The Brain: Alzheimer's and dementia news and discussions

weatheriscool
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Class of diabetes drugs cuts dementia risk in older adults, research shows
https://medicalxpress.com/news/2022-12- ... older.html
by Erin Howe, University of Toronto

A class of medication for type 2 diabetes may help older people with the condition reduce their risk of dementia.

The findings are contained in a new study by Walter Swardfager, an assistant professor of pharmacology and toxicology at the Temerty Faculty of Medicine and a scientist in the Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Research Institute, and graduate student Che-Yuan (Joey) Wu. Their research is published in the journal Diabetes Care.

The research shows that sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with a 20% lower dementia risk when compared to another kind of medication known as dipeptidyl peptidase-4 inhibitors (DPP4).

Often, the first medication prescribed to people with type 2 diabetes is metformin. When metformin alone doesn't have the desired effect, additional therapies such as SGLT2 and DPP4 inhibitors may be added or substituted. For many patients, physicians will choose between these two classes of drugs.

SGLT2 inhibitor medications, which include dapagliflozin and empagliflozin, are commonly prescribed. These drugs lower blood sugar by causing the kidneys to remove sugar from the body through urine. DPP4 inhibitor medications—which include linagliptin, saxagliptin and sitagliptin—work by blocking the action of an enzyme that destroys an insulin-producing hormone.
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New evidence links nasal viral infections to rapid Alzheimer's progression
By Rich Haridy
December 18, 2022
https://newatlas.com/science/nasal-vira ... s-disease/

A new study has presented more evidence backing up a hypothesis suggesting viral infections in the olfactory system can accelerate the progression of Alzheimer's disease (AD). Instead of focusing on specific viruses, the research looked at the relationship between biomarkers of viral infections and neurodegeneration in the hippocampus.

For decades, researchers have reported an association between brain diseases and acute viral infections. The herpes simplex virus in particular has long been associated with the development of Alzheimer's disease. But exactly how viral infections could be influencing neurodegeneration has been unclear.

This new research focused specifically on the olfactory system. Loss of one's sense of smell has been found to be a potential early marker of Alzheimer's neurodegeneration. So, the question explored here is whether viral infections in the nose play a role in accelerating Alzheimer's decline.

To investigate this, the researchers analyzed post-mortem brain tissue from several individuals who died with Alzheimer's disease. Compared to tissue samples taken from age-matched cognitively healthy subjects, the Alzheimer's group displayed substantial markers of viral infection and inflammation in the olfactory tract – a key pathway that leads to the hippocampus.
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Researchers develop blood test that can reliably detect Alzheimer’s disease
https://www.engadget.com/researchers-de ... 20271.html

When doctors need to confirm an Alzheimer's diagnosis, they often turn to a combination of brain imaging and cell analysis. Both have their downsides. The latter involves a lumbar puncture, an invasive and painful procedure that’s more commonly known as a spinal tap. A doctor will insert a needle into the lower back to extract a sample of the patient’s cerebrospinal fluid. A lab technician then tests the sample for signs of progressive nerve cell loss and excessive amyloid and tau protein accumulation. MRI scans are less invasive but they’re often expensive and accessibility is an issue; not every community has access to the technology.

The next best tool for diagnosing Alzheimer’s disease is a blood test. While some can detect abnormal tau protein counts, they’re less effective at spotting the telltale signs of neurodegeneration. But that could soon change. This week, in the journal Brain, a multinational team made up of researchers from Sweden, Italy, the UK and US detailed a new antibody-based blood test they recently developed. The new test can detect brain-derived tau proteins, which are specific to Alzheimer’s disease. Following a study of 600 patients, the team found their test could reliably distinguish the illness from other neurodegenerative diseases.
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FDA approves new Alzheimer's drug that appears to slow progression of disease
Source: NBC News
The Food and Drug Administration on Friday approved an Alzheimer’s drug shown in clinical trials to slow cognitive decline in patients in the early stages of the illness. The approval offers patients renewed hope after repeated failures to find effective treatments, even though there have been reports of side effects with the new drug, experts say.

The drug, lecanemab, which will be sold under the name Leqembi, is a monoclonal antibody infusion given every two weeks. The FDA approved Leqembi for use in people with mild cognitive impairment or early Alzheimer’s disease. The drug was approved in an accelerated pathway, which allows early approval for promising new medications that "fill an unmet medical need."

At the same time, companies are required to conduct additional clinical trials to confirm the benefits of their drugs or risk their removal from the market. The agency said its decision was based on a phase 3 clinical trial of 1,795 patients, which found the drug, developed by drugmakers Eisai and Biogen, slowed cognitive decline in people who received it by 27% after 18 months.

The FDA did not seek the advice of its advisory committee — which it did do before it controversially approved another Alzheimer’s drug developed by Biogen, called Aduhelm, in 2021. Leqembi is not a cure; it aims to slow the progression of the disease by removing clumps of beta-amyloid — long thought by scientists to be one of the main causes of the disease — from the brain.
Read more: https://www.nbcnews.com/health/health-n ... -rcna62928
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Human-approved medication brings back 'lost' memories in mice
https://medicalxpress.com/news/2023-01- ... -mice.html
by University of Groningen

Students sometimes pull an all-nighter to prepare for an exam. However, research has shown that sleep deprivation is bad for your memory. Now, University of Groningen neuroscientist Robbert Havekes discovered that what you learn while being sleep deprived is not necessarily lost, it is just difficult to recall.

Together with his team, he has found a way to make this "hidden knowledge" accessible again days after studying while sleep-deprived using optogenetic approaches, and the human-approved asthma drug roflumilast. These findings were published in the journal Current Biology.

Havekes, associate professor of Neuroscience of Memory and Sleep at the University of Groningen, the Netherlands, and his team have extensively studied how sleep deprivation affects memory processes. "We previously focused on finding ways to support memory processes during a sleep deprivation episode," says Havekes. However, in his latest study, his team examined whether amnesia as a result of sleep deprivation was a direct result of information loss, or merely caused by difficulties retrieving information.

"Sleep deprivation undermines memory processes, but every student knows that an answer that eluded them during the exam might pop up hours afterwards. In that case, the information was, in fact, stored in the brain, but just difficult to retrieve."

Neurons in the hippocampus

To address this question, Havekes and his team used an optogenetic approach: using genetic techniques, they caused a light-sensitive protein (channelrhodopsin) to be produced selectively in neurons that are activated during a learning experience. This made it possible to recall a specific experience by shining light on these cells. "In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, the area in the brain where spatial information and factual knowledge are stored," says Havekes.
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New test could detect Alzheimer's disease 3.5 years before clinical diagnosis
https://medicalxpress.com/news/2023-01- ... nosis.html
by King's College London
New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has established a blood-based test that could be used to predict the risk of Alzheimer's disease up to 3.5 years before clinical diagnosis.

The study, published in the journal Brain, supports the idea that components in the human blood can modulate the formation of new brain cells, a process termed neurogenesis. Neurogenesis occurs in an important part of the brain called the hippocampus that is involved in learning and memory.

While Alzheimer's disease affects the formation of new brain cells in the hippocampus during the early stages of the disease, previous studies have only been able to study neurogenesis in its later stages through autopsies.

To understand the early changes, researchers collected blood samples over several years from 56 individuals with Mild Cognitive Impairment (MCI), a condition where someone will begin to experience a worsening of their memory or cognitive ability. While not everyone experiencing MCI goes on to develop Alzheimer's disease, those with the condition progress to a diagnosis at a much higher rate than the wider population. Of the 56 participants in the study, 36 went on to receive a diagnosis of Alzheimer's disease.
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Potential therapeutic target for schizophrenia identified

by Melissa Rohman, Northwestern University
https://medicalxpress.com/news/2023-02- ... renia.html
Targeting calcium signaling in neurons represents a promising therapeutic approach for treating a rare form of schizophrenia, according to a Northwestern Medicine study published in Biological Psychiatry.

"This is the first time that human neurons are made and characterized from schizophrenia patients with the 16p11.2 duplication, one of the most prominent genetic risk factors in schizophrenia, and the first time that calcium signaling is found as a central abnormality in schizophrenia neurons," said Peter Penzes, Ph.D., the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences and senior author of the study.

Schizophrenia is characterized by auditory and visual hallucinations, delusions, and trouble with forming and sorting thoughts, which severely impacts productivity and overall quality of life. The disease, which affects roughly one percent of the general population, has strong genetic associations, however the exact genes involved are unknown.

Patients with schizophrenia can be treated with antipsychotics, however those drugs only address "positive symptoms," such as hallucinations and delusions, and neglect to treat cognitive symptoms such as thought disorder. Despite the availability of antipsychotics, only some patients will respond to them and the development of new treatments has been met with challenges, according to Penzes.

"This has been hampered by the fact that studies in animal models, such as mice, do not translate well to humans. In other words, some new drugs may work well in experimental animal studies, but fail when taken into human clinical trials," said Penzes, who is also a professor of Neuroscience, of Pharmacology and director of the Center for Autism and Neurodevelopment.

A potential solution to developing new therapies for schizophrenia is induced pluripotent stem cells (iPSCs), cells derived from a patient's blood or skin that can be reprogrammed to be any type of cell in the body, including neurons.
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Study Suggests Fructose Could Drive Alzheimer’s Disease
February 13 , 2023

Introduction:
(EurekAlert) AURORA, Colo. (Feb. 13, 2023) – An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer’s disease (AD), according to researchers at the University of Colorado Anschutz Medical Campus.

The study, published recently in The American Journal of Clinical Nutrition, offers a new way of looking at a fatal disease characterized by abnormal accumulations of proteins in the brain that slowly erode memory and cognition.

“We make the case that Alzheimer’s disease is driven by diet,” said the study’s lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension. The study co-authors include Maria Nagel, MD, research professor of neurology at the CU School of Medicine.

Johnson and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

Conclusion:
We suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease,” Johnson said.
Read more here: https://www.eurekalert.org/news-releases/979532
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weatheriscool
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Children's bad dreams linked to a higher risk of dementia and Parkinson's disease in adulthood, finds new study

by Abidemi Otaiku, The Conversation
https://medicalxpress.com/news/2023-02- ... entia.html
Can children's dreams foretell events that will happen nearly 40 years into the future? Yes, according to the results of my latest study published in the journal eClinicalMedicine.

More specifically, it showed that children who experience regular bad dreams and nightmares between the ages of seven and 11, may be nearly twice as likely to develop cognitive impairment (the core feature of dementia) by the time they reach age 50. And they may be up to seven times more likely to be diagnosed with Parkinson's disease by age 50.

For some background to these startling findings, in 2022 I discovered that middle-aged and older adults who experience frequent bad dreams and nightmares could be more than twice as likely to develop dementia or Parkinson's in the future.

Given that a large proportion of people who experience regular nightmares as adults also report having had regular nightmares when they were children, this made me wonder whether having lots of bad dreams during childhood might predict the development of dementia or Parkinson's disease later in life.
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Alzheimer's: New study supports amyloid hypothesis but suggests alternative treatment
https://medicalxpress.com/news/2023-03- ... tment.html
by Columbia University

An analysis of human brain cells provides new evidence in support of the "amyloid hypothesis," the prevailing idea that Alzheimer's is caused by the accumulation of beta-amyloid proteins in the brain.

In the study, Columbia University researchers found that amyloid sparks an alliance between two proteins in the brain's neurons and this pairing is linked to about half of the gene changes that are known to occur in the disease, triggering the rapid accumulation of tau proteins, a primary driver of neurodegeneration in the disease.

"This protein pair seems very central to the disease, and because it does not appear to have another function in the brain, it is a good target for a new therapy," says the study's senior author, Ulrich Hengst, Ph.D., associate professor of pathology & cell biology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at the Columbia University Vagelos College of Physicians and Surgeons.
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