Affordable, Non-Invasive Test May Detect Who is Most at Risk for Alzheimer’s

(University of Texas at Dallas) Individuals with amnestic mild cognitive impairment (aMCI) are at twice the risk of others in their age group of progressing to Alzheimer’s disease. Although no conclusive test exists to predict who will develop Alzheimer’s, new research from the Center for BrainHealth at The University of Texas at Dallas is attempting to identify a potential biomarker that could offer a more complete picture of who is most at risk.

In a study published in the latest edition of the Journal of Alzheimer’s Disease, researchers identify a specific variation in brain waves of individuals with aMCI. The findings depict a pattern of delayed neural activity that is directly related to the severity of impairment in cognitive performance on a word finding task and may indicate an early dysfunction of progression to Alzheimer’s disease.

Impaired episodic memory, the ability to retain new memories such as recent conversations, events, or upcoming appointments, is a hallmark symptom of Alzheimer’s disease. While mild cognitive impairment (MCI) is the recognized clinical state between healthy aging and Alzheimer’s disease, aMCI is a specific type characterized by deficits in episodic memory.

The potential diagnostic approach utilizes electroencephalogram (EEG) technology, a more affordable and non-invasive alternative to other available methods such as MRI or a spinal tap, to measure neural responses while participants access semantic memory or long-term memory representative of general knowledge and concepts.

“This is a promising start at looking at a group of MCI patients. The long-term goal is whether this can be applied to individual patients one day,” says study principal investigator John Hart, Jr., M.D., Medical Science Director at the Center for BrainHealth and Distinguished Chair in Neuroscience and the Jane and Bud Smith Distinguished Chair.

Study findings show that individuals with aMCI performed less accurately and more slowly on the semantic memory task than healthy controls. EEG results illustrated delayed brain activity during the task. When researchers took into account performance on an episodic memory evaluation, they found that the worse the episodic memory performance, the greater the delayed activity that appeared in the EEG.

For the study, 16 individuals with aMCI and 17 age matched healthy controls were monitored by EEG and presented with pairs of words that either described features of an object or were randomly paired. For example, ‘humps’ and ‘desert’ would evoke the memory of the word ‘camel’, but ‘humps’ and ‘monitor’ would be considered a random pair. Participants were then asked to indicate by button press whether the pair conjured any particular object memory or not.

“The majority of EEG research in aMCI has focused on looking at the mind ‘at rest’, but we are looking at the brain while it is engaged in the object memory retrieval process.

We think this might be more sensitive and more specific in pointing out certain cognitive deficits, in this case semantic memory, than other non-EEG methods available, because EEG reflects direct neural activity,” explained study lead author Hsueh-Sheng Chiang, M.D., Ph.D., a research doctoral student at the Center for BrainHealth time of the study who is now a post-doctoral fellow at UT Southwestern Medical Center.

“This protocol could potentially provide complementary information for diagnosis of pre-dementia stages including MCI and identify neural changes that can occur in cases of Alzheimer’s disease.”

Chiang and Hart will continue to validate this prospective diagnostic tool that has the potential to help identify or predict those who may progress to Alzheimer’s disease. The research team plans to recruit more participants and to follow them longitudinally in combination with other objective measures to examine the potentiality of applying this EEG tool as an early disease marker.

Raksha Anand Mudar, Ph.D., from the University of Illinois at Urbana-Champaign was a principal investigator, and researchers from UT Southwestern Medical Center and John Hopkins University School of Medicine also co-authored the article.

This work was made possible by grants from the National Institute of Health (RCI-AG035954, P30AG12300), the RGK foundation, Alzheimer’s Association New Investigator Grant (NIRG-11-173815) the Berman Research Initiative at the Center for BrainHealth, and the Linda and Joel Robuck Friends of BrainHealth New Scientist Award.

About the Center for BrainHealth
The Center for BrainHealth® at The University of Texas at Dallas is a scientific research institute committed to understanding, protecting and healing the brain. With more than 60 fully funded research projects, scientific exploration at the Center for BrainHealth is leading edge, innovative, improving lives today and translating groundbreaking discoveries into practical clinical application. Cognitive neuroscience experts at the Center for BrainHealth® and its Brain Performance Institute™ are dedicated to developing and delivering effective, evidence-based protocols to build brain resilience, achieve brain regeneration, reverse losses in cognitive capacity and train the brain to maximize performance in people of all ages and stages. For more information, visit www.centerforbrainhealth.org and brainperformanceinstitute.com.

Citation

http://www.j-alz.com/content/affordable-non-invasive-test-may-detect-who-most-risk-alzheimers

Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2015

 

 

High Blood Sugar May Boost Alzheimer’s Risk

(WebMD News from HealthDay) High blood sugar associated with prediabetes may increase the risk for Alzheimer’s disease, a new study suggests.

Researchers found that insulin resistance — higher-than-normal levels of blood sugar that often precede type 2 diabetes — was related to poorer performance on memory tests taken by late-middle-age adults.

“The findings are interesting because people with diabetes are at increased risk for developing Alzheimer’s disease, but we are only now learning why they may be at increased risk,” said lead researcher Barbara Bendlin, an assistant professor of medicine at the University of Wisconsin-Madison.

The study results suggest that insulin resistance could increase the risk for Alzheimer’s disease by altering the way the brain uses sugar (glucose), which is its primary fuel, she said.

However, “by altering insulin resistance in midlife, it may be possible to reduce future risk of Alzheimer’s disease,” Bendlin said. Medications and a healthy lifestyle are possible ways to do that, she said.

According to the American Diabetes Association, 29.1 million Americans have diabetes, and more than half of adults older than 64 have prediabetes. Poor diet, obesity and sedentary lifestyles are associated with insulin resistance, Bendlin noted.

“Healthier lifestyles may contribute to healthier brain aging by reducing insulin resistance,” Bendlin said.

One expert cautioned that having prediabetes, or insulin resistance, doesn’t mean you’re doomed to develop Alzheimer’s, the most common form of dementia.

This study shows that insulin resistance may make mental functioning worse and may be linked to reduced use of insulin in areas of the brain associated with Alzheimer’s disease, but this does not mean that insulin resistance leads to Alzheimer’s, said Dr. Luca Giliberto, an investigator at the Litwin-Zucker Research Center for the Study of Alzheimer’s Disease at the Feinstein Institute for Medical Research in Manhasset, N.Y.

“We do not know what causes Alzheimer’s disease,” said Giliberto, who was not involved in the study. “We don’t know if lowering blood sugar will prevent Alzheimer’s.”

For the study, Bendlin’s team gave memory tests to 150 adults with no mental impairments, at average age of 61. The researchers also measured insulin resistance and had the participants undergo a PET brain scan.

More than two-thirds of the participants had a parent who suffered from Alzheimer’s, about 40 percent had a gene mutation associated with increased Alzheimer’s risk and roughly 5 percent had type 2 diabetes, according to the study.

The researchers found insulin resistance was associated with poorer processing of sugar throughout the brain. Worse performance in immediate memory was linked to lower sugar metabolism in the left medial temporal lobe, the authors said.

The report was published July 27 online in JAMA Neurology.

Dr. Sam Gandy, director of the Center for Cognitive Health at Mount Sinai Hospital in New York City, said it appears there may be a difference

“between the dementia related to full-blown diabetes, which seems to be primarily dementia caused by hardening of the arteries in the brain, and the mental impact of insulin resistance, which some investigators believe is associated with Alzheimer’s.”

In the brain, insulin helps transmit messages between cells, he noted.

“We have long thought of Alzheimer’s as a disease of defective brain signaling,” said Gandy, who had no role in the study.

“Conceivably, there is also a disease of defective insulin signaling, which this paper would support.”

If that’s true, Gandy added,

“then efforts at sensitizing the brain to insulin, using drugs such as pioglitazone [Actos, a diabetes drug], would make sense and might well lead to slowing of degeneration.”

Giliberto recommended healthy living as the best way to keep blood sugar under control and perhaps protect mental health.

“Increasing our health by reducing fats, reducing sugar, improving insulin resistance may reduce the risk of other factors, such as diabetes, on the susceptibility to Alzheimer’s disease and mental decline,” Giliberto said.

Citation

By Steven Reinberg

http://www.webmd.com/diabetes/news/20150727/high-blood-sugar-may-boost-alzheimers-risk

Copyright © 2013-2015 HealthDay. All rights reserved.

 

Alzheimer’s Worsens Twice as Fast in Women, Study Finds

(NBC News) Women with memory problems that may signal early Alzheimer’s descend into dementia twice as fast as men, researchers said Tuesday.

It helps explain why so many more women than men have Alzheimer’s disease, they said. Two-thirds of Americans suffering from Alzheimer’s are women.

Women in their 60s are twice as likely to develop Alzheimer’s as they are to get breast cancer, the Alzheimer’s Association says.

It may have something to do with the biology of the brain, researchers told the annual Alzheimer’s Association International Conference in Washington, D.C.

“We haven’t done enough work parsing out some of the gender differences,” said Kristine Yaffe of the University of California San Francisco.

Women are more likely to have depression, a risk factor for Alzheimer’s, and women are more vulnerable to stress, another risk factor.

“Probably what this is going to be about is a complicated interaction between genetics, hormones and the way the brain develops,” Yaffe said.

Some studies are shedding just a little light on what may be happening.

Katherine Lin of Duke University and colleagues studied 400 people with mild cognitive impairment — a loss of memory and thinking skills that doesn’t yet strongly affect someone’s life but that can become Alzheimer’s.

They used an 11-part test that’s routine for diagnosing memory loss and Alzheimer’s. Women, they found, declined at a rate of more than two points a year on the test, compared to men who declined at a rate of just over one point a year.

“Our findings suggest that men and women at risk of Alzheimer’s may be having two very different experiences,” said Lin, a student at Duke who said she become interested in Alzheimer’s research after a female relative was diagnosed with the disease.

Some other researchers say they have hints about what may be going on.

Dr. Katie Schenning of Oregon Health & Science University and colleagues found that the combination of surgery and anesthesia could affect brain volume and thinking – and that women are more affected by this than men.

It didn’t matter what type of anesthesia it was, Schenning told a news conference.

“Women exposed to surgery and anesthesia had a more rapid rate of decline…than men exposed to anesthesia,” she said.

Her team studied 527 people, 182 of whom had surgery with anesthesia. They had comparable years of education and were equally likely to have the APOE4 gene, which puts people at a higher risk of Alzheimer’s.

People often come out of anesthesia with confusion, an effect that usually wears off fairly quickly. But some people never quite recover. This happened to both men and women, but it measurable declines came faster in women and women had more evidence of brain shrinkage after surgery than men did, Schenning’s team found.

“It was not just anesthesia but the combination of surgery and anesthesia,” Schenning said.

Her team couldn’t see a different between different types of anesthetics but she said that would be an important thing to look at. In the meantime, people considering elective surgery should discuss this risk with their doctors, she said.

Dr. Michael Weiner of the University of California San Francisco has another piece of the puzzle. His team did PET scans of people’s brains, and found women in general have more of the brain-clogging protein called amyloid that is a hallmark of Alzheimer’s.

His team looked at 1,000 people: 273 normal people, 557 with mild cognitive impairment and 145 who had diagnosed Alzheimer’s.

“Women have more amyloid in the brain than men even when you adjust for other factors,” Weiner told a news conference.

Having the APOE4 gene did not seem to matter for women – they still had more amyloid in their brains, and this effect became much greater once they had Alzheimer’s.

Dr. Roberta Brinton of the University of Southern California says much more work needs to be done on sex differences in the brain. She led a three-day workshop of experts who agreed that hormones such as estrogen and testosterone must play a role, although it’s not clear at all what, precisely, that role is. Women also have metabolic differences, she said, and it may be that women are affected differently by diet and exercise than men are.

It’s clear that exercise and a healthy diet do affect people’s risk of Alzheimer’s.

More than 5 million Americans have Alzheimer’s disease now. The Alzheimer’s Association says more than 28 million baby boomers will develop the disease between now and 2050, and the cost of caring for them will consume nearly 25 percent of Medicare spending in 2040.

Citation

Maggie Fox

http://www.nbcnews.com/health/aging/alzheimers-worsens-twice-fast-women-study-finds-n395741

© 2015 NBCnews.com

 

Older Adults Can Improve Brain Function by Raising Their Fitness Level

(University of Kansas Medical Center) New research conducted at the University of Kansas Medical Center indicates that older adults can improve brain function by raising their fitness level.

Jeffrey Burns, M.D., professor of neurology and co-director of the KU Alzheimer’s Disease Center, led a six-month trial conducted with healthy adults ages 65 and older who showed no signs of cognitive decline. The results of the study were published on July 9 in the journal PLOS ONE.

The randomized controlled trial attempted to determine the ideal amount of exercise necessary to achieve benefits to the brain. Trial participants were placed in a control group that did not have monitored exercise, or they were put into one of three other groups. One group moderately exercised for the recommended amount of 150 minutes per week, a second exercised for 75 minutes per week, and a third group exercised for 225 minutes per week.

All groups who exercised saw some benefit, and those who exercised more saw more benefits, particularly in improved visual-spatial processing — the ability to perceive where objects are in space and how far apart they are from each other. Participants who exercised also showed an increase in their overall attention levels and ability to focus.

“Basically, the more exercise you did, the more benefit to the brain you saw,” Burns said. “Any aerobic exercise was good, and more is better.”

The research indicated that the intensity of the exercise appeared to matter more than the duration.

“For improved brain function, the results suggest that it’s not enough just to exercise more,” said Eric Vidoni, PT, Ph.D., research associate professor of neurology at KU Medical Center and a lead author of the journal article.

“You have to do it in a way that bumps up your overall fitness level.”

Marjorie Troeh, of Independence, Mo., participated in the trial. Troeh, 80, was placed in the lowest level of exercise group. She said she signed up for the study in part to motivate herself to exercise more.

“I love exercising my mind, but I hate exercising my body,” she said, adding that the findings about the exercise being linked to better brain function were new to her.

“I knew about the evidence that said exercise was good for endurance and agility, but I really didn’t make any connection with that and brain health.”

Troeh, who lives an independent living facility, said she was glad to have the opportunity to contribute to the fight against Alzheimer’s by participating in a trial, as she had a grandmother and an aunt who battled the disease.

“I’m surrounded by people who face memory problems,” she said. “I’m really anxious to do anything I can to further knowledge in this area.”

Scientists at the KU Alzheimer’s Disease Center have focused on the relationship between exercise and brain metabolism for years and are conducting a number of research studies on how exercise may help prevent or delay the onset of Alzheimer’s.

Citation

By Andy Hyland

http://www.kumc.edu/news-listing-page/new-research-shows-older-adults-can-improve-brain-function-by-raising-their-fitness-level.html

Journal Reference:

Eric D. Vidoni, David K. Johnson, Jill K. Morris, Angela Van Sciver, Colby S. Greer, Sandra A. Billinger, Joseph E. Donnelly, Jeffrey M. Burns. Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial. PLOS ONE, 2015; 10 (7): e0131647 DOI: 10.1371/journal.pone.0131647

 

New Alzheimer’s Study Reveals How Spouse-Caregivers Sustain Relationships

(Florida Atlantic University)  When a spouse is cognitively impaired, marital communication is impaired. As Alzheimer’s disease (AD) progresses, language problems increase in frequency — such as searching for the right word, repeating the same word, asking the same question over and over, or substituting one word for another.

As a result of the decline in communication, married couples affected by AD suffer isolation, depression and estrangement. Limited research has existed on communication in couples affected by AD and existing research primarily focuses on identifying communication deficits — until now.

In a unique study conducted at the Christine E. Lynn College of Nursing at Florida Atlantic University, researchers looked at how couples affected by AD maintained their relationships, over the course of many years of marriage, and uncovered 10 patterns of communication that help couples sustain engagement in their relationships.

Findings from the study are published in the current issue of the International Journal of Human Caring in an article titled “Maintaining Caring Relationships in Spouses Affected by Alzheimer’s Disease.”

Christine L. Williams, DNSc, author of the publication and professor and director of the Ph.D. in Nursing Program in FAU’s College of Nursing, is a board-certified clinical nurse specialist in adult psychiatric mental health nursing, and designed a first-of-its-kind program to study caregiver-spouse interactions.

“There is a knowledge gap regarding how couples affected by Alzheimer’s disease manage their relationship to sustain hope, connection, meaning and engagement,” said Williams.

“Instead of focusing our study on what wasn’t working in their relationships, we looked at patterns that support intimacy.

There is a pressing need for research on maintaining a caring relationship despite progressive decline as it may lead to interventions to foster constructive communication.”

In the study, Williams used Jean Watson’s caritas framework, which values the human relationship as the central focus and provides the appropriate framework to study caregiver-spouse interactions. Members of Williams’ research team visited 15 couples in their home once a week for 10 weeks.

Couples had long-term marriages with an average of 47 years, were middle-income and generally well educated. The mean age for caregivers was 77 and 80 for spouses with AD. Most of the caregivers were female (68.8 percent) and reported that they had performed the role of caregiver for an average of four years.

Couples were asked to converse on a topic of their choice for 10 minutes, which were recorded once the researcher left the room. Using this method, researchers were able to observe naturally occurring everyday conversations, which involved both verbal and non-verbal behavior and non-linguistic aspects of the conversation such as pauses.

Thirty conversations were analyzed with qualitative methods. Three overall themes of spousal care were identified: engaging with compassion; patiently reaching out; and trusting in the existence of deep attachment. In addition, 10 communication patterns were identified.

Communication patterns included “news of the day,” which provided caregivers and spouses normalcy and serenity by talking about the mundane activities of daily life; “sharing memories,” whereby caregivers attempted to reminisce with their spouses about memories of people and past events; “storytelling,” as caregivers persevered in telling a detailed story although the conversation seemed like a monologue with no verbal participation from the spouses; and “delighting in the unexpected,” as caregivers were overjoyed when their spouses contributed more to the conversation than expected.

The researchers also observed that caregivers accepted a spouse’s version of the story, valuing the relationship more than being right and therefore refrained from interrupting or interjecting.

“It was evident that caregiving spouses bore most of the responsibility in maintaining the caring relationship, but there was evidence that the spouse affected by Alzheimer’s disease actively participated as well,” said Williams.

“In one conversation, maintaining eye contact with the spouse was the only obvious evidence of engagement. In another interaction, singing familiar songs provided an avenue for active involvement between partners.”

More than 5 million Americans are currently affected by Alzheimer’s disease and 15.4 million caregivers are responsible for their care. Most caregivers report significant stress and decreased well-being related to caregiving and evidence is mounting that they have increased morbidity and mortality rates. The largest proportion of AD family caregivers are spouses.

“These caring ways of relating are of value because they provide information about what is possible in marital relationships affected by Alzheimer’s disease,” said Williams.

“Illuminating ways that couples demonstrate caring can be a source of strength to those who feel hopeless, discouraged and ready to give up, and can empower nurses to reach out to couples.”

Citation

http://www.sciencedaily.com/releases/2015/07/150713095148.htm

Journal Reference:

Christine L. Williams. Maintaining Caring Relationships in Spouses Affected by Alzheimer’s Disease. International Journal of Human Caring, July 2015

Copyright 2015 ScienceDaily or by third parties, where indicated.

 

Clinical Trials Results and New Data Analyses in Amyloid-Related therapies from the Alzheimer’s Association International Conference 2015

(Alzheimer’s Association)  Clinical trial results from three studies of investigational therapies related to amyloid protein were presented today at the Alzheimer’s Association International Conference® 2015 (AAIC® 2015) in Washington, D.C.

They included:

  • A new “delayed-start” analysis of negative Phase 3 clinical trials of solanezumab (Lilly) which suggests that the drug may slow the progression of mild Alzheimer’s disease.
  • A biomarker-only analysis of a discontinued Phase 3 clinical trial of gantenerumab (Roche) that shows the drug engaged its target in the brain and generated positive biological changes.
  • New data from PRIME, the Phase 1b study of aducanumab (Biogen).

Two abnormal structures called amyloid plaques and tau tangles are prime suspects in damaging and killing brain cells in Alzheimer’s disease and other dementias. Plaques are deposits of a protein fragment called beta-amyloid that build up in the spaces between nerve cells. Tangles are twisted fibers of another protein called tau that build up inside cells.

“The data from these new analyses present exciting possibilities, and we look forward to the results of future studies in these experimental drugs,” said Maria Carrillo, PhD, Chief Science Officer, Alzheimer’s Association.

“For the delayed-start analysis in particular, if it proves to be true, it is the strongest argument to date for early Alzheimer’s diagnosis, because getting the drug earlier makes a significant difference in the outcome.”

“Last month, we witnessed historic bipartisan support in both chambers of Congress for the largest increase in Alzheimer’s research funding to date. This included a call for a 60 percent increase of approximately $350 million for Alzheimer’s research by the Senate Appropriations Subcommittee,” Carrillo added.

“Yet, even with the proposed increase, Alzheimer’s funding still receives far less than what leading experts say is required to meet the primary goal of the National Plan to Address Alzheimer’s Disease – to prevent and effectively treat Alzheimer’s by 2025. Leading experts convened by the Alzheimer’s Association stated that $2 billion per year is needed to make real advances in treating and preventing Alzheimer’s.”

Delayed-Start Analysis of Solanezumab (Lilly) Up To 3.5 Years

Showing that an investigational treatment has slowed the progression of a degenerative brain disease like Alzheimer’s is extremely challenging. Researchers have proposed overcoming this problem with a type of study called a “delayed-start” trial. In delayed-start studies, patients are randomly assigned to start active treatment at the beginning of the study or are placed in a “delayed-start” group that receives a placebo treatment for a period of time before being given the active experimental therapy. Researchers then compare the two groups at a later, pre-defined point in time to assess their response to the treatment.

  • If the experimental treatment is limited to reducing Alzheimer’s symptoms, both early-start and delayed-start participants should experience the same benefit. For example, if a treatment is maximally effective after two months, it would take both groups two months from the time they first receive it to have comparable reductions in their symptoms, and the delayed start group would “catch up” to the early start group and be functioning at a similar level.
  • If the treatment can actually slow disease progression, both groups will benefit, but the group that started active treatment later in the study will have progressed further in the disease before they got the drug – while they were on placebo. As a result, the late starters will not be able to “catch up” to the group whose disease progression was slowed for the full duration of the study.

At AAIC 2015, Hong Liu-Seifert, PhD, Research Advisor for the Alzheimer’s Disease Global Development Team at Eli Lilly and Company, Indianapolis, Indiana; Paul Aisen, MD, Director of the Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego; and colleagues shared results of a new statistical approach to delayed-start analysis for the experimental drug solanezumab (Lilly).

Their presentation was based on a pooled analysis of 1,322 people enrolled in the completed, 18-month EXPEDITION (EXP) and EXPEDITION2 (EXP2) placebo-controlled clinical trials, and a two-year extension trial known as EXPEDITION-EXT (EXP-EXT). EXP and EXP2 did not achieve statistical significance on their primary endpoints.

In EXP-EXT, all participants receive solanezumab, but patients and site personnel remain blinded to original treatment assignment, preserving the randomized, double-blind nature of the entire 3.5-year delayed-start design. The primary time point assessment for the delayed-start analyses was pre-specified at 28 weeks into the delayed-start period.

The researchers found that:

  • Treatment differences at 28 weeks in EXP-EXT between the early start and delayed start groups for cognition (ADAS-Cog14) and function (ADCS-iADL) were similar to differences at the end of the placebo-controlled period, within a pre-defined margin. In other words, the delayed starters did not “catch up.”
  • Treatment differences between the early start and delayed start groups for ADAS-Cog14 and ADCS-iADL remained significant through 52 weeks.

“The results support the potential benefit of starting treatment with solanezumab earlier rather than later in disease progression, and suggest there is persistence of treatment effect even after the delayed-start patients are given the drug,” Aisen said.

“This analysis method is also planned for the ongoing EXPEDITION3 study.”

Simultaneously with presentation at AAIC 2015, results from the delayed-start analysis of solanezumab in mild Alzheimer’s will be published in Alzheimer’s & Dementia: Translational Research & Clinical Investigations.

Biomarker Results from Phase 3 Gantenerumab (Roche) Trial in Early Alzheimer’s

In December 2014, dosing of gantenerumab (Roche) in the two-year, Phase 3 SCarlet RoAD trial in people with early symptoms of Alzheimer’s was stopped based on preliminary results that indicated the chance of successful completion was very low; patients in the study continue to be followed.

Gantenerumab is a human monoclonal antibody that binds to, and may stimulate the removal of, aggregated forms of beta amyloid protein in the brain. In SCarlet RoAD, people with amyloid build-up in the brain and some signs of impairment of mental processes (such as memory difficulties) received once-monthly placebo or one of two doses of gantenerumab (105 mg or 225 mg).

Overall, patients treated with gantenerumab did not experience cognitive benefit compared to patients treated with placebo, but there was evidence of efficacy in patients with faster progressing disease who had higher exposure to the drug. At AAIC 2015, researchers reported data about the biological activity of the drug.

According to the researchers, gantenerumab produced dose-related reductions on levels of amyloid (not statistically significant), as measured by brain amyloid PET scans, and tau (statistically significant), a protein marker of brain cell degeneration that can be measured in the cerebrospinal fluid.

  • CSF p-Tau mean % change from baseline at Week 104: placebo (n=63) +2.62 ± 21.89; 105 mg gantenerumab (n=62) -4.85 ± 12.42; 225 mg gantenerumab (n=58) -7.52 ± 9.85.
  • CSF t-Tau: mean % change from baseline at Week 104: placebo (n=62) +3.11 ± 21.12; 105 mg gantenerumab (n=60) -1.45 ± 13.55; 225 mg gantenerumab (n=57) -2.94 ± 10.37.
  • No changes in CSF Abeta 42 levels were found.
  • Amyloid-PET observed mean % change from baseline in cortical composite SUVr at Week 100: placebo (n=20) -1.11 ± 8.02; 105 mg gantenerumab (n=11) +0.19 ± 12.70; 225 mg gantenerumab (n=18) -5.37 ± 7.92.

“This is the first study showing clear changes on both standard biomarkers in people with very early Alzheimer’s,” said Philip Scheltens, MD, PhD, professor of cognitive neurology and director of the Alzheimer’s Center at the VU University Medical Center in Amsterdam, Netherlands and a principal investigator of SCarlet RoAD.

“These findings are consistent with brain amyloid clearance and an effect on downstream markers of neurodegeneration. They also suggest that the gantenerumab dose in the Phase 3 Scarlet RoAD trial likely was too low. Future trials should examine higher doses of the drug.”

New Data from Phase 1b Study of Aducanumab (Biogen) in Prodromal or Mild Alzheimer’s

Aducanumab (BIIB037) is a monoclonal antibody targeting aggregated forms of amyloid beta protein – a hallmark of Alzheimer’s disease progression is the accumulation of beta amyloid in the brain.

At AAIC 2015, Biogen presented new results from a prespecified interim analysis of PRIME, the Phase 1b study of aducanumab in patients with prodromal or mild Alzheimer’s. The data included results from patients treated up to 54 weeks with the 6 mg/kg dose.

Earlier this year, Biogen announced interim results from the 1, 3 and 10 mg/kg arms of PRIME after one year of treatment as well as the 6 mg/kg arm up to 30 weeks. Those results marked the first time an investigational drug for Alzheimer’s demonstrated a statistically significant reduction on amyloid plaque as well as a statistically significant slowing of clinical impairment in patients with prodromal or mild disease. These promising early results must be expanded and replicated in larger populations.

PRIME is the ongoing Phase 1b randomized, double-blind, placebo-controlled, multiple-dose study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of aducanumab in patients with prodromal or mild Alzheimer’s. Biogen required patients enrolled in PRIME to have evidence of beta amyloid accumulation (detected by PET scan) and to have met clinical criteria for prodromal or mild Alzheimer’s.

Citation

About AAIC

The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of leading researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2015 home page: www.alz.org/aaic/
AAIC 2015 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call 800.272.3900.

https://www.alz.org/aaic/releases_2015/wed-7amET.asp

© 2015 Alzheimer’s Association. All rights reserved.

 

What is the Mediterranean Diet? What are the Benefits of the Mediterranean Diet?

(Medical News Today) Traditionally, Western Europe has two broad nutritional approaches – the Northern European and Southern European. The Mediterranean Diet is Southern European, and more specifically focuses on the eating habits of the people of Crete, much of Greece, and southern Italy.

Today, Spain, southern France, and Portugal are also included; even though Portugal does not have a Mediterranean coast.

This Medical News Today information article provides details on what the Mediterranean diet includes, its global recognition, and the health benefits of the diet. This article forms part of a series called What Are The Eight Most Popular Diets Today?.

What Does the Mediterranean Diet Include?

  • Lots of plant foods
  • Fresh fruit as dessert
  • High consumption of beans, nuts, cereals (in the form of wheat, oats, barley, corn or brown rice) and seeds
  • Olive oil as the main source of dietary fat
  • Cheese and yogurt as the main dairy foods
  • Moderate amounts of fish and poultry
  • No more than about four eggs each week
  • Small amounts of red meat each week (compared to northern Europe)
  • Low to moderate amounts of wine
  • 25% to 35% of calorie intake consists of fat
  • Saturated fat makes up no more than 8% of calorie intake
Olive oil
Olive oil is one of the main sources of dietary fat.

Fats – the Mediterranean diet is known to be low in saturated fat, high in monounsaturated fat, and high in dietary fiber.

Legumes – the Mediterranean diet includes plenty of legumes. Legumes are plants in the pea family that produce pods which slit open naturally along a seam, revealing a row of seeds.

Examples of legumes include peas, chick peas, lentils, alfafa and beans.

Scientists from the University of Toronto reported in Archives of Internal Medicine, October 2012 issue, that eating more legumes helps improve glycemic control in people with diabetes type 2, as well as lessening the risk of developing coronary heart disease.

The Mediterranean Diet – Worldwide Recognition

Became popular in the 1990s – even though the American Scientist Dr. Ancel Keys (1904-2004) publicized the Mediterranean diet while he was stationed in Italy, it was not until about the 1990s that it was widely recognized and followed elsewhere by nutritionally conscious people.

An enigma – compared to other Western diets, the Mediterranean diet was seen by others as a bit of an enigma. Although fat consumption is high, the prevalence of hypertension, cardiovascular disease, obesity, cancer and diabetes has always been significantly lower in Mediterranean countries than northern European countries and the USA. The American diet is more similar to the northern European diet – with high red meat consumption, greater consumption of butter and animal fats, and a lower intake of fruit and vegetables, compared to the eating habits of Italy, Greece, southern France, and Spain.

More popular in non-English speaking nations – the non-English speaking countries of northern Europe, such as Scandinavia, the Netherlands, Belgium, Germany, Switzerland and Austria have adopted the Mediterranean diet to a much greater degree than English speaking nations, such as the UK, Ireland, the USA, Australia and New Zealand.

Dietary habits in Canada vary; with the French-speaking Quebec areas tending more towards a Mediterranean diet, compared to the rest of the country. Many experts believe that is why developed English-speaking nations have a lower life expectancy than the other developed nations.

Mediterranean countries consume higher quantities of red wine, while northern European countries and the USA consume more beer. Red wine contains flavonoids, which are powerful antioxidants, according to a study in the Journal of Natural Products.

The Mediterranean diet, compared to the Anglo-saxon diet, contains much higher quantities of unprocessed foods.

What are the Benefits of the Mediterranean Diet?

Studies have been carried out which compare the health risks of developing certain diseases, depending on people’s diets. People who adopted the Mediterranean diet have been compared with those who have an American or Northern European diet.

An article published in Food Technology in October 2012 explained that plant-based diets either considerably reduce or totally eliminate people’s genetic propensity to developing chronic diseases, such as diabetes type 2, cardiovascular disease, and cancer.

Mediterranean diet helps prevent a genetic risk of stroke – a variant (mutation) in the Transcription Factor 7-like 2 (TCF7L2) gene, which is associated with the development of type 2 diabetes, is also linked to higher stroke risk, especially if a person carries two copies (homozygous carriers).

Scientists from Tufts University, USA, and the CIBER Fisiopatología de la Obesidad y Nutriciόn, Spain, found that the Mediterranean diet may protect homozygous carriers of the mutated gene.

The researchers wrote in the journal Diabetes Care “Being on the Mediterranean diet reduced the number of strokes in people with two copies of the variant. The food they ate appeared to eliminate any increased stroke susceptibility, putting them on an even playing field with people with one or no copies of the variant.”

An Italian study published in BMJ Open reported that people who stick to a Mediterranean diet tend to have better HRQL (health-related quality of life). They added that the link is stronger with mental than physical health. “Dietary total antioxidant and fibre content independently explain this relationship,” they added.

The following health benefits have been observed by people who have a Mediterranean diet:

  • It’s good for your heart – researchers at McMaster University found an association between good heart health and certain food groups or dietary patterns including vegetables, nuts, monounsaturated fatty acids, and overall ‘healthy’ dietary patterns, such as the Mediterranean diet. The study was publshed in the Archives of Internal Medicine.6
  • It can prevent diabetes – a study published by the BMJ7 revealed that the traditional Mediterranean diet can help protect people from type 2 diabetes.

Recent developments on the benefits of the Mediterranean diet from MNT news

‘Better than low-fat diet’ for cardiovascular risk. A study published in the American Journal of Medicine suggested that people who adopt a whole diet approach – such as a Mediterranean diet – have a lower risk of heart attack and cardiovascular-related death than those who follow a strictly low-fat diet.

Following the Mediterranean diet could slow aging process. Vegetables, fruits, nuts, copious amounts of olive oil and a glass of wine with a meal; while the Mediterranean diet sounds like a the makings of a delicious lifestyle, it has also long been regarded as one of the healthiest ways to eat. Now, researchers have suggested that the diet could also help slow the aging process.

Extra nuts or oil with Mediterranean diet could protect memory. Researchers in Spain have suggested that following a Mediterranean diet supplemented with additional portions of antioxidant-rich extra virgin olive oil or mixed nuts could protect cognitive functioning in older adults.

Mediterranean diet could reduce risk of endometrial cancer. The Mediterranean diet is often regarded as one of the healthiest diets around, and a newly published study adds further support to these claims. Researchers suggest that adhering closely to the diet can cut the risk of endometrial cancer in women by more than half.

Video – The Mediterranean Diet

This New York Times video talks about how the Mediterranean diet helped people with cardiovascular diseases.

Citation

Written by Christian Nordqvist

http://www.medicalnewstoday.com/articles/149090.php

MediLexicon International Ltd, Bexhill-on-Sea, UK

© 2004-2015 All rights reserved.

 

Scientists Develop Antibody to Treat Traumatic Brain Injury and Prevent Long-Term Neurodegeneration

(Beth Israel Deaconess Medical Center) New research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides the first direct evidence linking traumatic brain injury to Alzheimer’s disease and chronic traumatic encephalopathy (CTE) — and offers the potential for early intervention to prevent the development of these debilitating neurodegenerative diseases. TBI can result from repetitive contact sport injuries or from exposure to military blasts, and is one of the most significant risk factors for both Alzheimer’s disease and CTE.

In a study published today in the online edition of the journal Nature, the researchers found that a misshapen isoform of the tau protein can develop as soon as 12 hours after TBI, setting in motion a destructive course of events that can lead to widespread neurodegeneration. Importantly, the researchers have developed a potent antibody that can selectively detect and destroy this highly toxic protein.

“TBI is a leading cause of death and disability in children and young adults and also affects approximately 20 percent of the more than two million troops who have deployed to Iraq and Afghanistan,” said co-senior author Kun Ping Lu, MD, PhD, Chief of the Division of Translational Therapeutics in the Department of Medicine at BIDMC and Professor of Medicine at Harvard Medical School (HMS).

“Our study shows that an early neurodegenerative process induced by the toxic tau protein can begin just hours after a traumatic brain injury. In both cell models of stress and in mouse models simulating sport- and military-related TBI, the production of this pathogenic protein, called cis P-tau, disrupts normal neurological functioning, spreads to other neurons and leads to widespread neuronal death.

We have developed a potent monoclonal antibody that can prevent the onset of widespread neurodegeneration by identifying and neutralizing this toxic protein and restoring neurons’ structural and functional abilities.”

Alzheimer’s disease is the most common form of dementia in older individuals and currently affects more than 5 million Americans and 30 million people worldwide. Chronic traumatic encephalopathy is a degenerative brain disease associated with a number of neurological symptoms including risk-taking, aggression and depression. CTE can also lead to progressive dementia.

Previous research has shown that abnormal phosphorylation of the tau protein underlies Alzheimer’s and other neurodegenerative diseases. In recent years, the Lu laboratory discovered that tau exists in two isoforms, or shapes — one functioning and one disease-causing.

“Healthy tau protein is found in the brain and serves to assemble and support microtubules, the ‘scaffolding systems’ that give neurons their unique shape and are integral to memory and normal brain functioning,” explained Lu.

But in Alzheimer’s, CTE and other neurodegenerative diseases, collectively called tauopathies, tau becomes tangled and unable to function properly.

“Recent studies of CTE in the brains of boxers, American football players and blast-exposed veterans have identified extensive neurofibrillary tau tangles,” he said.

“But, because these tangles were not detected until months or, more likely, years after TBI, it has not been known whether tauopathy is a cause or a consequence of TBI-related neurodegenerative disease. We have now shown that it is a cause of these diseases.”

Co-senior author of the new study Xiao Zhen Zhou, MD, also an investigator in BIDMC’s Division of Translational Therapeutics and Assistant Professor of Medicine at HMS, had previously developed polyclonal antibodies capable of distinguishing between two distinct isoforms of the phosphorylated tau protein. The isoform known as trans is in a relaxed shape and is important for normal brain functioning. The other isoform, known as cis, is in a twisted shape and is prone to becoming tangled. Cis P-tau is an early pathogenic protein leading to tauopathy and memory loss in Alzheimer’s disease.

“In this new study, we wanted to find out whether cis P-tau is present following TBI and, if so, how to eliminate it from the brain without disrupting the healthy functioning of trans P-tau,” said Zhou.

“We generated a monoclonal antibody able to detect and eliminate cis P-tau very early in the disease process.”

Monoclonal antibody technology is a popular drug development approach. Working like a lock and key, it enabled the investigators to both detect and neutralize only the toxic cis P-tau.

After confirming the existence of this toxic cis tau isoform in the brain tissue of humans who had died of CTE, the authors simulated contact-sport and blast-related injuries in mouse models, and found that the brain’s induction of cis P-tau is dependent on injury severity and frequency.

“Mild TBI, also known as a concussion, results in moderate and transient cis P-tau induction,” explained Lu. “However, repetitive concussions, as might occur in contact sports, can result in robust and persistent cis P-tau induction. This is similar to what is produced following a single severe TBI caused by a blast or impact.”

Subsequent experiments revealed that the cis P-tau protein disrupts the brain’s microtubule scaffolding systems and the transport of mitochondria, the powerhouse that provides energy for neuronal function, and eventually leads to neuron death by apoptosis. The research also showed that, over time, cis P-tau progressively spreads throughout the brain. Treating TBI with cis antibody eliminated the toxic cis P-tau, prevented widespread tauopathy and neuron death and restored brain structure and function.

“These experiments told us that cis P-tau has the ability to kill one neuron after another, eventually leading to widespread neurofibrillary tangles and brain atrophy, which are the hallmark lesions of both Alzheimer’s disease and CTE,” said Lu.

“We have determined that cis P-tau is an early driver of neurodegenerative disease after brain injury and that tauopathy it is a cause of TBI-related Alzheimer’s disease and CTE.

We have also determined that the cis antibody can treat TBI and prevent its long-term consequences in mouse models.

The next important steps will be to establish cis P-tau as a new biomarker to help enable early detection, and to humanize the cis antibody for treating patients with TBI.”

“Alzheimer’s disease and chronic traumatic encephalopathy are terrible diseases that progressively rob individuals of their memory, judgment and ability to function,” said study coauthor Alvaro Pascual-Leone, MD, PhD, Chief of the Division of Cognitive Neurology at BIDMC and Professor of Neurology at HMS.

Pascual-Leone also serves as Associate Director of the Football Players Health Study (FPHS) at Harvard University, a multi-year initiative to discover new approaches to diagnose, treat and prevent injuries in professional football players.

“High-profile cases of CTE, such as that of the late football player Junior Seau, have vividly demonstrated the tragic consequences of this affliction,” he added.

“We need to learn more about CTE’s causes in order to develop better ways of diagnosing and treating it, and this study offers us a promising early intervention to prevent the pathologic consequences of this disease.

These findings additionally offer us a new way to approach Alzheimer’s disease, which poses a staggering unsustainable burden throughout the world. Alzheimer’s afflicts both individuals and their families and, it deprives society of the contributions of experienced and wise elders.”

The study was funded, in part, by National Institutes of Health grants (T32HD040128, UO1NS86659-01; P30AG13846; R01AG029385, R01CA167677; RHL111430; R01AG046319) as well as grants from the Alzheimer’s Association and from the Football Players Health Study at Harvard University, a research partnership with the National Football League Players Association.

Citation

http://www.bidmc.org/News/In-Research/2015/July/nature-kun-ping-lu.aspx

© 2015 Beth Israel Deaconess Medical Center