the risks and benefits, we began to discuss an intensely personal and subjective question: Does he want to live longer with Alzheimer’s disease?
This question is ethically challenging. Alzheimer’s, like cancer and heart disease, is a chronic, progressive and potentially terminal disease. In talking to patients with such diseases, contemporary medical ethics tells doctors to help them reflect on the quality of life they want. But the more I talk to people like Robert and his wife, the more I’m convinced that this approach isn’t sufficient.
Usually, patients and doctors don’t start talking about the value of living longer until the progression of chronic disease triggers a discussion. But I can’t rely on that approach with patients like Robert, since as his dementia worsens, he’ll experience increasing problems with attention, concentration, memory, speech and writing. In time, he won’t be able to rely on himself to direct his own care.
For now, though, he’s able to, and that is why I asked him a question I’ve begun to incorporate into my clinical practice: “Is there a point later on when you’d want to stop treatment?”
He nodded yes and talked about how he enjoys walking around Philadelphia and volunteering with a not-for-profit organization. He knows in time he won’t be able to do those activities, and that’s when he wants to stop treatment. Then words began to fail him. In phrases that were more fragments than sentences, he mentioned diapers, trouble eating, living in a nursing home, not recognizing people. “Being a vegetable. You know,” he insisted. “No quality of life.”
ET scans show the effects of Alzheimer’s disease on the brain. Credit: SCIENCE SOURCE
Like many patients, Robert defined his quality of life by his ability to care for himself, in terms of eating, dressing and using the toilet. I understand why. “I’ll never send him to an adult daycare,” “I’d rather die than live in a nursing home”—these pronouncements are all too common, emotionally charged reactions to America’s disorganized, underfunded and understaffed system of dementia care. But this system can be improved, if we muster the political will.
What Robert was most worried about was losing the behaviors that define who he is. He’s worried about how damage to his brain will damage his mind. The phrase “being a vegetable” is a good example of our impoverished vocabulary for talking about how dementia transforms the mind. Our culture is polluted with words and phrases like “vegetable,” “zombie” and “second childhood.” As patients and their families take up the question of whether to live longer with Alzheimer’s disease, they need better ways of thinking about how Alzheimer’s is a disease of the mind—and I think we can do this without turning dementia care into a philosophy seminar.
Some creatures have a mind. Some don’t. A squash flower moves toward light, but most botanists would agree that it doesn’t desire to face the warm sun or experience joy and delight in moving. Human beings do. An amoeba moves toward sugar but doesn’t feel the same pleasure a person does when she reaches for something sweet on a dessert tray. When our memory combines these experiences into a meaningful stream, it creates the feeling of being ourselves.
The human mind isn’t simply the product of the brain but of a system that couples together brain and environment, called the “extended mind.” All of us use smartphones, notepads and other people to keep our minds functioning, and so to be ourselves. The more Alzheimer’s damages a person’s brain, the more of these extensions they require to maintain their mind. As Robert develops problems with spatial memory, for instance, his smartphone can guide him home on his walks around Philadelphia. He may require the assistance of his wife or an aide to continue volunteering. With these accommodations, his feeling of what it is like to be himself may be largely unaffected.
When I explain the new Alzheimer’s drugs to patients and caregivers, I reiterate that one of the most effective treatments is the presence of another human being. Caregiving is more than housekeeping; it means perceiving the mind of the person living with dementia and supporting it. I find explaining this coupled system to patients and caregivers helps them understand how Alzheimer’s affects both of them—what I call “the feeling of being us.” In some sense they both have Alzheimer’s disease. The decision whether to slow this disease is truly an interdependent decision.
Robert reflected on the role of his wife in the decision whether to stop treatment: “I guess she’ll decide.” One factor that will guide her is her perception of his mind, her answer to the question “What is it like to be Robert?” “For now,” she reflected, “Robert is Robert.” He agrees.
The wife of another patient, who I’ll call Walter, answered differently. Her husband often confuses her with other people: “I think sometimes he’s scared, maybe in denial,” she said. But she went on to explain that she still sees his joy at concerts and dance performances. As long as he has this ability, she wants him to receive one of the new treatments. Her desire shows how, despite disabilities and distortions of reality, caregivers and patients can find connection and meaning. It also shows how the arts can help achieve this.
In time, for some patients and caregivers, the feeling of “being us” dissipates. The patient’s mind becomes hard to perceive, and the scaffolding that supports it becomes exhausting to maintain. “She’s a thousand times worse” was one daughter’s summing up of her mother’s severe stage dementia. The reason wasn’t just losses in function or cognition but in her mother’s capacity to joke and laugh in that way that was “so totally her.” In the following months, the daughter enrolled her in hospice care.
Today’s revolution in Alzheimer’s treatment needs a revolution in culture, changing the conversation from quality of life to quality of mind. Doctors need to ask patients “What it is like to be you,” and foster support with people, activities and technologies that create connection and meaning. If we do this, we’ll be better equipped to make the difficult decisions about whether to start or to stop treatment.
Jason Karlawish is a physician, co-director of the Penn Memory Center and the author of “The Problem of Alzheimer’s: How Science, Culture and Politics Turned a Rare Disease into a Crisis and What We Can Do About It.”
CNMRI: Neurology, Sleep Medicine, MRI 