Long-term Use of Proton Pump Inhibitors Could Increase the Risk of Developing Dementia

“We’ve been able to show that proton pump inhibitors affect the synthesis of the neurotransmitter acetylcholine, which plays a significant part in conditions such as Alzheimer’s disease,” says Taher Darreh-Shori, senior researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “Since there’s no effective treatment for the disease, it’s important to avoid risk factors. We therefore want to draw attention to this so that the drugs aren’t used needlessly for a long time.”

Proton pump inhibitors (PPIs) work by blocking the pumps that transport acidic hydrogen ions from the cells that form the mucosa. When the pumps are out of action, there is a reduction in acid and, ultimately, the corrosive damage it does to tissue. Population studies have previously shown higher rates of dementia in people using PPIs (see background material), but what form such a connection could take has remained unknown – until now.

Inhibited synthetization of important neurotransmitter

First, the researchers used 3D computer simulations to examine how six PPI variants based on different active substances interacted with an enzyme called choline acetyletransferase, the function of which is to synthesize the neurotransmitter acetylcholine. As a neurotransmitter, acetylcholine is needed for passing signals among nerve cells, but this only works if enough of the substance is produced. The simulations showed that all the tested drugs were able to bind with the enzyme.

The researchers then analysed the effect of this binding. They found that all the drugs inhibited the enzyme, resulting in a reduced production of acetylcholine, where the stronger the binding, the stronger the inhibitory effect. Drugs based on the active substances omeprazole, esomeprazole, tenatoprazole and rabeprazole had the greatest affinity and were therefore the strongest inhibitors of the enzyme, while the variants pantoprazole and lansoprazole were the weakest (see illustration).

Complementary studies are now needed to examine whether these laboratory observations represent what occurs in the body. However, Darreh-Shori is already advising against the overuse of PPIs.

Avoid excessive use

“Special care should be taken with the more elderly patients and those already diagnosed with dementia,” he says. “The same also applies to patients with muscle weakness diseases such as ALS, as acetylcholine is an essential motor neurotransmitter. In such cases, doctors should use the drugs that have the weakest effect and prescribe them at lowest dose and for as short a time as possible.”

“I would, however, like to stress that the correct use of the drugs is safe also in the elderly, as long as the drugs are used for a limited time and when they’re really needed, as our nervous system is pretty flexible when it comes to tolerating short-term impact,” he adds.

Source: Karolinska Institutet


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Hearing Loss and the Connection to Alzheimer’s Disease, Dementia

Sound has the power to stimulate the brain, which is why hearing loss has the potential to have a profound effect on health – especially among older adults.

About 1 in 3 people in the United States between the ages of 65 and 74 has hearing loss, according to the National Institutes of Health. A 2016 study in the American Journal of Public Health found about two-thirds of adults ages 70 or older suffer from hearing impairment that may affect daily communication.

Hearing loss is associated with cognitive decline, though more research is needed to determine the degree of the connection, said Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medical College in New York City.

A 2011 study in Archives of Neurology, now named JAMA Neurology, found those with mild hearing loss had nearly twice the risk of developing dementia compared to people with normal hearing. Those with moderate loss had three times the risk, while those with severe loss had five times the risk.

“All we know is that people who tend to have hearing loss tend to have more dementia,” Iadecola said. “It doesn’t mean that the hearing loss is causing the dementia, it doesn’t mean that the dementia is causing the hearing loss.”

There were about 5 million people in the United States living with Alzheimer’s disease and related dementias in 2014, about 1.6% of the U.S. population, according to the Centers for Disease Control and Prevention. The number is expected to grow to 13.9 million, or roughly 3.3% of the population, by 2060.

Dementia can develop for a variety of reasons, including vascular, neurogenerative and neuroimmune conditions, Iadecola said. “Each has a different impact on the brain.”

One theory behind the connection between dementia and hearing loss is that dementia creates certain conditions that may affect the ability to hear, Iadecola said. Or, he added, it could be the reverse, with hearing loss somehow impairing the brain’s ability to function.

“If you break down what hearing is, it is a major component in our ability to connect with the rest of the world,” said Nicholas Reed, an audiologist and core faculty member at the Cochlear Center for Hearing and Public Health at Johns Hopkins Bloomberg School of Public Health in Baltimore.

Hearing loss is “highly related to social isolation and loneliness,” he said, “and we’ve known for a long time that social isolation and loneliness are related to important age-related health outcomes like dementia and cognitive decline.”

Reed is part of a Johns Hopkins team leading a federally funded study looking at the potential of hearing treatments to reduce cognitive decline in older adults. It’s the kind of research that could make a difference in the quality of life of older populations for generations to come.

Results aren’t expected for a few years. For now, Reed said, while existing research hasn’t definitively concluded whether hearing aids can help, “I think many of us believe that most likely, hearing care does help.”

But not everyone with mild hearing loss needs a hearing aid right away, he said. “You very much may be able to get by adjusting the way you live your life. Making sure you face sounds you want to hear, making sure you’re avoiding background noise for important conversations, and use simple amplifiers to help in more difficult situations.”

He advises people to start getting their hearing checked regularly in their 60s, and to use earplugs at loud sporting events or concerts, regardless of age.

Reed points to a 2017 report from The Lancet International Commission on Dementia Prevention, Intervention and Care as proof of the importance of prevention. The report identified hearing loss as one of nine potentially modifiable risk factors that contributed to about 35% of dementia cases, with hearing loss the biggest contributor at 9%.

“What that means is 9% of dementia cases could be eliminated theoretically if all hearing loss were eliminated,” Reed said. That assumes, however, there were no other contributing factors, he said.

Staying healthy overall, like getting enough exercise and preventing high blood pressure, also may affect hearing health.

“In terms of health, the primary concern as we go through aging, is to maintain our ability to function independently as much as possible,” Iadecola said, “and hearing is one of the central elements of this.”

Source: American Heart Association


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Study: Eating Mostly Processed Meats, Starches and Sugary Snack May Lead to Dementia

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

“How foods are consumed, not only the quantity consumed, may be important for dementia prevention,” said lead researcher Cecilia Samieri, a senior researcher in epidemiology at the University of Bordeaux in France.

In other words, it’s the total combination of foods, or “network,” that may be damaging, she and her team discovered.

Dementia was more common among folks who ate mostly processed meats like ham and sausages, starches like potatoes, and snacks such as cookies and cakes. People without dementia were more likely to eat a diverse diet that included fruits, vegetables, seafood and poultry, according to the findings.

This study, however, can’t prove that these foods cause dementia or that healthier foods prevent it, said Keith Fargo, director of scientific programs and outreach at the Alzheimer’s Association.

Still, Fargo noted that dementia, including Alzheimer’s disease, can start developing decades before any symptoms appear, and long-term diet factors may play a role.

“Worse eating habits toward charcuterie and snacking were evident years before dementia diagnosis in our cohort. In contrast, diverse and healthy diets appear to decrease the risk to develop dementia,” Samieri said. Charcuterie includes bacon, ham, sausages and salami.

For the study, Samieri and her colleagues looked at 209 people with dementia and 418 without it in France. Participants were an average of 78 years old and followed for 12 years. They had completed a food questionnaire five years earlier.

Years before the diagnosis, those who developed dementia during the study had a diet very different from those who did not develop dementia, Samieri said.

In people with dementia, highly processed meats, such as sausages, cured meats and paté, formed the “hub” of their diet. These meats were mostly eaten in combination with potatoes, alcohol and sweet snacks, Samieri said.

Moreover, it wasn’t the amount of these foods that seemed to increase the risk for dementia, but rather not eating other healthier foods, she said.

Other studies have found that a diet rich in green leafy vegetables, berries, nuts, whole grains and fish may lower the risk of dementia, Samieri said.

It’s not possible to tell from this study what it is about certain foods that might raise the risk for dementia, she said.

It may be that they’re close to the so-called Western diet that has been linked with heart disease, obesity and diabetes, but that’s only a guess, Samieri noted.

It’s also possible that the frequency of eating unhealthy foods, rather than the quantity, is important in the risk for dementia, she said.

“These findings suggest that promoting a diverse and healthy diet rather than diets centered on processed meats and unhealthy foods could lower the risk to develop dementia, although this deserves confirmation in a randomized controlled trial,” Samieri said.

Fargo said that no one nutrient or kind of food needs to be eliminated from the diet to protect people from dementia.

“It’s really more about the universe of foods that you’re eating, it’s not about one particular food,” he said.

Fargo said having a cheeseburger once in a while probably won’t hurt you, but they shouldn’t be the mainstay of your diet. Skip the fries and cola as the combination may be even unhealthier, he noted.

“Be thoughtful about your dietary intake,” Fargo said. “It’s not about making sure you’re getting one particular nutrient or cutting out one particular kind of food. It’s more about a healthy approach to eating in general, and making sure you’re getting a broad variety and nutritious foods.”

The study was funded by the Alzheimer’s Association and published online in the journal Neurology.

Source: HealthDay


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Foods That May Protect Against Dementia

Sari Harrar wrote . . . . . . . . .

Older adults who munched, crunched, and sipped the most flavonols—beneficial compounds in fruit, vegetables, tea, and wine—were 48 percent less likely to develop Alzheimer’s disease than people who consumed the least, according to a January 2019 report in Neurology. “This observational study does not prove cause and effect, but it adds to the idea that food is very important for brain health,” says the study’s lead author, Thomas M. Holland, MD, a researcher at Rush University in Chicago.

Dr. Holland and colleagues tracked 921 women and men for three to nine years, using yearly cognitive and memory tests plus in-person medical exams to diagnose dementia likely caused by Alzheimer’s. Participants—who had no signs of dementia at the start of the study—filled out annual food questionnaires, which the scientists used to estimate daily flavonol intake. Those who consumed at least 15.3 milligrams of flavonols—the amount in a small leafy green salad, one serving of cooked vegetables, or a half-cup of berries—per day had the lowest risk even after researchers adjusted for exercise levels, education, mentally stimulating activities, and the APOE4 gene, which increases the risk of developing Alzheimer’s in late life.

“Flavonols have anti-inflammatory and antioxidant properties,” Dr. Holland explains. “Antioxidants help destroy free radicals, which damage cells. Anti-inflammatories reduce inflammation, a natural process that can damage cells if it is overactive or sustained for too long.” In animal studies, flavonols boosted memory and learning and decreased Alzheimer-like brain changes.

“The study strengthens the argument for a potentially beneficial role of fruits and vegetables in brain function and provides an additional reason to consume them,” says Nikolaos Scarmeas, MD, associate professor of clinical neurology at Columbia University in New York City and the National and Kapodistrian University of Athens, Greece, who was not involved with Dr. Holland’s study.

“Flavonols may hold promise for promoting brain health,” says David Seres, MD, associate professor of medicine at the Institute of Human Nutrition at Columbia University in New York City. “But we need long-term, randomized, controlled studies involving thousands of people willing to follow a diet for several years to show that flavonols affect the human brain and that those benefits reduce the risk for Alzheimer’s.”

One such study is the US Pointer trial, which began earlier this year. During the two-year intervention, which involves 2,000 participants, researchers will investigate the effects of a healthy diet, exercise, brain-stimulating activities, socialization, and controlling cardiovascular conditions (such as high blood pressure) on Alzheimer’s disease and dementia risk. It’s based on the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, known as FINGER, in which participants who changed their habits experienced significant improvement in their thinking and memory compared with a control group.

“We estimate results in six or seven years,” says Dr. Holland, assistant trial director and medical advisor for the study’s branch at Rush University.

Until then, experts agree that a healthy diet is important for preventing poor blood circulation in the brain, which increases the risk of stroke, subtly damages small blood vessels, and contributes to vascular dementia, the most common cause of dementia after Alzheimer’s disease. (Often people have both vascular dementia and Alzheimer’s.)

To keep your brain in good shape, the experts recommend these lifestyle shifts:

Adopt healthy habits. “Flavonols are just one component of a healthy diet, and a healthy diet is just one part of prevention,” says Dr. Holland. An easy checklist to follow to lower the risk for cerebrovascular disease is the American Heart Association’s “Simple 7”: Eat healthy, exercise, quit smoking, maintain a healthy weight, prevent or treat high blood pressure, check for and treat high blood sugar, and avoid or treat high cholesterol. Also, remain socially engaged and participate in brain-stimulating activities. In a Mayo Clinic study published in Neurology in August 2019, older adults who played card games, did crossword puzzles, used a computer, or did crafts had a lower risk for developing mild cognitive impairment than those who didn’t.

Modify your meals. A good diet includes more produce and whole grains and less added sugar and saturated fats. “Try having a salad containing raw leafy greens every day or every other day, plus another cooked vegetable you like and some berries every day,” suggests Dr. Holland. “Choose colorful fruits and vegetables, so you get a wide range of vitamins, minerals, and other beneficial bioactives—components such as flavonols that influence physiological and cellular activity in the body.” Cook with seasonings like fresh dill, oregano, parsley, and tarragon; they all have flavonols. Tea, olive oil, oranges, and red wine contain small amounts of flavonols, but they were among the foods that contributed most to participants’ total intake in the study.

Forgo supplements. “Although supplements may be needed for certain medical conditions, they are not a stand-in for healthy foods, which also provide vitamins, minerals, fiber, and healthy fats,” says Dr. Holland.

Flavonol-Rich Foods

In their flavonol study, researchers at Rush University in Chicago found that people who consumed the most flavonols overall had a lower risk for an Alzheimer’s disease diagnosis than those who consumed the least. You won’t find flavonols listed on the nutrition panel of food packages, but according to the US Department of Agriculture, these foods contain them:

  • Almonds
  • Apples, dried
  • Apricots, dried
  • Arugula
  • Asparagus
  • Beet greens
  • Black beans
  • Blueberries
  • Broccoli
  • Brussels sprouts
  • Chinese cabbage
  • Collard greens
  • Cowpeas
  • Cranberries
  • Endive
  • Figs, dried
  • Golden raisins
  • Kale
  • Kidney beans
  • Kohlrabi
  • Mustard greens
  • Okra
  • Onions
  • Pears, dried
  • Pink beans
  • Pinto beans
  • Radicchio
  • Red cabbage
  • Rutabaga
  • Salsa
  • Scallions
  • Sour cherries
  • Spinach
  • Sun-dried tomatoes
  • Swiss chard
  • Tomato paste
  • Watercress
  • White beans
  • Zante currants

Source: Brain&Life

Dirty Air Might Raise Your Odds for Dementia

Alan Mozes wrote . . . . . . . . .

Smog drives up dementia risk, particularly for older men and women with heart disease, according to a new Swedish study.

For more than a decade, researchers tracked exposure to air pollution and dementia cases among nearly 3,000 Stockholm residents aged 60 and up.

Lead author Dr. Giulia Grande noted that exposure to dirty air has long been linked to an increased risk for lung and heart disease.

“More recently, several research groups have started to focus on the damages of air pollution on the brain — for example, its impact on cognitive functions in older adults,” she said.

The current research builds on that work. Participants were 74 years old on average and nearly two-thirds were women. All were free of dementia when the study began in 2001; they were tracked until 2013.

With strict air pollution rules in place, Stockholm has relatively good ambient air quality, said Grande, of the Aging Research Center at the Karolinska Institute and Stockholm University.

Her team pegged the city’s average annual pollution levels at about 2.5 microns of particulate matter or less — a level considered “low” by international standards.

Still, more than 12% of participants (364) developed dementia over the study period, the findings showed.

“And we found that people continuously exposed to higher levels of air pollution were at increased risk of dementia, as compared with those exposed to lower levels,” Grande said. That link was especially strong among participants who had a history of heart failure, ischemic heart disease or stroke.

Almost half of the pollution-related cases of dementia were connected to stroke, Grande said.

The findings dovetail with other research that has linked cardiovascular disease to a more rapid rate of cognitive (“thinking”) decline.

But why would air pollution increase dementia risk in the first place?

“Unfortunately, the biological mechanisms through which air pollution affects the brain are not completely understood,” Grande said. “But several pathways are possible.”

One possibility is that after inhaled pollutants penetrate the brain, they speed up accumulation of plaques that increase dementia risk, she said.

Poor air quality could also have an indirect effect, Grande added. Air pollution is an established risk to heart health and an “important trigger” for heart attacks and stroke. So, it could be the onset of heart disease that paves the way for development of dementia, she said.

That line of thinking made sense to Dr. Jesus Araujo, director of environmental cardiology at the David Geffen School of Medicine at UCLA. He said the kind of vascular damage brought on by heart disease may be an essential pre-requisite for dementia.

Araujo added that extensive evidence indicates that air pollution can trigger inflammation and hardening of the arteries (atherosclerosis), while also throwing the immune system out of whack (oxidative stress).

All of these factors “are important in the development of both cardiovascular disease and dementia,” according to Araujo, who was not involved with the new study.

Grande said the findings are one more reason to strengthen existing air-quality laws.

“By 2050, 68% of the world population is expected to live in urban areas, being continuously exposed to air pollution,” she pointed out. Her team projects that global dementia numbers will triple by 2050.

“Together with the worldwide aging of the population, this poses global challenges when it comes to preventive strategies for dementia,” Grande said. “So establishing and characterizing the relationship between air pollution and dementia has enormous impact.”

The report was published online in JAMA Neurology.

Source: HealthDay


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