Alzheimer’s

Dementia Predicted 10 Years Before Diagnosis

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Blood proteins identified those at risk for all-cause, Alzheimer’s, or vascular dementia.Share on LinkedIn. Opens in a new tab or window

A computer rendered cutaway of a blood flowing through a vessel

Blood protein profiles predicted future dementia in healthy adults, a large longitudinal study showed.

Blood samples from over 50,000 people in the U.K. Biobank showed that four proteins — glial fibrillary acidic protein (GFAP), neurofilament light (NfL), growth differentiation factor-15 (GDF-15), and latent-transforming growth factor beta-binding protein 2 (LTBP2) — consistently were associated with subsequent all-cause dementia, Alzheimer’s disease, or vascular dementia over 14 years, according to Jin-Tai Yu, MD, PhD, of Fudan University in Shanghai, and co-authors.

Combining GFAP or GDF-15 with demographics led to an area under the curve (AUC) of 0.891 for all-cause dementia prediction, 0.872 for Alzheimer’s prediction, and 0.912 for vascular dementia prediction, the researchers reported in Nature Agingopens in a new tab or window. Cognitive tests did not improve predictive power significantly.

People with higher GFAP levels were 2.32 times more likely to develop dementia, Yu and colleagues said. GFAP and LTBP2 were highly specific for dementia prediction, they added.

GFAP and NfL levels began changing at least 10 years before dementia diagnosis, with concentrations rising most steeply in people with all-cause dementia or Alzheimer’s.

Previous models to detect dementia risk depended largely on cerebrospinal fluid or imaging data, Yu noted. “The proteomic biomarkers are more [easy] to access and non-invasive, and they can substantially facilitate the application of large-scale population screening,” he said in a statement.

The study adds “to what we know about changes in blood that occur very early in diseases that cause dementia, which will be important for early diagnosis in the future,” wrote Tara Spires-Jones, DPhil, of the University of Edinburgh in Scotland, in a postopens in a new tab or window on the U.K. Science Media Centre.

“However, it is important to note that these are still scientific research studies and that there are currently no blood tests available for routine use that can diagnose dementia with certainty,” Spires-Jones emphasized.

GFAP, a marker of astrogliosis, and NfL, a marker of axonal injury, have predicted dementia symptoms a decade before they emergedopens in a new tab or window in an inherited form of Alzheimer’s disease. Plasma GFAP also has been proposed as a potential biomarkeropens in a new tab or window of Alzheimer’s-related pathologies.

The U.K. Biobank findings “appear robust given the knowledge we already have about GFAP being highly associated with Alzheimer’s disease and NfL not being specific for any one dementia,” Amanda Heslegrave, PhD, of University College London, postedopens in a new tab or window on the Science Media Centre site. “[T]he message to take away here is that, for accurate diagnosis and differentiation between dementias, we need focused panels of biomarkers.”

Yu and colleagues used data from the prospective U.K. Biobank cohortopens in a new tab or window to assess 1,463 plasma proteins. Blood samples were collected between 2006 and 2010. Baseline median age was 58. About 54% of the cohort was female and 94% was white.

The study included 52,645 participants without baseline dementia. Over a median follow-up of 14.1 years, 1,417 people were diagnosed with dementia, including 219 incident cases within 5 years, 833 within 10 years, and 584 beyond 10 years.

The researchers combined the top protein markers associated with incident dementia and demographic variables like age, sex, education, and family history to produce a predictive model for dementia risk over 10 years. They trained the model with data from two-thirds of the cohort (35,096 people) and tested its performance using data from the remaining third.

For 10-year risk, GFAP combined with demographic characteristics predicted all-cause dementia (AUC 0.872) and Alzheimer’s disease (AUC 0.847). Plasma GDF15 combined with demographic characteristics predicted 10-year incident vascular dementia with an AUC of 0.895.

Besides dementia, no significant association emerged between baseline GFAP and risks of other neurodegenerative diseases (HR 1.06, 95% CI 0.94-1.20, P>0.999), neurological disorders (HR 0.94, 95% CI 0.88-1.00, P=0.493) or mental and behavioral disorders (HR 1.05, 95% CI 0.95-1.15, P>0.999), “indicating that GFAP may be specific for dementia,” Yu and co-authors suggested.

The study had several limitations, the researchers noted. Plasma amyloid and tau-related proteins were not included in the analysis. Dementia incidence was lower than what other cohorts have reported, most likely because U.K. Biobank participants were younger at enrollment. The findings also have not been validated in an independent, external cohort.

Data could hold the key to stopping Alzheimer’s

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Data could hold the key to stopping Alzheimer’s

More data sharing will accelerate progress towards an Alzheimer’s breakthrough.

My family loves to do jigsaw puzzles. It’s one of our favorite activities to do together, especially when we’re on vacation. There is something so satisfying about everyone working as a team to put down piece after piece until finally the whole thing is done.

In a lot of ways, the fight against Alzheimer’s disease reminds me of doing a puzzle. Your goal is to see the whole picture, so that you can understand the disease well enough to better diagnose and treat it. But in order to see the complete picture, you need to figure out how all of the pieces fit together.

Right now, all over the world, researchers are collecting data about Alzheimer’s disease. Some of these scientists are working on drug trials aimed at finding a way to stop the disease’s progression. Others are studying how our brain works, or how it changes as we age. In each case, they’re learning new things about the disease.

But until recently, Alzheimer’s researchers often had to jump through a lot of hoops to share their data—to see if and how the puzzle pieces fit together. There are a few reasons for this. For one thing, there is a lot of confusion about what information you can and can’t share because of patient privacy. Often there weren’t easily available tools and technologies to facilitate broad data-sharing and access. In addition, pharmaceutical companies invest a lot of money into clinical trials, and often they aren’t eager for their competitors to benefit from that investment, especially when the programs are still ongoing.

Unfortunately, this siloed approach to research data hasn’t yielded great results. We have only made incremental progress in therapeutics since the late 1990s. There’s a lot that we still don’t know about Alzheimer’s, including what part of the brain breaks down first and how or when you should intervene. But I’m hopeful that will change soon thanks in part to the Alzheimer’s Disease Data Initiative, or ADDI.

I worked with a coalition of partners to create ADDI, because we believe that more data sharing will accelerate progress towards an Alzheimer’s breakthrough. To make this happen, ADDI created the Alzheimer’s Disease workbench.

This workbench hosts an open, global, and easy-to-use set of tools and resources. The goal is to simplify how researchers and data scientists around the world work together and share data, code, and knowledge in order to make advances in the field.

Instead of having to navigate dozens of individual databases, scientists will be able to access and upload information to a patient database from around the world. The workbench also facilitates access to datasets from failed drug trials, since many pharmaceutical companies have decided that the benefits of sharing their data outweigh the risks. And all the data is in compliance with privacy laws, so researchers don’t have to worry about compromising anyone’s personal information.

I’m optimistic that this will make a real difference in Alzheimer’s research, because there are many examples where we’ve made progress on diseases after bringing together large amounts of data. One is malnutrition. Several years ago, our foundation launched an initiative to pool information about childhood growth to try to see when exactly a child who ends up stunted starts falling behind.

That information produced some fascinating insights. For example, we learned that, in South Asia, weather cycles play a huge role in whether a child recovers from a period where he or she doesn’t get enough to eat. If you’re born during monsoon season—when food can be harder to come by—you still have a decent shot at getting back on a normal growth curve eventually. But if your mother was in her third trimester during monsoon season, you’re much less likely to get back on track. This insight has implications for how we address malnutrition in that region, and we would have never discovered it without pooling lots of different data sources.

The Alzheimer’s workbench will finally be available to scientists this month after a year and a half in development. (If you work in data science or Alzheimer’s research, or are just a curious researcher, you can explore the AD Workbench here.) But even though the workbench is only now becoming broadly available, we’re already seeing huge benefits from it—just not on the disease we expected.

In the early days of the COVID-19 pandemic, our foundation decided to use the Alzheimer’s workbench framework to create a platform for sharing information on the novel coronavirus. This platform is letting scientists from all around the world collaborate to understand more about the virus and its impacts. Each insight we gain about the virus moves us closer to the end of the pandemic, just as each insight about Alzheimer’s moves us closer to a breakthrough.

I want to be clear: data alone is not going to find the miracle treatment or the diagnostic we need to stop Alzheimer’s (or COVID-19). But what it can do is let us test hypotheses and point us in the right direction.

Nearly forty million people around the world have Alzheimer’s or dementia today. We have no way to stop or even slow the disease at this point. I lost my dad to Alzheimer’s two months ago, and I wouldn’t wish that experience on anyone. My hope is that the data sharing facilitated by ADDI will move us closer to a world where no one has to watch someone they love suffer from this awful disease.

Can slow breathing guard against Alzheimer’s?

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A woman practicing deep breathing (Credit: Getty Images)

There are believed to be many benefits to slow, controlled breathing. Researchers may have found another – a surprising protection against Alzheimer’s.

Stop scrolling. Now inhale slowly, concentrating on expanding your lungs, to a count of five. Exhale, just as slowly and deliberately, as you count to five.

You might find that, in just that 10 seconds, you suddenly feel just a little bit more relaxed or centred. Follow the same practice for 20 minutes a few times a week and – according to the research – you might not just reap the benefits of feeling calmer. You may also be helping to protect against various diseases, including, a recent study has suggested, even Alzheimer’s disease.

The benefits of breathing exercises – sometimes called “breathwork” – have been recognised for millennia. In more recent decades, scientific studies seem to support what people in many cultures, particularly in Asia, have long practiced: that deliberate breathing may help to improve a variety of health conditions, including hypertension, stress, anxiety, and even chronic pain.

In the latest study, researchers measured biomarkers in blood plasma that are associated with a higher risk of developing Alzheimer’s, particularly amyloid beta 40 and 42. Half of the 108 participants were told to try to bring themselves to a place of calm by imagining a serene scene, listening to relaxing sounds, and closing their eyes – essentially, mindfulness meditation. The goal was to decrease their heart rate oscillations, encouraging their heart rate to have a steadier, more consistent beat

The other group followed a breathing exercise on a computer screen – when a square rose over the course of five seconds, they inhaled, and when it dropped for five seconds, they exhaled. This kind of deep, slow breathing has been found to increase heart rate oscillations – making the time interval between heart beats more variable (hence a higher “heart rate variability”). Both groups practiced the technique twice a day, for 20 to 40 minutes each time, for five weeks.

When they looked at participants’ blood samples four weeks into their practice, the results came as a “surprise”, says Mara Mather, professor of gerontology, psychology and biomedical engineering  at the University of Southern California and one of authors of the study. The breathing exercises aimed at increasing heart rate variability decreased levels of amyloid beta. The mindfulness exercises, which decreased heart rate variability, made those levels higher.Traditional breathing exercises are practiced all around the world and are said to bring a variety of benefits (Credit: Getty Images)

Traditional breathing exercises are practiced all around the world and are said to bring a variety of benefits

Although no definitive single cause has been identified for causing Alzheimer’s, clumps of amyloid beta protein known as plaques have been found to be one of key features of the disease. Certain types of this protein can be particularly toxic when they clump together inside brain cells, causing them damage that affects their normal function and causes them to die.

Mather and her team hadn’t expected the levels of amyloid beta to be “affected so robustly”. And it wasn’t just for older adults who already might have been more susceptible to having higher levels of amyloid beta. “The effects were significant in both younger and older adults,” Mather says.

“This is an intriguing finding because, in healthy adults, lower plasma levels of amyloid beta are associated with lower risk of getting Alzheimer’s disease later,” she says. “Slow-paced breathing might have benefits not only for emotional well-being – but also for improving biomarkers associated with Alzheimer’s disease.”

The researchers aren’t sure why, exactly, this might be. But one hypothesis is that slow, deliberate breathing may mimic some of the benefits of deep sleep, which research has found might clear neurotoxic waste products from the brain and nervous system at a faster rate. The build-up of these waste products seems to play a role in the development of Alzheimer’s.

The key factor seems to be how each exercise affected heart rate variability (HRV), which reflects how much fluctuation there is between heartbeats. Research has indicated that heart rate variability is a good metric for the functioning of the nervous system, and, therefore, an indicator of overall health and various health conditions, from depression and chronic stress to viral infection and sepsis. Intriguingly, more variability (ie a less consistent pattern) seems to be far healthier, perhaps because it shows the body’s ability to adapt to stressors.

A regular practice of deliberate, slow-paced breathing seems to be something that could benefit most people

Regardless of the exact mechanism, Mather says, a regular practice of deliberate, slow-paced breathing seems to be something that could benefit most people.

Hope in the fight against amyloid protein

A new drug called donanemab has shown promise in a global trial for helping to clear the build-up of amyloid beta protein associated with Alzheimer’s disease.

The drug has been described as a “turning point” in the fight against Alzheimer’s after it appeared to slow the pace of the disease by around a third.

The results suggest that removing amyloid beta clumps from the brain can help to alter the course of the disease and help patients to retain much of their daily routine.

“We don’t yet know what dose is optimal. But it probably doesn’t have to be every day – my guess at this point is that doing 20 minutes 4-5 times per week would have benefits,” she says.

The study didn’t compare different types of breathing techniques, so they don’t know yet which type of breathing pattern might be most effective. “What we do know is that breathing at whichever pace between nine and 14 seconds per breath that increased that individual’s heart rate oscillations the most was effective at reducing plasma amyloid beta levels,” Mather says.

The research has also yet to be replicated in larger numbers of patients to confirm whether a meaningful long-term effect can be seen. Some scientists have also expressed doubts about how effective or reliable breathing techniques could be compared to drug treatments.

But it is far from the only study in recent years to have found health benefits of breathing exercises. Studies have found, for example, that breathwork may reduce blood pressure in people with hypertension, help relieve symptoms of anxiety and depression, and reduce insomnia. A recent meta-analysis, meanwhile, found that it could lower stress and improve mental health.

Breathwork is starting to make its way beyond yoga and meditation classes to corporate retreats and even schools. In New York City, mayor Eric Adams recently announced that all public schools will have to teach daily mindful breathing sessions to students. As he put it: “There’s a science to breathing.” There are plenty of researchers, it turns out, starting to agree with him.

Good or bad? High levels of HDL or “good” cholesterol may be linked to dementia, reveals study

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Earlier studies have suggested that high-density lipoprotein (HDL) cholesterol is associated with several health benefits, such as promoting heart health. But, according to a recent study, high levels of HDL cholesterol could be linked to a greater risk of dementia.

The study, which was led by Monash University in Melbourne, involved thousands of volunteers from Australia and the United States. The study ran for more than six years and the findings were published in the journal Lancet Regional Health Western Pacific.

Cholesterol is a lipid or a waxy type of fat. It is produced by the liver, but people can also receive cholesterol by consuming it from food products from animals, and the ingested cholesterol is then transported throughout the body by blood.

The body needs cholesterol to:

  • Help form cell membrane layers
  • Help the liver make bile for digestion
  • Produce certain hormones
  • Produce vitamin D

There are two primary types of cholesterol: High-density lipoprotein (HDL) and low-density lipoprotein (LDL).

Very low-density lipoproteins are a third type of cholesterol that carry triglycerides or the fat the body stores up and uses for energy between meals.

LDL is called bad cholesterol because it can build up on the walls of blood vessels, which then narrow the passageways. If a blood clot forms and gets stuck in one of these narrowed passageways, it can trigger a heart attack or a stroke.

HDL is often called good cholesterol because it absorbs other types of cholesterol and carries them away from arteries and back to the liver, which then eliminates it from the body. Additionally, HDL cholesterol is called “good” cholesterol because it can remove other types of cholesterol from the bloodstream.

HDL: Good or bad for overall health?

While conducting the study, scientists recorded 850 incidences of dementia in 18,668 participants. The research team discovered that volunteers with high HDL cholesterol of more than 80 milligrams per deciliter had a 27 percent greater risk of dementia.

They also reported that there was a 42 percent increase in dementia risk for volunteers older than 75.

High HDL cholesterol was linked to an increased risk of all-cause dementia in both middle-aged and older individuals.

“The association appears strongest in those 75 years and above,” explained the researchers.

Even considering different variables such as country, age, sex, daily exercise, education, alcohol consumption and weight change over time, the researchers advised that the link between high HDL cholesterol and dementia remained “significant.” (Related: Study: Life’s Essential 8 could help you live healthier longer.)

Monira Hussain, a senior research fellow at Monash University’s School of Public Health and Preventive Medicine, said the study findings can be used to help improve understanding of dementia, but more research is needed.

Hussain said while it has been confirmed that HDL cholesterol has a crucial role in cardiovascular health, the study suggests that continued research can help shed more light on the “role of very high HDL cholesterol in the context of brain health.”

Hussain added that it is worth considering very high HDL cholesterol levels in prediction algorithms for dementia risk.

Researchers recruited a larger cohort for the HDL/dementia risk study

For the study, the research team recruited 16,703 Australians older than 70 years, along with 2,411 people older than 65 years from the United States.

The volunteers examined during the research had no physical disability, cardiovascular disease, dementia, or life-threatening illness at the time of recruitment for the study. They were also “cognitively healthy.”

According to the scientists, while several studies have indicated a connection between HDL cholesterol and adverse health events, evidence regarding its connection to dementia remains unknown.

The researchers said an analysis of a medical database examining the link between high HDL cholesterol and dementia revealed that there was only one study from Denmark that established a link.

“Only one study of cohorts from Denmark was identified which suggested that high HDL-C is associated with dementia in people aged 47–68 years,” said the scientists.

Because early-onset dementia may have a different pathophysiology than late-onset dementia, the researchers advised that it is important to extend these results to well-characterized prospective studies of older individuals who are cognitively intact at the study onset.

The data analysis was conducted between October 2022 and January 2023, before publishing the study.

The scientists said their study is the “most comprehensive study” to report high HDL cholesterol and the risk of dementia in the elderly.

There’s a Scary Link Between Bad Sleep And The Onset of Alzheimer’s

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Sleep disruption could be a very early sign.

Fragmented sleep, marked by repeated wake-ups during the night and a need to nap during the day, could be an early sign of Alzheimer’s disease, according to new research.

A study recently published in the journal JAMA Neurology found that adults with healthy memories who had disrupted circadian rhythms – also known as sleep cycles – had protein buildups of a substance called amyloid plaque, which can serve as an early sign of Alzheimer’s.

The damage that causes Alzheimer’s-associated memory loss can begin 15 or 20 years before symptoms of the disease become evident.

Other studies have shown that there’s a connection between poor sleep and Alzheimer’s or dementia as well.

This new study provides more evidence of that link, and indicates that sleep disruption might be a very early warning sign of future neurodegenerative disease.

The findings also suggest that working to treat sleep issues early may help protect brain health down the road – though more research is needed to find out.

For the new study, researchers tracked the sleep cycles of 189 cognitively healthy adults with an average age of 66. They also analysed their brains to look for Alzheimer’s-related proteins and plaques.

Most of the participants had relatively normal sleep cycles, and 139 had no signs of amyloid protein buildup. Some of those people had sleep problems, but they could mostly be explained by age, sleep apnea, or other causes.

But the 50 subjects in the study whose brains had Alzheimer’s-related proteins all had disrupted body clocks.

“It wasn’t that the people in the study were sleep-deprived,” lead study author Erik Musiek said in a press release.

“But their sleep tended to be fragmented. Sleeping for eight hours at night is very different from getting eight hours of sleep in one-hour increments during daytime naps.”

The researchers also disrupted the sleep rhythms of mice in another study and found that doing so led to a buildup of amyloid plaque in their brains.

Other recent research has shown that people who report sleeping poorly show more signs of Alzheimer’s. One recent study found that even disrupting someone’s sleep for a night could lead to a spike in Alzheimer’s-related proteins.

To be clear, that doesn’t mean that one night of bad sleep leads to Alzheimer’s. But it does make sleep trouble even more disturbing than the tired feeling that lingers after a restless night – which is good motivation to fix poor sleeping habits.

The big question that remains is whether bad sleep causes the protein buildup that’s linked to Alzheimer’s, or whether people whose brains are already changing have more trouble sleeping.

It’s quite possible that both are true.

Some research has indicated that any sleep disruption seems to lead to brain changes (in mice and people). We know that sleep has a cleansing function and that in deep sleep our brain washes away some proteins that regularly build up.

But we also know that once these buildups exist, people have a harder time getting that cleansing deep sleep.

In other words, regular poor sleep could lead to a vicious cycle that makes it harder to get the rest the brain needs.

The upside of all this is that it could mean that intervening to fix sleep problems early could lead to improved brain health down the road.

There are plenty of reasons to try to get a good night’s sleep – this seems to be an especially good one.