Tag: Alzheimer’s disease

One of the few drugs that has been FDA-approved for patients with Alzheimer’s disease now identified as possibly increasing risk of a life-threatening condition of muscle breakdown

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Many people with Alzheimer’s disease take the drug donepezil (brand name Aricept) to help ease symptoms for a time. But those on the drug should be aware of a rare but potentially life-threatening side effect. The drug can cause muscles to break down, leading to a condition called rhabdomyolysis that can lead to kidney damage and even death.

The risk of hospitalization for rhabdomyolysis was more than double that for those taking Aricept compared to other Alzheimer’s drugs, a new study reports.

Still, the condition is very rare, and anyone taking Aricept should not stop taking it. But because rhabdomyolysis is potentially very serious, patients should be aware of the problem and seek medical care should symptoms arise.

The main symptom of rhabdomyolysis, or rhabdo as it is commonly called, is intense muscle pain or weakness that does not go away. Urine can also turn dark. Emergency treatment is needed to manage the condition and may require a week or longer stay in the hospital.

For the study, Canadian researchers analyzed data on 220,353 men and women over age 65 who had gotten a prescription between 2002 and 2017 for one of three Alzheimer’s drugs: donepezil, rivastigmine (Execlon) or galantamine (Razadyne).

There were 88 hospitalizations for rhabdo among 152,300 patients taking donepezil (0.06 percent prevalence), compared to 16 cases among the 68,053 patients taking one of the other drugs (0.02 percent prevalence).

The authors note that doctors should rule out rhabdo if someone on an Alzheimer’s drug comes to the hospital because of constant muscle pain. Still, the condition remains very rare (about 25,000 per year in the U.S. from all causes), and most of the cases in the current study were not life-threatening.

Other medications may also trigger the condition, including antipsychotic medications, which are also often prescribed to people with Alzheimer’s disease to allay symptoms like agitation and aggression. Cholesterol-lowering statin drugs have also been tied to an increased risk of rhabdo. It is possible that Aricept cannot trigger rhabdo alone. Further studies will be required to determine what other cofactors might act with Aricept to trigger rhabdo.

The condition more commonly arises after intense physical exertion, often in people who have not been training regularly. The condition can arise in military recruits undergoing basic training, and in people beginning high-intensity workouts at the gym.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Jamie L. Fleet, Eric McArthur, Aakil Patel, et al: “Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study.” CMAJ – Canadian Medical Association Journal, Sept. 16, 2019

Alzheimer’s Directly Kills Brain Cells That Keep You Awake

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Brain tissue from deceased patients with Alzheimer’s has more tau protein buildup (brown spots) and fewer neurons (red spots) as compared to healthy brain tissue.

By Yasemin Saplakoglu

Alzheimer’s disease might be attacking the brain cells responsible for keeping people awake, resulting in daytime napping, according to a new study.

Excessive daytime napping might thus be considered an early symptom of Alzheimer’s disease, according to a statement from the University of California, San Francisco (UCSF).

Some previous studies suggested that such sleepiness in patients with Alzheimer’s results directly from poor nighttime sleep due to the disease, while others have suggested that sleep problems might cause the disease to progress. The new study suggests a more direct biological pathway between Alzheimer’s disease and daytime sleepiness.

In the current study, researchers studied the brains of 13 people who’d had Alzheimer’s and died, as well as the brains from seven people who had not had the disease. The researchers specifically examined three parts of the brain that are involved in keeping us awake: the locus coeruleus, the lateral hypothalamic area and the tuberomammillary nucleus. These three parts of the brain work together in a network to keep us awake during the day.

The researchers compared the number of neurons, or brain cells, in these regions in the healthy and diseased brains. They also measured the level of a telltale sign of Alzheimer’s: tau proteins. These proteins build up in the brains of patients with Alzheimer’s and are thought to slowly destroy brain cells and the connections between them.

The brains from patients who had Alzheimer’s in this study had significant levels of tau tangles in these three brain regions, compared to the brains from people without the disease. What’s more, in these three brain regions, people with Alzheimer’s had lost up to 75% of their neurons.

“It’s remarkable because it’s not just a single brain nucleus that’s degenerating, but the whole wakefulness-promoting network,” lead author Jun Oh, a research associate at UCSF, said in the statement. “This means that the brain has no way to compensate, because all of these functionally related cell types are being destroyed at the same time.”

The researchers also compared the brains from people with Alzheimer’s with tissue samples from seven people who had two other forms of dementia caused by the accumulation of tau: progressive supranuclear palsy and corticobasal disease. Results showed that despite the buildup of tau, these brains did not show damage to the neurons that promote wakefulness.

“It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease,” Oh said in the statement. “Understanding why this is the case is something we need to follow up in future research.”

Though amyloid proteins, and the plaques that they form, have been the major target in several clinical trials of potential Alzheimer’s treatments, increasing evidence suggests that tau proteins play a more direct role in promoting symptoms of the disease, according to the statement.

The new findings suggest that “we need to be much more focused on understanding the early stages of tau accumulation in these brain areas in our ongoing search for Alzheimer’s treatments,” senior author Dr. Lea Grinberg, an associate professor of neurology and pathology at the UCSF Memory and Aging Center, said in the statement.

The findings were published Monday (Aug. 12) in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

https://www.livescience.com/alzheimers-attacks-wakefulness-neurons.html?utm_source=notification

Low-carb ‘keto’ diet (‘Atkins-style’) may modestly improve cognition in older adults

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In a pilot study of 14 older adults with mild cognitive problems suggestive of early Alzheimer’s disease, Johns Hopkins Medicine researchers report that a high-fat, low-carbohydrate diet may improve brain function and memory.

Although the researchers say that finding participants willing to undertake restrictive diets for the three-month study—or partners willing to help them stick to those diets—was challenging, those who adhered to a modified Atkins diet (very low carbohydrates and extra fat) had small but measurable improvements on standardized tests of memory compared with those on a low-fat diet.

The short-term results, published in the April issue of the Journal of Alzheimer’s Disease, are far from proof that the modified Atkins diet has the potential to stave off progression from mild cognitive impairment to Alzheimer’s disease or other dementias. However, they are promising enough, the researchers say, to warrant larger, longer-term studies of dietary impact on brain function.

“Our early findings suggest that perhaps we don’t need to cut carbs as strictly as we initially tried. We may eventually see the same beneficial effects by adding a ketone supplement that would make the diet easier to follow,” says Jason Brandt, Ph.D., professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine. “Most of all, if we can confirm these preliminary findings, using dietary changes to mitigate cognitive loss in early-stage dementia would be a real game-changer. It’s something that 400-plus experimental drugs haven’t been able to do in clinical trials.”

Brandt explains that, typically, the brain uses the sugar glucose—a product of carbohydrate breakdown—as a primary fuel. However, research has shown that in the early stage of Alzheimer’s disease the brain isn’t able to efficiently use glucose as an energy source. Some experts, he says, even refer to Alzheimer’s as “type 3 diabetes.”

Using brain scans that show energy use, researchers have also found that ketones—chemicals formed during the breakdown of dietary fat—can be used as an alternative energy source in the brains of healthy people and those with mild cognitive impairment. For example, when a person is on a ketogenic diet, consisting of lots of fat and very few sugars and starches, the brain and body use ketones as an energy source instead of carbs.

For the current study, the researchers wanted to see if people with mild cognitive impairment, often an indicator of developing Alzheimer’s disease, would benefit from a diet that forced the brain to use ketones instead of carbohydrates for fuel.

After 2 1/2 years of recruitment efforts, the researchers were able to enroll 27 people in the 12-week diet study. There were a few dropouts, and so far, 14 participants have completed the study. The participants were an average age of 71. Half were women, and all but one were white.

To enroll, each participant required a study partner (typically a spouse) who was responsible for ensuring that the participant followed one of two diets for the full 12 weeks. Nine participants followed a modified Atkins diet meant to restrict carbs to 20 grams per day or less, with no restriction on calories. The typical American consumes between 200 and 300 grams of carbs a day. The other five participants followed a National Institute of Aging diet, similar to the Mediterranean diet, that doesn’t restrict carbohydrates, but favors fruits, vegetables, low- or fat-free dairy, whole grains and lean proteins such as seafood or chicken.

The participants and their partners were also asked to keep food diaries. Prior to starting the diets, those assigned to the modified Atkins diet were consuming about 158 grams of carbs per day. By week six of the diet, they had cut back to an average of 38.5 grams of carbs per day and continued dropping at nine weeks, but still short of the 20-gram target, before rising to an average of 53 grams of carbs by week 12. Participants on the National Institute of Aging diet continued to eat well over 100 grams of carbs per day.

Each participant also gave urine samples at the start of the dietary regimens and every three weeks up to the end of the study, which were used to track ketone levels. More than half of the participants on the modified Atkins diet had at least some ketones in their urine by six weeks into the diet until the end; as expected, none of the participants on the National Institute of Aging control diet had any detectable ketones.

Participants completed the Montreal Cognitive Assessment, the Mini-Mental State Examination and the Clinical Dementia Rating Scale at the start of the study. They were tested with a brief collection of neuropsychological memory tests before starting their diets and at six weeks and 12 weeks on the diet. At the six-week mark, the researchers found a significant improvement on memory tests, which coincided with the highest levels of ketones and lowest carb intakes.

When comparing the results of tests of delayed recall—the ability to recollect something they were told or shown a few minutes earlier—those who stuck to the modified Atkins diet improved by a couple of points on average (about 15% of the total score), whereas those who didn’t follow the diet on average dropped a couple of points.

The researchers say the biggest hurdle for researchers was finding people willing to make drastic changes to their eating habits and partners willing to enforce the diets. The increase in carbohydrate intake later in the study period, they said, suggests that the diet becomes unpalatable over long periods.

“Many people would rather take a pill that causes them all kinds of nasty side effects than change their diet,” says Brandt. “Older people often say that eating the foods they love is one of the few pleasures they still enjoy in life, and they aren’t willing to give that up.”

But, because Brandt’s team observed promising results even in those lax with the diet, they believe that a milder version of the high-fat/low-carb diet, perhaps in conjunction with ketone supplement drinks, is worth further study. As this study also depended on caregivers/partners to do most of the work preparing and implementing the diet, the group also wants to see if participants with less severe mild cognitive impairment can make their own dietary choices and be more apt to stick to a ketogenic diet.

A standardized modified Atkins diet was created and tested at Johns Hopkins Medicine in 2002, initially to treat some seizure disorders. It’s still used very successfully for this purpose.

According to the Alzheimer’s Association, about 5.8 million Americans have Alzheimer’s disease, and by 2050 the number is projected to increase to 14 million people.

Jason Brandt et al. Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer’s Disease, Journal of Alzheimer’s Disease (2019). DOI: 10.3233/JAD-180995

https://medicalxpress.com/news/2019-06-low-carb-keto-diet-atkins-style-modestly.html

A newly identified type of dementia that is sometimes mistaken for Alzheimer’s disease

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Doctors have newly outlined a type of dementia that could be more common than Alzheimer’s among the oldest adults, according to a report published Tuesday in the journal Brain.

The disease, called LATE, may often mirror the symptoms of Alzheimer’s disease, though it affects the brain differently and develops more slowly than Alzheimer’s. Doctors say the two are frequently found together, and in those cases may lead to a steeper cognitive decline than either by itself.

In developing its report, the international team of authors is hoping to spur research — and, perhaps one day, treatments — for a disease that tends to affect people over 80 and “has an expanding but under-recognized impact on public health,” according to the paper.

“We’re really overhauling the concept of what dementia is,” said lead author Dr. Peter Nelson, director of neuropathology at the University of Kentucky Medical Center.

Still, the disease itself didn’t come out of the blue. The evidence has been building for years, including reports of patients who didn’t quite fit the mold for known types of dementia such as Alzheimer’s.

“There isn’t going to be one single disease that is causing all forms of dementia,” said Sandra Weintraub, a professor of psychiatry, behavioral sciences and neurology at Northwestern University Feinberg School of Medicine. She was not involved in the new paper.

Weintraub said researchers have been well aware of the “heterogeneity of dementia,” but figuring out precisely why each type can look so different has been a challenge. Why do some people lose memory first, while others lose language or have personality changes? Why do some develop dementia earlier in life, while others develop it later?

Experts say this heterogeneity has complicated dementia research, including Alzheimer’s, because it hasn’t always been clear what the root cause was — and thus, if doctors were treating the right thing.

What is it?

The acronym LATE stands for limbic-predominant age-related TDP-43 encephalopathy. The full name refers to the area in the brain most likely to be affected, as well as the protein at the center of it all.

“These age-related dementia diseases are frequently associated with proteinaceous glop,” Nelson said. “But different proteins can contribute to the glop.”

In Alzheimer’s, you’ll find one set of glops. In Lewy body dementia, another glop.

And in LATE, the glop is a protein called TDP-43. Doctors aren’t sure why the protein is found in a modified, misfolded form in a disease like LATE.

“TDP-43 likes certain parts of the brain that the Alzheimer’s pathology is less enamored of,” explained Weintraub, who is also a member of Northwestern’s Mesulam Center for Cognitive Neurology and Alzheimer’s Disease.

“This is an area that’s going to be really huge in the future. What are the individual vulnerabilities that cause the proteins to go to particular regions of the brain?” she said. “It’s not just what the protein abnormality is, but where it is.”

More than a decade ago, doctors first linked the TDP protein to amyotrophic lateral sclerosis, otherwise known as ALS or Lou Gehrig’s disease. It was also linked to another type of dementia, called frontotemporal lobar degeneration.

LATE “is a disease that’s 100 times more common than either of those, and nobody knows about it,” said Nelson.

The new paper estimates, based on autopsy studies, that between 20 and 50% of people over 80 will have brain changes associated with LATE. And that prevalence increases with age.

Experts say nailing down these numbers — as well as finding better ways to detect and research the disease — is what they hope comes out of consensus statements like the new paper, which gives scientists a common language to discuss it, according to Nelson.

“People have, in their own separate bailiwicks, found different parts of the elephant,” he said. “But this is the first place where everybody gets together and says, ‘This is the whole elephant.’ ”

What this could mean for Alzheimer’s

The new guidelines could have an impact on Alzheimer’s research, as well. For one, experts say some high-profile drug trials may have suffered as a result of some patients having unidentified LATE — and thus not responding to treatment.

In fact, Nelson’s colleagues recently saw that firsthand: a patient, now deceased, who was part of an Alzheimer’s drug trial but developed dementia anyway.

“So, the clinical trial was a failure for Alzheimer’s disease,” Nelson said, “but it turns out he didn’t have Alzheimer’s disease. He had LATE.”

Nina Silverberg, director of the Alzheimer’s Disease Research Centers Program at the National Institute on Aging, said she suspects examples like this are not the majority — in part because people in clinical trials tend to be on the younger end of the spectrum.

“I’m sure it plays some part, but maybe not as much as one might think at first,” said Silverberg, who co-chaired the working group that led to the new paper.

Advances in testing had already shown that some patients in these trials lacked “the telltale signs of Alzheimer’s,” she said.

In some cases, perhaps it was LATE — “and it’s certainly possible that there are other, as yet undiscovered, pathologies that people may have,” she added.

“We could go back and screen all the people that had failed their Alzheimer’s disease therapies,” Nelson said. “But what we really need to do is go forward and try to get these people out of the Alzheimer’s clinical trials — and instead get them into their own clinical trials.”

Silverberg describes the new paper as “a roadmap” for research that could change as we come to discover more about the disease. And researchers can’t do it without a large, diverse group of patients, she added.

“It’s probably going to take years and research participants to help us understand all of that,” she said.

https://www.cnn.com/2019/04/30/health/dementia-late-alzheimers-study/index.html

A Dozen Dolphins Have Beached Themselves, Showing The Deadly Hallmark of Alzheimer’s disease

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by Carly Cassella

Over a dozen dolphins, stranded on the beaches of Florida and Massachusetts, have been found with brains full of amyloid plaques, a hallmark of Alzheimer’s disease. The scientists who made the discovery think it may be a warning to us all: alongside the Alzheimer’s-like plaques, the team also found the environmental toxin BMAA.

Produced by blue-green algae blooms, this neurotoxin is easily caught up in the ocean food web, and chronic dietary exposure has long been suspected to be a cause of neurological disease, including Alzheimers, Parkinson’s and Amyotrophic Lateral Sclerosis (ALS).

The presence of both BMAA and amyloid plaques in 13 stranded dolphins now adds even more weight to this hypothesis.

“Dolphins are an excellent sentinel species for toxic exposures in the marine environment,” says neurologist Deborah Mash from the University of Miami.

“With increasing frequency and duration of cyanobacterial blooms in coastal waters, dolphins might provide early warning of toxic exposures that could impact human health.”

They might also be a good animal model for how BMAA could trigger Alzheimer’s disease. In 2017, it was discovered that dolphins are the only known wild animal to show signs of this common human disease.

Meanwhile, dolphins that inhabit Florida coastal waters are also commonly exposed to recurring harmful algae blooms (HABs). This might just be a coincidence, but experiments have shown that chronic BMAA dietary exposure can trigger neurodegenerative changes in both humans and non-human primates.

“Acute and chronic exposures to such toxins can be harmful to both humans and animals resulting in respiratory illnesses, severe dermatitis, mucosal damage, cancer, organ failure and death,” the authors write.

As the world warms at a rapid rate, these HABs are only becoming more frequent, and the authors worry that dolphins will accumulate even more BMAA as a result, “both by exposure to HABs and by the ingestion of prey previously exposed to the cyanotoxin”.

As such, these creatures may very well be our first indication of poor environmental conditions, and while it’s still not clear if these blooms directly lead to Alzheimer’s in dolphins or in humans, the researchers say it’s a risk we shouldn’t be willing to take.

“The $64,000 question is whether these marine mammals experienced cognitive deficits and disorientation that led to their beaching,” says co-author Paul Alan Cox, an ethnobotanist at the Brain Chemistry Labs in Jackson Hole.

“Until further research clarifies this question, people should take simple steps to avoid cyanobacterial exposure.”

This study has been published in PLOS ONE.

https://www.sciencealert.com/beached-dolphins-had-alzheimer-s-like-plaques-and-it-s-a-warning-to-us-all

New neurons for life? Old people can still make fresh brain cells, study finds

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By Emily Underwood

One of the thorniest debates in neuroscience is whether people can make new neurons after their brains stop developing in adolescence—a process known as neurogenesis. Now, a new study finds that even people long past middle age can make fresh brain cells, and that past studies that failed to spot these newcomers may have used flawed methods.

The work “provides clear, definitive evidence that neurogenesis persists throughout life,” says Paul Frankland, a neuroscientist at the Hospital for Sick Children in Toronto, Canada. “For me, this puts the issue to bed.”

Researchers have long hoped that neurogenesis could help treat brain disorders like depression and Alzheimer’s disease. But last year, a study in Nature reported that the process peters out by adolescence, contradicting previous work that had found newborn neurons in older people using a variety of methods. The finding was deflating for neuroscientists like Frankland, who studies adult neurogenesis in the rodent hippocampus, a brain region involved in learning and memory. It “raised questions about the relevance of our work,” he says.

But there may have been problems with some of this earlier research. Last year’s Nature study, for example, looked for new neurons in 59 samples of human brain tissue, some of which came from brain banks where samples are often immersed in the fixative paraformaldehyde for months or even years. Over time, paraformaldehyde forms bonds between the components that make up neurons, turning the cells into a gel, says neuroscientist María Llorens-Martín of the Severo Ochoa Molecular Biology Center in Madrid. This makes it difficult for fluorescent antibodies to bind to the doublecortin (DCX) protein, which many scientists consider the “gold standard” marker of immature neurons, she says.

The number of cells that test positive for DCX in brain tissue declines sharply after just 48 hours in a paraformaldehyde bath, Llorens-Martín and her colleagues report today in Nature Medicine. After 6 months, detecting new neurons “is almost impossible,” she says.

When the researchers used a shorter fixation time—24 hours—to preserve donated brain tissue from 13 deceased adults, ranging in age from 43 to 87, they found tens of thousands of DCX-positive cells in the dentate gyrus, a curled sliver of tissue within the hippocampus that encodes memories of events. Under a microscope, the neurons had hallmarks of youth, Llorens-Martín says: smooth and plump, with simple, undeveloped branches.

In the sample from the youngest donor, who died at 43, the team found roughly 42,000 immature neurons per square millimeter of brain tissue. From the youngest to oldest donors, the number of apparent new neurons decreased by 30%—a trend that fits with previous studies in humans showing that adult neurogenesis declines with age. The team also showed that people with Alzheimer’s disease had 30% fewer immature neurons than healthy donors of the same age, and the more advanced the dementia, the fewer such cells.

Some scientists remain skeptical, including the authors of last year’s Nature paper. “While this study contains valuable data, we did not find the evidence for ongoing production of new neurons in the adult human hippocampus convincing,” says Shawn Sorrells, a neuroscientist at the University of Pittsburgh in Pennsylvania who co-authored the 2018 paper. One critique hinges on the DCX stain, which Sorrells says isn’t an adequate measure of young neurons because the DCX protein is also expressed in mature cells. That suggests the “new” neurons the team found were actually present since childhood, he says. The new study also found no evidence of pools of stem cells that could supply fresh neurons, he notes. What’s more, Sorrells says two of the brain samples he and his colleagues looked at were only fixed for 5 hours, yet they still couldn’t find evidence of young neurons in the hippocampus.

Llorens-Martín says her team used multiple other proteins associated with neuronal development to confirm that the DCX-positive cells were actually young, and were “very strict,” in their criteria for identifying young neurons.

Heather Cameron, a neuroscientist at the National Institute of Mental Health in Bethesda, Maryland, remains persuaded by the new work. Based on the “beauty of the data” in the new study, “I think we can all move forward pretty confidently in the knowledge that what we see in animals will be applicable in humans, she says. “Will this settle the debate? I’m not sure. Should it? Yes.”

https://www.sciencemag.org/news/2019/03/new-neurons-life-old-people-can-still-make-fresh-brain-cells-study-finds?utm_campaign=news_daily_2019-03-25&et_rid=17036503&et_cid=2734364

Having great-grandparents or cousins with Alzheimer’s disease substantially increases your risk of developing it also.

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Having a parent with Alzheimer’s disease has been known to raise a person’s risk of developing the disease, but new research published in Neurology suggests that having second- and third-degree relatives who have had Alzheimer’s may also increase risk.

“Family history is an important indicator of risk for Alzheimer’s disease, but most research focuses on dementia in immediate family members, so our study sought to look at the bigger family picture,” said Lisa A. Cannon-Albright, PhD, University of Utah School of Medicine, Salt Lake City, Utah. “We found that having a broader view of family history may help better predict risk. These results potentially could lead to better diagnoses and help patients and their families in making health-related decisions.”

For the study, researchers looked at the Utah Population Database, which includes the genealogy of Utah pioneers from the 1800s and their descendants up until modern day. The database is linked to Utah death certificates, which show causes of death, and in a majority of cases, contributing causes of death.

In that database, researchers analysed data from over 270,800 people who had at least 3 generations of genealogy connected to the original Utah pioneers including genealogy data for both parents, all 4 grandparents, and at least 6 of 8 great-grandparents. Of those, 4,436 have a death certificate that indicates Alzheimer’s disease as a cause of death.

Results showed that people with 1 first-degree relative with Alzheimer’s disease (18,494 people) had a 73% increased risk of developing the disease. Of this group of people, 590 developed Alzheimer’s disease; the researchers would have expected this group to have 341 cases.

People with 2 first-degree relatives were 4 times more likely to develop the disease; those with 3 were 2.5 times more likely; and those with 4 were nearly 15 times more likely to develop Alzheimer’s disease.

Of the 21 people in the study with 4 first-degree relatives with Alzheimer’s, 6 had the disease. The researchers would have expected only 0.4 people to develop the disease.

Those with 1 first-degree relative and 1 second-degree relative had a 21 times greater risk. Examples of this would be a parent and one grandparent with the disease, or a parent and one aunt or uncle. There were 25 people in this category in the study; 4 of them had the disease when researchers would have expected 0.2 cases.

Those who had only third-degree relatives, and 3 such relatives, with Alzheimer’s disease had a 43% greater risk of developing the disease. An example of this would be two great-grandparents with the disease, along with one great uncle, but no parents or grandparents with the disease. Of the 5,320 people in this category, 148 people had the disease when researchers would have expected 103.

“More and more, people are increasingly seeking an estimate of their own genetic risk for Alzheimer’s disease,” said Dr. Cannon-Albright. “Our findings indicate the importance of clinicians taking a person’s full family history that extends beyond their immediate family members.”

She noted that among all of the study participants, 3% had a family history that doubled their risk of Alzheimer’s disease, and a little over one-half of a percent had a family history that increased their risk by ≥3 times that of a person without a family history of the disease.

Limitations of the study include that not all individuals dying from Alzheimer’s disease may have had a death certificate listing it as cause of death. Dr. Cannon-Albright said death certificates are known to underestimate the prevalence of the disease.

“There are still many unknowns about why a person develops Alzheimer’s disease,” she said. “A family history of the disease is not the only possible cause. There may be environmental causes, or both. There is still much more research needed before we can give people a more accurate prediction of their risk of the disease.”

Reference:
https://n.neurology.org/content/early/2019/03/13/WNL.0000000000007231

https://dgnews.docguide.com/having-great-grandparents-cousins-alzheimer-s-linked-higher-risk?overlay=2&nl_ref=newsletter&pk_campaign=newsletter&nl_eventid=20119

Scientists ‘Clear’ Alzheimer’s Plaque From Mice Using Only Light And Sound

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Clumps of harmful proteins that interfere with brain functions have been partially cleared in mice using nothing but light and sound.

Research led by MIT has found strobe lights and a low pitched buzz can be used to recreate brain waves lost in the disease, which in turn remove plaque and improve cognitive function in mice engineered to display Alzheimer’s-like behaviour.

It’s a little like using light and sound to trigger their own brain waves to help fight the disease.

This technique hasn’t been clinically trialled in humans as yet, so it’s too soon to get excited – brain waves are known to work differently in humans and mice.

But, if replicated, these early results hint at a possible cheap and drug-free way to treat the common form of dementia.

So how does it work?

Advancing a previous study that showed flashing light 40 times a second into the eyes of engineered mice treated their version of Alzheimer’s disease, researchers added sound of a similar frequency and found it dramatically improved their results.

“When we combine visual and auditory stimulation for a week, we see the engagement of the prefrontal cortex and a very dramatic reduction of amyloid,” says Li-Huei Tsai, one of the researchers from MIT’s Picower Institute for Learning and Memory.

It’s not the first study to investigate the role sound can play in clearing the brain of the tangles and clumps of tau and amyloid proteins at least partially responsible for the disease.

Previous studies showed bursts of ultrasound make blood vessels leaky enough to allow powerful treatments to slip into the brain, while also encouraging the nervous system’s waste-removal experts, microglia, to pick up the pace.

Several years ago, Tsai discovered light flickering at a frequency of about 40 flashes a second had similar benefits in mice engineered to build up amyloid in their brain’s nerve cells.

“The result was so mind-boggling and so robust, it took a while for the idea to sink in, but we knew we needed to work out a way of trying out the same thing in humans,” Tsai told Helen Thomson at Nature at the time.

The only problem was this effect was confined to visual parts of the brain, missing key areas that contribute to the formation and retrieval of memory.

While the method’s practical applications looked a little limited, the results pointed to a way oscillations could help the brain recover from the grip of Alzheimer’s disease.

As our brain’s neurons transmit signals they also generate electromagnetic waves that help keep remote regions in sync – so-called ‘brain waves’.

One such set of oscillations are defined as gamma-frequencies, rippling across the brain at around 30 to 90 waves per second. These brain waves are most active when we’re paying close attention, searching our memories in order to make sense of what’s going on.

Tsai’s previous study had suggested these gamma waves are impeded in individuals with Alzheimer’s, and might play a pivotal role in the pathology itself.

Light was just one way to trick the parts of the brain into humming in the key of gamma. Sounds can also manage this in other areas.

Instead of the high pitched scream of ultrasound, Tsui used a much lower droning noise of just 40 Hertz, a sound only just high enough for humans to hear.

Exposing their mouse subjects to just one hour of this monotonous buzz every day for a week led to a significant drop in the amount of amyloid build up in the auditory regions, while also stimulating those microglial cells and blood vessels.

“What we have demonstrated here is that we can use a totally different sensory modality to induce gamma oscillations in the brain,” says Tsai.

As an added bonus, it also helped clear the nearby hippocampus – an important section associated with memory.

The effects weren’t just evident in the test subjects’ brain chemistry. Functionally, mice exposed to the treatment performed better in a range of cognitive tasks.

Adding the light therapy from the previous study saw an even more dramatic effect, clearing plaques in a number of areas across the brain, including in the prefrontal cortex. Those trash-clearing microglia also went to town.

“These microglia just pile on top of one another around the plaques,” says Tsai.

Discovering new mechanisms in the way nervous systems clear waste and synchronise activity is a huge step forward in the development of treatments for all kinds of neurological disorders.

Translating discoveries like this to human brains will take more work, especially when there are potential contrasts in how gamma waves appear in mice and human Alzheimer’s brains.

So far early testing for safety has shown the process seems to have no clear side effects.

This research was published in Cell.

https://www.sciencealert.com/astonishing-new-study-treats-alzheimer-s-in-mice-with-a-light-and-sound-show

Eating mushrooms may reduce the risk of cognitive decline

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A team from the Department of Psychological Medicine and Department of Biochemistry at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS) has found that seniors who consume more than two standard portions of mushrooms weekly may have 50 per cent reduced odds of having mild cognitive impairment (MCI).

A portion was defined as three quarters of a cup of cooked mushrooms with an average weight of around 150 grams. Two portions would be equivalent to approximately half a plate. While the portion sizes act as a guideline, it was shown that even one small portion of mushrooms a week may still be beneficial to reduce chances of MCI.

“This correlation is surprising and encouraging. It seems that a commonly available single ingredient could have a dramatic effect on cognitive decline,” said Assistant Professor Lei Feng, who is from the NUS Department of Psychological Medicine, and the lead author of this work.

The six-year study, which was conducted from 2011 to 2017, collected data from more than 600 Chinese seniors over the age of 60 living in Singapore. The research was carried out with support from the Life Sciences Institute and the Mind Science Centre at NUS, as well as the Singapore Ministry of Health’s National Medical Research Council. The results were published online in the Journal of Alzheimer’s Disease on 12 March 2019.

Determining MCI in seniors

MCI is typically viewed as the stage between the cognitive decline of normal ageing and the more serious decline of dementia. Seniors afflicted with MCI often display some form of memory loss or forgetfulness and may also show deficit on other cognitive function such as language, attention and visuospatial abilities. However, the changes can be subtle, as they do not experience disabling cognitive deficits that affect everyday life activities, which is characteristic of Alzheimer’s and other forms of dementia.

“People with MCI are still able to carry out their normal daily activities. So, what we had to determine in this study is whether these seniors had poorer performance on standard neuropsychologist tests than other people of the same age and education background,” explained Asst Prof Feng. “Neuropsychological tests are specifically designed tasks that can measure various aspects of a person’s cognitive abilities. In fact, some of the tests we used in this study are adopted from commonly used IQ test battery, the Wechsler Adult Intelligence Scale (WAIS).”

As such, the researchers conducted extensive interviews and tests with the senior citizens to determine an accurate diagnosis. “The interview takes into account demographic information, medical history, psychological factors, and dietary habits. A nurse will measure blood pressure, weight, height, handgrip, and walking speed. They will also do a simple screen test on cognition, depression, anxiety,” said Asst Prof Feng.

After this, a two-hour standard neuropsychological assessment was performed, along with a dementia rating. The overall results of these tests were discussed in depth with expert psychiatrists involved in the study to get a diagnostic consensus.

Mushrooms and cognitive impairment

Six commonly consumed mushrooms in Singapore were referenced in the study. They were golden, oyster, shiitake and white button mushrooms, as well as dried and canned mushrooms. However, it is likely that other mushrooms not referenced would also have beneficial effects.

The researchers believe the reason for the reduced prevalence of MCI in mushroom eaters may be down to a specific compound found in almost all varieties. “We’re very interested in a compound called ergothioneine (ET),” said Dr. Irwin Cheah, Senior Research Fellow at the NUS Department of Biochemistry. “ET is a unique antioxidant and anti-inflammatory which humans are unable to synthesise on their own. But it can be obtained from dietary sources, one of the main ones being mushrooms.”

An earlier study by the team on elderly Singaporeans revealed that plasma levels of ET in participants with MCI were significantly lower than age-matched healthy individuals. The work, which was published in the journal Biochemical and Biophysical Research Communications in 2016, led to the belief that a deficiency in ET may be a risk factor for neurodegeneration, and increasing ET intake through mushroom consumption might possibly promote cognitive health.

Other compounds contained within mushrooms may also be advantageous for decreasing the risk of cognitive decline. Certain hericenones, erinacines, scabronines and dictyophorines may promote the synthesis of nerve growth factors. Bioactive compounds in mushrooms may also protect the brain from neurodegeneration by inhibiting production of beta amyloid and phosphorylated tau, and acetylcholinesterase.

Next steps

The potential next stage of research for the team is to perform a randomised controlled trial with the pure compound of ET and other plant-based ingredients, such as L-theanine and catechins from tea leaves, to determine the efficacy of such phytonutrients in delaying cognitive decline. Such interventional studies will lead to more robust conclusion on causal relationship. In addition, Asst Prof Feng and his team also hope to identify other dietary factors that could be associated with healthy brain ageing and reduced risk of age-related conditions in the future.

https://medicalxpress.com/news/2019-03-mushrooms-cognitive-decline.html

Could an eye doctor diagnose Alzheimer’s before you have symptoms?

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By Samiha Khanna

A quick eye exam might one day allow eye doctors to check up on both your eyeglasses prescription and your brain health.

A study of more than 200 people at the Duke Eye Center published March 11 in the journal Ophthalmology Retina suggests the loss of blood vessels in the retina could signal Alzheimer’s disease. Authors of the study include the Neurology Department’s James Burke, MD, PhD, and Cynthia Dunn, PA-C.

In people with healthy brains, microscopic blood vessels form a dense web at the back of the eye inside the retina, as seen in 133 participants in a control group.

In the eyes of 39 people with Alzheimer’s disease, that web was less dense and even sparse in places. The differences in density were statistically significant after researchers controlled for factors including age, sex, and level of education, said Duke ophthalmologist and retinal surgeon Sharon Fekrat, MD, the study’s senior author.

“We’re measuring blood vessels that can’t be seen during a regular eye exam and we’re doing that with relatively new noninvasive technology that takes high-resolution images of very small blood vessels within the retina in just a few minutes,” she said. “It’s possible that these changes in blood vessel density in the retina could mirror what’s going on in the tiny blood vessels in the brain, perhaps before we are able to detect any changes in cognition.”

The study found differences in the retinas of those with Alzheimer’s disease when compared to healthy people and to those with mild cognitive impairment, often a precursor to Alzheimer’s disease.

With nearly 6 million Americans living with Alzheimer’s disease and no viable treatments or noninvasive tools for early diagnosis, its burden on families and the economy is heavy. Scientists at Duke Eye Center and beyond have studied other changes in the retina that could signal trouble upstream in the brain, such as thinning of some of the retinal nerve layers.

“We know that there are changes that occur in the brain in the small blood vessels in people with Alzheimer’s disease, and because the retina is an extension of the brain, we wanted to investigate whether these changes could be detected in the retina using a new technology that is less invasive and easy to obtain,” said Dilraj S. Grewal, M.D., a Duke ophthalmologist and retinal surgeon and a lead author on the study. The Duke study used a noninvasive technology called optical coherence tomography angiography (OCTA). OCTA machines use light waves that reveal blood flow in every layer of the retina.

An OCTA scan could even reveal changes in tiny capillaries — most less than half the width of a human hair — before blood vessel changes show up on a brain scan such as an MRI or cerebral angiogram, which highlight only larger blood vessels. Such techniques to study the brain are invasive and costly.

“Ultimately, the goal would be to use this technology to detect Alzheimer’s early, before symptoms of memory loss are evident, and be able to monitor these changes over time in participants of clinical trials studying new Alzheimer’s treatments,” Fekrat said.

In addition to Fekrat and Grewal, study authors include Stephen P. Yoon, Atalie C. Thompson, Bryce W. Polascik, Cynthia Dunn and James R. Burke.

The research was supported by National Institutes of Health (P30EY005722), the 2018 Unrestricted Grant from Research to Prevent Blindness, and the Karen L. Wrenn Alzheimer’s Disease Award.

https://neurology.duke.edu/about/news/could-eye-doctor-diagnose-alzheimer%E2%80%99s-you-have-symptoms