The Startling Link Between Sugar and Alzheimer’s

Olga Khazan wrote . . . . . . . . .

In recent years, Alzheimer’s disease has occasionally been referred to as “type 3” diabetes, though that moniker doesn’t make much sense. After all, though they share a problem with insulin, type 1 diabetes is an autoimmune disease, and type 2 diabetes is a chronic disease caused by diet. Instead of another type of diabetes, it’s increasingly looking like Alzheimer’s is another potential side effect of a sugary, Western-style diet.

In some cases, the path from sugar to Alzheimer’s leads through type 2 diabetes, but as a new study and others show, that’s not always the case.

A longitudinal study, published Thursday in the journal Diabetologia, followed 5,189 people over 10 years and found that people with high blood sugar had a faster rate of cognitive decline than those with normal blood sugar—whether or not their blood-sugar level technically made them diabetic. In other words, the higher the blood sugar, the faster the cognitive decline.

“Dementia is one of the most prevalent psychiatric conditions strongly associated with poor quality of later life,” said the lead author, Wuxiang Xie at Imperial College London, via email. “Currently, dementia is not curable, which makes it very important to study risk factors.”

Melissa Schilling, a professor at New York University, performed her own review of studies connecting diabetes to Alzheimer’s in 2016. She sought to reconcile two confusing trends. People who have type 2 diabetes are about twice as likely to get Alzheimer’s, and people who have diabetes and are treated with insulin are also more likely to get Alzheimer’s, suggesting elevated insulin plays a role in Alzheimer’s. In fact, many studies have found that elevated insulin, or “hyperinsulinemia,” significantly increases your risk of Alzheimer’s. On the other hand, people with type 1 diabetes, who don’t make insulin at all, are also thought to have a higher risk of Alzheimer’s. How could these both be true?

Schilling posits this happens because of the insulin-degrading enzyme, a product of insulin that breaks down both insulin and amyloid proteins in the brain—the same proteins that clump up and lead to Alzheimer’s disease. People who don’t have enough insulin, like those whose bodies’ ability to produce insulin has been tapped out by diabetes, aren’t going to make enough of this enzyme to break up those brain clumps. Meanwhile, in people who use insulin to treat their diabetes and end up with a surplus of insulin, most of this enzyme gets used up breaking that insulin down, leaving not enough enzyme to address those amyloid brain clumps.

According to Schilling, this can happen even in people who don’t have diabetes yet—who are in a state known as “prediabetes.” It simply means your blood sugar is higher than normal, and it’s something that affects roughly 86 million Americans.

Schilling is not primarily a medical researcher; she’s just interested in the topic. But Rosebud Roberts, a professor of epidemiology and neurology at the Mayo Clinic, agreed with her interpretation.

In a 2012 study, Roberts broke nearly 1,000 people down into four groups based on how much of their diet came from carbohydrates. The group that ate the most carbs had an 80 percent higher chance of developing mild cognitive impairment—a pit stop on the way to dementia—than those who ate the smallest amount of carbs. People with mild cognitive impairment, or MCI, can dress and feed themselves, but they have trouble with more complex tasks. Intervening in MCI can help prevent dementia.

Rebecca Gottesman, a professor of neurology at Johns Hopkins, cautions that the findings on carbs aren’t as well-established as those on diabetes. “It’s hard to be sure at this stage, what an ‘ideal’ diet would look like,” she said. “There’s a suggestion that a Mediterranean diet, for example, may be good for brain health.”

But she says there are several theories out there to explain the connection between high blood sugar and dementia. Diabetes can also weaken the blood vessels, which increases the likelihood that you’ll have ministrokes in the brain, causing various forms of dementia. A high intake of simple sugars can make cells, including those in the brain, insulin resistant, which could cause the brain cells to die. Meanwhile, eating too much in general can cause obesity. The extra fat in obese people releases cytokines, or inflammatory proteins that can also contribute to cognitive deterioration, Roberts said. In one study by Gottesman, obesity doubled a person’s risk of having elevated amyloid proteins in their brains later in life.

Roberts said that people with type 1 diabetes are mainly only at risk if their insulin is so poorly controlled that they have hypoglycemic episodes. But even people who don’t have any kind of diabetes should watch their sugar intake, she said.

“Just because you don’t have type 2 diabetes doesn’t mean you can eat whatever carbs you want,” she said. “Especially if you’re not active.” What we eat, she added, is “a big factor in maintaining control of our destiny.” Roberts said this new study by Xie is interesting because it also shows an association between prediabetes and cognitive decline.

That’s an important point that often gets forgotten in discussions of Alzheimer’s. It’s such a horrible disease that it can be tempting to dismiss it as inevitable. And, of course, there are genetic and other, non-nutritional factors that contribute to its progression. But, as these and other researchers point out, decisions we make about food are one risk factor we can control. And it’s starting to look like decisions we make while we’re still relatively young can affect our future cognitive health.

“Alzheimer’s is like a slow-burning fire that you don’t see when it starts,” Schilling said. It takes time for clumps to form and for cognition to begin to deteriorate. “By the time you see the signs, it’s way too late to put out the fire.”

Source: The Atlantic

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At Risk for Alzheimer’s? Exercise Might Help Keep It at Bay

Dennis Thompson wrote . . . . . . . . .

Even if you are at high risk for Alzheimer’s disease, a little more exercise may buy you time, new research suggests.

Folks with elevated levels of a brain protein called beta amyloid tend to be more likely to develop Alzheimer’s disease and experience rapid brain decline later in life, previous research has found.

But apparently they can delay the onset of Alzheimer’s through regular exercise, scientists report.

“People who had elevated levels of amyloid, which is one of the earliest changes you see with Alzheimer’s disease, had slower rates of cognitive decline and brain volume loss over time if they had greater levels of physical activity,” said lead researcher Jennifer Rabin. She is a scientist with the Hurvitz Brain Sciences Program at the Sunnybrook Research Institute in Toronto.

It didn’t take much exercise to enjoy this protection, either.

The data suggests that people who walked 8,300 to 8,900 steps per day significantly delayed the onset of Alzheimer’s, Rabin said.

Previous studies have shown that older people who exercise generally tend to stay sharp longer into old age, but this new research shows physical activity is specifically protective for folks who have these early brain changes related to Alzheimer’s, said Dr. Howard Fillit. He’s executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation.

“This population is different than what’s been studied before because you’re looking at people who are clinically normal but have evidence of Alzheimer’s disease in their brains,” said Fillit, who wasn’t involved with the research.

For this study, Rabin and her colleagues asked 182 participants in the Harvard Aging Brain Study to wear a pedometer for a week, to gauge their usual level of physical activity. Brain scans were used to detect levels of amyloid beta in their brains.

Beta amyloid tends to clump in the brains of Alzheimer’s patients, collecting in sticky plaques between neurons and possibly disrupting brain cell function.

The researchers then tracked the participants over as many as seven years, with annual tests to check the status of their brain function. Repeat scans also were performed to see whether their brains had started to shrink, which is a sign of Alzheimer’s progression.

The study found that people who walked more tended to stay sharper and experience a slower loss of brain volume.

What’s notable is that the brain benefits of exercise were independent of the benefits for heart and blood vessel health, Fillit said.

That means that physical activity is helping the brain in ways beyond preventing micro-strokes that can contribute to dementia, Fillit and Rabin said.

Physical activity might be preserving brain function by reducing inflammation, improving overall flow of blood to the brain, or helping people get better sleep, Rabin said.

Exercise also has been associated with higher levels of BDNF [brain-derived neurotrophic factor], a brain chemical that “is the most powerful neuroprotective growth factor that we know,” Fillit said.

“It doesn’t have to be Tour de France-level training,” Fillit said. “It can just be getting on a treadmill or an elliptical and getting your heart rate up.”

Rabin warned that while physical activity apparently helps mitigate amyloid-related declines in brain function, people with higher levels of beta amyloid are not likely to age as well as those without any amyloid in their brains.

But it’s possible that if those folks combine exercise with heart-healthy habits such as eating right and controlling their blood pressure, they might further reduce their risk of future brain loss, Rabin added.

“If you’re engaging in a host of good lifestyle choices, you maybe could get yourself back to a normal aging trajectory,” Rabin said.

The findings were published online July 16 in the journal JAMA Neurology and presented on the same day at the Alzheimer’s Association International Conference, in Los Angeles.

Source: HealyhDay


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A New and Better Way to ‘Stage’ Alzheimer’s Patients?

Steven Reinberg wrote . . . . . . . . .

One of the hallmarks of Alzheimer’s is the accumulation of beta-amyloid plaques in the brain, but what part those plaques play in the development of the disease isn’t clear.

Now researchers have taken the first steps to trace the progression of plaque buildup in living patients. This way of “staging” the disease has implications for research and one day may help doctors treat this debilitating, fatal disease.

“It is possible to stage individuals in terms of how advanced their beta-amyloid deposition is, using PET scans,” said lead researcher Dr. Niklas Mattsson, an associate professor of clinical neuroscience at Lund University in Sweden.

When beta-amyloid appears, it follows certain stages, he explained. Some brain regions are involved early, others at the intermediate stage, and some in the late stage of Alzheimer’s.

“These stages are also associated with other hallmarks of Alzheimer’s disease, such as levels of tau [another type of protein] in cerebral spinal fluid, cognitive decline and the wasting away of brain cells,” Mattsson added.

“This staging system can be used both to improve research and perhaps also in clinical trials, to see if certain drugs are likely to be most effective in certain stages of Alzheimer’s,” Mattsson said.

By the time Alzheimer’s is typically diagnosed, the brain is already destroyed, said Meredith Braskie, an assistant professor of neurology at the University of Southern California in Los Angeles. She was not involved with the study.

The disease takes years to develop, which is why finding a way to diagnose it early is important, Braskie said. Most studies on plaque have been done on the brains of dead people.

“This study is important because they were looking at how amyloid spreads in living patients and coming up with stages for that,” Braskie said.

Although no cure exists for Alzheimer’s today, this finding could also help in testing drugs as they are developed, she said.

But, “this isn’t directly related to patient care,” Braskie said. “It’s more for research to see if treatments are working.”

For the study, Mattsson and his colleagues used PET scans from the Alzheimer’s Disease Neuroimaging Initiative database. Among the 741 participants, 304 had no cognitive impairment, 384 had mild cognitive impairment, and 53 had Alzheimer’s disease. Patients were followed up at two, four and six years.

At the start of the study, about 98% of the 2,072 scans weren’t staged. Of those in the earliest stage of plaque development, about 15% would likely progress to a more advanced stage, as would 71% of those at stage 1 and 53% of those at stage 2.

As patients moved from stage 1 to stages 2 and 3, amyloid plaque developed in more vital areas of the brain, the researchers noted.

Interestingly, nearly 1% of the patients reverted to a lower stage, the researchers found. Higher stages were linked to higher concentrations of tau in cerebral spinal fluid. More tau in stage 2 indicated a more rapid progression to cognitive decline. The researchers were able to confirm their findings in a different group of 474 patients.

The areas affected in the brain differed in each stage and were also linked to differences in genetics, blood circulation, brain cell behavior and cholesterol levels.

“I think that it is clear from these data that the earlier the diagnosis of Alzheimer’s is supported by amyloid imaging, the earlier clinicians are likely to initiate drug therapy,” said Dr. Sam Gandy. He’s chair of Alzheimer’s Disease Research and director of the Mount Sinai Center for Cognitive Health and NFL Neurological Care in New York City.

This would be a change from current practice, which is not to start drug therapy until patients have advanced beyond the mild cognitive impairment and are well into mild Alzheimer’s disease, said Gandy, who had no part in the study.

However, Gandy isn’t sure that beginning drug therapy when mild cognitive impairment starts and a scan shows plaque would benefit all or only some patients.

Also, he would like to see if the staging system would work the same way among patients with and without the APOE gene mutations, which are linked to Alzheimer’s.

“These data would potentially have some impact on care and on designing future research studies,” Gandy said. “Whether those changes in practice would have meaningful benefits for patients is not clear.”

The report was published online in the journal JAMA Neurology, to coincide with a presentation of the findings at the Alzheimer’s Association annual meeting, in Los Angeles.

Source: HealthDay


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Hormone Treatment for Prostate Cancer Linked to Heightened Alzheimer’s Risk

E.J. Mundell wrote . . . . . . . . .

Soon after a man is diagnosed with prostate cancer, drugs that lower levels of testosterone are often offered as treatment, since testosterone fuels the cancer’s growth.

But a major new study suggests that this approach might have an unwanted side effect: Higher odds for Alzheimer’s disease and other dementias.

“Our results suggest that clinicians need to raise their awareness about potential long-term cognitive effects of hormone therapy and discuss these risks with their patients,” said study author Ravishankar Jayadevappa.

He’s a research associate professor of geriatrics at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

One expert said it does raise troubling questions.

“Most of us are becoming as afraid of getting Alzheimer’s as we are of getting cancer,” said Dr. Elizabeth Kavaler, a urology specialist at Lenox Hill Hospital in New York City. “When a study pits one debilitating condition against another, it instills fear in patients.”

But the treatment — called androgen-deprivation therapy — remains the “gold standard” for many cases of prostate cancer, according to Kavaler. Therefore, the new data means “tough decision-making” for patients and their physicians, she said.

In the new study, Jayadevappa’s group took a look back at U.S. National Cancer Institute data on over 154,000 prostate cancer patients who were diagnosed between 1996 and 2003. About 62,000 received hormone-depleting therapy within two years of their diagnosis, while about 92,000 did not.

In total, 13% of men who had received the therapy went on to develop Alzheimer’s disease over eight years of follow-up, compared to 9% who hadn’t gotten the treatment, the study found. According to the researchers, the lifetime prevalence of Alzheimer’s disease in men generally is about 12%.

When the team looked at diagnoses of all forms of dementia, 22% of those who’d received the therapy received such a diagnosis, compared to 16% of those who hadn’t undergone hormonal therapy.

Jayadevappa’s team noted that earlier, smaller studies have found similar trends.

However, “to our knowledge, this is one of the largest studies to date examining this association, and it followed patients for an average of eight years after their prostate cancer diagnosis,” he said in a university news release.

As the researchers noted, androgen-deprivation therapy is an effective means of slowing the progress of prostate cancers. However, it is now typically only used in cases of advanced disease, or cases where the chances of a tumor recurrence are high.

The approach also has other deleterious side effects, including impaired sexual function, and potential harm to bones and cardiovascular health.

The study also can only point to an association between hormonal treatment and raised odds for dementia, it cannot prove cause and effect. But Jayadevappa’s team noted that they tried to account for other factors, such as age, the presence of other medical conditions and the severity of the prostate cancer.

Dr. Maria Torroella Carney is chief of geriatric and palliative medicine at Northwell Health in New Hyde Park, N.Y. Looking over the findings, she said they warrant further study, but it’s not time for men who’ve gotten hormonal therapy to panic.

Carney stressed that the study couldn’t prove cause and effect, and other factors might account for the higher risk of dementia.

Men receiving hormonal therapy tended to be “older, sicker and had more advanced prostate cancer,” Carney noted, and sicker patients already have higher odds of dementia.

In addition, the study didn’t reveal whether or not men who got the therapy lived longer than those who didn’t. If they did live longer, their odds of dementia would also increase over time, Carney explained.

Study co-author Dr. Thomas Guzzo agreed that no one should make rash decisions on prostate cancer care based on this study alone.

“I think we need to look at these patients on an individual level,” said Guzzo, who is chief of urology at the University of Pennsylvania. “Certainly, there are patients who need hormonal therapy and benefit from it greatly,” he said in a university news release. “There are others where the evidence is less clear, and in these patients, we should consider the risk of hormonal therapy versus the benefit in treating their prostate cancer. This should be a shared decision-making process with the patient.”

The study was published online in JAMA Network Open.

Source: HealthDay


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New Blood Test for Detecting Alzheimer’s Disease

Researchers from Lund University, together with the Roche pharmaceutical company, have used a method to develop a new blood marker capable of detecting whether or not a person has Alzheimer’s disease. If the method is approved for clinical use, the researchers hope eventually to see it used as a diagnostic tool in primary healthcare. This autumn, they will start a trial in primary healthcare to test the technique.

Currently, a major support in the diagnostics of Alzheimer’s disease is the identification of abnormal accumulation of the substance beta-amyloid, which can be detected either in a spinal fluid sample or through brain imaging using a PET scanner.

“These are expensive methods that are only available in specialist healthcare. In research, we have therefore long been searching for simpler diagnostic tools”, says Sebastian Palmqvist, associate professor at the unit for clinical memory research at Lund University, physician at Skåne University Hospital and lead author of the study.

In this study, which is a collaboration between several medical centres, the researchers investigated whether a simple blood test could identify people in whom beta-amyloid has started to accumulate in the brain, i.e. people with underlying Alzheimer’s disease. Using a simple and precise method that the researchers think is suitable for clinical diagnostics and screening in primary healthcare, the researchers were able to identify beta-amyloid in the blood with a high degree of accuracy.

“Previous studies on methods using blood tests did not show particularly good results; it was only possible to see small differences between Alzheimer’s patients and healthy elderly people. Only a year or so ago, researchers found methods using blood sample analysis that showed greater accuracy in detecting the presence of Alzheimer’s disease. The difficulty so far is that they currently require advanced technology and are not available for use in today’s clinical procedures”, says Sebastian Palmqvist.

The results are published in JAMA Neurology and based on studies of blood analyses collected from 842 people in Sweden (The Swedish BioFINDER study) and 237 people in Germany. The participants in the study are Alzheimer’s patients with dementia, healthy elderly people and people with mild cognitive impairment.

The method studied by the researchers was developed by Roche and is a fully automated technique which measures beta-amyloid in the blood, with high accuracy in identifying the protein accumulation.

“We have collaborated with Roche for a long time and it is only now that we are starting to approach a level of accuracy that is usable in routine clinical care around the world”, says Oskar Hansson, professor of neurology and head of the unit for clinical memory research at Lund University.

The researchers believe that this new blood sample analysis could be an important complement for screening individuals for inclusion in clinical drug trials against Alzheimer’s disease or to improve the diagnostics in primary care which will allow more people to get the currently available symptomatic treatment against Alzheimer’s disease.

“The next step to confirm this simple method to reveal beta-amyloid through blood sample analysis is to test it in a larger population where the presence of underlying Alzheimer’s is lower. We also need to test the technique in clinical settings, which we will do fairly soon in a major primary care study in Sweden. We hope that this will validate our results”, concludes Sebastian Palmqvist.

Source : Lund University


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