New Guideline: Try Exercise to Improve Memory and Thinking

(Mayo Clinic) For patients with mild cognitive impairment, don’t be surprised if your health care provider prescribes exercise rather than medication. A new guideline for medical practitioners says they should recommend twice-weekly exercise to people with mild cognitive impairment to improve memory and thinking.

The recommendation is part of an updated guideline for mild cognitive impairment published in the Dec. 27 online issue of Neurology, the medical journal of the American Academy of Neurology.

“Regular physical exercise has long been shown to have heart health benefits, and now we can say exercise also may help improve memory for people with mild cognitive impairment,” says Ronald Petersen, M.D., Ph.D., lead author, director of the Alzheimer’s Disease Research Center, Mayo Clinic, and the Mayo Clinic Study of Aging.

“What’s good for your heart can be good for your brain.” Dr. Petersen is the Cora Kanow Professor of Alzheimer’s Disease Research.

Mild cognitive impairment is an intermediate stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Symptoms can involve problems with memory, language, thinking and judgment that are greater than normal age-related changes.

Generally, these changes aren’t severe enough to significantly interfere with day-to-day life and usual activities. However, mild cognitive impairment may increase the risk of later progressing to dementia caused by Alzheimer’s disease or other neurological conditions. But some people with mild cognitive impairment never get worse, and a few eventually get better.

The academy’s guideline authors developed the updated recommendations on mild cognitive impairment after reviewing all available studies. Six-month studies showed twice-weekly workouts may help people with mild cognitive impairment as part of an overall approach to managing their symptoms.

Dr. Petersen encourages people to do aerobic exercise: Walk briskly, jog, whatever you like to do, for 150 minutes a week — 30 minutes, five times or 50 minutes, three times. The level of exertion should be enough to work up a bit of a sweat but doesn’t need to be so rigorous that you can’t hold a conversation. “Exercising might slow down the rate at which you would progress from mild cognitive impairment to dementia,” he says.

Another guideline update says clinicians may recommend cognitive training for people with mild cognitive impairment. Cognitive training uses repetitive memory and reasoning exercises that may be computer-assisted or done in person individually or in small groups. There is weak evidence that cognitive training may improve measures of cognitive function, the guideline notes.

The guideline did not recommend dietary changes or medications. There are no drugs for mild cognitive impairment approved by the U.S. Food and Drug Administration.

More than 6 percent of people in their 60s have mild cognitive impairment across the globe, and the condition becomes more common with age, according to the American Academy of Neurology. More than 37 percent of people 85 and older have it.

With such prevalence, finding lifestyle factors that may slow down the rate of cognitive impairment can make a big difference to individuals and society, Dr. Petersen notes.

“We need not look at aging as a passive process; we can do something about the course of our aging,” he says.

“So if I’m destined to become cognitively impaired at age 72, I can exercise and push that back to 75 or 78. That’s a big deal.”

The guideline, endorsed by the Alzheimer’s Association, updates a 2001 academy recommendation on mild cognitive impairment. Dr. Petersen was involved in the development of the first clinical trial for mild cognitive impairment and continues as a worldwide leader researching this stage of disease when symptoms possibly could be stopped or reversed.

Citation

https://www.sciencedaily.com/releases/2017/12/171228145026.htm

Story Source:

Materials provided by Mayo Clinic. Original written by Susan Barber Lindquist. Note: Content may be edited for style and length.

Journal Reference:

Ronald C. Petersen, Oscar Lopez, Melissa J. Armstrong, Thomas S.D. Getchius, Mary Ganguli, David Gloss, Gary S. Gronseth, Daniel Marson, Tamara Pringsheim, Gregory S. Day, Mark Sager, James Stevens, Alexander Rae-Grant. Practice guideline update summary: Mild cognitive impairment. Neurology, 2017; DOI: 10.1212/WNL.0000000000004826

Copyright 2018 ScienceDaily or by other parties, where indicated.

 

 

New Research Suggests High-intensity Exercise Boosts Memory

(McMaster University)The health advantages of high-intensity exercise are widely known but new research from McMaster University points to another major benefit: better memory.

The findings could have implications for an aging population which is grappling with the growing problem of catastrophic diseases such as dementia and Alzheimer’s.

Scientists have found that six weeks of intense exercise — short bouts of interval training over the course of 20 minutes — showed significant improvements in what is known as high-interference memory, which, for example, allows us to distinguish our car from another of the same make and model.

The study is published in the Journal of Cognitive Neuroscience.

The findings are important because memory performance of the study participants, who were all healthy young adults, increased over a relatively short period of time, say researchers.

They also found that participants who experienced greater fitness gains also experienced greater increases in brain-derived neurotrophic factor (BDNF), a protein that supports the growth, function and survival of brain cells.

“Improvements in this type of memory from exercise might help to explain the previously established link between aerobic exercise and better academic performance,” says Jennifer Heisz, an assistant professor in the Department of Kinesiology at McMaster and lead author of the study.

“At the other end of our lifespan, as we reach our senior years, we might expect to see even greater benefits in individuals with memory impairment brought on by conditions such as dementia,” she says.

For the study, 95 participants completed six weeks of exercise training, combined exercise and cognitive training or no training (the control group which did neither and remained sedentary). Both the exercise and combined training groups improved performance on a high-interference memory task, while the control group did not.

Researchers measured changes in aerobic fitness, memory and neurotrophic factor, before and after the study protocol.

The results reveal a potential mechanism for how exercise and cognitive training may be changing the brain to support cognition, suggesting that the two work together through complementary pathways of the brain to improve high-interference memory.

Researchers have begun to examine older adults to determine if they will experience the same positive results with the combination of exercise and cognitive training.

“One hypothesis is that we will see greater benefits for older adults given that this type of memory declines with age,” says Heisz. “However, the availability of neurotrophic factors also declines with age and this may mean that we do not get the synergistic effects.”

This research was also covered by the New York Times: Exercise May Enhance the Effects of Brain Training.

Citation
http://dailynews.mcmaster.ca/article/ workouts-to-remember-new-research-suggests-high-intensity-exercise-boosts-memory/

By Michelle Donovan, November 22, 2017

Journal Reference:

Jennifer J. Heisz, Ilana B. Clark, Katija Bonin, Emily M. Paolucci, Bernadeta Michalski, Suzanna Becker, Margaret Fahnestock. The Effects of Physical Exercise and Cognitive Training on Memory and Neurotrophic FactorsJournal of Cognitive Neuroscience, 2017; 29 (11): 1895 DOI: 10.1162/jocn_a_01164

 

Support the BOLD Infrastructure for Alzheimer’s Act

(Alzheimer’s Association) The Alzheimer’s Association is proud to support the Building Our Largest Dementia (BOLD) Infrastructure for Alzheimer’s Act, new bipartisan legislation to address Alzheimer’s as a public health crisis. Learn more about the bill, then tell your senators and representatives to support the BOLD Infrastructure for Alzheimer’s Act!

This week Congress began taking steps to address Alzheimer’s as a public health issue. Senators Collins, Cortez Masto, Capito and Kaine, as well as Representatives Guthrie, Tonko, Smith and Waters introduced the bipartisan BOLD Infrastructure for Alzheimer’s Act to improve our nation’s Alzheimer’s public health infrastructure.

Tell your Senators and Representative to support this legislation by taking action below.
The BOLD Infrastructure for Alzheimer’s Act (S. 2076/H.R.4256) would improve the nationwide response to this public health crisis by advancing effective public health interventions across the country and in your state.

The legislation would also provide resources to state and local public health officials to increase early detection and diagnosis, reduce risk, prevent avoidable hospitalizations, reduce health disparities, support the needs of caregivers and support care planning for people living with the disease.

Additionally, collecting data on cognitive decline and Alzheimer’s caregivers can help identify the impact of dementia in your state, leading to more effective action. This legislation would increase the collection, analysis and timely reporting of data on cognitive decline and caregiving issues.

Click here to show your support:  Alzheimer’s Act (S. 2076/H.R.4256)


The BOLD Infrastructure for Alzheimer’s Act

Working with bipartisan Congressional champions the Alzheimer’s Association, through the Alzheimer’s Impact Movement (AIM), was instrumental in the development and introduction of the Building Our Largest Dementia (BOLD) Infrastructure for Alzheimer’s Act (S. 2076/H.R. 4256). The bill will create an Alzheimer’s public health infrastructure across the country to implement effective Alzheimer’s interventions,such as increasing early detection and diagnosis, reducing risk and preventing avoidable hospitalizations.

The BOLD Infrastructure for Alzheimer’s Act will also increase implementation of the Centers for Disease Control and Prevention’s (CDC) Public Health Road Map nationwide by establishing Alzheimer’s centers of excellence, providing cooperative agreements to public health departments, and increasing data collection, analysis and timely reporting. Learn more about the BOLD Infrastructure for Alzheimer’s Act.


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Citation
Copyright © 2017 Alzheimer’s Association®. All rights reserved.

Saving Neurons May Offer New Approach For Treating Alzheimer’s Disease

(University of Iowa Health Care) A soon-to-be-published study by researchers from the Iowa Neuroscience Institute indicates that protecting nerve cells with a specific compound helps prevent memory and learning problems in lab animals.

Senior study author Andrew Pieper, MD, PhD, and first author Jaymie Voorhees, PhD, have found that treatment with a neuroprotective compound that saves brain cells from dying also prevents the development of depression-like behavior and the later onset of memory and learning problems in a rat model of Alzheimer’s disease.

Although the treatment protects the animals from Alzheimer’s-type symptoms, it does not alter the buildup of amyloid plaques and neurofibrillary tangles in the rat brains.

“We have known for a long time that the brains of people with Alzheimer’s disease have amyloid plaques and neurofibrillary tangles of abnormal tau protein, but it isn’t completely understood what is cause or effect in the disease process,” says Pieper, professor of psychiatry in the UI Carver College of Medicine and associate director of the Iowa Neuroscience Institute at the University of Iowa.

“Our study shows that keeping neurons alive in the brain helps animals maintain normal neurologic function, regardless of earlier pathological events in the disease, such as accumulation of amyloid plaque and tau tangles,” he says.

The images show brain tissue from Alzheimer’s rats that were untreated (left) or treated (right) with the neuroprotective compound. The white “holes” indicated by the arrows are areas of brain cell death, and are more numerous in the untreated rats. Although the treatment protects the animals from neuronal cell death and Alzheimer’s-type symptoms, it does not alter the buildup of amyloid plaques and neurofibrillary tangles in the rat brains. ​

The Impact of Alzheimer’s Disease

Alzheimer’s disease is a devastating neurodegenerative condition that gradually erodes a person’s memory and cognitive abilities. Estimates suggest that more than 5 million Americans are living with Alzheimer’s disease and it is the sixth leading cause of death in the United States, according to the National Institute on Aging.

In addition to the impact on cognition and memory, Alzheimer’s disease also can affect mood, with many people experiencing depression and anxiety before the cognitive decline is apparent. People who develop depression for the first time late in life are at a significantly increased risk of developing Alzheimer’s disease.

“Traditional therapies have targeted the characteristic lesions in Alzheimer’s disease, amyloid deposition, and tau pathologies,” says Voorhees, first author of the study, which is an article-in-press in Biological Psychiatry. “The findings of this study show that simply protecting neurons in Alzheimer’s disease without addressing the earlier pathological events may have potential as a new and exciting therapy.”

A Compound to Protect Brain Cells

Pieper and Voorhees used an experimental compound called P7C3-S243 to prevent brain cells from dying in a rat model of Alzheimer’s disease.

The original P7C3 compound was discovered by Pieper and colleagues almost a decade ago, and P7C3-based compounds have since been shown to protect newborn neurons and mature neurons from cell death in animal models of many neurodegenerative diseases, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury.

P7C3 compounds also have been shown to protect animals from developing depression-like behavior in response to stress-induced killing of nerve cells in the hippocampus, a brain region critical to mood regulation and cognition.

The researchers tested the P7C3 compound in a well-established rat model of Alzheimer’s disease. As these rats age, they develop learning and memory problems that resemble the cognitive impairment seen in people with Alzheimer’s disease.

The new study, however, revealed another similarity with Alzheimer’s patients. By 15 months of age, before the onset of memory problems, the rats developed depression-like symptoms. Developing depression for the first time late in life is associated with a significantly increased risk for developing Alzheimer’s disease, but this symptom has not been previously seen in animal models of the disease.

The Study’s Approach

Over a three-year period, Voorhees tested a large number of male and female Alzheimer’s and wild type rats that were divided into two groups. One group received the P7C3 compound on a daily basis starting at six months of age, and the other group received a placebo. The rats were tested at 15 months and 24 months of age for depressive-type behavior and learning and memory abilities.

At 15 months of age, all the rats—both Alzheimer’s model and wild type, treated and untreated—had normal learning and memory abilities. However, the untreated Alzheimer’s rats exhibited pronounced depression-type behavior, while the Alzheimer’s rats that had been treated with the neuroprotective P7C3 compound behaved like the control rats and did not show depressive-type behavior.

At 24 months of age (very old for rats), untreated Alzheimer’s rats had learning and memory deficits compared to control rats. In contrast, the P7C3-treated Alzheimer’s rats were protected and had similar cognitive abilities to the control rats.

The team also examined the brains of the rats at the 15-month and 24-month time points. They found the traditional hallmarks of Alzheimer’s disease—amyloid plaques, tau tangles, and neuroinflammation—were dramatically increased in the Alzheimer’s rats regardless of whether they were treated with P7C3 or not. However, significantly more neurons survived in the brains of Alzheimer’s rats that had received the P7C3 treatment.

“This suggests a potential clinical benefit from keeping the brain cells alive even in the presence of earlier pathological events in Alzheimer’s disease, such as amyloid accumulation, tau tangles, and neuroinflammation,” Pieper says.

“In cases of new-onset late-life depression, a treatment like P7C3 might be particularly useful as it could help stabilize mood and also protect from later memory problems in patients with Alzheimer’s disease.”

Citation

https://medicine.uiowa.edu/content/saving-neurons-may-offer-new-approach-treating-alzheimer%E2%80%99s-disease-0

Journal Reference:

Jaymie R. Voorhees et al. (-)-P7C3-S243 protects a rat model of Alzheimer’s disease from neuropsychiatric deficits and neurodegeneration without altering amyloid deposition or reactive glia. Biological Psychiatry, November 2017 DOI: 10.1016/j.biopsych.2017.10.023

Copyright © 2017 The University of Iowa

 

New Research Shows Where in the Brain the Earliest Signs of Alzheimer’s Occur

(Lund University) Researchers at Lund University in Sweden have for the first time convincingly shown where in the brain the earliest signs of Alzheimer’s occur. The discovery could potentially become significant to future Alzheimer’s research while contributing to improved diagnostics.

The image illustrates where in the brain the earliest signs of Alzheimer’s occur through accumulation of the β-amyloid protein.

In Alzheimer’s, the initial changes in the brain occur through retention of the protein, beta-amyloid. The process begins 10-20 years before the first symptoms become noticeable in the patient.

In Nature Communications, a research team headed by Professor Oskar Hansson at Lund University has now presented results showing where in the brain the initial accumulation of beta-amyloid occurs. It is in the inner parts of the brain, within one of the brain’s most important functional networks — known as the default mode network.

“A big piece of the puzzle in Alzheimer’s research is now falling into place. We previously did not know where in the brain the earliest stages of the disease could be detected. We now know which parts of the brain are to be studied to eventually explain why the disease occurs,” says Sebastian Palmqvist, associate professor at Lund University and physician at Skåne University Hospital.

The default mode network is one of several networks, each of which has a different function in the brain. It is most active when we are in an awake quiescent state without interacting with the outside world, for example, when daydreaming. The network belongs to the more advanced part of the brain. Among other things, it processes and links information from lower systems.

The study, conducted in collaboration with Michael Schöll, associate senior lecturer at the University of Gothenburg, and William Jagust, professor at the University of California, is based on data from more than 400 people in the United States who have an increased risk of developing Alzheimer’s, and about as many participants from the Swedish research project, BioFINDER. The brain status of all the participants was monitored for two years, and compared to a control group without any signs of Alzheimer’s.

The difficulty of determining which individuals are at risk of developing dementia later in life, in order to subsequently monitor them in research studies, has been an obstacle in the research world. The research team at Lund University has therefore developed a unique method to identify, at an early stage, which individuals begin to accumulate ?-amyloid and are at risk.

The method combines cerebrospinal fluid test results with PET scan brain imaging. This provides valuable information about the brain’s tendency to accumulate ?-amyloid.

In addition to serving as a roadmap for future research studies of Alzheimer’s disease, the new results also have a clinical benefit:

“Now that we know where Alzheimer’s disease begins, we can improve the diagnostics by focusing more clearly on these parts of the brain, for example in medical imaging examinations with a PET camera,” says Oskar Hansson, professor at Lund University, and medical consultant at Skåne University Hospital.

Although the first symptoms of Alzheimer’s become noticeable to others much later, the current study shows that the brain’s communication activity changes in connection with the early retention of beta-amyloid. How, and with what consequences, will be examined by the research team in further studies.

Citation

http://www.lunduniversity.lu.se/article/new-research-shows-where-in-the-brain-the-earliest-signs-of-alzheimers-occur

Journal Reference:

Sebastian Palmqvist, Michael Schöll, Olof Strandberg, Niklas Mattsson, Erik Stomrud, Henrik Zetterberg, Kaj Blennow, Susan Landau, William Jagust, Oskar Hansson. Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-01150-x

Copyright Lund University

 

How Brain Cells Die in Alzheimer’s and Frontotemporal Dementia

(Emory Health Sciences) Removal of a regulatory gene called LSD1 in adult mice induces changes in gene activity that that look unexpectedly like Alzheimer’s disease, scientists have discovered.

Researchers also discovered that LSD1 protein is perturbed in brain samples from humans with Alzheimer’s disease and frontotemporal dementia (FTD). Based on their findings in human patients and mice, the research team is proposing LSD1 as a central player in these neurodegenerative diseases and a drug target.

The results are scheduled for publication in Nature Communications.

LSD1-stained samples from Alzheimer’s brain resemble patterns seen with the protein Tau.
Credit: Emory Alzheimer’s Disease Research Center; Christopher et al Nature Comms (2017). Creative Commons 4.0

In the brain, LSD1 (lysine specific histone demethylase 1) maintains silence among genes that are supposed to be turned off. When the researchers engineered mice that have the LSD1 gene snipped out in adulthood, the mice became cognitively impaired and paralyzed. Plenty of neurons were dying in the brains of LSD1-deleted mice, although other organs seemed fine. However, they lacked aggregated proteins in their brains, like those thought to drive Alzheimer’s disease and FTD.

“In these mice, we are skipping the aggregated proteins, which are usually thought of as the triggers of dementia, and going straight to the downstream effects,” says David Katz, PhD, assistant professor of cell biology at Emory University School of Medicine.

Katz’s lab didn’t set out to create mice with neurodegenerative disease. LSD1 was known to be critical in early stages of embryonic development, and he and his colleagues were interested in LSD1’s role in sperm generation. Graduate students Michael Christopher (Genetics and Molecular Biology) and Dexter Myrick (Neuroscience) are co-first authors of the paper.

When the researchers looked at the patterns of gene activity that were altered in the LSD1-deleted mice, they noticed signs of inflammation and other changes in cell metabolism and signaling. These changes resemble those previously seen in people with Alzheimer’s disease and some types of FTD, but not in Parkinson’s or ALS.

A more surprising finding came when they examined brain tissue samples from Alzheimer’s and FTD patients, in collaboration with Allan Levey, MD, PhD, director of Emory’s Alzheimer’s Disease Research Center.

“We were amazed to see the accumulation of LSD1 in neurofibrillary tangles in Alzheimer’s, and in TDP-43 aggregates in FTD,” Levey says.

“In both diseases, the LSD1 protein was aberrantly localized in the cytoplasm, along with these pathologies. Since LSD1 is normally localized in the nucleus, these findings provided clues to how it might be linked to the massive yet selective neurodegeneration that we observed in the LSD1-deficient mice, in the same cortical and hippocampal regions known to be vulnerable in these two distinct human neurodegenerative diseases.”

LSD1 Acts as an Epigenetic Enforcer

LSD1 erases epigenetic marks on histones, proteins that package DNA in the nucleus. In this situation, epigenetic refers to information that is not carried in the DNA itself, since the marks influence the activity of genes associated with the modified packaging. LSD1 is important during embryonic reprogramming, when genes from the egg and sperm adjust to the changed environment in the newly fertilized egg.

The prevailing view is: neurons and other differentiated cells are committed to their fate — they can’t change into something else. The authors believe that LSD1 is involved in enforcing this commitment, by suppressing the activity of genes that are turned on in other cell types.

When LSD1 is taken away, gene activity goes a little haywire in neurons. For example, they turn on a set of genes that are usually active in embryonic stem cells. Neurons seem to be more sensitive to LSD1’s deletion, in that muscle, liver, kidney and other tissues do not appear to undergo cell death in response.

Katz thinks the re-activated stem cell genes is only part of the problem; instead, LSD1’s absence seems to unleash a combination of several stresses, which mirror the stresses on brain cells seen in Alzheimer’s disease and FTD. LSD1 has not been linked to neurodegenerative diseases before, so Katz says he has encountered skepticism from the field.

“If we were just killing brain cells, we wouldn’t expect the patterns of what we see in the mice to look so much like human patients,” he says.

“We also wouldn’t necessarily expect LSD1 to be affected in the human patients.”

Katz’s team is continuing to probe LSD1’s connection to known players in Alzheimer’s disease and FTD, such as the protein Tau, the major component of tangles. Potential drugs to fight neurodegenerative diseases could be found among compounds that stop LSD1 from interacting with the neurofibrillary tangles or somehow boost LSD1’s function, he says.

The research was supported by the National Institute of Neurological Disorders and Stroke (R01NS087142) and the National Institute of General Medical Sciences (5R25GM089615, T32GM008490).

Citation

http://news.emory.edu/stories/2017/10/katz_alzheimers_nature_communications/index.html

Journal Reference:

Michael A. Christopher, Dexter A. Myrick, Benjamin G. Barwick, Amanda K. Engstrom, Kirsten A. Porter-Stransky, Jeremy M. Boss, David Weinshenker, Allan I. Levey, David J. Katz. LSD1 protects against hippocampal and cortical neurodegeneration. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-00922-9

Copyright © 2017 Emory University

 

Elderly Who Have Trouble Identifying Odors Face Risk of Dementia

(University of Chicago Medical Center)  A long-term study of nearly 3,000 adults, aged 57 to 85, found that those who could not identify at least four out of five common odors were more than twice as likely as those with a normal sense of smell to develop dementia within five years.

Although 78 percent of those tested were normal — correctly identifying at least four out of five scents — about 14 percent could name just three out of five, five percent could identify only two scents, two percent could name just one, and one percent of the study subjects were not able to identify a single smell.

Five years after the initial test, almost all of the study subjects who were unable to name a single scent had been diagnosed with dementia. Nearly 80 percent of those who provided only one or two correct answers also had dementia, with a dose-dependent relationship between degree of smell loss and incidence of dementia.

“These results show that the sense of smell is closely connected with brain function and health,” said the study’s lead author, Jayant M. Pinto, MD, a professor of surgery at the University of Chicago and ENT specialist who studies the genetics and treatment of olfactory and sinus disease.

“We think smell ability specifically, but also sensory function more broadly, may be an important early sign, marking people at greater risk for dementia.”

“We need to understand the underlying mechanisms,” Pinto added, “so we can understand neurodegenerative disease and hopefully develop new treatments and preventative interventions.”

“Loss of the sense of smell is a strong signal that something has gone wrong and significant damage has been done,” Pinto said. “This simple smell test could provide a quick and inexpensive way to identify those who are already at high risk.”

The study, “Olfactory Dysfunction Predicts Subsequent Dementia in Older US Adults,” published September 2?, 2017, in the Journal of the American Geriatrics Society, follows a related 2014 paper, in which olfactory dysfunction was associated with increased risk of death within five years. In that study, loss of the sense of smell was a better predictor of death than a diagnosis of heart failure, cancer or lung disease.

For both studies, the researchers used a well-validated tool, known as “Sniffin’Sticks.” These look like a felt-tip pen, but instead of ink, they are infused with distinct scents. Study subjects smell each item and are asked to identify that odor, one at a time, from a set of four choices. The five odors, in order of increasing difficulty, were peppermint, fish, orange, rose and leather.

Test results showed that:

  • 78.1 percent of those examined had a normal sense of smell; 48.7 percent correctly identified five out of five odors and 29.4 percent identified four out of five.
  • 18.7 percent, considered “hyposmic,” got two or three out of five correct.
  • The remaining 3.2 percent, labelled “anosmic,” could identify just one of the five scents (2.2%), or none (1%).

The olfactory nerve is the only cranial nerve directly exposed to the environment. The cells that detect smells connect directly with the olfactory bulb at the base of the brain, potentially exposing the central nervous system to environmental hazards such as pollution or pathogens. Olfactory deficits are often an early sign of Parkinson’s or Alzheimer’s disease. They get worse with disease progression.

Losing the ability to smell can have a substantial impact on lifestyle and wellbeing, said Pinto, a specialist in sinus and nasal diseases and a member of the Section of Otolaryngology-Head and Neck Surgery at UChicago Medicine.

“Smells influence nutrition and mental health,” Pinto said.

People who can’t smell face everyday problems such as knowing whether food is spoiled, detecting smoke during a fire, or assessing the need a shower after a workout. Being unable to smell is closely associated with depression as people don’t get as much pleasure in life.”

“This evolutionarily ancient special sense may signal a key mechanism that also underlies human cognition,” noted study co-author Martha K. McClintock, PhD, the David Lee Shillinglaw Distinguished Service Professor of Psychology at the University of Chicago, who has studied olfactory and pheromonal communication throughout her career.

McClintock noted that the olfactory system also has stem cells which self-regenerate, so “a decrease in the ability to smell may signal a decrease in the brain’s ability to rebuild key components that are declining with age, leading to the pathological changes of many different dementias.”

In an accompanying editorial, Stephen Thielke, MD, a member of the Geriatric Research, Education and Clinical Center at Puget Sound Veterans Affairs Medical Center and the psychiatry and behavioral sciences faculty at the University of Washington, wrote:

“Olfactory dysfunction may be easier to quantify across time than global cognition, which could allow for more-systematic or earlier assessment of neurodegenerative changes, but none of this supports that smell testing would be a useful tool for predicting the onset of dementia.”

“Our test simply marks someone for closer attention,” Pinto explained. “Much more work would need to be done to make it a clinical test. But it could help find people who are at risk. Then we could enroll them in early-stage prevention trials.”

“Of all human senses,” Pinto added, “smell is the most undervalued and underappreciated — until it’s gone.”

Both studies were part of the National Social Life, Health and Aging Project (NSHAP), the first in-home study of social relationships and health in a large, nationally representative sample of men and women ages 57 to 85.

The study was funded by the National Institutes of Health — including the National Institute on Aging and the National Institute of Allergy and Infectious Disease — the Institute of Translational Medicine at the University of Chicago, and the McHugh Otolaryngology Research Fund.

Additional authors were Dara Adams, David W. Kern, Kristen E. Wroblewski and William Dale, all from the University of Chicago. Linda Waite is the principal investigator of NSHAP, a transdisciplinary effort with experts in sociology, geriatrics, psychology, epidemiology, statistics, survey methodology, medicine, and surgery collaborating to advance knowledge about aging.

Citation

https://www.sciencedaily.com/releases/2017/09/170929093251.htm

Journal Reference:

Dara R. Adams, David W. Kern, Kristen E. Wroblewski, Martha K. McClintock, William Dale, Jayant M. Pinto. Olfactory Dysfunction Predicts Subsequent Dementia in Older U.S. AdultsJournal of the American Geriatrics Society, 2017; DOI: 10.1111/jgs.15048

Copyright 2017 ScienceDaily or by other parties, where indicated.

 

Sharpest Image of Alzheimer’s Fibrils Shows Previously Unknown Details

(Forschungszentrum Juelich) A team of researchers from Germany and the Netherlands have determined the structure of an amyloid fibril with previously unachieved resolution. The fibrils of the body’s own amyloid beta (Aβ) protein are the main constituent of Alzheimer’s disease related and characteristic pathological protein deposits in the brain. The atomic-level three-dimensional structure elucidated by scientists from Forschungszentrum Jülich, Heinrich Heine University Düsseldorf, the Centre for Structural Systems Biology in Hamburg, and Maastricht University displays previously unknown structural details which can answer many questions on the growth of harmful deposits and also explain the effect of genetic risk factors. The results have been published in the journal Science.


This is a 3-D reconstruction of an amyloid fibril from two protofilaments (red/blue) calculated from cryo-electron microscopy images. Credit: Forschungszentrum Jülich / HHU Düsseldorf / Gunnar Schröder

The structure reveals how the many single Aβ protein molecules are staggered in layers on top of each other and are arranged into so-called protofilaments. Two of these protofilaments are twinned around each other to form a fibril. If several of these fibrils become entangled, then this gives rise to the typical deposits or plaques that are detected in the brain tissues of Alzheimer’s patients.

“This is a milestone on the road to a fundamental understanding of amyloid structures and the related diseases,” explains Prof. Dieter Willbold, director of the Institute of Physical Biology at the Heinrich Heine University Düsseldorf and director of the Institute of Complex Systems (ICS-6) of the Forschungszentrum Jülich.

“The fibril structure answers many questions about the mechanism of fibril growth and identifies the role played by a whole series of familial mutations that lead to early onset of Alzheimer’s disease,” says Willbold.

The resolution of 4 angstroms, corresponding to 0.4 nanometres, achieved by the team is within the typical magnitude of atomic radii and atomic bond lengths. In contrast to previous work, the model shows for the first time the exact position and interactions of the proteins. The Aβ molecules of the entangled protofilaments are thus not at the same level, but like a zipper they are staggered by half an interval. Furthermore, the structure elucidates the location and conformation of all 42 amino acid residues of the many individual Aβ protein molecules for the first time.

This novel and detailed structure provides a new basis for understanding the structural effect of a number of genetic modifications that increase the risk of developing the disease. They stabilize the fibrils — as can now be seen — by changing the blueprint of the protein at defined locations. This e.g. also explains why in nature mice do not develop Alzheimer’s and why a small section of the Icelandic population seems to be more or less resistant to the disease. Their variants of Aβ differ by three or one amino acid residues, respectively, which are apparently important for the stability of the fibrils.

Methodological Diversity at the Highest Technological Level

In contrast to the plaques which are typical for the disease discovered by Alois Alzheimer more than 100 years ago, the fibril structure now uncovered cannot be directly observed under the light microscope. It took more than a year to analyse the data the scientists had obtained using the cryo-electron microscopy facility at Maastricht University. Moreover, measurements using solid-state nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction experiments helped to supplement and fully support the picture of the fibril structure and validate the data obtained.

“The individual images in cryo-electron microscopy are usually extremely noisy since proteins are very sensitive to electron radiation and the pictures can only be generated with very low radiation intensity,” explains Jun.-Prof. Gunnar Schröder from Forschungszentrum Jülich and Heinrich Heine University Düsseldorf.

Using a computer-assisted procedure, he combined thousands of individual images and thus extracted high-resolution structural data from them.

“This is a step that can be very complicated if the sample is heterogeneous, that is to say if it consists of differently formed fibrils. In the past, this was almost always the case with the amyloid fibrils and represented one of the major obstacles for the analysis. However, we now had a fairly unique specimen with very homogeneous fibrils — 90 % of them had the same shape and symmetry,” says Schröder.

Dr. Lothar Gremer from Forschungszentrum Jülich and Heinrich Heine University Düsseldorf succeeded in producing the fibril specimen. “The crucial step was to greatly retard the growth of the fibrils in the specimen, from a few hours to several weeks. Thereby the individual Aβ molecules got enough time to arrange themselves into homogeneous fibrils in a very uniform and highly ordered way,” adds Gremer, who initiated and coordinated the study.

Investigations of the fibril specimen by solid-state nuclear magnetic resonance spectroscopy provided additional data to build the model and helped to validate the structure. “NMR enabled us to obtain additional information such as which amino acid residues form salt bridges thus enhancing the stability of the fibrils,” explains Prof. Henrike Heise from Heinrich Heine University Düsseldorf and Jülich’s Biomolecular NMR Center. X-ray diffraction experiments supervised by Prof. Jörg Labahn at the Centre for Structural Systems Biology in Hamburg additionally confirmed the results.

Background: Cryo-electron Microscopy

Cryo-electron microscopy is a relatively new research method for determining the structure of protein molecules. In the past scientists mainly used X-ray crystallography and nuclear magnetic resonance spectroscopy. In 2015, cryo-electron microscopy was elected as research method of the year by the journal Nature Methods on the basis of the remarkable progress made.

With the long-established method of X-ray crystallography, the proteins first have to be converted into a crystalline form, whereas with cryo-electron microscopy and also NMR spectroscopy, the protein building blocks can be investigated in their natural state. In the case of cryo-electron microscopy, the specimens are first dissolved in water, then flash frozen, and finally investigated with an electron microscope. This method has particular advantages when it comes to investigating large structures composed of hundreds or thousands of proteins.

The establishment of a facility for high-resolution cryo-electron microscopy will in future give scientists at Jülich the opportunity to investigate biological molecules by this relatively new procedure. A joint application for such a facility has already been made by Forschungszentrum Jülich and Heinrich Heine University Düsseldorf and is known by the abbreviation ER-C 2.0.

Background: Development of Alzheimer’s Treatment

In addition to basic research, Jülich’s Institute of Complex Systems (ICS-6) is also developing a novel treatment strategy with its own drug candidate. It is planned to found a spin-off company named Priavoid GmbH this year with the mission of continuing this development. According to the current schedule, it is envisaged that the drug candidate will be tested on humans as part of a phase 1 study in November 2017.

Citation

http://www.fz-juelich.de/SharedDocs/Pressemitteilungen/UK/EN/2017/17-09-08-alzheimer-fibrillen.html;jsessionid=30A2E049FFBED856F2982F75E840FB50

Journal Reference:

Lothar Gremer, Daniel Schölzel, Carla Schenk, Elke Reinartz, Jörg Labahn, Raimond B. G. Ravelli, Markus Tusche, Carmen Lopez-Iglesias, Wolfgang Hoyer, Henrike Heise, Dieter Willbold, Gunnar F. Schröder. Fibril structure of amyloid-ß(1-42) by cryoelectron microscopy. Science, 2017; eaao2825 DOI: 10.1126/science.aao2825