Native California medicinal plant may hold promise for treating Alzheimer's

Salk scientists identify possible healing compound in Yerba santa

February 20, 2019

Science Daily/Salk Institute

The medicinal powers of aspirin, digitalis, and the anti-malarial artemisinin all come from plants. A discovery of a potent neuroprotective and anti-inflammatory chemical in a native California shrub may lead to a treatment for Alzheimer's disease based on a compound found in nature.

"Alzheimer's disease is a leading cause of death in the United States," says Senior Staff Scientist Pamela Maher, a member of Salk's Cellular Neurobiology Laboratory, run by Professor David Schubert. "And because age is a major risk factor, researchers are looking at ways to counter aging's effects on the brain. Our identification of sterubin as a potent neuroprotective component of a native California plant called Yerba santa (Eriodictyon californicum) is a promising step in that direction."

Native California tribes, which dubbed the plant "holy herb" in Spanish, have long used Yerba santa for its medicinal properties. Devotees brew its leaves to treat respiratory ailments, fever and headaches; and mash it into a poultice for wounds, sore muscles and rheumatism.

To identify natural compounds that might reverse neurological disease symptoms, Maher applied a screening technique used in drug discovery to a commercial library of 400 plant extracts with known pharmacological properties. The lab had previously used this approach to identify other chemicals (called flavonoids) from plants that have anti-inflammatory and neuroprotective properties.

Through the screen, the lab identified a molecule called sterubin as Yerba santa's most active component. The researchers tested sterubin and other plant extracts for their impact on energy depletion in mouse nerve cells, as well as other age-associated neurotoxicity and survival pathways directly related to the reduced energy metabolism, accumulation of misfolded, aggregated proteins and inflammation seen in Alzheimer's. Sterubin had a potent anti-inflammatory impact on brain cells known as microglia. It was also an effective iron remover -- potentially beneficial because iron can contribute to nerve cell damage in aging and neurodegenerative diseases. Overall, the compound was effective against multiple inducers of cell death in the nerve cells, according to Maher.

"This is a compound that was known but ignored," Maher says. "Not only did sterubin turn out to be much more active than the other flavonoids in Yerba santa in our assays, it appears as good as, if not better than, other flavonoids we have studied."

Next, the lab plans to test sterubin in an animal model of Alzheimer's, then determine its drug-like characteristics and toxicity levels in animals. With that data, Maher says, it might be possible to test the compound in humans, although it would be critical to use sterubin derived from plants grown under standardized, controlled conditions. She says the team will likely generate synthetic derivatives of sterubin.

https://www.sciencedaily.com/releases/2019/02/190220174105.htm

Chronic inflammation in middle age may lead to thinking and memory problems later

February 13, 2019

Science Daily/American Academy of Neurology

People who have chronic inflammation in middle-age may develop problems with thinking and memory in the decades leading up to old age.

There are two kinds of inflammation. Acute inflammation happens when the body's immune response jumps into action to fight off infection or an injury. It is localized, short-term and part of a healthy immune system. Chronic inflammation is not considered healthy. It is a low-grade inflammation that lingers for months or even years throughout the body. It can be caused by autoimmune disorders like rheumatoid arthritis or multiple sclerosis, physical stress or other causes. Symptoms of chronic inflammation include joint pain or stiffness, digestive problems and fatigue.

Ways to reduce chronic inflammation include getting regular exercise, following an anti-inflammatory heart healthy diet, and getting enough sleep.

"Chronic inflammation is tough on the body, and can damage joints, internal organs, tissue and cells," said study author Keenan A. Walker, PhD, of Johns Hopkins University in Baltimore, Md. "It can also lead to heart disease, stroke and cancer. While other studies have looked at chronic inflammation and its effects on the brain in older people, our large study investigated chronic inflammation beginning in middle age and showed that it may contribute to cognitive decline in the decades leading up to old age."

As part of the Atherosclerosis Risk in Communities (ARIC) Study, researchers followed 12,336 people with an average age of 57 for approximately 20 years. Researchers took blood samples from participants at the start of the study, measuring four biomarkers of inflammation: fibrinogen, white blood cell count, von Willebrand factor, and factor VIII. They created a composite inflammation score for the four biomarkers. Three years later, researchers measured C-reactive protein, another blood biomarker of inflammation. Participants were divided into four groups based on their composite inflammation scores and C-reactive protein levels.

Participants' thinking and memory skills were tested at the beginning of the study, six to nine years later, and at the end of the study.

Researchers found the group with the highest levels of inflammation biomarkers had an 8-percent steeper decline in thinking and memory skills over the course of the study than the group with the lowest levels of inflammation biomarkers. The group with the highest C-reactive protein levels had a 12-percent steeper decline in thinking and memory skills than the group with the lowest levels. These results were derived after researchers adjusted for other factors that could affect thinking and memory skills, such as education, heart disease and high blood pressure. Further analyses revealed that inflammation-associated declines in thinking were most prominent in areas of memory, compared to other aspects of thinking such as language and executive functioning.

"Overall, the additional change in thinking and memory skills associated with chronic inflammation was modest, but it was greater than what has been seen previously associated with high blood pressure in middle age," Walker said.

"Many of the processes that can lead to a decline in thinking and memory skills are believed to begin in middle age, and it is in middle age that they may also be most responsive to intervention," said Walker. "Our results show that chronic inflammation may be an important target for intervention. However, it's also possible that chronic inflammation is not a cause and instead a marker of, or even a response to, neurodegenerative brain diseases that can lead to cognitive decline."

A limitation of the study was that participants with higher levels of chronic inflammation at the start of the study were more likely to drop out or die before the final follow-up visit, so surviving participants may not be representative of the general population.

Future studies could include more frequent assessments of thinking and memory skills. They could also examine a larger variety of inflammation markers in the blood.

https://www.sciencedaily.com/releases/2019/02/190213160535.htm

With age comes hearing loss and a greater risk of cognitive decline

But study suggests higher education might counter effects of milder hearing impairment

February 12, 2019

Science Daily/University of California - San Diego

In a new study, researchers report that hearing impairment is associated with accelerated cognitive decline with age, though the impact of mild hearing loss may be lessened by higher education

Hearing impairment is a common consequence of advancing age. Almost three-quarters of U.S. adults age 70 and older suffer from some degree of hearing loss. One unanswered question has been to what degree hearing impairment intersects with and influences age-related cognitive decline.

In a new study, researchers at University of California San Diego School of Medicine report that hearing impairment is associated with accelerated cognitive decline with age, though the impact of mild hearing loss may be lessened by higher education.

The findings are published in the February 12, 2019 issue of the Journal of Gerontology: Series A Medical Sciences.

A team of scientists, led by senior author Linda K. McEvoy, PhD, professor in the departments of Radiology and Family Medicine and Public Health, tracked 1,164 participants (mean age 73.5 years, 64 percent women) in the longitudinal Rancho Bernardo Study of Healthy Aging for up to 24 years. All had undergone assessments for hearing acuity and cognitive function between the years 1992 to 1996 and had up to five subsequent cognitive assessments at approximately four-year intervals. None used a hearing aid.

The researchers found that almost half of the participants had mild hearing impairment, with 16.8 percent suffering moderate-to-severe hearing loss. Those with more serious hearing impairment showed worse performance at the initial visit on a pair of commonly used cognitive assessment tests: the Mini-Mental State Exam (MMSE) and the Trail-Making Test, Part B. Hearing impairment was associated with greater decline in performance on these tests over time, both for those with mild hearing impairment and those with more severe hearing impairment.

However, the association of mild hearing impairment with rate of cognitive decline was modified by education. Mild hearing impairment was associated with steeper decline among study participants without a college education, but not among those with higher education. Moderate-to-severe hearing impairment was associated with steeper MMSE decline regardless of education level.

"We surmise that higher education may provide sufficient cognitive reserve to counter the effects of mild hearing loss, but not enough to overcome effects of more severe hearing impairment," said McEvoy.

Degree of social engagement did not affect the association of hearing impairment with cognitive decline. "This was a somewhat unexpected finding" said first author Ali Alattar. "Others have postulated that cognitive deficits related to hearing impairment may arise from social isolation, but in our study, participants who had hearing impairment were as socially engaged as those without hearing loss."

The findings, said the authors, emphasize the need for physicians to be aware that older patients with hearing impairments are at greater risk for cognitive decline. They also emphasized the importance of preventing hearing loss at all ages, since hearing impairment is rarely reversible. One important way to protect hearing, they said, is to minimize loud noise exposure since this is the largest modifiable risk factor for hearing impairment.

https://www.sciencedaily.com/releases/2019/02/190212134802.htm

Exercise may improve thinking skills in people as young as 20

January 30, 2019

Science Daily/American Academy of Neurology

Regular aerobic exercise such as walking, cycling or climbing stairs may improve thinking skills not only in older people but in young people as well, according to a new study. The study also found that the positive effect of exercise on thinking skills may increase as people age.

The specific set of thinking skills that improved with exercise is called executive function. Executive function is a person's ability to regulate their own behavior, pay attention, organize and achieve goals.

"As people age, there can be a decline in thinking skills, however our study shows that getting regular exercise may help slow or even prevent such decline," said study author Yaakov Stern, PhD, of Columbia University in New York, and a member of the American Academy of Neurology. "We found that all participants who exercised not only showed improvements in executive function but also increased the thickness in an area of the outer layer of their brain."

The study involved 132 people between the ages of 20 and 67 who did not smoke or have dementia but who also did not exercise at the start of the study and were determined to have below average fitness levels. Participants were randomly assigned to six months of either aerobic exercise or stretching and toning four times a week. The two groups were equally balanced for age, sex, education as well as memory and thinking skills at the start of the study.

All participants either exercised or stretched and toned at a fitness center and checked in weekly with coaches monitoring their progress. They all wore heart rate monitors as well. Participants' thinking and memory skills were evaluated at the start of the study as well as at three months and at the end of the six-month study.

Participants in the exercise group chose from aerobic activities including walking on a treadmill, cycling on a stationary bike or using an elliptical machine. They ramped up their activity during the first month, then during the remainder of the six-month study they trained at 75 percent of their maximum heart rate. People in the stretching and toning group did exercises to promote flexibility and core strength.

Researchers measured participants' aerobic capacity using a cycling machine called an ergometer that estimates exercise intensity. Participants also had MRI brain scans at the start and end of the study.

Researchers found that aerobic exercise increased thinking skills. From the beginning of the study to the end, those who did aerobic exercise improved their overall scores on executive function tests by 0.50 points, which was a statistically significant difference from those who did stretching and toning, who improved by 0.25 points. At age 40, the improvement in thinking skills was 0.228 standard deviation units higher in those who exercised compared to those who did stretching and toning and at age 60, it was 0.596 standard deviation units higher.

"Since a difference of 0.5 standard deviations is equivalent to 20 years of age-related difference in performance on these tests, the people who exercised were testing as if they were about 10 years younger at age 40 and about 20 years younger at age 60," Stern said.

He added, "Since thinking skills at the start of the study were poorer for participants who were older, our findings suggest that aerobic exercise is more likely to improve age-related declines in thinking skills rather than improve performance in those without a decline."

Researchers also found an increase in the thickness of the outer layer of the brain in the left frontal area in all those who exercised, suggesting that aerobic exercise contributes to brain fitness at all ages.

"Our research confirms that exercise can be beneficial to adults of any age," said Stern.

Overall, researchers did not find a link between exercise and improved memory skills. However, those with the genetic marker for dementia, the APOE ?4 allele, showed less improvement in thinking skills.

A limitation of the study is the small number of participants. Larger studies over longer periods of time may allow researchers to see other effects in thinking and memory skills.

The study was supported by the National Institutes of Health.

https://www.sciencedaily.com/releases/2019/01/190130161638.htm

How exercise may protect against Alzheimer's

February 8, 2019

Science Daily/Columbia University Irving Medical Center

A hormone called irisin -- produced during exercise -- may protect neurons against Alzheimer's disease.

Athletes know a vigorous workout can release a flood of endorphins: "feel-good" hormones that boost mood. Now there's evidence that exercise produces another hormone that may improve memory and protect against Alzheimer's disease, according to a study co-led by Ottavio Arancio, MD, PhD, a researcher at Columbia University's Vagelos College of Physicians and Surgeons and Taub Institute for Research on Alzheimer's Disease and the Aging Brain.

The study was published in Nature Medicine.

Physical activity is known to improve memory, and studies suggest it may also reduce the risk of Alzheimer's disease. But researchers don't understand why.

A few years ago, exercise researchers discovered a hormone called irisin that is released into the circulation during physical activity. Initial studies suggested that irisin mainly played a role in energy metabolism. But newer research found that the hormone may also promote neuronal growth in the brain's hippocampus, a region critical for learning and memory.

"This raised the possibility that irisin may help explain why physical activity improves memory and seems to play a protective role in brain disorders such as Alzheimer's disease" says Arancio, who is a professor of pathology and cell biology and of medicine at Columbia University Vagelos College of Physicians and Surgeons.

Irisin is reduced in brains of people with Alzheimer's

In the new study, Arancio and his colleagues at the Federal University of Rio de Janeiro in Brazil and Queens University in Canada first looked for a link between irisin and Alzheimer's in people. Using tissue samples from brain banks, they found that irisin is present in the human hippocampus and that hippocampal levels of the hormone are reduced in individuals with Alzheimer's.

To explore what irisin does in the brain, the team turned to mice. These experiments show that irisin, in mice, protects the brain's synapses and the animals' memory: When irisin was disabled in the hippocampus of healthy mice, synapses and memory weakened. Similarly, boosting brain levels of irisin improved both measures of brain health.

Swimming boosts irisin, protects memory in mice

The researchers then looked at the effect of exercise on irisin and the brain. In the study's most compelling experiments, the researchers found that mice who swam nearly every day for five weeks did not develop memory impairment despite getting infusions of beta amyloid -- the neuron-clogging, memory-robbing protein implicated in Alzheimer's.

Blocking irisin with a drug completely eliminated the benefits of swimming, the researchers also found. Mice who swam and were treated with irisin-blocking substances performed no better on memory tests than sedentary animals after infusions with beta amyloid.

Together the findings suggest that irisin could be exploited to find a novel therapy for preventing or treating dementia in humans, Arancio says. His team is now searching for pharmaceutical compounds that can increase brain levels of the hormone or can mimic its action.

"In the meantime, I would certainly encourage everyone to exercise, to promote brain function and overall health," he said. "But that's not possible for many people, especially those with age-related conditions like heart disease, arthritis, or dementia. For those individuals, there's a particular need for drugs that can mimic the effects of irisin and protect synapses and prevent cognitive decline."

https://www.sciencedaily.com/releases/2019/02/190208173511.htm

Absentmindedness points to earlier warning signs of silent strokes among people at risk

February 6, 2019

Science Daily/Baycrest Centre for Geriatric Care

Adults who notice that they frequently lose their train of thought or often become sidetracked may in fact be displaying earlier symptoms of cerebral small vessel disease, otherwise known as a 'silent stroke,' suggests a recent study.

Researchers uncovered that individuals with damage to the brain's white matter, caused by silent strokes, reported poor attentiveness and being distracted more frequently on day-to-day tasks, according to a recently published paper in the journal Neurobiology of Aging. Despite these complaints, about half of the people with identified white matter damage scored within the normal range on formal laboratory assessments of attention and executive function (a person's ability to plan, stay organized and maintain focus on overall goals).

"Our results indicate that in many cases of people who were at a higher risk of silent stroke and had one, they saw a notable difference in their ability to stay focused, even before symptoms became detectable through a neuropsychological test," says Ayan Dey, lead author on the paper and a graduate student at Baycrest's Rotman Research Institute (RRI) and the University of Toronto. "If a person feels this may be the case, concerns should be brought to a doctor, especially if the person has a health condition or lifestyle that puts them at a higher risk of stroke or heart disease."

Cerebral small vessel disease is one of the most common neurological disorders of aging. This type of stroke and changes in the brain's blood flow (vascular changes) are connected to the development of vascular dementia and a higher risk of Alzheimer's disease and other dementias.

The strokes are "silent" since they don't cause lasting major changes seen with an overt stroke, such as affecting a person's ability to speak or paralysis. Despite a lack of obvious symptoms, cerebral small vessel disease causes damage to the brain's white matter (responsible for communication among regions), which can cause memory and cognitive issues over time.

Typically, this type of stroke is uncovered incidentally through MRI scans or once the brain damage has worsened, says Dey.

"There are no effective treatments for Alzheimer's disease, but brain vascular changes can be prevented or reduced through smoking cessation, exercise, diet and stress management, as well as keeping one's blood pressure, diabetes and cholesterol under control," says Dr. Brian Levine, senior author on the paper, RRI senior scientist and professor of Psychology and Neurology at the University of Toronto. "With the right diagnosis, these interventions and lifestyle changes give older adults who are at risk for cognitive decline some options for maintaining brain health."

The study looked at results from 54 adults (between the ages of 55 to 80), who also possessed at least one risk factor for a stroke, such as high blood pressure, high cholesterol, diabetes, sleep apnea, a history of smoking, past mini strokes and advanced age above 75.

Research participants had their brains scanned by MRI and scientists analyzed brain tissue damage, specifically in relation to white matter, to determine injuries caused by cerebral small vessel disease. They also took part in a number of neurocognitive tests and questionnaires that assessed their attention and executive function.

Following up on this study, researchers will analyze functional brain imaging and electrical brain activity from participants to look at the differences in brain networks. They hope to uncover why some people are still able to perform well on cognitive assessments, despite damage to the brain.

"The question that remains is whether overcoming these changes in the brain is a natural ability some people have or if this is something that can be built up over time," says Dey. "If it's something that can be developed, is it something we can train?"

https://www.sciencedaily.com/releases/2019/02/190206091417.htm

A new culprit in cognitive decline in Alzheimer's disease

Study finds blood protein destroys memory storage sites in the brain and may lead to new treatments

February 5, 2019

Science Daily/Gladstone Institutes

Scientists have shown for the first time that a blood-clotting protein called fibrinogen is responsible for a series of molecular and cellular events that can destroy connections between neurons in the brain and result in cognitive decline.

It has long been known that patients with Alzheimer's disease have abnormalities in the vast network of blood vessels in the brain. Some of these alterations may also contribute to age-related cognitive decline in people without dementia. However, the ways in which such vascular pathologies contribute to cognitive dysfunction have largely remained a mystery. Until now, that is.

Scientists at the Gladstone Institutes, led by Senior Investigator Katerina Akassoglou, PhD, showed for the first time that a blood-clotting protein called fibrinogen is responsible for a series of molecular and cellular events that can destroy connections between neurons in the brain and result in cognitive decline.

Akassoglou and her team used state-of-the-art imaging technology to study both mouse brains and human brains from patients with Alzheimer's disease. They also produced the first three-dimensional volume imaging showing that blood-brain barrier leaks occur in Alzheimer's disease.

In their study, published in the scientific journal Neuron, the researchers found that fibrinogen, after leaking from the blood into the brain, activates the brain's immune cells and triggers them to destroy important connections between neurons. These connections, called synapses, are critical for neurons to communicate with one another.

Previous studies have shown that elimination of synapses causes memory loss, a common feature in Alzheimer's disease and other dementias. Indeed, the scientists showed that preventing fibrinogen from activating the brain's immune cells protected mouse models of Alzheimer's disease from memory loss.

"We found that blood leaks in the brain can cause elimination of neuronal connections that are important for memory functions," explains Akassoglou, who is also a professor of neurology at UC San Francisco (UCSF). "This could change the way we think about the cause and possible cure of cognitive decline in Alzheimer's disease and other neurological diseases."

The team showed that fibrinogen can have this effect even in brains that lack amyloid plaques, which are the focus of diverse treatment strategies that have failed in large clinical trials. The researchers showed that injecting even extremely small quantities of fibrinogen into a healthy brain caused the same kind of immune cell activation and loss of synapses they saw in Alzheimer's disease.

"Traditionally, the build-up of amyloid plaques in the brain has been seen as the root of memory loss and cognitive decline in Alzheimer's disease," says Mario Merlini, first author of the study and a staff research scientist in Akassoglou's laboratory at Gladstone. "Our work identifies an alternative culprit that could be responsible for the destruction of synapses."

The scientists' data help explain findings from recent human studies in which elderly people with vascular pathology showed similar rates of cognitive decline as age-matched people with amyloid pathology. However, patients with both types of pathology had much worse and more rapid cognitive decline. Other studies also identified vascular pathology as a strong predictor of cognitive decline that can act independently of amyloid pathology.

"Given the human data showing that vascular changes are early and additive to amyloid, a conclusion from those studies is that vascular changes may have to be targeted with separate therapies if we want to ensure maximum protection against the destruction of neuronal connections that leads to cognitive decline," says Akassoglou.

Interestingly, Akassoglou and her colleagues recently developed an antibody that blocks the interaction between fibrinogen and a molecule on the brain's immune cells. In a previous study, they showed this antibody protected mouse models of Alzheimer's disease from brain inflammation and neuronal damage.

"These exciting findings greatly advance our understanding of the contributions that vascular pathology and brain inflammation make to the progression of Alzheimer's disease," said Lennart Mucke, MD, co-author of the study and director of the Gladstone Institute of Neurological Disease. "The mechanisms our study identified may also be at work in a range of other diseases that combine leaks in the blood-brain barrier with neurological decline, including multiple sclerosis, traumatic brain injury, and chronic traumatic encephalopathy. It has far-reaching therapeutic implications."

https://www.sciencedaily.com/releases/2019/02/190205115419.htm

Scientists shed light on processes behind age-related decline in brain structures

January 31, 2019

Science Daily/Cardiff University

Aging can cause damage to support cells in the white matter, which in turn may lead to damage in the grey matter of the hippocampus, finds a new study.

The discovery gives researchers a new area to focus on in the search for treatments that can protect cognitive function.

Claudia Metzler-Baddeley, from Cardiff University's Brain Imaging Research Centre (CUBRIC), said: "The brain is made up of grey and white matter. While grey matter contains neuronal cells, which perform computations in our brain, the white matter contains connections and support cells that help the communication between different areas.

"Our new study not only confirms that aging leads to both grey matter decline in the hippocampus and white matter decline in the surrounding area, but also reveals the causal relationship between the two.

"Using a method called mediation analysis, we discovered that ageing of the white matter was accounting for ageing of hippocampal grey matter and not the other way around. Our results suggest that damage to the support cells may affect tissue health in the hippocampus, a region important for memory and involved in Alzheimer's disease.

"This is an exciting find. If hard-working support cells in the white matter start to misfunction with age, then therapies that protect these support cells may aid in the fight against the damage that ageing can do to our cognitive ability."

The study, which looked at the brains of 166 healthy volunteers, was carried out using state-of-the-art brain imaging techniques at CUBRIC and was jointly funded by the Alzheimer's Society and the BRACE Alzheimer's charity.

https://www.sciencedaily.com/releases/2019/01/190131104936.htm

'Bugs' in the gut might predict dementia in the brain

January 30, 2019

Science Daily/American Heart Association

The makeup of bacteria and other microbes in the gut may have a direct association with dementia risk, according to preliminary research to be presented in Honolulu at the American Stroke Association's International Stroke Conference 2019, a world premier meeting for researchers and clinicians dedicated to the science and treatment of cerebrovascular disease.

Researchers studying the population of bacteria and microbes in the intestines, known as gut microbiota, have found these "bugs" impact risks for diseases of the heart and more. Japanese researchers studied 128 (dementia and non-dementia) patients' fecal samples and found differences in the components of gut microbiota in patients with the memory disorder suggesting that what's in the gut influences dementia risk much like other risk factors.

The analysis revealed that fecal concentrations of ammonia, indole, skatole and phenol were higher in dementia patients compared to those without dementia. But levels of Bacteroides -- organisms that normally live in the intestines and can be beneficial -- were lower in dementia patients.

"Although this is an observational study and we assessed a small number of the patients, the odds ratio is certainly high suggesting that gut bacteria may be a target for the prevention of dementia," said Naoki Saji, M.D., Ph.D., study author and vice director of the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology in Japan.

https://www.sciencedaily.com/releases/2019/01/190130075751.htm

What you eat could impact your brain and memory

January 28, 2019

Science Daily/Iowa State University

High levels of a satiety hormone could decrease a person's likelihood of developing Alzheimer's disease. For individuals who have higher levels of the hormone, their chance of having mild cognitive impairment or Alzheimer's disease decreased by 65 percent.

You may be familiar with the saying, "You are what you eat," but did you know the food you eat could impact your memory?

Auriel Willette, assistant professor, and his team of researchers in Iowa State University's Department of Food Science and Human Nutrition discovered a satiety hormone that, at higher levels, could decrease a person's likelihood of developing Alzheimer's disease. A paper outlining the results of their study recently was accepted for publication in Neurobiology of Aging.

Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the researchers looked at the satiety hormone, Cholecystokinin (CCK), in 287 people. CCK is found in both the small intestines and the brain. In the small intestines, CCK allows for the absorption of fats and proteins. In the brain, CCK is located in the hippocampus, which is the memory-forming region of the brain, Willette said.

The researchers found for individuals who have higher CCK levels, their chance of having mild cognitive impairment, a precursor state to Alzheimer's disease, or Alzheimer's disease decreased by 65 percent.

"It will hopefully help to shed further light on how satiety hormones in the blood and brain affect brain function," Willette said.

Why CCK?

 Alexandra Plagman, lead author and graduate student in nutritional science, said they chose to focus on CCK because it is highly expressed in memory formation. The researchers wanted to see if there was any significance between levels of CCK and levels of memory and gray matter in the hippocampus and other important areas.

They also looked p-tau and tau proteins, which are thought to be toxic to the brain, to see how these might impact CCK and memory. They found that as tau levels increased, higher CCK was no longer related to less memory decline.

The researchers hope this study will encourage others to look into the nutritional aspect of diets, versus just looking at caloric intake. Plagman already is looking at how diet impacts an individual's CCK levels through researching fasting glucose and ketone bodies.

"By looking at the nutritional aspect, we can tell if a certain diet could prevent Alzheimer's disease or prevent progression of the disease," Plagman said.

"The regulation of when and how much we eat can have some association with how good our memory is," Willette added. "Bottom line: what we eat and what our body does with it affects our brain."

https://www.sciencedaily.com/releases/2019/01/190128111705.htm