Posts Tagged ‘dementia’

Our thinking skills in childhood could offer a glimpse into how our minds might work at the age of 70, according to a study spanning decades.

The research started in 1946, when 502 8-year-olds, who were born in the U.K. in the same week, took tests to measure their thinking and memory skills. The participants took cognitive tests again between the ages of 69 and 71.

The participants also had scans, including a positron emission tomography (PET) scan that detects amyloid-beta plaques in the brain. These sticky collections of protein are linked to Alzheimer’s disease.

The study, published in the journal Neurology, shows those with the highest test scores in childhood were more likely to have high scores later in life. Kids in the top 25 percent had a greater chance of being in that same quartile at 70.

Educational attainment and socioeconomic status also appeared to make a difference. Those who were college-educated scored around 16 percent better in tests than those who left school before they hit 16. Participants who had a white-collar job were able to remember, on average, 12 details from a short story, versus 11 if they had a manual job. Overall, women did better than men when their memory and thinking speed were tested.

Participants who were found to have amyloid-beta plaques in their brains, meanwhile, scored lower on cognitive tests. In one assessment where participants had to find the missing pieces in five geometric shapes, those with the plaque got 23 out of 32 problems correct, versus 25 for those without the plaques.

Dr. Jonathan M. Schott of University College London commented: “Finding these predictors is important because if we can understand what influences an individual’s cognitive performance in later life, we can determine which aspects might be modifiable by education or lifestyle changes like exercise, diet or sleep, which may, in turn, slow the development of cognitive decline.

“Our study found that small differences in thinking and memory associated with amyloid plaques in the brain are detectable in older adults even at an age when those who are destined to develop dementia are still likely to be many years away from having symptoms.”

Earlier this year, Schott and his team published a separate study in the journal The Lancet Neurology that showed having high blood pressure in a person’s mid-30s was linked to higher levels of blood vessel damage in the brain, as well as shrinkage of the organ.

Professor Tara Spires-Jones from the UK Dementia Research Institute at the University of Edinburgh, who did not work on the new study, told Newsweek the findings add to other studies that suggest our genetics, as well as environmental factors, play a role in how we maintain our thinking skills as we age.

“However, this does not mean that all of your brain power during aging is determined during childhood,” she said. “There is good scientific evidence from this study and many others that keeping your brain and body active are likely to reduce your risk of developing Alzheimer’s disease, even as adults.”

Learning, socializing and exercise can all help, she said.

“One way this works is by building new connections between brain cells, called synapses. Synapses are the building blocks of memory, so building up a robust network of synapses, sometimes called ‘brain reserve’ is thought to be the biology behind the finding that more education is associated with a lower risk of dementia and age-related cognitive decline,” explained Spires-Jones.

Spires-Jones suggested amyloid-beta plaques might be linked with lower tests scores in the study because they build up and damage the connections between brain cells, called synapses, impairing brain function.

“Amyloid plaques are also widely thought to initiate a toxic cascade that leads to dementia in Alzheimer’s disease, including the build-up and spread of another pathology called ‘tangles,'” she said.

She said the study was “very strong” but limited because observational studies can’t explain the links that emerge, and the participants were all white so the results might not relate to other populations.

“It will be important in future work to try and understand the biological underpinnings for the associations between childhood intelligence and better cognitive ability during aging,” she said.

https://www.newsweek.com/dementia-aging-study-brains-tests-1468657

By Nicholas Bakalar

Trans fatty acids, known to increase the risk for heart disease, stroke and diabetes, have now been linked to an increased risk for dementia.

Researchers measured blood levels of elaidic acid, the most common trans fats, in 1,628 men and women 60 and older and free of dementia. Over the following 10 years, 377 developed some type of dementia.

Trans fats, which are added to processed food in the form of partially hydrogenated vegetable oils, increase levels of LDL, or “bad” cholesterol. Meat and dairy products naturally contain small amounts of trans fats, but whether these fats raise bad cholesterol is unknown.

After controlling for other factors, the scientists found that compared with those in the lowest one-quarter in blood levels of elaidic acid, those in the highest were 50 percent more likely to develop any form of dementia and 39 percent more likely to develop Alzheimer’s disease in particular. Elaidic acid levels were not associated with vascular dementia considered alone. The study is in Neurology.

The senior author, Dr. Toshiharu Ninomiya, a professor of public health at Kyushu University in Japan, said the study is observational so cannot prove cause and effect. “It is difficult to avoid trans fats completely, and the risk of a small amount of trans fats is unclear,” he said. “But it would be better to try to avoid them as much as possible.”

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


Findings indicate that smaller volumes of grey matter are associated with non-‘O’ blood types. Image credit: The researchers.

A pioneering study conducted by leading researchers at the University of Sheffield has revealed blood types play a role in the development of the nervous system and may cause a higher risk of developing cognitive decline.

The research, carried out in collaboration with the IRCCS San Camillo Hospital Foundation in Venice, shows that people with an ‘O’ blood type have more grey matter in their brain, which helps to protect against diseases such as Alzheimer’s, than those with ‘A’, ‘B’ or ‘AB’ blood types.

Research fellow Matteo De Marco and Professor Annalena Venneri, from the University’s Department of Neuroscience, made the discovery after analysing the results of 189 Magnetic Resonance Imaging (MRI) scans from healthy volunteers.

The researchers calculated the volumes of grey matter within the brain and explored the differences between different blood types.

The results, published in The Brain Research Bulletin, show that individuals with an ‘O’ blood type have more grey matter in the posterior proportion of the cerebellum.

In comparison, those with ‘A’, ‘B’ or ‘AB’ blood types had smaller grey matter volumes in temporal and limbic regions of the brain, including the left hippocampus, which is one of the earliest part of the brain damaged by Alzheimer’s disease.

These findings indicate that smaller volumes of grey matter are associated with non-‘O’ blood types.

As we age a reduction of grey matter volumes is normally seen in the brain, but later in life this grey matter difference between blood types will intensify as a consequence of ageing.

“The findings seem to indicate that people who have an ‘O’ blood type are more protected against the diseases in which volumetric reduction is seen in temporal and mediotemporal regions of the brain like with Alzheimer’s disease for instance,” said Matteo DeMarco.

“However additional tests and further research are required as other biological mechanisms might be involved.”

Professor Annalena Venneri added: “What we know today is that a significant difference in volumes exists, and our findings confirm established clinical observations. In all likelihood the biology of blood types influences the development of the nervous system. We now have to understand how and why this occurs.”

https://neurosciencenews.com/blood-type-cognitive-decline-2087/

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 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

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