There’s Still No Proven Way to Prevent Alzheimer’s

(HealthDay News) Medical science has failed to prove that any treatment, therapy or brain exercise can help prevent dementias such as Alzheimer’s disease, an extensive new review has concluded.

No medications, over-the-counter remedies or brain training programs have been proven in solid clinical trials to ward off dementia, researchers with the Minnesota Evidence-Based Practice Center in Minneapolis stated after reviewing dozens of previously published studies.

“The upshot is there isn’t a magic bullet,” said review co-author Mary Butler, co-director of the center and an assistant professor with the University of Minnesota School of Public Health.

The best evidence the investigators found indicates that healthy living is a person’s best defense against dementia, Butler said. That means eat right, exercise, treat health problems such as high blood pressure, and remain socially active.

“Of those interventions we were able to find that were tested, the few that showed potential for benefit or even hinting at benefit are really very similar to the kinds of public health messages we put out there in general about healthy aging,” Butler said.

The researchers conducted four side-by-side evidence reviews to test different categories of proposed therapies and treatments for Alzheimer’s:

  • Physical activity. Low-strength evidence from 16 trials showed that combining different types of activity — exercise, diet and cognitive training — might improve performance on brain tests.
  • Prescription drugs. No medications appeared to protect the brain in data from 51 trials. The drugs studied included those specifically for dementia as well as drugs to treat other health problems of aging, such as diabetes, high blood pressure, elevated cholesterol and ebbing hormone levels.
  • Vitamins and supplements. There’s no evidence from 38 trials that any over-the-counter tablets or pills can prevent dementia or Alzheimer’s disease. This included omega-3 fatty acids, ginkgo biloba and vitamins B, C, D and E.
  • Cognitive training. Brain exercises did not ward off dementia in 11 clinical trials.

“There is some moderate evidence that cognitive engagement brings some benefits, but those benefits are local,” Butler said.

“If we train on memory, our memory might improve. If we train on processing, our processing speed might improve. But there isn’t any good evidence to directly link that to changes in how many people develop dementia.”

Dean Hartley, director of science initiatives at the Alzheimer’s Association, said people shouldn’t be discouraged by this review. It doesn’t rule out any possible treatments for dementia — it just notes that science hasn’t proven that any of them work.

“What we need is more research, and that’s what this brings to light,” Hartley said.

Further, it’s a good sign that some evidence indicates that lifestyle changes like exercise and a healthy diet can help with dementia, Hartley continued.

“We can all be doing these now because they aren’t things that are going to hurt us, and will generalize to our health,” he said. “A healthy heart is a healthy brain. We will see that benefit to the brain.”

Alzheimer’s researcher Dr. Luca Giliberto also sees the evidence review as positive, but from a different angle: He hopes the review will shake up the field of research.

“Finally, somebody had the guts to state the fact that we don’t understand what’s going on with dementia and Alzheimer’s,” said Giliberto, an assistant professor with the Feinstein Institute for Medical Research in Manhasset, N.Y. “There’s nothing we currently are able to do to stop Alzheimer’s pathology.”

Researchers need to return to the basics and focus on figuring out why people develop Alzheimer’s before they start testing cures, he said.

“We have to go back to the bench and reinvent the pathology, reinvent everything about Alzheimer’s and these types of dementias,” Giliberto said. “We do not know enough, and we need to stop spending money and time on minor things like supplements and so forth because they are not the answer.”

If nothing else, these studies should lead seniors to stop spending money on online brain training programs, Butler said.

“There just isn’t anything to support that kind of financial expenditure for people with limited financial resources,” she said. “There are probably better things you can do with your time and resources than that. It might just be plain more enjoyable to spend time with people rather than chasing a computer screen.”

People also should be wary of purported “cures” or “preventions” for Alzheimer’s, said Dr. Gisele Wolf-Klein, director of geriatric education with Northwell Health in New Hyde Park, N.Y.

“None of the medications that have been looked at so far have been proven to reverse or even slow down significantly the degradation of cognition,” Wolf-Klein said.

“That doesn’t mean that in the future we won’t be able to find something,” she said. “But as of today, all the prescription medications have failed to slow down or provide cognitive protection.”

The researchers’ findings, presented in four reviews, are published in the Dec. 19 issue of Annals of Internal Medicine.

Citation

https://medlineplus.gov/news/fullstory_170505.html

SOURCES: Mary Butler, Ph.D., co-director, Minnesota Evidence-Based Practice Center and assistant professor, University of Minnesota School of Public Health; Dean Hartley, Ph.D., director of science initiatives, Alzheimer’s Association; Luca Giliberto, M.D., Ph.D., assistant professor, Feinstein Institute for Medical Research, Manhasset, N.Y.; Gisele Wolf-Klein, M.D., director, geriatric education, Northwell Health, New Hyde Park, N.Y.; Dec. 19, 2017, Annals of Internal Medicine

HealthDay Copyright (c) 2017 HealthDay. All rights reserved.

 

What’s The Connection Between Hearing and Cognitive Health?

(NIH) Hearing loss occurs in approximately one in three people age 65 to 74 and nearly one in two people age 75 and older in the United States, making it one of the most common conditions affecting older adults. Last year, the National Academies of Sciences, Engineering, and Medicine released Hearing Health Care for Adults: Priorities for Improving Access and Affordability, a report that highlights the importance of hearing health to communication and overall quality of life, and proposes recommendations to increase the availability and affordability of hearing health care.

Doctor checking a patient's ears

NIA-funded research has indicated that hearing loss may impact cognition and dementia risk in older adults. A 2011 study found that older adults with hearing loss were more likely to develop dementia than older adults with normal hearing.

In fact, there was a relationship between level of uncorrected hearing loss and level of dementia risk: mild hearing loss was associated with a two-fold increase in risk; moderate hearing loss with a three-fold increase in risk, and severe hearing loss with a five-fold increase in risk. (Lin et al., 2011).

Furthermore, a more recent study found that cognitive abilities (including memory and concentration) declined faster in older adults with hearing loss, as compared to older adults with normal hearing (Lin et al., 2013). These observations by scientists raise the question: can cognitive decline and/or dementia onset be slowed or stopped by correcting hearing loss?

Trial Launched to Test Hearing Intervention Impact on Cognitive Decline

The NIA has recently funded the Aging, Cognition, and Hearing Evaluation in Elders (ACHIEVE) clinical trial led by Drs. Frank Lin and Josef Coresh at Johns Hopkins University to examine the potential benefits of hearing rehabilitation. ACHIEVE will recruit 850 cognitively normal adults aged 70-84 with hearing loss from four locations (Hagerstown MD, Jackson MS, Minneapolis MN, and Winston-Salem NC). Individuals will be randomly assigned to either the hearing intervention (hearing needs assessment, fitting of hearing devices, education/counseling) or control intervention (health education).

ACHIEVE participants will be followed for three years and information on hearing function, cognition, and demographics (e.g. age, sex, education level) will be collected at several timepoints. The primary outcome of the study will be to determine if the hearing rehabilitative intervention changes the rates of cognitive decline as compared to the group receiving health education. Additionally, the researchers will examine if the intervention impacts physical and social functioning, quality of life, and physical activity.

This trial should further our knowledge on the relationship between age-related hearing loss and cognition and dementia. For further information on the trial, please visit www.achievestudy.org .

Citation

https://www.nia.nih.gov/news/whats-connection-between-hearing-and-cognitive-health

References

Lin FR, Metter EJ, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L. Hearing loss and incident dementia. Arch Neurol. 2011;68(2):214–220.

Lin FR, Yaffe K, Xia J, Xue Q, Harris TB, Purchase-Helzner E, Satterfield S, Ayonayon HN, Ferrucci L, Simonsick EM, Health ABC Study Group. Hearing loss and cognitive decline in older adults. JAMA Intern Med. 2013;173(4):293–299.

 

Lithium in Water Associated with Slower Rate of Alzheimer’s Disease Deaths

(Journal of Alzheimer’s Disease) Trace elements of lithium in drinking water can slow death rates from Alzheimer’s disease, Brock University research has found.

Rates of diabetes and obesity, which are important risk factors for Alzheimer’s disease, also decrease if there is a particular amount of lithium in the water, says the study, published recently in the Journal of Alzheimer’s Disease.

Postdoctoral fellow Val Fajardo and Rebecca MacPherson, Assistant Professor in the Department of Health Sciences, collected statistics on various lithium levels in drinking water in 234 counties across Texas.

Lithium is a water-soluble alkali metal found in igneous rocks and mineral springs. It is commonly used to treat bipolar and other mood disorders, but at much higher doses than what occurs naturally in drinking water.

The research team, which included Associate Professor of Health Sciences Paul LeBlanc, compared lithium levels naturally found in tap water with Alzheimer’s disease mortality rates, along with the incidence of obesity and diabetes, in the Texas counties.

“We found counties that had above the median level of lithium in tap water (40 micrograms per litre) experienced less increases in Alzheimer’s disease mortality over time, whereas counties below that median level had even higher increases in Alzheimer’s deaths over time,” says Fajardo.

The frequency of obesity and Type 2 diabetes also went down when the drinking water contained similar lithium levels, the researchers found.

Fajardo says he and his team focused on Texas because data on lithium levels were “freely available.”

Previous studies have demonstrated lithium’s ability to protect against Alzheimer’s disease, obesity and diabetes.

“However, we are one of the first groups to show that lithium’s potential protective effect against Alzheimer’s disease, obesity and diabetes may translate to the population setting through very low levels of lithium in tap water,” says Fajardo.

The Brock research comes on the heels of an August study from the University of Copenhagen linking high lithium levels in drinking water to decreases in dementia rates.

But Fajardo warns it’s too early to start advising authorities to add lithium to drinking water.

“There’s so much more research we have to do before policy-makers look at the evidence and say, OK, let’s start supplementing tap water with lithium just like we do in some municipalities with fluoride to prevent tooth decay,” he says.

Citation

https://www.j-alz.com/content/lithium-water-associated-slower-rate-alzheimer%E2%80%99s-disease-deaths

Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2017

 

Inflammation Drives Progression of Alzheimer’s

(DZNE & University of Bonn) According to a study by scientists of the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn now published in the journal Nature, inflammatory mechanisms caused by the brain’s immune system drive the progression of Alzheimer’s disease. These findings, which rely on a series of laboratory experiments, provide new insights into pathogenetic mechanisms that are believed to hold potential for tackling Alzheimer’s before symptoms manifest. The researchers envision that one day this may lead to new ways of treatment. Further institutions both from Europe and the US also contributed to the current results.

Alzheimer’s disease is a devastating neurodegenerative condition ultimately leading to dementia. An effective treatment does not yet exist. The disease is associated with the aberrant aggregation of small proteins called “Amyloid-beta” (Abeta) that accumulate in the brain and appear to harm neurons.

In recent years, studies revealed that deposits of Abeta, known as “plaques,” trigger inflammatory mechanisms by the brain’s innate immune system. However, the precise processes that lead to neurodegeneration and progression of pathology have thus far not been fully understood.

“Deposition and spreading of Abeta pathology likely precede the appearance of clinical symptoms such as memory problems by decades. Therefore, a better understanding of these processes might be a key for novel therapeutic approaches. Such treatments would target Alzheimer’s at an early stage, before cognitive deficits manifest,” says Prof. Michael Heneka, a senior researcher at the DZNE and Director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn.

An Inflammatory Cascade

Prof. Heneka, who is also involved in the cluster of excellence “ImmunoSensation” at the University of Bonn, and coworkers have been investigating the role of the brain’s immune response in the progression of Abeta pathology for some time already.

Previous work by the group that was published in Nature in 2013, had established that the molecular complex NLRP3, which is an innate immune sensor, is activated in brains of Alzheimer’s patients and contributes to the pathogenesis of Alzheimer’s in the murine model. NLRP3 is a so-called inflammasome that triggers production of highly pro-inflammatory cytokines.

Furthermore, upon activation, NLRP3 forms large signaling complexes with the adapter protein ASC, which are called “ASC specks” that can be released from cells.

“The release of ASC specks from activated cells has so far only been documented in macrophages and their relevance in disease processes has so far remained a mystery,” says Prof. Eicke Latz, director of the Institute of Innate Immunity and member of the cluster of excellence “ImmunoSensation” at the University of Bonn.”

Inflammatory proteins (called “ASC specks”, red) within the nucleus of an aggregate of Amyloid-beta peptides (blue). Furthermore, immune cells (green) are shown. Researchers of the DZNE and the University of Bonn report in “Nature” on the role of inflammatory mechanisms in Alzheimer’s disease. Image reconstruction of microscopy imaging data by Dario Tejera, University of Bonn.

Connection between Inflammation and Neurodegeneration

In the current study, it was demonstrated that ASC specks are also released from activated immune cells in the brain, the “microglia.” Moreover, the findings provide a direct molecular link to classical hallmarks of neurodegeneration.

“We found that ASC specks bind to Abeta in the extracellular space and promote aggregation of Abeta, thus directly linking innate immune activation with the progression of pathology,” Heneka says.

Novel Approach for Therapy?

This view is supported by a series of experiments in mouse models of Alzheimer’s disease. In these, the researchers investigated the effects of ASC specks and its component, the ACS protein, on the spreading of Abeta deposits in the brain.

“Additionally, analysis of human brain material indicates at several levels that inflammation and Abeta pathology may interact in a similar fashion in humans. Together our findings suggest that brain inflammation is not just a bystander phenomenon, but a strong contributor to disease progression,” Heneka says.

“Therefore, targeting this immune response will be a novel treatment modality for Alzheimer’s.”

 

Citation

https://www.dzne.de/en/about-us/public-relations/news/2017/press-release-no-24.html

Journal Reference:

Carmen Venegas, Sathish Kumar, Bernardo S. Franklin, Tobias Dierkes, Rebecca Brinkschulte, Dario Tejera, Ana Vieira-Saecker, Stephanie Schwartz, Francesco Santarelli, Markus P. Kummer, Angelika Griep, Ellen Gelpi, Michael Beilharz, Dietmar Riedel, Douglas T. Golenbock, Matthias Geyer, Jochen Walter, Eicke Latz, Michael T. Heneka. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s diseaseNature, 2017; 552 (7685): 355 DOI: 10.1038/nature25158

 

Clinical Trials for Alzheimer’s Disease: What’s New?

(BrightFocus Foundation) Not since 2003 has a new medication been approved by the FDA for treatment of Alzheimer’s disease (AD). Fortunately, this long dry spell may be nearing an end. This article explores a variety of clinical trials that may one day provide new treatments and methods to more effectively manage Alzheimer’s disease.

The End of a Long Dry Spell

More than 400 clinical trials are currently looking at new treatments for Alzheimer’s disease (AD) and many of them are actively recruiting. Many of these studies are based on decreasing the harmful effects of a toxic protein called amyloid-beta in the brain, but others reflect a broadening range of possible treatment approaches based on other theories about AD.

Pharmaceuticals under study include both medications and dietary supplements. In addition to these, many studies are exploring non-pharmaceutical strategies. These include behavioral interventions, exercise, and physical treatments including acupuncture, electromagnetic devices, and even surgery. The representative trials discussed here are found in the registry of ongoing studies located at www.clinicaltrials.gov, which can be accessed for information about activity and enrollment.

Targeting Amyloid

The “amyloid hypothesis” is still regarded by many as a key explanation for AD’s development and progression. According to the amyloid hypothesis, the large amyloid precursor protein (APP) found on brain cell membranes undergoes an abnormal clipping by enzymes (called beta and gamma secretase), resulting in a toxic protein fragment called amyloid-beta.

Amyloid-beta, which circulates in blood and cerebrospinal fluid, can interfere with the part of the nerve cell, called the synapse, which is involved in transmitting electrical or chemical signals to other nerve cells. Furthermore, amyloid-beta sticks together and forms deposits in the brain, where in combination with an inflammatory reaction and brain cell death produce the amyloid plaques that are characteristic of AD.

Amyloid-beta is also thought by some researchers to induce the chemical change that eventually results in destruction of another important component of nerve cells’ internal structure. This results in neurofibrillary tangles, the other hallmark microscopic finding of AD.

The amyloid hypothesis has led to testing of medications which target the production, accumulation and persistence of amyloid-beta in the brain. Results, so far, have been mixed — but good enough to encourage further exploration.

Stopping the Production of Amyloid-Beta

The inhibition of enzymes that produce toxic amyloid, beta and gamma secretases, remains an active area of investigation. The first gamma secretase inhibitors proved too dangerous for use because of side effects. Selective beta secretase inhibitors have been better tolerated and are currently in testing. A partial list of these includes MK8931, JNJ54861911, and LY3314814.

Blocking the Accumulation of Amyloid-Beta

The accumulation of amyloid-beta into plaques has been targeted in various ways. One current trial, for example, is exploring a drug, called sargramostim, to reduce the accumulation of amyloid-beta.

Ramping Up the Immune System

Experimental medications have also been using the immune system to interfere with amyloid-beta accumulation, and to remove amyloid from the bloodstream, the cerebrospinal fluid, and even from brain plaques.

Nearly 20 years ago, amyloid was used in an “active vaccine” to stimulate the body’s natural development of disease-fighting antibodies. This effort failed for a couple of reasons. First, the production of the right kind of antibodies was unreliable due to the reduced responsiveness of the immune system in the older adults who received this treatment. In addition, vaccinated subjects who did react to the vaccine sometimes developed a life-threatening brain inflammation called aseptic meningitis.

A second generation of immunotherapy agents have relied upon “passive immunity,” which means that the patient receives an injection of pre-made antibodies that have a limited duration of action before they are eliminated or destroyed by the body.

Bapineuzumab, the first widely-tested passive immunotherapy, was withdrawn from development due to limited effectiveness and concern about adverse effects including tiny brain bleeds. Testing of solanezumab as a treatment for mild dementia was deemed unsuccessful. Newer agents, safer and possibly more effective, include aducanamab, crenezumab, gantenerumab, and others.

Though these injections are all passive immunotherapies, they vary significantly in their mechanism of attack on beta-amyloid. Variously, they attack amyloid-beta or plaques, in the peripheral circulation or in the brain.

A couple of immunotherapies are also being explored as preventive treatments in the normal elderly or those at significant genetic risk for AD (the DIAN study, for example).

The newest immunotherapy players represent a re-emergence of the active vaccine approach which, if successful, could be less costly and more lasting in its effectiveness. One experimental vaccine, called CAD106, induces immunity to amyloid-beta without exciting an autoimmune response. Another vaccine, called Lu AF20513, invigorates the aging immune system.

Some researchers working on AD have followed the dictum of famed bank robber Willy Sutton by “going where the money is,” or seems to be, by exploring therapies based on the amyloid hypothesis, while others have follow the well-known advice of 18th century moralist Samuel Palmer, who advised “Don’t venture all your eggs in one basket.” Competing theories about the development and progression of AD have opened up a wide range of therapeutic possibilities, many of which are currently being tested.

Aiming at Tau

One very strong school of researchers has insisted on the focusing on the protein called tau, which results in brain cell death through destruction of the neurons’ internal structure. TRx0237 is inhibits the accumulation of tau and is currently in testing. AADvac1 is a vaccine that targets abnormal tau protein.

Blood Sugar and the Brain

The brain’s damaged ability to use glucose (blood sugar) in AD is so important that some researchers call AD “Diabetes Type 3.” This observation has led to treatments aimed at repairing a metabolic defect by enhancing the effect of insulin. Intranasal insulin is in testing with promising early results. Improvement of blood sugar control is also the goal of trials using the drugs pioglitazone and exanatide.

Taming Inflammation

The importance of inflammation in exacerbation of amyloid-beta’s neuron-destroying effects has led to trials of medications with anti-inflammatory properties. The combination treatment ALZT-OPT1 includes oral ibuprofen with use of the inhaled anti-inflammatory medication, cromolyn. Benfotiamine, the medication studied in another trial, is a derivative of thiamine with anti-inflammatory properties.

Improving Cognition with Serotonin

Serotonin neurotransmission failure is a demonstrated aspect of AD, and several experimental medications attempt to correct that problem. RVT-101 and LuAE58054 are two examples of medications that are in clinical trials. Altering the brain’s serotonin activity seems to help cognitive difficulties in schizophrenia, and may also prove helpful in cognitive difficulties associated with AD.

Dietary Supplements

We all know that “We are what we eat,” and our brains can be helped or harmed by what we put in our mouths. Dietary supplements in current AD clinical trials include lithium water, omega-3 fatty acids with lipoic acid, the genistein, resveratrol, curcumin, and grape seed extract. Many of these attempt to reduce brain cell destruction through antioxidant and/or anti-inflammatory effects.

Another dietary trial includes the medical food, AC-1204, which contains long-chain triglyceride molecules that provide the insulin-resistant AD brain with an energy source alternative to glucose.

Non-Medication Approaches

Behavioral Management

In light of the limited benefits seen with currently available medications, a range of behavioral interventions is also being tested in AD clinical trials. Preliminary results, being followed up in ongoing trials, support the value of yoga and physical activity. Hearing aids are being tested as a means of reducing sensory isolation experienced by AD patients with hearing problems. Behavioral management algorithms such as the DICE approach (Describe, Investigate, Create, Evaluate) are also being tested.

Other Strategies

More invasive non-medication approaches in current testing include electroacupuncture, repetitive transcranial magnetic stimulation, direct cranial stimulation, and deep brain stimulation. Among the most invasive clinical trials, current research is also exploring the value of CERE-110 (adeno-associated virus-based delivery of nerve growth factor, delivered as an injection into the brain).

Treatments to Manage Agitation, Insomnia and Apathy

While efforts to prevent or treat the cognitive symptoms of AD remain a primary focus, researchers have also recognized that we need treatments for the non-cognitive behavioral symptoms of AD and other dementias. Preliminary results suggest that we may be on the verge of more effective approaches to managing these behavioral symptoms. In addition to the familiar medications being tested (memantine for agitation, aripiprazole for agitation, mirtazapine for sleep, methylphenidate for apathy), several new medications are also in clinical trials for AD behavioral symptoms.

Tetrahydrocannabinol (the active principle in marijuana) is being tested for agitation treatment. The dopamine blocking drug, brexiprazole, may have promise in treating agitation. Pimavanserin, reduces psychotic symptoms in Parkinson’s disease, is being tested for management of psychotic symptoms in a broader group of major neurocognitive disorders.

Summary

With progress in these clinical trials, and others not included here, we will learn more about how to prevent, slow, and perhaps even someday reverse the devastating effects of Alzheimer’s disease. Participation in a clinical trial should be considered as a way of advancing knowledge and possibly benefiting from a treatment not yet widely available, but clinical trials are not without risk. In some cases, participation in a clinical trial delays treatment with a standard (if less effective) approach. Clinical trials, too, can expose a subject to unhelpful placebo treatment and/or toxic effects of an experimental medication, so participation should only be undertaken after a careful consideration of the risks and benefits as well as the other available treatment options.

For many people affected by AD, however, clinical trials offer both individual hope and an opportunity for altruism. One day, one or more of these new approaches may make a real difference in our ability to fight a disease that remains the most relentless of our major causes of death.

Information on Clinical Trials

For More Detailed Information

  • Godyń J, Jończyk J, Panek D, Malawska B. Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol Rep. 2016;68(1):127-38.

This content was last updated on: October 10, 2017

Citation
https://www.brightfocus.org/alzheimers/article/clinical-trials-alzheimers-disease-whats-new

By James M. Ellison, MD, MPH, Swank Memory Care Center, Christiana Care Health System

Copyright 2017 BrightFocus Foundation. All rights reserved.

Moderate Physical Activity Linked to Increases in Metabolism Across Brain Regions

(NIH) Can exercise change how your brain works? A new study suggests that how, and how often, older adults exercise could impact breakdown of glucose in the brain. Decreases in brain metabolism (hypometabolism) have been shown to be a characteristic of Alzheimer’s disease and predictive of cognitive decline and the conversion to Alzheimer’s in older adults. Physical activity has been shown to modulate brain glucose metabolism, but it is unclear what level of intensity and duration may be beneficial.

A recent NIA-supported study from the University of Wisconsin led by Dr. Ozioma Okonkwo found that even moderate physical activity may increase metabolism in brain regions important for learning and memory.

The study asked cognitively normal, late-middle age (average age 64 years old) participants to wear an accelerometer for 7 consecutive days to measure daily physical activity. Scientists were then able to determine the amount of time each individual engaged in light (e.g., a slow walk), moderate (e.g., a fast walk), and vigorous activities (e.g., run).

The physical activity data were analyzed to determine how they corresponded with glucose metabolism within brain areas that have been demonstrated to be impacted in people with Alzheimer’s.

Increasing levels of engagement in moderate physical activity were associated with increases in cerebral glucose metabolism across all brain regions examined. Vigorous activity showed an increase in metabolism only in the hippocampus (an area important for learning and memory). Light physical activity was not associated with changes in metabolism in any of the brain regions examined.

Further, how long one engaged in moderate physical activity impacted the amount of brain glucose metabolism. The more time spent performing moderate level of physical activity (average 43.3 min/day to average 68.1 min/day), the greater the increase in brain glucose metabolism.

Overall, this study adds to encouraging evidence that physical activity may be beneficial for neurometabolic function. Specifically, it makes a critical contribution to the efforts to identify the intensity and duration of physical activity that confer the most advantage for combating Alzheimer’s-related changes in mid-life.

Citation

https://www.nia.nih.gov/news/moderate-physical-activity-linked-increases-metabolism-across-brain-regions

Reference: Dougherty RJ, et al. Moderate physical activity is associated with cerebral glucose metabolism in adults at risk for Alzheimer’s diseaseJournal of Alzheimer’s Disease. 2017;58:1089–1097.

 

Connections Between Diabetes and Alzheimer’s Disease

(The Diabetes Council) Relatively recently, it has been proposed that Alzheimer’s Disease (AD) is a form of diabetes that primarily affects the nerve cells of the brain.[1],[2]  Many researchers and physicians now refer to AD as Type3Diabetes or T3D.

Alzheimer’s Disease

Alzheimer’s Disease is a form of dementia characterized by loss of short-term memory, confusion, forgetfulness and difficulties in speech.  Later stages can be characterized by delusional thinking, repetitive behaviors, loss of long-term memory, sometime rapid mood swings and incontinence. It can only be definitively diagnosed by autopsy and microscopic examination of the brain when large amounts of protein (beta amyloid, tau) show up as tangled “threads” in the nerve cells. Currently, there is no blood or other test to diagnose AD.

Alzheimer’s disease is believed to affect 20% of those over 65 to varying degrees. By the time an individual is in their 80s, the chances that they will show signs of AD reach 50%.

AD, like T1D and T2D is a slowly progressive disease with both environmental and genetic factors at play. Studies have indicated that those individuals with T2D have a 50-65% higher risk of AD. Also, both AD and T2D are chronic inflammatory diseases with evidence of similar types of damage (oxidative) to the cells of the body.

Most importantly, recent evidence indicates that the nerve cells of the brain show insulin resistance and resistance to another hormone, insulin-like growth factor or IGF.  Insulin resistance and IGF resistance is considered a sign of prediabetes. Since glucose (blood sugar) is the primary source of energy for brain cells, it is thought likely that the increasing degree of insulin and IGF resistance essentially starves the brain cells of its most importance energy source. Over the long term, this chronic “starvation” may lead to oxidative damage, the protein “tangles” seen at biopsy and the signs and symptoms of AD.

Clinical studies on individuals with early AD have shown promise treating AD with insulin or a class of diabetes drugs, the PPAR (Peroxisome Proliferator-Activated Receptor) agonists. Examples of the PPAR agonists, which can help stabilize blood glucose and blood lipid (fat) levels include the glitazones (pioglitazone (Actos) and rosiglitazone (Avandia)).  Another class of drugs, the fibrates, also act in part as PPAR agonists.  These drugs include fenofibrate (Tricor) and Gemfibrozil (Lopid).  Fibrates and glitazones are currently being investigated as treatment for AD.

Alzheimer’s Disease and Diet

Early evidence that was largely forgotten indicated that there were dietary associations with AD, much as there are with heart disease and diabetes. Laboratory animals fed a diet high in nutrients along with specific anti-oxidant nutrients such as Vitamin C and Vitamin E had better abilities to learn new tasks and had fewer problems with memory.  A relatively small number of human studies have also indicated that healthy diets higher in anti-oxidants, particularly Vitamin E, could provide significant protection against the common signs of dementia.

There is also an association with a diet high in saturated fats for both T2D and AD. High intakes of saturated fats and even moderate intakes of trans fats (found most commonly in fast foods) doubled or tripled the risk of AD. On the other hand, high intakes of polyunsaturated fats (PUFAs) such as omega-3 fats was protective for both AD and T2D.  Omega-3 fats are known to be anti-inflammatory and to reduce aggregation of proteins (as seen in biopsies of brains from individuals with AD) and to reduce blood clotting (helping to prevent strokes due to blood clots).

A recent headline reads “Alzheimer’s could be the most catastrophic impact of junk food.”[3] Another headline in The New Scientist reads “Food for thought: Eat your way to dementia” [4] Junk food and fast food is high in trans fats and in saturated fats, relatively low in nutrients and particularly low in anti-inflammatory and antioxidant nutrients.  It is believed, therefore, that AD and diabetes, particularly T2D, can be prevented or the effects lessened by eating a healthy diet high in vital nutrients, staying away from fast foods and processed foods, and instead eating unprocessed whole foods and a diet high in fruits, vegetables, beans, legumes, nuts, seeds and whole grains.

Sugar as a Chronic Toxin for the Brain

There are many researchers who consider sugar to be toxic drug.[5] Sugar cane has been cultivated for over 8000 years, but only recently has sugar, in the form of table sugar (sucrose) been widely available to nearly everyone on the planet.  Diabetes, obesity, heart disease and now Alzheimer’s Disease have been associated with increased consumption of sugar, either in the form of table sugar or, more recently, in the form of high fructose corn syrup (HFCS), which is added (in large amounts) to many processed foods. HFCS is part glucose and part fructose, a sugar with a similar chemical structure. The liver is the only organ that can convert fructose to glucose—this can put significant strain on the liver.  Fatty liver is a condition that has been associated with high intakes of HFCS, insulin resistance and with T2D and obesity.  High levels of blood sugars are thought to be the underlying cause of nerve and vessel damage in diabetes, and now in Alzheimer’s disease. All this data is used as evidence that sugar, when consumed in high amounts, acts like a slowly acting toxin.

One of the lines of proof used to show that sugar acts like a drug on the brain is the comparison of brain scans (MRI and PET scans) comparing the brains of individuals who are obese (considered “sugar addicts”) to those of cocaine addicts—the results are strikingly similar. When obese individuals eat sugar, the areas of the brain that are “lit up” are the same areas that are “lit up” when cocaine addicts take cocaine.[6]

Summary

We know that a poor diet high in processed foods and containing high levels of sugar can predispose an individual to diabetes, heart disease, obesity and now Alzheimer’s disease.  We know that insulin resistance is associated with both diabetes and with Alzheimer’s disease and that drugs that combat diabetes are being studied as treatments for Alzheimer’s disease.  We know that individuals with diabetes have a higher risk for AD. We also know that sugar is suspected to be the ultimate culprit in nerve and blood vessel damage and that at least some researchers consider sugar to be both a toxin and a drug.  While more research needs to be done, it is getting clearer that indeed, Alzheimer’s disease can justifiably be considered to be caused by insulin resistance in the brain and a form of diabetes that primarily affects the brain and its function.

Citation

Connections Between Diabetes and Alzheimer’s Disease

References

  1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/
  2. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes? J Alzheimers Dis. 2005;7(1):63–80.
  3. Monbiot G. Alzheimer’s could be the most catastrophic impact of junk food. Guardian 10 Sept 2012.
  4. Trivedi B. Food for thought: Eat your way to dementia. New Scientist 3 Sept 2012; issue 2880.
  5. http://blogs.scientificamerican.com/brainwaves/is-sugar-really-toxic-sifting-through-the-evidence/
  6. http://www.webmd.com/food-recipes/your-brain-on-sugar

 

 

 

Specks in Brain Attract Alzheimer’s Plaque-Forming Protein

(ScienceNews) Results in mice suggest a possible approach for stopping amyloid-beta accumulation.

Globs of an inflammation protein beckon an Alzheimer’s protein and cause it to accumulate in the brain, a study in mice finds. The results, described in the Dec. 21/28 Nature, add new details to the relationship between brain inflammation and Alzheimer’s disease.

GANGING UP  The Alzheimer’s protein amyloid-beta can form clumps around specks of an inflammatory protein in between brain cells, research on mice suggests.

Researchers suspect that this inflammatory cycle is an early step in the disease, which raises the prospect of being able to prevent the buildup of amyloid-beta, the sticky protein found in brains of people with Alzheimer’s disease.

“It is a provocative paper,” says immunologist Marco Colonna of Washington University School of Medicine in St. Louis.

Finding an inflammatory protein that can prompt A-beta to clump around it is “a big deal,” he says.

Researchers led by Michael Heneka of the University of Bonn in Germany started by studying specks made of a protein called ASC that’s produced as part of the inflammatory response. (A-beta itself is known to kick-start this inflammatory process.) Despite being called specks, these are large globs of protein that are created by and then ejected from brain immune cells called microglia when inflammation sets in. A-beta then accumulates around these ejected ASC specks in the space between cells, Haneke and colleagues now propose.

A-beta can directly latch on to ASC specks, experiments in lab dishes revealed. The two proteins were also caught in close contact in brain tissue taken from people with Alzheimer’s disease. Researchers didn’t see any ASC specks mingling with A-beta in the brains of people without the disease.

Mice engineered to produce lots of A-beta had telltale signs of its accumulation in their brains at 8 and 12 months of age, roughly comparable to middle age in people. But in mice that also lacked the ability to produce ASC specks, this A-beta brain load was much lighter, and these mice performed better on a memory test. Similar reductions in A-beta loads came when researchers used an antibody to prevent A-beta from sticking to ASC specks, results that suggest the specks are needed for A-beta to clump up.

The details show “a quite new and specific mechanism” that’s worth exploring for potential treatments, says Richard Ransohoff, a neuroinflammation biologist at Third Rock Ventures, a venture capital firm in Boston.

To be effective as a treatment, an antibody like the one in the study that kept A-beta from sticking to ASC would need to be able to enter the brain and persist at high levels — a big challenge, Ransohoff says. Still, the results are promising, he says. “I like the data. I like the line of experimentation.”

Many questions remain. The results are mainly from mice, and it’s not clear whether ASC specks and A-beta have similar interactions in human brains. Nor is it obvious how to stop the A-beta from accumulating around the specks without affecting the immune system more generally.

What’s more, the role of the microglia immune cells that release ASC specks is complex, Colonna says. In some cases, microglia serve as brain protectors by surrounding and sequestering sticky A-beta plaques in the brain (SN: 11/30/13, p. 22). But the current results suggest that by releasing ASC specks, the same cells can also make A-beta accumulation worse. The dueling roles of the cells — protective in some cases and potentially harmful in others — make it challenging to figure out how to tweak their behavior therapeutically, Colonna says.

Citation

https://www.sciencenews.org/article/specks-brain-alzheimers-plaque-forming-protein

By Laura Sander

Journal Reference

C. Venegas et al. Microglia-derived ASC specks cross- seed amyloid-β in Alzheimer’s diseaseNature. Vol. 552, December 21/28, 2017, p. 355. doi:10.1038/nature25158.

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