Those with elevated risk of Alzheimer's may show memory changes up to 40 years before onset

by Steve Yozwiak, Translational Genomics Research Institute

Credit: CC0 Public Domain

Results from a study of nearly 60,000 individuals suggest those at higher risk of developing Alzheimer's disease due to family history may demonstrate changes in memory performance as early as their 20s.

20 jun 2019--Researchers from the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and the University of Arizona gathered the data through an online word-pair memory test called MindCrowd, one of the world's largest scientific assessments of how healthy brains function.

Published today in the scientific journal eLife, study datasuggests that those with a family history of Alzheimer's disease, and who are younger than 65, on average do not perform as well as their peers who do not have a family history of Alzheimer's, the most common form of dementia.

The study results suggest that the family history effect is particularly pronounced among men, as well as those with lower educational attainment, diabetes, and carriers of a common genetic change in APOE, a gene long associated with Alzheimer's disease risk.

While family history has previously been associated with the risk of Alzheimer's, this is the first study of its kind, and in these numbers, that indicates this risk can be detected up to four decades before the typical age of onset. The study looked at 59,571 MindCrowd participants aged 18-85, and the effect of family history was shown across every age group, up until age 65.

"In this study we show that family history is associated with reduced paired-associate learning performance as many as four decades before the typical onset of Alzheimer's disease," said Dr. Matt Huentelman, TGen Professor of Neurogenomics, and the study's senior author

Because there is no cure or proven way of slowing progressive memory-loss among those with Alzheimer's, early indicators of the disease can help those at risk to focus on ways to help stave off dementia.

"Risk reduction for Alzheimer's disease is now more critical than ever due to the continued lack of a cure or effective disease-slowing treatment," said Dr. Joshua S. Talboom, a Postdoctoral Fellow in TGen's Neurogenomics Division, and a member of Dr. Huentelman's lab.

"This study supports recommendations underscoring the importance of living a healthy lifestyle and properly treating disease states such as diabetes," said Dr. Talboom, the study's lead author. "Our findings specifically highlight the positive effects of such interventions for those with a family history risk of Alzheimer's, opening the door to the development of more targeted risk-reduction approaches to combat the disease."

In addition, this study underscores the utility of web-based participant recruitment to research studies like MindCrowd, facilitating large sample sizes in a cost- and time-effective fashion, said Dr. Lee Ryan, a University of Arizona Alzheimer's researcher, who along with the UA's Dr. Betty Glisky, helped Dr. Huentelman develop MindCrowd. Drs. Ryan and Glisky were contributing authors to the study.

"It should be acknowledged that that web-based studies are not without concerns. However, we propose that the advantage of considerably larger sample sizes and enriched participant diversity in online research mostly diminishes the potential disadvantages," Dr. Ryan said.

The MindCrowd study (www.mindcrowd.org) began in 2013. By August 2018, it had nearly 60,000 qualified participants, whose performance is reflected in the study. Today, more than 115,000 people, aged 18-95—from all 50 states and 150 nations around the world—have completed the MindCrowd assessment.

MindCrowd cannot tell you if you have Alzheimer's. What it does give researchers is a set of data baselines about how people not suffering from the disease perform at different ages; among men and women, among those with quick and slow physical responses, among those who smoke and those who don't, and among many other demographic, lifestyle and health factors.

Establishing these baselines will help researchers to more properly evaluate Alzheimer's patients and usher in a new era of what the MindCrowd developers describe as Precision Aging.

Alzheimer's is a progressive neurological disorder that typically presents clinically as deficits in memory and thinking. It is estimated that more than 5 million Americans are living with Alzheimer's, and that by 2050 that number will nearly triple to almost 14 million.

The Arizona Alzheimer's Consortium, the Norwegian University of Science and Technology, and the University of Miami also contributed to the study.

The study is titled "Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors."

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More information: Joshua S Talboom et al. Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors, eLife (2019). DOI: 10.7554/eLife.46179

Journal information: eLife 

Provided by Translational Genomics Research Institute 

Opioid analgesics increase the risk of pneumonia among persons with Alzheimer's disease

by University of Eastern Finland

Credit: CC0 Public Domain

Opioid analgesics were associated with a 30 percent increase in the risk of pneumonia in persons with Alzheimer's disease, a recent study from the University of Eastern Finland shows. The risk was most pronounced in the first two months of use. This is the first study to investigate the association between opioids and pneumonia in this population. The results were published in the Journal of Alzheimer's Disease.

10 jun 2019--The risk of pneumonia was highest among those using strong opioids, such as oxycodone or fentanyl, but the risk was also increased among those using buprenorphine, tramadol or codeine. Persons with active cancer were excluded from the study, and other diseases and drug use were accounted for in the analyses. Opioids impair the cough reflex and respiratory functions and cause sedation, possibly underlying the increased risk for pneumonia.

Pneumonia is a severe but relatively common complication among persons with Alzheimer's disease, and often leads to hospitalization and even death. Opioids are important in the treatment of severe acute pain, but treatment should be initiated at a low dose and regularly assessed for both benefit and harm. The diagnosis and assessment of pain is challenging among persons with Alzheimer's disease due to problems in communication.

The study is part of the MEDALZ cohort, which included 5,623 persons with Alzheimer's disease diagnosed in Finland during 2010-2011. Each person initiating opioid use was matched with a comparison person with Alzheimer's disease who did not initiate opioid use but had the same age, gender and year of Alzheimer's diagnosis. Data for the study were derived from Finnish nationwide registers.

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More information: Aleksi Hamina et al. Hospital-Treated Pneumonia Associated with Opioid Use Among Community Dwellers with Alzheimer's Disease, Journal of Alzheimer's Disease (2019). DOI: 10.3233/JAD-181295

Journal information: Journal of Alzheimer's Disease 

Provided by University of Eastern Finland 

Eyes, ears and nose may aid Alzheimer's disease prevention and treatment

The researchers analysed blood vessel patterns in retinal photographs to identify individuals with AD.Image: Olivier Martins

01 fev 2015--Detecting a decline in certain sensory functions may become the future of preventing Alzheimer's disease (AD), with research showing smell testing and retinal imaging to be strong predictors of dementia risk.

Edith Cowan University Centre of Excellence for Alzheimer's Disease Research neuroscientist and clinical psychologist Dr Hamid Sohrabi says that easy and cost-effective tools for identification of subjects in the early stages of AD is critical to improve outcomes.

"We know that memory tests are very good at identifying people who already have dementia, but we need to recognise that they are at high risk well before memory decline commences because at the latter stage the brain would be irreversibly damaged," he says.

With clinical trials so far failing to effectively halt the progression of AD, Dr Sohrabi says scientists believe the main reason for failure is starting treatment too late when damage to the brain is too great to be reversible.

Along with work on blood biomarkers and neuropsychometric tests, Dr Sohrabi is developing a body of evidence supporting the use of smell and eye imaging assessment as predictors of future cognitive decline.

In a group of 308 46-86 year olds, the group demonstrated that poor ability to discriminate different smells significantly predicted cognitive decline at a three year follow-up.

Retinal photos identify AD sufferers

Similarly, analysis of blood vessel patterns in retinal photographs, taken as part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, allowed them to correctly identify individuals with AD from healthy subjects with very high accuracy.

"There's evidence of beta amyloid [a protein involved in the brain disease of AD] depositing in the eye—if we can detect it in the eye before it starts accumulating in the brain that may be one way of predicting who is at higher risk," he says.

In collaboration with Dr Brett Robertson and Dr Dona Jayakody from the Ear Science Institute Australia, Dr Sohrabi will now investigate the role of hearing loss in AD prediction with the hope of a combined sensory deficit score of hearing, eye and olfactory function with strong clinical effectiveness.

"Combining the three senses may put us in the best position to predict who is at a higher risk of developing dementia due to AD," Dr Sohrabi says.

"The best way to prevent neuropathology happening is to start finding those at higher risk, early."

A comprehensive review of innovations in AD diagnosis was published in Alzheimer's and Dementia.

More information: "Olfactory discrimination predicts cognitive decline among community-dwelling older adults": ro.ecu.edu.au/cgi/viewcontent.… context=ecuworks2012

Provided by Science Network WA

Scientists look to heart disease and strokes for clues to treating Alzheimer's

A growing body of research suggests that the most common cause of dementia in older people is a mix of vascular and Alzheimer's-related brain abnormalities, and that approximately half of people who die with Alzheimer's also have evidence of strokes in their brains. Furthermore, when strokes and hallmark Alzheimer's plaques and tangles are combined, it increases a person's likelihood of experiencing dementia. Stroke, or as it is known more generally as cerebrovascular disease, occurs with aging and is made worse by conditions like smoking, hypertension or diabetes.

16 jan 2015--Recommendations by a group of scientists to bolster research on how Alzheimer's and vascular conditions progress together and influence each other are available online today, in advance of publication, by Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The authors hope this research agenda, if executed, will uncover new clues for effectively treating or preventing dementia.

"We are encouraged by the potential for new treatment strategies for dementia to arise from studying the crossover of vascular factors with the progression of Alzheimer's," says Heather M. Snyder, Ph.D., director of medical and scientific operations for the Alzheimer's Association, and first author of the new article. "In terms of next steps, we need to develop the research tools and collaborations necessary to further scientific investigation in this promising area of study."

Cerebrovascular disease can be prevented with a variety of drug and lifestyle interventions; however, this has not yet been established for dementia. Snyder says, "Whether improved control of vascular risk factors can be translated to decreased dementia risk is not known, but results from a number of studies suggest that it is possible, and this untapped potential definitely deserves greater research attention."

In December 2013, the Alzheimer's Association, with scientific input from the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS) and National Heart, Lung and Blood Institute (NHLBI), convened a group of scientific experts to discuss the scientific findings to date and gaps in research on vascular contributions in Alzheimer's and related forms of dementia. The newly-published article summarizes the meeting and discussions, including an outline of next steps.

"Blood vessels that deliver nutrients to the brain and carry away waste are vital for normal cognitive function," says co-author Roderick Corriveau, Ph.D., the NINDS program director who oversees dementia research. "Understanding vascular contributions to cognitive impairment and dementia, including changes due to stroke, heart disease and diabetes, are critically important to guide the development of preventions and treatments for dementia."

"Inadequate blood flow can damage and eventually kill cells anywhere in the body," says Donna M. Wilcock, Ph.D., a neurovascular researcher who is an assistant professor in the Department of Physiology at the University of Kentucky College of Medicine in Lexington and a co-author of the paper. "Since the brain has one of the body's richest networks of blood vessels, it is especially vulnerable. Considering this and demonstrated success in reducing risk for heart disease, stroke and other vascular-related diseases through healthy lifestyle modifications and use of medications, it only makes sense to increase our understanding of the role vascular factors play in Alzheimer's and dementia."

The authors of the article recommend filling gaps in several key areas of research, including:

• The relationship between diabetes and insulin resistance and risk of vascular disease, Alzheimer's and related dementia.
• Genetic factors that may influence vascular processes and other changes in the brain.
• Impact of immune system response on blood flow in the brain in the progression of Alzheimer's disease.
• The role of fat breakdown in the brain in the removal of amyloid build-up that leads to the hallmark brain plaques in Alzheimer's disease.
• Controlling the impact of vascular risk factors on memory and thinking abilities.

The authors also conclude that biological markers, which are used to detect and measure disease progression, of key vascular processes related to impairment of brain function, memory and thinking abilities are needed to move this research further and faster.

"Having the methods to detect early signs of vascular-related brain injury or disease with the greatest impact on Alzheimer's and dementia would greatly enhance our efforts to develop effective therapies," says David Knopman, M.D., professor of neurology at the Mayo Clinic College of Medicine in Rochester, MN, and a co-author of the paper. "Especially needed are tools that are highly accurate and do not require invasive procedures to collect and measure." Dr. Knopman is vice chair of the Alzheimer's Association Medical and Scientific Advisory Council.

Among the biological markers the authors say are necessary are:

• Ability to detect amyloid in blood vessels in the brain.
• Imaging technology that can detect changes from dying brain tissue.
• Indicators of risk for Alzheimer's in pre-diabetic individuals.
• Improved methods for measuring the impact of blood flow in the brain on memory and thinking abilities.

"Future investment for these areas of scientific discovery will be essential to galvanize the scientific community and provide forums of communication between the dementia and vascular fields," the authors state in the paper.

As a further next step, research sessions and scientific presentations focusing on the relationship between vascular factors, Alzheimer's disease and related dementias are being planned for upcoming major scientific and medical conferences—including meetings hosted or sponsored by the Alzheimer's Association, the American Heart Association, and the National Institutes of Health.

Provided by Alzheimer's Association

Moderate coffee consumption may lower the risk of Alzheimer's disease by up to 20 percent, study suggests

Credit: George Hodan/public domain

29 nov 2014--Drinking 3-5 cups of coffee per day may help to protect against Alzheimer's Disease, according to research highlighted in an Alzheimer Europe session report published by the Institute for Scientific Information on Coffee (ISIC), a not-for-profit organisation devoted to the study and disclosure of science related to coffee and health.

The number of people in Europe aged over 65 is predicted to rise from 15.4% of the population to 22.4% by 20251 and, with an aging population, neurodegenerative diseases such as Alzheimer's Disease are of increasing concern. Alzheimer's Disease affects one person in twenty over the age of 65, amounting to 26 million people world-wide

Recent scientific evidence has consistently linked regular, moderate coffee consumption with a possible reduced risk of developing Alzheimer's Disease. An overview of this research and key findings were presented during a satellite symposium at the 2014 Alzhemier Europe Annual Congress.

The session report from this symposium highlights the role nutrition can play in preserving cognitive function, especially during the preclinical phase of Alzhemier's, before symptoms of dementia occur. The report notes that a Mediterranean diet, consisting of fish, fresh fruit and vegetables, olive oil and red wine, has been associated with a reduced risk for development of Alzheimer's Disease. Research suggests that compounds called polyphenols are responsible for this protective effect, these compounds are also found in high quantities in coffee.

Epidemiological studies have found that regular, life-long moderate coffee consumption is associated with a reduced risk of developing Alzheimer's Disease with the body of evidence suggesting that coffee drinkers can reduce their risk of developing the disease by up to 20%. A recent paper, suggested that moderate coffee consumption was associated with a lower risk of developing dementia over a four year follow-up period, however the effect diminished over longer follow up period.

Finally, the report explores the compounds within coffee, which may be responsible for this protective effect, identifying caffeine and polyphenols as key candidates. Caffeine helps prevent the formation of amyloid plaques and neurofibrulary tangles in the brain - two hallmarks of Alzheimer's Disease. In addition to this, both caffeine and polyphenols reduce inflammation and decrease the deterioration of brain cells - especially in the hippocampus and cortex, areas of the brain involved in memory.

Dr. Arfram Ikram, an assistant professor in neuroepidemiology at Erasmus Medical Centre Rotterdam, presented his findings at the symposium. He commented: "The majority of human epidemiological studies suggest that regular coffee consumption over a lifetime is associated with a reduced risk of developing Alzheimer's Disease, with an optimum protective effect occurring with three to five cups of coffee per day."

Dr. Iva Holmerova, vice chairperson of Alzheimer Europe, commented: "The findings presented in this report are very encouraging and help to develop our understanding of the role nutrition can play in protecting against Alzheimer's Disease. Coffee is a very popular beverage enjoyed by millions of people around the world and I'm pleased to know that moderate, lifelong consumption can have a beneficial effect on the development of Alzheimer's Disease."

The session report details the key scientific research presented by Dr. Neville Vassallo, Dr. Arfan Ikram and Dr. Astrid Nehlig during a session entitled: Nutrition and Cognitive Function, which took place on the 23rd October in Glasgow, UK.

Provided by Institute for Scientific Information on Coffee

Help beat Alzheimer's with the click of a mouse

UA researchers Lee Ryan (left) and Betty Glisky created an online memory test that they hope will provide data that helps them better understand Alzheimer's disease. Credit: Beatriz Verdugo/UANews

28 nov 2014--The ambitious MindCrowd project, which includes two UA researchers, aims to gather data from 1 million people across the globe.

If you've got 10 minutes and an Internet connection, you may be able to help researchers answer pressing questions about Alzheimer's disease.

As many as 5 million Americans are living with Alzheimer's, and while scientists are learning more about the disease every day, its exact cause remains unknown.

Researchers, including two neuropsychologists from the University of Arizona, are now leveraging the power of the Internet to collect information they hope will help them to better understand the human memory and possible risk factors for Alzheimer's.

The ambitious project, called MindCrowd, aims in its first phase to engage an unprecedented 1 million people across the globe in online memory testing. Anyone can take the test, which takes about 10 minutes to complete on the MindCrowd website.

Those who meet certain criteria in the first phase of testing may later be invited to participate in the project's second phase, which will include additional online memory tests, as well as genetic testing of participants' saliva.

Researchers ultimately hope to be able to identify genetic markers that are linked to learning and memory, which could be a major step toward understanding and treating Alzheimer's disease and other brain disorders.

A global reach

MindCrowd is a collaborative effort among the Translational Genomics Institute in Phoenix (also known as TGen), the UA and the Alzheimer's Prevention Initiative.

Professors Elizabeth Glisky, head of the UA psychology department, and Lee Ryan, associate head of the UA psychology department and associate director of the UA's Evelyn F. McKnight Brain Institute, developed the online test.

More than 50,000 people have taken the test as of this month, which is National Alzheimer's Disease Awareness Month.

"We're pretty excited about this. We don't know of anybody else who's done anything like this or been able to get this many people participating in a research study," said Glisky, also a member of the UA's Evelyn F. McKnight Brain Institute.

As many as 5 million Americans are living with Alzheimer's disaese. Researchers are using the Internet to conduct memory testing that may help them solve the puzzle of what causes the disease.

The MindCrowd website was created with the average Internet user in mind. Anyone can take the test from the comfort of home, and they will instantly see their results and how they stack up against others.

"We designed our study site from a marketing and user experience perspective, very much as if we were a business asking our customers to 'do something,' instead of designing it to look and feel like what it really is, a scientific study run by scientists who work in academia," said MindCrowd principal investigator Matt Huentelman, an associate professor in TGen's Neurogenomics Division. "That really is part of our success, I believe—the user experience was foremost in our mind because that would drive participation."

The MindCrowd test is now being translated into as many as 10 different languages to make it more accessible to people across the globe.

"Most studies are done in a confined area, but this is an opportunity to get data from all over the world," Glisky said. "Using the Internet, we have an opportunity to see across really large numbers of people with really different ages, different backgrounds, different histories, different everything. It really gives us an opportunity to look at a lot of variables that we can't look at as easily with a population that's confined to one region."

The study's cross-cultural findings could be a significant contribution to the Alzheimer's literature, Ryan said. "The majority of the studies out there focus on Caucasian individuals, so we don't really know as much about cognitive functioning in other groups."

Initial findings on gender, education, family history

The MindCrowd team already has some initial findings, which Huentelman presented last week during the Society for Neuroscience's annual meeting in Washington, D.C.

Among those findings: Women performed better on the memory test than men across all age groups, from 18 to 85. Individuals who reported having a higher level of education also tended to have higher scores. And people who reported having a family history of Alzheimer's disease scored consistently lower than those who did not report a family history of the disease.

"When you control for all other factors, you see that individuals with a family history of Alzheimer's disease do more poorly on the test, even in the youngest ages, and we're very interested in that," Ryan said.

Anyone can take the MindCrowd test, developed by UA researchers to collect information about the brain and memory.

The first-phase testing focuses only on verbal memory, asking participants to memorize word pairings. Phase-two tests, which also are being developed by Glisky and Ryan, will look at verbal, visual and spatial memory, for a broader scope.

Also during phase two, which is expected to launch sometime in the spring, TGen will conduct genetic testing of saliva samples mailed in by selected participants. Additional data will be collected through brain scans of certain participants, done at the UA.

"The ultimate goal is to figure out to what extent there is a genetic component here," Glisky said. "We know there are some genetic components but not one that's absolute."

The gene variant ApoE4 is a known genetic risk factor for Alzheimer's disease. However, not everyone with the gene variant will develop the disease, and not everyone who develops the disease has the gene variant.

"A significant number of people—about half—with a family history of Alzheimer's are not E4 positive, so it's a mystery," Ryan said. "Maybe there's another specific gene that nobody's found yet, or it's a cluster of genes or some combination or profile of genes. You would need really large numbers of people to find those kinds of patterns, so we're pretty excited about exploring that."

By evaluating the memory test results alongside genetic data, the researchers also will be able to look at possible relationships between genetics and demographic or environmental factors, Glisky said.

"The answers to the questions about Alzheimer's disease are going to be very complicated," she said. "So far, we haven't been wildly successful at coming up with treatments, and that is at least partly because we don't fully understand the disease and the factors that are involved."

Using the Internet to crowdsource such a large and diverse number of study participants hopefully will give researchers enough data to start answering some of the many questions that remain about Alzheimer's, Glisky said.

"I think this study could lead towards improved genetic treatments, drug treatments, environmental treatments, cognitive treatments, behavioral interventions down the road," she said. "It could be the first step to be able to think about prevention and treatment."

Provided by University of Arizona

New Alzheimer's-related memory disorder identified

Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

14 nov 2014--A multi-institutional study has defined and established criteria for a new neurological disease closely resembling Alzheimer's disease called primary age-related tauopathy (PART). Patients with PART develop cognitive impairment that can be indistinguishable from Alzheimer's disease, but they lack amyloid plaques. Awareness of this neurological disease will help doctors diagnose and develop more effective treatments for patients with different types of memory impairment.

The study, co-led by Peter T. Nelson, MD, PhD, of the University of Kentucky's Sanders-Brown Center on Aging, and John F. Crary, MD, PhD, of Columbia University Medical Center, was published in the current issue of Acta Neuoropathologica.

"To make an Alzheimer's diagnosis you need to see two things together in a patient's brain: amyloid plaques and structures called neurofibrillary tangles composed of a protein called tau," said Dr. Nelson, a professor of neuropathology at the University of Kentucky's Sanders-Brown Center on Aging. "However, autopsy studies have demonstrated that some patients have tangles but no plaques and we've long wondered what condition these patients had."

Plaques in the brain, formed from the accumulation of amyloid protein, are a hallmark of Alzheimer's disease. Until now, researchers have considered cases with only tangles to be either very early-stage Alzheimer's or a variant of the disease in which the plaques are harder to detect. However, previous in-depth biochemical and genetic studies have failed to reveal the presence of any abnormal amyloid in these patients. Although tangle-only patients can have memory complaints, the presence of plaques is a key requirement for an Alzheimer's diagnosis.

In the current study, investigators from the United States (including five from Sanders-Brown), Canada, Europe, and Japan came together to formalize criteria for diagnosing this new neurological disorder. The study establishes that PART is a primary tauopathy, a disease directly caused by the tau protein in tangles. Many of the neurofibrillary tangles in Alzheimer's brain, in contrast, are thought to arise secondarily to amyloid or some other stimuli. The researchers propose that individuals who have tangles resembling those found in Alzheimer's but have no detectable amyloid plaques should now be classified as PART  is most severe in patients of advanced age, but is generally mild in younger elderly individuals. The reason for this is currently unknown, but unlike Alzheimer's disease, in which the tangles spread throughout the brain, in PART cases the tangles are restricted mainly to structures important for memory.

It is too early to tell how common PART is, but given that tangles are nearly universal in the brains of older individuals, it might be more widespread than generally recognized. While further studies are required, new diagnostic tests using brain scans and cerebrospinal fluid biomarkers for amyloid and tau are finding surprisingly high proportions of patients (as many as 25% in some studies) with mild cognitive impairment that are positive for tau but negative for amyloid.

"Until now, PART has been difficult to treat or even study because of lack of well-defined criteria," said Dr. Nelson. "Now that the scientific community has come to a consensus on what the key features of PART are, this will help doctors diagnose different forms of memory impairment early. These advancements will have a big impact on our ability to recognize and develop effective treatments for brain diseases seen in older persons."

Identifying the type of neurological disorder in the early stages of disease is critical if treatment is to begin before irreparable brain damage has occurred. However, in the absence of clear criteria, different forms of neurological disorders have been hard to distinguish. As a result, PART patients may have confounded clinical trials of amyloid-targeting drugs for Alzheimer's disease as these treatments are unlikely to be effective against tangles. Along with the development of better biomarkers and genetic risk factors for dementia, the new diagnosis criteria will help PART patients to receive more targeted therapy and improve the accuracy of clinical trials for Alzheimer's drugs.

Provided by University of Kentucky

Alzheimer's patients can still feel the emotion long after the memories have vanished

Jade Angelica, founder and director of Healing Moments Alzheimer’s Ministry in Dubuque, Iowa, considers caring for her mother, Jeanne, to be the most important work of her life. Jade’s mother died from Alzheimer’s in 2011. Jade is author of the book "Where Two Worlds Touch: A Spiritual Journey Through Alzheimer's Disease." Edmarie Guzman-Velez and her colleagues reference Jade’s book in their research paper, “Feelings Without Memory in Alzheimer Disease” published in the journal Cognitive and Behavioral Neurology. Credit: Jade Angelica.

A new University of Iowa study further supports an inescapable message: caregivers have a profound influence—good or bad—on the emotional state of individuals with Alzheimer's disease. Patients may not remember a recent visit by a loved one or having been neglected by staff at a nursing home, but those actions can have a lasting impact on how they feel.

26 sept 2014--The findings of this study are published in the September 2014 issue of the journal Cognitive and Behavioral Neurology, and can be viewed online for free here.

UI researchers showed individuals with Alzheimer's disease clips of sad and happy movies. The patients experienced sustained states of sadness and happiness despite not being able to remember the movies.

"This confirms that the emotional life of an Alzheimer's patient is alive and well," says lead author Edmarie Guzmán-Vélez, a doctoral student in clinical psychology, a Dean's Graduate Research Fellow, and a National Science Foundation Graduate Research Fellow.

Guzmán-Vélez conducted the study with Daniel Tranel, UI professor of neurology and psychology, and Justin Feinstein, assistant professor at the University of Tulsa and the Laureate Institute for Brain Research.

Tranel and Feinstein published a paper in 2010 that predicted the importance of attending to the emotional needs of people with Alzheimer's, which is expected to affect as many as 16 million people in the United States by 2050 and cost an estimated $1.2 trillion.

"It's extremely important to see data that support our previous prediction," Tranel says. "Edmarie's research has immediate implications for how we treat patients and how we teach caregivers."

This is a coronal view of the hippocampus brain region of a patient with Alzheimer’s disease. Credit: Daniel Tranel's Laboratory at the UI's Department of Neurology.

Despite the considerable amount of research aimed at finding new treatments for Alzheimer's, no drug has succeeded at either preventing or substantially influencing the disease's progression. Against this foreboding backdrop, the results of this study highlight the need to develop new caregiving techniques aimed at improving the well-being and minimizing the suffering for the millions of individuals afflicted with Alzheimer's.

For this behavioral study, Guzmán-Vélez and her colleagues invited 17 patients with Alzheimer's disease and 17 healthy comparison participants to view 20 minutes of sad and then happy movies. These movie clips triggered the expected emotion: sorrow and tears during the sad films and laughter during the happy ones.

About five minutes after watching the movies, the researchers gave participants a memory test to see if they could recall what they had just seen. As expected, the patients with Alzheimer's disease retained significantly less information about both the sad and happy films than the healthy people. In fact, four patients were unable to recall any factual information about the films, and one patient didn't even remember watching any movies.

Before and after seeing the films, participants answered questions to gauge their feelings. Patients with Alzheimer's disease reported elevated levels of either sadness or happiness for up to 30 minutes after viewing the films despite having little or no recollection of the movies.

Quite strikingly, the less the patients remembered about the films, the longer their sadness lasted. While sadness tended to last a little longer than happiness, both emotions far outlasted the memory of the films.

The fact that forgotten events can continue to exert a profound influence on a patient's emotional life highlights the need for caregivers to avoid causing negative feelings and to try to induce positive feelings.

"Our findings should empower caregivers by showing them that their actions toward patients really do matter," Guzmán-Vélez says. "Frequent visits and social interactions, exercise, music, dance, jokes, and serving patients their favorite foods are all simple things that can have a lasting emotional impact on a patient's quality of life and subjective well-being."

Provided by University of Iowa

Diametric shift in 2 protein levels spurs Alzheimer's plaque accumulation

A diametric shift in the levels of two proteins involved in folding, moving and cutting other proteins enables accumulation of the destructive brain plaque found in Alzheimer's disease, researchers report.

03 dec 2011--VPS35 is a protein that folds others into specific positions to unleash their functions. When levels are reduced as they are in aging, it unleashes the normally dormant BACE1, a protein responsible for beta amyloid plaque production, Georgia Health Sciences University researchers report in The Journal of Cell Biology.

When researchers modified a mouse model of Alzheimer's so that VPS35 production was essentially cut in half, BACE1 activity was increased, accelerating aging and development of related problems such as memory deficits and poor communication between brain cells as well as beta amyloid accumulation, said Dr. Wen-Cheng Xiong, developmental neurobiologist and Weiss Research Professor at GHSU and the study's corresponding author.

It was known that expression of VPS35 was down and BACE1 was up in Alzheimer's but the direct relationship was unknown, Xiong said. "We believe impaired function of VPS35 could be a risk factor for Alzheimer's and Parkinson's diseases," Xiong said. Discovering the relationship makes VPS35 a potential biomarker for the diseases as well as a target for new therapies to keep VPS35 elevated. The accelerated aging model Xiong developed and patented will enable these future drug studies.

This unhealthy balance causes cells to accumulate more waste than their recycling systems can handle. Additionally misfolded proteins end up in the wrong cell compartment where they form aggregates that eventually kill the cell. Being in the wrong place is what enables BACE1 activity to increase: it ends up stuck in a cell compartment called the endosome where high acidity levels activate the protein. As BACE1 becomes more numerous and active, it chops up more potentially productive proteins, turning them into garbage.

"Each protein knows its destination, lifespan and when it should be degraded; everything is controlled. With aging, their trafficking, their control system is disrupted," Xiong said.

Future questions include what reduces VPS35 levels, such as increased levels of reactive oxygen species that come with age, and whether exercise can help keep them up. 'We think VPS35 will be a new, hot and hopefully productive area for Alzheimer's and Parkinson's research," Xiong said.

The protein is classified a retromer. Retromers are important to recycling inside cells. While silent in healthy adults, BACE1 plays an important role in brain development.

Provided by Georgia Health Sciences University

Insulin may slow Alzheimer's, study finds

Inhaling a concentrated cloud of insulin through the nose twice a day appears to slow - and in some cases reverse - symptoms of memory loss in people with early signs of Alzheimer's disease, a new pilot study has found.

26 sept 2011--The study involved only 104 people and is considered very preliminary. But it suggests that a safe, simple and cheap measure that boosts flagging metabolism in key areas of the brain could hold off or possibly derail the progression of the devastating neurological disorder in its early stages. The results were published online Monday by the journal Archives of Neurology.

Insulin is a metabolic hormone best known for its role in treating diabetes, a condition in which the hormone is either insufficiently produced or poorly used by the body's organs. But in recent years, studies have found that people with diabetes and prediabetes are at heightened risk of developing Alzheimer's, and autopsies have shown that diabetics whose condition was tightly managed had fewer of the brain tangles and plaques that are the hallmark of disease. Studies involving animals have suggested that insulin deficiency in the brain may be a key factor in the progression of Alzheimer's.

Researchers from the Veterans Affairs' Puget Sound Health Care System in Washington state decided to test insulin on people without diabetes who had been diagnosed with mild to moderate Alzheimer's or amnestic mild cognitive impairment, a disorder characterized by increased forgetfulness that often progresses to dementia. Study participants were divided into three groups: 36 of them inhaled 20 milligrams of insulin twice a day for four months, 38 got 40 mg twice a day, and 30 were given a saline solution.

After two months of treatment, those treated with 20 mg of insulin had improved performance on a memory test. The gains persisted after four months of treatment and were still evident two months after the insulin treatment stopped.

Patients who got the higher dose of insulin had no change in their memory abilities, while those who got the placebo saw a decline. The differences between those on insulin and those on the placebo were "small in absolute terms," the authors wrote. But they were robust enough that by generally accepted research standards, they are unlikely to have been the result of chance.

Subjects taking either dose of insulin were rated by their caregivers as holding steady in their overall social, mental and everyday functioning, while those on the sham medication were rated as having declined. And on physician-administered tests of cognitive function, subjects taking insulin showed less decline than those on the placebo.

In a subset of subjects who underwent additional measurements, researchers found that there were fewer amyloid plaque deposits, protein tangles and other physiological hallmarks of Alzheimer's in those whose memory improved most on the insulin treatment compared with those who had weak responses or were on the placebo.

But the persistence of insulin's effect was a mixed picture. Two months after the insulin treatments stopped, caregivers of subjects in all three groups noted similar declines in their overall daily function.

Dr. Jacobo Mintzer, an Alzheimer's expert at the Medical University of South Carolina in Charleston who was not involved in the study, hailed the research as "a new way of thinking" about treating dementia.

"As a clinician, I would not tell my patients to get their hopes up," he said. "But as a scientist, I always get very encouraged when the paradigm shifts," as he said it has here.

An estimated 5.4 million Americans are believed to have Alzheimer's, according to the Alzheimer's Association. Scientists acknowledge that while they can diagnose the disease earlier and offer medications to temporarily slow the progression of symptoms, they have been stymied in their search for ways to prevent, halt or reverse it.

It will take a larger study involving more patients over a longer time to figure out whether nasally administered insulin merely slows the march of Alzheimer's or thwarts it, said Laurie Ryan, a neuropsychologist who directs clinical trials involving dementia at the National Institute on Aging, which funded the pilot study.

In the meantime, she said, intranasal insulin has two things going for it: Insulin is already in wide use at relatively low cost, and the nasal inhaler allows it to be delivered directly and safely to the brain. That minimizes the risk of the hormone affecting blood sugar levels elsewhere in the body, which could be dangerous to kidneys, eyes and blood vessels.

"A safe, easy delivery system - those are things we'd love to see for any kind of treatment for Alzheimer disease," she said.

Time to clear up misconceptions about Alzheimer's

Many age-related changes that may lead to Alzheimer’s disease can be greatly minimized by lifestyle changes that favor healthy diets, physical exercise, reduced exposure to toxins, lowered psychosocial stress, purposeful social interaction, and better protection from and treatment of traumatic brain injuries.

19 aug 2011--The general perception of Alzheimer’s disease, including the dominant theory about what causes it, needs to shift, according to an editorial co-written by a Penn State College of Medicine faculty member. In “Changing Perspectives on Alzheimer’s Disease: Thinking Outside the Amyloid Box,” Penn State College of Medicine’s Daniel George, said the common belief that scientists will soon conquer the disease is a misconception.

“What people commonly hear about Alzheimer’s disease is that a classic American success story is destined to unfold,” George said. “They hear that in the near future, biotechnology will soon conquer this scourge of the elderly, this stealer of decades that has become a growing global epidemic. Unfortunately, the scientific story is a bit more complicated.”

The editorial was published in the July issue of Journal of Alzheimer’s Disease.

The current dominant scientific theory as to the causation of Alzheimer’s disease assumes that toxic amyloid protein plaques in the brain are the causes of neuronal death. But George and fellow study author Simon D’Alton, University of Florida say this theory is proving to be an unsustainable premise.

“There are many heavily age-related factors that affect the brain negatively and occur prior to the appearance of these so-called toxic plaques,” George explained. “What this means is that Alzheimer’s disease is not caused by one thing, like toxic proteins, but is multi-factorial and far more complicated than originally thought. We can’t continue to treat Alzheimer’s disease as if it were a singular condition, like a virus; this is not an honest portrayal.”

George said the reason for nearly 20 drug trial failures in the past decade is due to being trapped in the ‘amyloid box’— trying to remove ‘toxic’ proteins without addressing the real causes that precede them.

“This is like an oil company responding to a spill by having workers scrub petroleum off the shoreline rather than managing the upstream processes and procedures that could have slowed or prevented the spill and spread of oil,” he said. “We also don’t know what the role of amyloid is in the brain. There is much evidence to support amyloid actually being protective rather than just toxic.”

Since the processes leading to Alzheimer’s disease are not understood, it is unlikely that a profound therapy will be produced in the next 20 years, the scientists say. Instead, they say, a shift in approach that reflects the true nature of Alzheimer’s as a chronic, multifaceted, decades-long ‘syndrome’ caused by gradual dysfunction of the aging body is needed. Many of these age-related changes can be greatly minimized by lifestyle changes that favor healthy diets, physical exercise, reduced exposure to toxins, lowered psychosocial stress, purposeful social interaction, and better protection from and treatment of traumatic brain injuries.

“Individuals need to know that they can increase their chances of maintaining a healthy brain as they age by taking these steps across their life course, and that help in the form of a pill or vaccine is unlikely to be realized in the near future,” George said. “Such an understanding can help people protect their aging brain and the brains of those they love and live amongst. Moreover, as we are all susceptible to aging processes, we should feel greater solidarity with those more severely affected by the changes of brain aging, who we can help in finding purpose, valued social roles, and acceptance rather than the stigma, marginalization, and fear fomented by the fading disease model.”

Provided by Pennsylvania State University

Falls may be early sign of Alzheimer's

Falls and balance problems may be early indicators of Alzheimer’s disease, researchers at Washington University School of Medicine in St. Louis report July 17, 2011, at the Alzheimer’s Association International Conference on Alzheimer’s Disease in Paris.

24 july 2011--Scientists found that study participants with brain changes suggestive of early Alzheimer’s disease were more likely to fall than those whose brains did not show the same changes. Until now, falls had only been associated with Alzheimer’s in the late stages of dementia.

“If you meet these people on the street, they appear healthy and have no obvious cognitive problems,” says lead author Susan Stark, PhD, associate professor of physical therapy and neurology. “But they have changes in their brain that look similar to Alzheimer‘s disease, and they have twice the typical annual rate of falls for their age group.”

Stark and her colleagues recruited 119 volunteers from studies of aging and health at Washington University’s Knight Alzheimer’s Disease Research Center. All the participants were 65 or older and cognitively normal.

Brain scans showed that 18 participants had high levels of amyloid plaques, a hallmark of Alzheimer's. The other 101 volunteers had normal amyloid levels in the brain.

Participants were given a journal and asked to note any falls. When they did so, the researchers followed up with a questionnaire and a phone interview about the falls. This follow-up allowed researchers to gather information for future analyses that will compare and contrast the nature of the falls.

About one in three adults age 65 or older typically fall each year. But in the 18 participants with high amyloid levels in the brain, two-thirds fell within the first eight months of the study. High levels of amyloid in the brain were the best predictor of an increased risk of falls.

“Falls are a serious health concern for older adults,” Stark says. “Our study points to the notion that we may need to consider preclinical Alzheimer’s disease as a potential cause.”

Provided by Washington University School of Medicine in St. Louis

Using MRI, researchers may predict which adults will develop Alzheimer's

Using MRI, researchers may be able to predict which adults with mild cognitive impairment are more likely to progress to Alzheimer's disease, according to the results of a study published online and in the June issue of Radiology.

07 april 2011--Mild cognitive impairment (MCI) is an intermediate stage between the decline in mental abilities that occurs in normal aging and the more pronounced deterioration associated with dementia, a group of brain disorders that includes Alzheimer's disease (AD).

Individuals with MCI develop AD at a rate of 15 to 20 percent per year, which is significantly higher than the one to two percent rate for the general population. Some people with MCI remain stable while others gradually decline and some quickly deteriorate.

"Being able to better predict which individuals with MCI are at greatest risk for developing Alzheimer's would provide critical information if disease-modifying therapies become available," said the study's lead author, Linda K. McEvoy, Ph.D., assistant professor in the Department of Radiology at the University of California, San Diego School of Medicine.

Dr. McEvoy and a team of researchers analyzed MRI exams from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large publicly and privately sponsored study, which performed imaging and other tests on hundreds of healthy individuals and others with MCI and early AD between 2005 and 2010 in hopes of identifying valuable biomarkers of the disease process.

Included in the study were a baseline MRI exam, serving as an initial point of measurement, and a second MRI performed a year later on 203 healthy adults, 317 patients with MCI and 164 patients with late-onset AD. The average age of the study participants was 75.

Using MRI, the researchers measured the thickness of the cerebral cortex — the outermost layer of the cerebral hemispheres of the brain that plays a key role in memory, attention, thought and language — and observed the pattern of thinning to compute a risk score. One of the characteristics of AD is a loss of brain cells, called atrophy, in specific areas of the cortex.

"MRI is very sensitive to brain atrophy," Dr. McEvoy said. "There's a pattern of cortical thinning associated with AD that indicates the patient is more likely to progress to AD."

Using the baseline MRI, the researchers calculated that the patients with MCI had a one-year risk of conversion to AD ranging from three to 40 percent.

"Compared to estimating a patient's risk of conversion based on a clinical diagnosis only, MRI provides substantially more informative, patient-specific risk estimates," Dr. McEvoy said. "The baseline MRI helped identify which patients were at very low risk of progressing to Alzheimer's and those whose risk was doubled."

By combining results of the baseline MRI and the MRI exam performed one year later, the researchers were able to calculate a rate of change in brain atrophy that was even more informative. The MCI patients' risk of disease progression based on the serial MR exams ranged from 3 to 69 percent.

"Rapid thinning of the cortex is reflective of a degenerative disorder," Dr. McEvoy explained.

Although no treatments currently exist that slow or prevent the neurodegeneration associated with AD, Dr. McEvoy said patients at high risk of progressing to AD might want to enroll in clinical trials of disease-modifying therapies. She said the information would also help ensure patients receive optimal care and allow families more time for planning.

More information: "Mild Cognitive Impairment: Baseline and Longitudinal Structural MR Imaging Measures Improve Predictive Prognosis." Collaborating with Dr. McEvoy were Dominic Holland, Ph.D., Donald J. Hagler, Jr., Ph.D., Christine Fennema-Notestine, Ph.D., James B. Brewer, M.D., Ph.D., and Anders M. Dale, Ph.D. http://radiology.rsna.org/

Provided by Radiological Society of North America

Subjects at risk of Alzheimer's may now be able to delay the onset of their first symptoms

For elderly subjects at risk of developing Alzheimer's disease, research shows that hope may lie in brain plasticity.

25 mar 2011--The human brain loses 5 to 10% of its weight between the ages of 20 and 90 years old. While some cells are lost, the brain is equipped with two compensatory mechanisms: plasticity and redundancy. Based on the results of her most recent clinical study published today in the online version of Brain: A Journal of Neurology, Dr. Sylvie Belleville, PhD in neuropsychology, the principal author of this study and Director of Research at the Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated with the Université de Montréal, has found that for elderly subjects at risk of developing Alzheimer's disease, hope may lie in brain plasticity.

"Brain plasticity refers to the brain's remarkable ability to change and reorganize itself. It was long thought that brain plasticity declined with age, however, our study demonstrates that this is not the case, even in the early stages of Alzheimer's disease", declares Sylvie Belleville.

These findings open countless new avenues of research including the possibility of improving the plasticity of affected areas of the brain, and slowing the decline in plasticity through pharmacological means or lifestyle changes, thereby allowing subjects with Alzheimer's disease to enjoy several more symptom-free years.

The hypothesis behind this research was that certain cells traditionally involved in other brain processes could, through a simple memory training program, temporarily take over since they themselves are not yet affected. According to Dr. Belleville: "Our research has validated our hypothesis. Not only were we able to use functional imaging to observe this diversification, but we also noted a 33% increase in the number of correct answers given during a post-training memory task by subjects with mild cognitive impairment (MCI) who, incidentally, are ten times more likely to develop Alzheimer's disease".

The training program that was used was designed to help elderly subjects with MCI develop strategies, such as the use of mnemonics, for example, and promote encoding and retrieval, such as word lists, for example, using alternative areas of the brain. "The hypothesis had already been raised, but our team was the first to provide scientific support, using a functional neuroimaging protocol", added Sylvie Belleville.

Researchers worked with thirty elderly subjects: 15 healthy adults and 15 with MCI. Magnetic resonance imaging was used to analyse brain activity in the two groups 6 weeks prior to memory training, one week prior to training and one week after training. Before the memory training, magnetic resonance imaging in both the healthy elderly subjects and those with MCI showed activation in areas of the brain traditionally associated with memory. As expected, decreased activation was observed in subjects with MCI. After training, brain areas in elderly subjects with MCI showed increased activation in areas typically associated with memory, but also in new areas of the brain usually associated with language processing, spatial and object memory and skill learning.

According to Dr. Belleville: "Analysis of brain activity during encoding as measured before and after the training program, indicates that increased post-training activation in the right inferior parietal gyrus is associated with post-intervention improvement. The healthy area of the brain has taken over for the area that is compromised."

Provided by University of Montreal

Fast, accurate test for Alzheimer's

Scientists at the National Institute for Health Research’s (NIHR) Biomedical Research Centre for Mental Health at the King’s College London Institute of Psychiatry (IoP) and South London and Maudsley NHS Foundation Trust (SLaM) are the first to use an advanced computer program to accurately detect the early signs of Alzheimer's disease from a routine clinical brain scan. The new scan can return 85 per cent accurate diagnostic results in under 24 hours.

10 mar 2011--The 'Automated MRI' software automatically compares or benchmarks someone’s brain scan image against 1200 others, each showing varying stages of Alzheimer’s disease. This collection of images is thought to be the largest of its kind in the world.

Normally in routine clinical practice, brain scans are used to simply exclude diseases that can mimic Alzheimer’s disease, but here automated MRI software is being used for the first time in a NHS setting (Memory Clinics) to make an early and accurate diagnosis of the illness.

Early diagnosis

Early diagnosis of Alzheimer's is clinically difficult and patients with the early signs are frequently not treated until their symptoms become stronger. The new scan however can return 85 per cent accurate diagnostic results in under 24 hours.

An early diagnosis allows someone to plan their care before the condition worsens - helping to prevent institutionalisation, dramatically improving their quality of life. It is also a cost effective and efficient way to manage and organise treatment of the disease.

The scan has been developed by scientists at the IoP, together with colleagues from the Karolinska Hospital in Stockholm.

The system is being 'field tested' over the next 12 months with patients attending SLaM memory services in Croydon, Lambeth and Southwark. The ‘field test’ will also provide a supply of research grade images, which has important implications for the development of the next generation of drugs for dementia and individualised treatments.

There are 750,000 people with dementia in the UK. The financial cost of dementia to the UK is over £20 billion a year. According to the Alzheimer’s Society, in just 15 years a million people will be living with dementia. This will soar to 1.7 million people by 2051.

Provided by King's College London

Speaking 2 languages may delay getting Alzheimer's

Mastering a second language can pump up your brain in ways that seem to delay getting Alzheimer's disease later on, scientists said Friday.

19 feb 2011--Never learned to habla or parlez? While the new research focuses mostly on the truly long-term bilingual, scientists say even people who tackle a new language later in life stand to gain.

The more proficient you become, the better, but "every little bit helps," said Ellen Bialystok, a psychology professor at York University in Toronto.

Much of the study of bilingualism has centered on babies, as scientists wondered why simply speaking to infants in two languages allows them to learn both in the time it takes most babies to learn one. Their brains seem to become more flexible, better able to multitask. As they grow up, their brains show better "executive control," a system key to higher functioning - as Bialystok puts it, "the most important part of your mind."

But does that mental juggling while you're young translate into protection against cognitive decline when you're old?

Bialystok studied 450 Alzheimer's patients, all of whom showed the same degree of impairment at the time of diagnosis. Half are bilingual - they've spoken two languages regularly for most of their lives. The rest are monolingual.

The bilingual patients had Alzheimer's symptoms and were diagnosed between four and five years later than the patients who spoke only one language, she told the annual meeting of the American Association for the Advancement of Science.

Being bilingual does nothing to prevent Alzheimer's disease from striking. But once the disease does begin its silent attack, those years of robust executive control provide a buffer so that symptoms don't become apparent as quickly, Bialystok said.

"They've been able to cope with the disease," she said.

Her work supports an earlier study from other researchers that also found a protective effect.

What is it about being bilingual that enhances that all-important executive control system?

Both languages are essentially turned on all the time, but the brain learns to inhibit the one you don't need, said psychology professor Teresa Bajo of the University of Granada in Spain. That's pretty constant activity.

That's not the only area. University of British Columbia psychologist Janet Werker studies infants exposed to two languages from birth to see why they don't confuse the two, and says bilingual babies learn very early to pay attention better.

Werker tested babies in Spain who were growing up learning both Spanish and Catalan. She showed the babies videos of women speaking languages they'd never heard - English and French - but with the sound off. By measuring the tots' attention span, Werker concluded that babies could distinguish between English and French simply by watching the speakers' facial cues. It could have been the different lip shapes.

"It looks like French people are always kissing," she joked, while the English "th" sound evokes a distinctive lip-in-teeth shape.

Whatever the cues, monolingual babies couldn't tell the difference, Werker said Friday at the meeting.

But what if you weren't lucky enough to be raised bilingual? Scientists and educators know that it becomes far harder to learn a new language after puberty.

Partly that's because adults' brains are so bombarded with other demands that we don't give learning a new language the same attention that a young child does, Bialystok said.

At the University of Maryland, scientists are studying how to identify adults who would be good candidates to master a new language, and then what types of training are best. Having a pretty strong executive control system, like the lifelong bilinguals have, is among the good predictive factors, said Amy Weinberg, deputy director of the university's Center for Advanced Study of Language.

But people don't have to master a new language to benefit some, Bialystok said. Exercising your brain throughout life contributes to what's called cognitive reserve, the overall ability to withstand the declines of aging and disease. That's the basis of the use-it-or-lose-it advice from aging experts who also recommend such things as crossword puzzles to keep your brain nimble.

"If you start to learn at 40, 50, 60, you are certainly keeping your brain active," she said.

More information: Science meeting: http://www.aaas.org/meetings/

Combining brain imaging, genetic analysis may help identify people at early risk of Alzheimer's

A new study from the Centre for Addiction and Mental Health (CAMH) has found evidence suggesting that a variation of a specific gene may play a role in late-onset Alzheimer's, the disease which accounts for over 90% of Alzheimer's cases. This innovative study has combined genetics and brain imaging to determine who may be at risk for developing late-onset Alzheimer's disease long before symptoms appear.

09 feb 2011--The gene, which is called brain-derived neurotrophic factor (BDNF), is crucial to maintaining healthy function of the brain, primarily the brain's memory centre of the hippocampus and entorhinal cortex, and is responsible for learning and memory function. Past research has found that less BDNF is present in the memory centre of those diagnosed with Alzheimer's disease. However genetic association studies alone have not produced definite findings regarding this gene. Instead, a combination of genetics and brain imaging were used to demonstrate clear effects of this gene in the brain.

In the study published today in the Archives of General Psychiatry, a variation of the BDNF gene called val66met, was tracked and examined in healthy individuals to see what effect it had on the brain. Genotyping was used to determine which study participants carried the gene variation. Then two types of brain imaging -- high-resolution magnetic resonance imaging (MRI) cortical thickness mapping and diffusion tensor imaging (DTI) (an MRI-based technique that measures key structural connections in the brain)-- were applied to measure the physical structures of the brain in each individual. This combination of genetic screening and imaging found that BDNF val66met gene variation influenced exactly those brain structures and connections that deteriorate at the earliest phases of Alzheimer's disease.

"Our sample consisted of healthy adults who passed all cognitive testing and displayed no clinical symptoms of Alzheimer's disease, yet the brains of those who carried the gene variation had differences in their brain structures consistent with changes we see in people at the earliest stages of Alzheimer's disease," said Dr. Aristotle Voineskos, physician and scientist at CAMH, and principal investigator of the study.

Participants who carried the variation were more likely to have thinner temporal lobe structures and disrupted white matter tract connections leading into the temporal lobe - the same structures and neural networks that have deteriorated in the brains of Alzheimer's patients when their brains are examined post-mortem.

"In the past, Alzheimer's disease could only be diagnosed and treated once outward symptoms became present," added Dr. Voineskos. "Early identification is key because, in addition to seeking therapeutic treatments early to reduce suffering, delaying Alzheimer's onset by only two years has the potential of saving the Canadian health care system nearly $15 billion over the next 10 years. The combination of brain imaging and genetics is a key approach that may help us to identify people at risk for Alzheimer's disease."

This breakthrough in image-genetics research can be valuable in the research of other brain diseases and will enable researchers to examine how a gene affects the brain and possibly intervene before a person develops an illness.

Provided by Centre for Addiction and Mental Health