Jon Hamilton Aging and Alzheimer's leave the brain starved of energy. Now scientists think they've found a way to aid the brain's metabolism — in mice. PM Images/Getty Images The brain needs a lot of energy — far more than any other organ in the body — to work properly. And aging and Alzheimer’s disease both seem to leave the brain underpowered. But an experimental cancer drug appeared to re-energize the brains of mice that had a form of Alzheimer’s — and even restore their ability to learn and remember. The finding, published in the journal Science, suggests that it may eventually be possible to reverse some symptoms of Alzheimer’s in people, using drugs that boost brain metabolism. The results also offer an approach to treatment that’s unlike anything on the market today. Current drugs for treating Alzheimer’s, such as lecanemab and donanemab, target the sticky amyloid plaques that build up in a patient’s brain. These drugs can remove plaques and slow the disease process, but do not improve memory or thinking. The result should help “change how we think about targeting this disease,” says Shannon Macauley, an associate professor at the University of Kentucky who was not involved in the study. The new research was prompted by a lab experiment that didn’t go as planned. A team at Stanford was studying an enzyme called IDO1 that plays a key role in keeping a cell’s metabolism running properly. They suspected that in Alzheimer’s disease, IDO1 was malfunctioning in a way that limited the brain’s ability to turn nutrients into energy. © 2024 npr

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 17: Learning and Memory
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 13: Memory and Learning
Link ID: 29462 - Posted: 09.04.2024

Juliana Ki In the United States, it's estimated that about 7 million people are living with Alzheimer's disease and related dementias. But the number of people with a formal diagnosis is far less than that. Now, a new study suggests the likelihood of getting a formal diagnosis may depend on where a person lives. Researchers at the University of Michigan and Dartmouth College found that diagnosis rates vastly differ across the country and those different rates could not simply be explained by dementia risk factors, like if an area has more cases of hypertension, obesity and diabetes. The reasons behind the disparity aren't clear, but researchers speculate that stigma as well as access to primary care or behavioral neurological specialists may impact the odds of getting a formal diagnosis. Sponsor Message "We tell anecdotes about how hard it is to get a diagnosis and maybe it is harder in some places. It's not just your imagination. It actually is different from place to place," said Julie Bynum, the study's lead author and a geriatrician at the University of Michigan Medical School. Those differences may have potential consequences. That's because a formal diagnosis of Alzheimer's opens up access to treatments that may slow down the brain changes associated with the disease. Without that formal diagnosis, patients also would not be eligible for clinical trials or insurance coverage for certain medications. Even in cases of dementia where treatment is not an option, a diagnosis can also help in the planning for a patient's care. The findings, published last week in the journal Alzheimer's & Dementia, emerged from two main questions: What percent of older adults are being diagnosed with dementia across communities in the U.S.? And is the percent we see different from what we would expect? © 2024 npr

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29444 - Posted: 08.21.2024

By Charles Q. Choi Tangles of tau protein track with cognitive impairments in Alzheimer’s disease. But even though tau is expressed throughout the brain, it clumps mainly in specific regions, such as the cortex and hippocampus. Other areas, such as the cerebellum and brainstem, are largely spared. Why tau aggregates this way has remained a mystery, but the answer may have to do with a previously overlooked, oversized and naturally occurring variant of the protein called “big tau,” according to a preprint posted 31 July on bioRxiv. Most tau isoforms range from 352 to 441 amino acids in size, but big tau comprises 758 amino acids. This supersized version is significantly more abundant in the cerebellum and brainstem than in the cortex and hippocampus of mice—and it is much less likely to form abnormal clumps than its smaller counterparts, the preprint shows. “Big tau can resist several key pathological changes related to [Alzheimer’s disease],” wrote study investigator Dah-eun Chloe Chung, a postdoctoral researcher in Huda Zoghbi’s lab at Baylor College of Medicine, in a post on X about the work. (Zoghbi declined to comment for this article because she says the study is currently under review for potential publication, and Chung did not respond to email requests for comment.) Scientists identified big tau in the peripheral nervous system in the 1990s, and it is the predominant tau isoform there. But most research on tau since then “ignores the existence of big tau,” according to a 2020 review. “No one has bothered to study this protein in the context of neurodegeneration,” says Veera Rajagopal, a research scientist at Regeneron, who did not take part in the new work. “All tau-related research has been focused on the shorter isoforms that play a key role in the tauopathies like Alzheimer’s disease, frontotemporal dementia and so on. Now many will go after this big guy.” © 2024 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29440 - Posted: 08.19.2024

By Greg Donahue In late 2018, after an otherwise-normal Christmas holiday, Laurie Beatty started acting strange. An 81-year-old retired contractor, he grew unnaturally quiet and began poring over old accounting logs from a construction business he sold decades earlier, convinced that he had been bilked in the deal. Listen to this article, read by Robert Petkoff Over the course of several days, Beatty slipped further into unreality. He told his wife the year was 1992 and wondered aloud why his hair had turned white. Then he started having seizures. His arms began to move in uncontrollable jerks and twitches. By the end of May, he was dead. Doctors at the Georges-L.-Dumont University Hospital Center in Moncton, the largest city in the province of New Brunswick, Canada, zeroed in on an exceedingly rare condition — Creutzfeldt-Jakob disease, caused by prions, misfolding proteins in the brain — as the most likely culprit. The doctors explained this to Beatty’s children, Tim and Jill, and said they would run additional tests to confirm the post-mortem diagnosis. Three months later, when the siblings returned to the office of their father’s neurologist, Dr. Alier Marrero, that’s what they were expecting to hear. Instead, Marrero told them that Laurie’s Creutzfeldt-Jakob test had come back negative. “We were all looking at one another,” Tim says, “because we were all very confused.” If Creutzfeldt-Jakob hadn’t killed their father, then what had? What Marrero said next was even more unsettling. “There’s something going on,” they recall him saying. “And I don’t know what it is.” It turned out that Laurie Beatty was just one of many local residents who had gone to Marrero’s office exhibiting similar, inexplicable symptoms of neurological decline — more than 20 in the previous four years. The first signs were often behavioral. One patient fell asleep for nearly 20 hours straight before a friend took her to the hospital; another found himself afraid to disturb the stranger who had sat down in his living room, only to realize hours later that the stranger was his wife. © 2024 The New York Times Company

Related chapters from BN: Chapter 17: Learning and Memory; Chapter 18: Attention and Higher Cognition
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 14: Attention and Higher Cognition
Link ID: 29434 - Posted: 08.15.2024

Andrew Gregory Health editor Almost half of dementia cases worldwide could be prevented or delayed, a study has found, as experts named 14 risk factors. The number of people living with dementia globally is forecast to nearly triple to 153 million by 2050, and researchers warn this presents a rapidly growing threat to health and social care systems. Global health and social costs linked to dementia exceed $1tn (£780bn) a year, the research shows. However, in a seismic report published by the Lancet, 27 of the world’s leading dementia experts concluded that far more cases could be avoided or delayed than previously thought. Addressing 14 modifiable risk factors, starting in childhood and continuing throughout life, could prevent or delay 45% of dementia cases, even as people live longer, the Lancet commission on dementia said. The findings were presented at the Alzheimer’s Association international conference in the US. In an interview with the Guardian, the lead author of the research, Prof Gill Livingston, said it was increasingly clear that there was much more that millions of people could and should do to reduce the risk of dementia. Speaking from the conference in Philadelphia, Livingston said: “Many people around the world believe dementia is inevitable but it’s not. Our report concludes that you can hugely increase the chances of not developing dementia or pushing back its onset. “It’s also important to stress that while we now have stronger evidence that longer exposure to risk has a greater effect … it’s never too early or too late to take action.” © 2024 Guardian News & Media Limited

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 17: Learning and Memory
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 13: Memory and Learning
Link ID: 29420 - Posted: 08.03.2024

By Laura Sanders Alzheimer’s disease is hard to diagnose. But proteins in the blood might provide clarity. A series of recent findings, presented at the annual Alzheimer’s Association International Conference in Philadelphia and in research papers, raise the possibility of a simple blood draw to help doctors figure out if a person’s cognitive problems are caused by Alzheimer’s — or something else. Decades ago, the only definitive way to get a diagnosis was an autopsy. Since then, scientists have figured out how to see the disease in living people. Spinal taps reveal levels of key proteins associated with the disease. And brain scans can illuminate the characteristic plaques and tangles that mar the brain in a person with Alzheimer’s disease. But spinal taps and brain scans are expensive and uncomfortable. A blood draw would lower barriers to diagnosis even further. That matters, because while Alzheimer’s has no cure, an easier, faster way to spot the disease could give people more time to discuss therapy options, including the newly available drugs that lower levels of amyloid, the sticky protein that accumulates in the brain in Alzheimer’s (SN: 7/17/23). Those drugs moderately slow the progression of the disease, but they come with serious side effects (SN: 6/7/21). “It’s an exciting moment,” says neuropathologist Eliezer Masliah of the National Institute on Aging in Bethesda, Md. “It’s an explosive moment,” one that has the potential to help reshape the diagnosis and treatment of the nearly 7 million people with Alzheimer’s in the United States, and millions more worldwide, he says. © Society for Science & the Public 2000–2024.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29419 - Posted: 08.03.2024

By Laura Hercher It is impossible, of course, to identify the precise moment we first suspected the changes in my mother were something other than normal aging. In my own imperfect memory, what rises up is the first morning of a weeklong trip to Rome, when my mother woke up at 2 A.M., got dressed and went down for breakfast. A hotel employee found her wandering from room to room, looking for toast and coffee. She was jet-lagged, my brother and I assured each other uneasily. It could happen to anyone. But weren’t there cues? Didn’t she notice the darkened lobby, the stillness, the clock? If we had known then, would it have helped? To date, no Food and Drug Administration–approved therapy exists for asymptomatic people at risk of Alzheimer’s disease (AD). My mother was not a smoker, drank in moderation, read books, took classes, and spent the week soaking up everything the tour guide had to tell her about Caravaggio and Bernini like she was prepping for the quiz. It was five years before my mother received a diagnosis of dementia. Today, a simple blood test can detect changes in the brain that predict AD up to 15 years before the first symptoms emerge. For researchers, tools for early detection give a peek at the full spectrum of AD, pinpointing early seeds of pathology deep inside the brain. Cognitive decline—what we typically think of as the disease itself—is merely an end-stage denouement. “Dementia is a result. Dementia is a symptom,” explains Clifford R. Jack, Jr., a neuroradiologist at the Mayo Clinic in Rochester, Minn., and chair of the Alzheimer’s Association (AA) working group responsible for new and controversial guidelines for the diagnosis of AD based on the underlying biology, not clinical presentation. Biomarkers for AD—signs of the physical changes in the brain that contribute to disease progression—have been available for more than two decades. In 2007 an international working group (IWG) of dementia experts described biomarkers as supporting evidence for a diagnosis of the disease, defined at that point largely as it was by neuropathologist Alois Alzheimer back in 1906: progressive memory loss, confusion and personality changes caused by distinctive plaques and tangles in the brain. For almost a century, those brain changes could only be confirmed on autopsy. While the affected person was alive, the label was merely presumptive. In fact, postmortem studies have found that up to 30 percent of people who received a clinical diagnosis of AD did not have the characteristic plaques and tangles.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29416 - Posted: 08.02.2024

Jon Hamilton A key protein that helps assemble the brain early in life also appears to protect the organ from Alzheimer’s and other diseases of aging. A trio of studies published in the past year all suggest that the protein Reelin helps maintain thinking and memory in ailing brains, though precisely how it does this remains uncertain. The studies also show that when Reelin levels fall, neurons become more vulnerable. There’s growing evidence that Reelin acts as a “protective factor” in the brain, says Li-Huei Tsai, a professor at MIT and director of the Picower Institute for Learning and Memory. “I think we’re on to something important for Alzheimer’s,” Tsai says. Various pieces of colorful trash, such as plastic bottle caps and plastics forks, are arranged in the shape of a human brain, on a light blue background. The research has inspired efforts to develop a drug that boosts Reelin or helps it function better, as a way to stave off cognitive decline. “You don't have to be a genius to be like, ‘More Reelin, that’s the solution,’” says Dr. Joseph Arboleda-Velasquez of Harvard Medical School and Massachusetts Eye and Ear. “And now we have the tools to do that.” From Colombia, a very special brain Reelin became something of a scientific celebrity in 2023, thanks to a study of a Colombian man who should have developed Alzheimer’s in middle age but didn’t. The man, who worked as a mechanic, was part of a large family that carries a very rare gene variant known as Paisa, a reference to the area around Medellin where it was discovered. Family members who inherit this variant are all but certain to develop Alzheimer’s in middle age. © 2024 npr

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 17: Learning and Memory
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 13: Memory and Learning
Link ID: 29413 - Posted: 07.31.2024

By Pam Belluck Scientists have made another major stride toward the long-sought goal of diagnosing Alzheimer’s disease with a simple blood test. On Sunday, a team of researchers reported that a blood test was significantly more accurate than doctors’ interpretation of cognitive tests and CT scans in signaling the condition. The study, published Sunday in the journal JAMA, found that about 90 percent of the time the blood test correctly identified whether patients with memory problems had Alzheimer’s. Dementia specialists using standard methods that did not include expensive PET scans or invasive spinal taps were accurate 73 percent of the time, while primary care doctors using those methods got it right only 61 percent of the time. “Not too long ago measuring pathology in the brain of a living human was considered just impossible,” said Dr. Jason Karlawish, a co-director of the Penn Memory Center at the University of Pennsylvania who was not involved in the research. “This study adds to the revolution that has occurred in our ability to measure what’s going on in the brain of living humans.” The results, presented Sunday at the Alzheimer’s Association International Conference in Philadelphia, are the latest milestone in the search for affordable and accessible ways to diagnose Alzheimer’s, a disease that afflicts nearly seven million Americans and over 32 million people worldwide. Medical experts say the findings bring the field closer to a day when people might receive routine blood tests for cognitive impairment as part of primary care checkups, similar to the way they receive cholesterol tests. “Now, we screen people with mammograms and PSA or prostate exams and other things to look for very early signs of cancer,” said Dr. Adam Boxer, a neurologist at the University of California, San Francisco, who was not involved in the study. “And I think we’re going to be doing the same thing for Alzheimer’s disease and hopefully other forms of neurodegeneration.” © 2024 The New York Times Company

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29410 - Posted: 07.31.2024

Richard Luscombe Federal health authorities on Tuesday gave approval to an experimental new drug that has shown to delay the onset of Alzheimer’s disease in trials. Donanemab, manufactured by Eli Lilly, is the second medication that has won the blessing of the Food and Drug Administration (FDA) to treat patients showing early symptoms of the disease, most prominently cognitive impairment. Last year, authorities cleared the drug lecanemab, marketed under the brand name Leqembi, after it demonstrated a similar decline in the progression of Alzheimer’s in a control group. The treatments are not a cure, but the first to physically alter the course of the disease rather than just addressing its symptoms, the FDA said. The video player is currently playing an ad. Indianapolis-based Eli Lilly reported the success of its trial a year ago, and subsequently applied for the FDA authorization that was announced today. Experts at the time said it “could be the beginning of the end of Alzheimer’s disease”, which affects almost 7 million people, mostly older Americans, according to the Alzheimer’s Association. “Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer’s disease, who urgently need effective treatment options,” Anne White, executive vice-president of Eli Lilly said on Tuesday, referring to donanemab by the brand name it will be sold under. © 2024 Guardian News & Media Limited

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29374 - Posted: 07.03.2024

By Gina Kolata and Pam Belluck A committee of independent advisers to the Food and Drug Administration voted unanimously on Monday that the benefits outweigh the risks of the newest experimental drug for Alzheimer’s disease. Alzheimer’s afflicts more than six million Americans. It has no cure, and there is no treatment or lifestyle modification that can restore memory loss or reverse cognitive decline. The drug, made by Eli Lilly, is donanemab. It modestly slowed cognitive decline in patients in the early stages of the disease but also had significant safety risks, including swelling and bleeding in the brain. The committee concluded, though, that the consequences of Alzheimer’s are so dire that even a modest benefit can be worthwhile. The F.D.A. usually follows the advice of the agency’s advisory committees but not always. The drug is based on a long-held hypothesis that Alzheimer’s disease begins when rough hard balls of amyloid, a protein, pile up in patients’ brains, followed by a cascade of reactions leading to the death of neurons. The idea is to treat Alzheimer’s by attacking amyloid, clearing it from the brain. Two similar amyloid-fighting drugs were approved recently: Leqembi, made by Eisai and Biogen, was approved last year. That drug’s risks and modest benefits are similar to those of donanemab. Aduhelm, made by Biogen, is the other drug and was approved in 2021 but was discontinued because there was insufficient evidence that it could benefit patients. Donanemab was expected to be approved earlier this year, but in March, the F.D.A. decided that, instead, it would require donanemab to undergo the scrutiny of an independent advisory committee, a surprise to Eli Lilly. © 2024 The New York Times Company

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29354 - Posted: 06.11.2024

Hannah Devlin Science correspondent A 10-minute brain scan could detect dementia several years before people develop noticeable symptoms, a study suggests. Scientists used a scan of “resting” brain activity to identify whether people would go on to develop dementia, with an estimated 80% accuracy up to nine years before people received a diagnosis. If the findings were confirmed in a larger cohort, the scan could become a routine procedure in memory clinics, scientists said. “We’ve known for a long time that the function of the brain starts to change many years before you get dementia symptoms,” said Prof Charles Marshall, who led the work at Queen Mary University of London. “This could help us to be more precise at identifying those changes using an MRI scan that you could do on any NHS scanner.” The research comes as a new generation of Alzheimer’s drugs are on the horizon. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is assessing lecanemab, made by Eisai and Biogen, and donanemab, made by Eli Lilly, and both drugs are widely expected to be licensed this year. “Predicting who is going to get dementia in the future will be vital for developing treatments that can prevent the irreversible loss of brain cells that causes the symptoms of dementia,” Marshall said. The researchers used functional MRI (fMRI) scans from 1,100 UK Biobank volunteers to detect changes in the brain’s “default mode network” (DMN). The scan measures correlations in brain activity between different regions while the volunteer lies still, not doing any particular task. The network, which reflects how effectively different regions are communicating with each other, is known to be particularly vulnerable to Alzheimer’s disease. © 2024 Guardian News & Media Limited

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 29349 - Posted: 06.08.2024

Leyland Cecco in Toronto A leading federal scientist in Canada has alleged he was barred from investigating a mystery brain illness in the province of New Brunswick and said he fears more than 200 people affected by the condition are experiencing unexplained neurological decline. The allegations, made in leaked emails to a colleague seen by the Guardian, have emerged two years after the eastern province closed its investigation into a possible “cluster” of cases. “All I will say is that my scientific opinion is that there is something real going on in [New Brunswick] that absolutely cannot be explained by the bias or personal agenda of an individual neurologist,” wrote Michael Coulthart, a prominent microbiologist. “A few cases might be best explained by the latter, but there are just too many (now over 200).” New Brunswick health officials warned in 2021 that more than 40 residents were suffering from a possible unknown neurological syndrome, with symptoms similar to those of the degenerative brain disorder Creutzfeldt-Jakob disease. Those symptoms were varied and dramatic: some patients started drooling and others felt as though bugs were crawling on their skin. A year later, however, an independent oversight committee created by the province determined that the group of patients had most likely been misdiagnosed and were suffering from known illnesses such as cancer and dementia. The committee and the New Brunswick government also cast doubt on the work of neurologist Alier Marrero, who was initially referred dozens of cases by baffled doctors in the region, and subsequently identified more cases. The doctor has since become a fierce advocate for patients he feels have been neglected by the province. © 2024 Guardian News & Media Limited

Related chapters from BN: Chapter 11: Motor Control and Plasticity; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 5: The Sensorimotor System; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 29342 - Posted: 06.04.2024

By Elissa Welle The traditional story of Alzheimer’s disease casts two key proteins in starring roles—each with clear stage directions: Plaques of sticky amyloid beta protein accumulate outside neurons as the condition unfolds, and tangles of tau protein gum up the insides of the cells. But it may be time for a rewrite. Amyloid beta, too, coalesces inside neurons and seems to mark them for early death, according to research posted on a preprint server last November. In brain slices from people with Alzheimer’s, but not in those from age-matched controls, cells containing intracellular amyloid beta decreased in number as the disease progressed. At first, the result appeared to be a mistake, says study investigator Alessia Caramello, a postdoctoral researcher in the UK Dementia Research Institute. Intracellular amyloid beta is “nowhere to be found” in most discussions of Alzheimer’s disease, she says. “It’s never mentioned. Never ever.” Instead, the field has long focused on the buildup of amyloid beta outside the cell. But even before those plaques form, there seems to be another pathological event, she says—namely intracellular amyloid—“Why not look at it?” The work from Caramello and her colleagues is not the first to suggest that amyloid beta, or Abeta for short, wreaks havoc inside neurons, not just in the extracellular space between them. This “inside-out” hypothesis, as it has been called, has implications for how scientists understand Alzheimer’s disease. In particular, it could help to account for some big mysteries around the condition—such as why the extent of amyloid beta plaques in the brain doesn’t always correlate with symptoms, why neurons die and why treatments to lessen plaques marginally slow down, but do not halt, the disease. “It just puts a totally different spin on how you need to address this,” says Gunnar Gouras, professor of experimental neurology at Lund University and a proponent of the inside-out hypothesis. “It’s really a cell biological, neurobiological issue that is a bit more complex. And we need to also study this instead of just saying, ‘Abeta is bad; we’ve got to get rid of it.’” © 2024 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29335 - Posted: 06.02.2024

By Ben Casselman Long before people develop dementia, they often begin falling behind on mortgage payments, credit card bills and other financial obligations, new research shows. A team of economists and medical experts at the Federal Reserve Bank of New York and Georgetown University combined Medicare records with data from Equifax, the credit bureau, to study how people’s borrowing behavior changed in the years before and after a diagnosis of Alzheimer’s or a similar disorder. What they found was striking: Credit scores among people who later develop dementia begin falling sharply long before their disease is formally identified. A year before diagnosis, these people were 17.2 percent more likely to be delinquent on their mortgage payments than before the onset of the disease, and 34.3 percent more likely to be delinquent on their credit card bills. The issues start even earlier: The study finds evidence of people falling behind on their debts five years before diagnosis. “The results are striking in both their clarity and their consistency,” said Carole Roan Gresenz, a Georgetown University economist who was one of the study’s authors. Credit scores and delinquencies, she said, “consistently worsen over time as diagnosis approaches, and so it literally mirrors the changes in cognitive decline that we’re observing.” The research adds to a growing body of work documenting what many Alzheimer’s patients and their families already know: Decision-making, including on financial matters, can begin to deteriorate long before a diagnosis is made or even suspected. People who are starting to experience cognitive decline may miss payments, make impulsive purchases or put money into risky investments they would not have considered before the disease. “There’s not just getting forgetful, but our risk tolerance changes,” said Lauren Hersch Nicholas, a professor at the University of Colorado School of Medicine who has studied dementia’s impact on people’s finances. “It might seem suddenly like a good move to move a diversified financial portfolio into some stock that someone recommended.” © 2024 The New York Times Company

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29334 - Posted: 06.02.2024

Nicola Davis Science correspondent Having two copies of a gene variant known to predispose people to Alzheimer’s could in fact represent a distinct genetic form of the disease, researchers have said. The variant, known as ApoE4, has long been known to increase the risk of developing Alzheimer’s, with two copies conferring greater risk than one. Now research has revealed almost everyone with two copies of the variant goes on to develop Alzheimer’s disease (AD), suggesting it is not only a risk factor but a cause. “Over 95% of the individuals [with two copies of ApoE4], have AD pathology either in the brain or in the biomarkers that we analysed,” said Dr Juan Fortea, the co-author of the research from the Sant Pau hospital in Barcelona. The video player is currently playing an ad. His team said the predicability of the age at which symptoms began was similar to other genetic forms of the disease such as autosomal-dominant Alzheimer’s disease (ADAD) and Alzheimer’s disease in Down syndrome (DSAD). Dr Victor Montal, a co-author from Barcelona Supercomputing Center, said the research had catalysed a paradigm shift in the understanding of the disease. “Whereas previously, the etiology of dementia was known in less than 1% of cases, our work has now enabled the identification of causative factors in over 15% of instances,” he said. However, the study did not shed light on the risk of developing dementia itself for people with two copies of ApoE4. © 2024 Guardian News & Media Limited

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29292 - Posted: 05.07.2024

By Joanne Silberner In March, the sons of Gabriel García Márquez, the Nobel Prize-winning Colombian writer, published a posthumous novel against the specific wishes their father expressed before he died in 2014 at the age of 87. García Márquez had struggled through several versions of the book as dementia set in, and, perhaps stung by uncharacteristic negative reviews from his previous novel, didn’t want the new one published. “Until August,” the story of a woman who travels to her mother’s grave once a year and takes a new lover on each visit, got mixed reviews. Some were outright harsh. In The New York Times, Michael Greenberg wrote “It would be hard to imagine a more unsatisfying goodbye.” García Márquez’s decline, he continued, “seems to have been steep enough to prevent him from holding together the kind of imagined world that the writing of fiction demands.” Wendy Mitchell, who was an administrator with England’s National Health Service until her diagnosis of early-onset Alzheimer’s disease in 2014, recalled the moment she learned of the publication plans last year. “I type every day for fear of dementia snatching away that creative skill, which I see as my escape from dementia,” she wrote last October in The Guardian. “Maybe Márquez thought the same?” The novel’s publication raises some vital questions about living with an aging and perhaps ailing brain. What do mild cognitive impairment and dementia do to our creativity? How do these conditions affect our ability to use words, formulate sentences, and craft stories? Neuroscientists have been exploring these questions for several decades. First, a few definitions. People with mild cognitive impairment have lost more of their cognitive functioning than others their age, and often struggle to remember things. But they’re capable of managing daily activities like dressing, eating, bathing, and finding their way around. In dementia, cognitive difficulties have increased enough to interfere with daily life, and personality changes are more likely.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29254 - Posted: 04.13.2024

By Catherine Offord Bone marrow transplants between mice can transmit symptoms and pathology associated with Alzheimer’s disease, according to a controversial study published today in Stem Cell Reports. Its authors found that healthy mice injected with marrow from a mouse strain carrying an extremely rare, Alzheimer’s-linked genetic mutation later developed cognitive problems and abnormal clumping of proteins in the brain. In claims that other scientists in the field have criticized as overstated, the team says its findings demonstrate “Alzheimer’s disease transmission” and support screening of human bone marrow, organ, and blood donors for mutations related to neurodegeneration. “The findings are not by any means conclusive,” says Lary Walker, a neuroscientist at Emory University. Although the team’s approach offers an interesting way to study potential causes of neurodegeneration, he says, “the mice do not have Alzheimer’s disease,” only certain symptoms that mimic those of the disorder and require further study. He and other scientists stress that the new findings should not deter people who medically need bone marrow or other transplants. Alzheimer’s is partly characterized by so-called plaques of beta amyloid, a fragment of a larger protein called APP, around cells in the brain. Although there are rare, early-onset versions of the disease driven by specific mutations in the gene coding for APP or related proteins, most cases arise in people over age 65 and don’t have a single known cause. Some research hints that in very unusual scenarios, Alzheimer’s could be transmitted via human tissue or medical equipment contaminated with disease-causing proteins. Earlier this year, for example, U.K. scientists described dementia and beta amyloid buildup in several people who had received injections of growth hormone from the brains of deceased donors. (The procedure was once a medical treatment for certain childhood disorders but was abandoned in the 1980s.)

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 5: Hormones and the Brain
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 8: Hormones and Sex
Link ID: 29225 - Posted: 03.30.2024

By Esther Landhuis In January 2023, the US Food and Drug Administration (FDA) approved lecanemab — an antibody medication that decreases β-amyloid protein build-up in the brain — as a treatment for Alzheimer’s disease. Pivotal evidence came from a large, randomized trial of people with early-stage Alzheimer’s, which afflicts around 32 million people worldwide. By the end of that 18-month study1, patients in the placebo group scored on average 1.66 points worse than their performance at baseline on a standard dementia test, which assesses cognitive and functional changes over time through interviews with a patient and their caregiver. The mean score of treated participants, by comparison, worsened by 1.21 points — a 27% slowing of cognitive decline. But is this improvement meaningful for patients and their families? There are two major categories of drugs used to treat Alzheimer’s disease and other progressive conditions: symptomatic drugs, which treat the symptoms, and disease-modifying drugs, which target the root cause. Donepezil and rivastigmine, for example, are symptomatic drugs that boost the activity of chemicals in the brain to compensate for declines in cognitive and memory function caused by Alzheimer’s disease, but they cannot stop its progression. Lecanemab, developed jointly by Japanese pharmaceutical company Eisai and American biotechnology firm Biogen, targets the underlying issue of amyloid build-up in the brain, and in doing so, could fundamentally change the course of the disease. An important feature of disease-modifying drugs is that their benefits are cumulative. Studies of patients with multiple sclerosis, for example, have shown the benefits of starting disease-modifying drugs earlier in the course of the disease compared with later, including improved mortality rates and reduced disability in the long term. Being able to quantify how long a disease-modifying drug can delay or halt the progression of Alzheimer’s disease could change how researchers understand — and communicate — its benefits. © 2024 Springer Nature Limited

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 29193 - Posted: 03.16.2024

By Katherine Ellison Jonel Dershem first noticed problems with her memory in 2016 after her breast cancer surgery. She was only 50 and at first blamed the lapses on chemotherapy, and then on her busy, stressful life. So did her husband and friends — and doctor. “I kept blowing it off,” said Dershem, an obstetrician from Voorhees, N.J., whose challenges began with little things like leaving a faucet running and progressed to trouble finishing routine tasks. “I was our family’s primary breadwinner. I didn’t want there to be any serious problems.” In December 2022, nearly seven years after her memory loss began, Dershem was diagnosed with mild cognitive impairment (MCI). Her delayed diagnosis wasn’t unusual, but experts say that needs to change. More than occasional forgetfulness, MCI causes problems that disrupt daily life but don’t make it impossible to function, said Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging. It is often but not always a precursor to dementia, he added. “It’s a subtle condition,” said Petersen, who in 1999 led the first study differentiating patients with MCI from healthy subjects and those with dementia. If you miss a golf date once, no worries, he said, but if “that happened a couple of times last week and people in your family are starting to worry about you — well, that may be MCI.” “With MCI, people can still drive, pay their bills and do their taxes — they just do so less efficiently,” Petersen said. A 2022 study in the journal Alzheimer’s & Dementia projected that 14.4 million people in the United States would have MCI in 2025, and 19.3 million in 2050. An American Academy of Neurology subcommittee estimated that about 1 in 10 people ages 70 to 74 had MCI, and 1 in 4 ages 80 to 84 in 2018.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 17: Learning and Memory
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 13: Memory and Learning
Link ID: 29178 - Posted: 03.05.2024