Diabetes and Depression Predict Dementia Risk in People with Slowing Minds

(University College London) People with mild cognitive impairment are at higher risk of developing dementia if they have diabetes or psychiatric symptoms such as depression, finds a new review led by UCL researchers.

Mild cognitive impairment (MCI) is a state between normal ageing and dementia, where someone’s mind is functioning less well than would be expected for their age. It affects 19% of people aged 65 and over, and around 46% of people with MCI develop dementia within 3 years compared with 3% of the general population.

The latest review paper, published in the American Journal of Psychiatry, analysed data from 62 separate studies, following a total of 15,950 people diagnosed with MCI. The study found that among people with MCI, those with diabetes were 65% more likely to progress to dementia and those with psychiatric symptoms were more than twice as likely to develop the condition.

“There are strong links between mental and physical health, so keeping your body healthy can also help to keep your brain working properly,” explains lead author Dr Claudia Cooper (UCL Psychiatry).

“Lifestyle changes to improve diet and mood might help people with MCI to avoid dementia, and bring many other health benefits.

This doesn’t necessarily mean that addressing diabetes, psychiatric symptoms and diet will reduce an individual’s risk, but our review provides the best evidence to date about what might help.”

The Alzheimer’s Society charity recommends that people stay socially and physically active to help prevent dementia. Their guidelines also suggest eating a diet high in fruit and vegetables and low in meat and saturated fats, such as the Mediterranean diet.

“Some damage is already done in those with MCI but these results give a good idea about what it makes sense to target to reduce the chance of dementia,” says senior author Professor Gill Livingston (UCL Psychiatry). “Randomised controlled trials are now needed.”

Professor Alan Thompson, Dean of the UCL Faculty of Brain Sciences, says:

“This impressive Systematic Review and meta-analysis from The Faculty of Brain Science’s Division of Psychiatry underlines two important messages.

Firstly, the impact of medical and psychiatric co-morbidities in individuals with mild cognitive impairment and secondly, the importance and therapeutic potential of early intervention in the prevention of dementia.

Confirming these findings and incorporating appropriate preventative strategies could play an important part in lessening the ever-increasing societal burden of dementia in our ageing population.”



Journal Reference:

Claudia Cooper, Andrew Sommerlad, Constantine G. Lyketsos, Gill Livingston. Modifiable Predictors of Dementia in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis. American Journal of Psychiatry, 2015; appi.ajp.2014.1 DOI: 10.1176/appi.ajp.2014.14070878

© UCL 1999–2015


Compound Found in Grapes, Red Wine May Help Prevent Memory Loss

(Texas A&M University) A compound found in common foods such as red grapes and peanuts may help prevent age-related decline in memory, according to new research published by a faculty member in the Texas A&M Health Science Center College of Medicine.

Ashok K. Shetty, Ph.D., a professor in the Department of Molecular and Cellular Medicine and Director of Neurosciences at the Institute for Regenerative Medicine, has been studying the potential benefit of resveratrol, an antioxidant that is found in the skin of red grapes, as well as in red wine, peanuts and some berries.

Resveratrol has been widely touted for its potential to prevent heart disease, but Shetty and a team that includes other researchers from the health science center believe it also has positive effects on the hippocampus, an area of the brain that is critical to functions such as memory, learning and mood.

Because both humans and animals show a decline in cognitive capacity after middle age, the findings may have implications for treating memory loss in the elderly. Resveratrol may even be able to help people afflicted with severe neurodegenerative conditions such as Alzheimer’s disease.

In a study published online Jan. 28 in Scientific Reports, Shetty and his research team members reported that treatment with resveratrol had apparent benefits in terms of learning, memory and mood function in aged rats.

“The results of the study were striking,” Shetty said. “They indicated that for the control rats who did not receive resveratrol, spatial learning ability was largely maintained but ability to make new spatial memories significantly declined between 22 and 25 months. By contrast, both spatial learning and memory improved in the resveratrol-treated rats.”

Shetty said neurogenesis (the growth and development of neurons) approximately doubled in the rats given resveratrol compared to the control rats. The resveratrol-treated rats also had significantly improved microvasculature, indicating improved blood flow, and had a lower level of chronic inflammation in the hippocampus.

“The study provides novel evidence that resveratrol treatment in late middle age can help improve memory and mood function in old age,” Shetty said.

This study was funded primarily by the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health. Shetty’s lab is now examining the molecular mechanisms that underlie the improved cognitive function following resveratrol treatment. He also plans to conduct studies to see whether lower doses of resveratrol in the diet for prolonged periods would offer similar benefits to the aged brain.


Ellen Davis


Journal Reference:

  1. Maheedhar Kodali, Vipan K. Parihar, Bharathi Hattiangady, Vikas Mishra, Bing Shuai, Ashok K. Shetty. Resveratrol Prevents Age-Related Memory and Mood Dysfunction with Increased Hippocampal Neurogenesis and Microvasculature, and Reduced Glial Activation. Scientific Reports, 2015; 5: 8075 DOI: 10.1038/srep08075

Copyright 2015 Texas A & M University

Mediterranean Diet Fights Stroke Risk

(MedPageToday) Women who most closely adhered to a Mediterranean-style diet — high in vegetables, whole grains, and healthy fats and low in meat, dairy and sugar — had a lower risk of ischemic, but not hemorrhagic stroke, researchers reported here.

Mediterranean-DietThe analysis of data from the ongoing, prospective California Teachers Study, which was designed to examine dietary patterns and breast cancer risk, found that following a Mediterranean diet reduced ischemic stroke risk by up to 18%, stroke neurologist Ayesha Sherzai, MD, of Columbia University Medical Center, New York City, said.

Mediterranean Diet Followers Had Lower Risk

The more closely the women followed the diet, the lower their risk of ischemic stroke, even after researchers adjusted for potential confounders like physical activity, smoking status, and cardiovascular risk factors.

“With stroke being one of the biggest disease burdens in the U.S. and throughout the world, and treatments not being as extensive as we would like them to be, diet is a risk factor that people can control,” Sherzai said.

The California Teachers Study enrolled close to 133,500 female teachers from across the state who were recruited in 1994. At recruitment the women filled out baseline lifestyle questionnaires, which included detailed information about their eating habits.

In the newly reported analysis, Sherzai and colleagues evaluated these eating patterns using a validated 9-point Mediterranean diet scoring system.

“The question was ‘In a U.S. population of women, what is the association between adhering to the Mediterranean diet and stroke risk, specifically stroke subtypes?” she said. “That hasn’t really been studied.”

In revised stroke prevention guidelines made public last fall, the American Heart Association (AHA)/American Stroke Association (ASA) for the first time recommended following a Mediterranean-style diet as a strategy to lower stroke risk. The recommendation followed the publication of several studies showing the diet to lower cardiovascular and stroke risk, including a 2013 randomized trial, published in the New England Journal of Medicine, which found that following a Mediterranean diet reduced the risk of heart attack and stroke in people at high risk for the events.

Mediterranean_Diet_Pyramid_Olive_Oil_EmporiumAHA also identified eating a healthy diet as one of the most important strategies for lowering cardiovascular risk in its initiative to reduce cardiovascular diseases and strokes by 20% by 2020.

Less Than 1% of Adults Over 50 Have Ideal Diets

But Sherzai said fewer than 1% of U.S. adults age 50 and over have an ideal dietary score. That is far lower than any other lifestyle factor related to stroke risk, she said.

In the newly reported analysis, women who ate diets high in fruits, vegetables, legumes, and monounsaturated fatty acids (MUFAs), scored high on the scale and points were deducted when the diets were high in meats, dairy, and sugar.

Olive oil, olives, avocados, and many nuts and seeds are good sources of MUFA.

“The higher the scores, the lower the stroke risk,” Sherzai said. “This basically confirms what other studies have found, but we were able to delineate between ischemic and hemorrhagic stroke.”

She added that it was not a big surprise that following a Mediterranean diet did not lower hemorrhagic stroke risk because diet does not really affect risk factors associated with stroke caused by weakened vessels that rupture and bleed into the brain.

And she said eating a healthier diet that may lower stroke risk shouldn’t mean big changes for most people.

“We aren’t saying that everybody has to strictly follow a Mediterranean diet, because we now know the components of this diet that are important,” she said.

“Eating a mostly plant-based diet and eating less meat and saturated fats can make a real difference in stroke risk,” she said, adding that most people should be able to make small, but significant changes in their diet, like switching from butter to olive oil and cutting back on their consumption of sugar, meats, and whole-fat dairy products.

Findings from the study were reported Thursday at the annual meeting of the International Stroke Conference, sponsored by the American Heart Association/American Stroke Association.



© 2015 MedPage Today, LLC. All rights reserved.


Prostate Cancer Drug Slows Memory Loss in Women with Alzheimer’s Disease

(University of Wisconsin-Madison) Women with Alzheimer’s disease showed stable cognition for a year when a drug that is more commonly used to treat advanced prostate cancer was added to their drug regimen, according to a new study from researchers at the University of Wisconsin-Madison.

“This is the first time any therapy has been shown to stabilize memory loss over a year,” says Dr. Craig Atwood, co-lead author of the study and associate professor of medicine at the UW School of Medicine and Public Health.

The study was published today in the Journal of Alzheimer’s Disease and is available here: http://iospress.metapress.com/content/n207096671247200

The clinical trial, initiated by Dr. Richard Bowen at the former Voyager Pharmaceutical Corporation, followed 109 women with mild to moderate Alzheimer’s disease. Some were treated with the drug leuprolide acetate (Lupron Depot), used to treat cancer in men and severe endometriosis in women, and with an acetylcholineesterase inhibitor such as Aricept, which improves mood in people with the condition but does little to slow memory loss. Others taking an acetylcholineesterase inhibitor received low-dose Lupron alone or a placebo.

It found that the women treated with both Aricept and high-dose Lupron Depot had almost no decline (0.18 points) in their scores on the ADAS-cog, a test of memory, compared with declines of 4.21 for those taking an acetylcholineesterase inhibitor and low-dose Lupron and 3.3 in those only taking an acetylcholineesterase inhibitor after one year.

Atwood explained that earlier epidemiological studies involving hundreds of thousands of patients had found that men who had prostate disease and were treated with Lupron had a 34 to 55 percent decreased risk of developing Alzheimer’s disease compared with prostate-cancer patients who didn’t receive the drug.

He explained that Lupron acts to suppress gonadotropin-releasing hormone (GnRH), which is produced in the brain and controls ovulation in women and spermatogenesis in men. This in turn decreases the production of gonadotropins, hormones that regulate the synthesis of sex steroids like estrogen and testosterone.

For these reasons, it is also used to treat estrogen-sensitive breast cancer, endometriosis, and premature puberty. Decreasing GnRH and gonadotropins with Lupron prevents some of the negative effects of elevated GnRH and gonadotropins on the brain, which occurs following menopause.

Post-menopausal women were chosen for this study because they no longer produce sex steroids; men could have been affected by the loss of testosterone caused by the Lupron.

“This promising combination therapy (acetylcholineesterase inhibitors and Lupron Depot) warrants testing in early and late stages of Alzheimer’s disease,” Atwood says.

“However, since the company that performed this study is now out of business, it remains to be seen whether this therapy will ever be tested in further clinical trials and reach the market.”



Copyright © 2015 Journal of Alzheimer’s Disease


Simple Blood Test Can Predict Risk of Dementia

(University of Copenhagen) Scientists at Rigshopitalet, Herlev Hospital and the University of Copenhagen identify a new biomarker that can predict the risk of developing dementia by way of a simple blood test. In the long term, this could mean better prevention and thus at least postponement of the illness and at best evading the development all together. The study was recently published in the Annals of Neurology.

Globally, in excess of 35 million people suffer dementia — in Denmark alone, there are approx. 80,000 who suffer this illness. Prevalence increases in step with aging, and as people’s life years are continually on the rise in most countries, there is also an increasing need to be able to identify the citizens who are at the greatest risk of suffering dementia.

As opposed to cardiovascular diseases, where the level of cholesterol in our blood indicates the risk of cardiac arrest, there are no such trustworthy markers in our blood in terms of diagnosing the risk of dementia setting in. However, Scientists at Rigshopitalet, Herlev Hospital and the University of Copenhagen have now identified a new biomarker, measurable in a simple blood test, which will help predict the onset of dementia.

More precise risk evaluation

“The blood test will help provide a more precise risk evaluation of a citizen’s risk of developing dementia later in life. Thus the citizens at the greatest risk of developing the illness are more easily identified than at present,” says Ruth Frikke-Schmidt, assistant clinical and research professor at the Faculty of Health and Medical Sciences at the University of Copenhagen and consultant physician at Rigshospitalet.

Researchers hope that with time, this new blood test will be applicable in clinical practice. “The blood test will enable an earlier and more focused prevention effort, thus prolonging the onset of the illness and raising the individual’s quality of life,” adds Ruth Frikke-Schmidt.

76,000 people partook in public studies

In the study, researchers show that a low level of the biomarker, the so-called apolipoprotein E, in our blood, increases the risk of developing dementia in the future. This was revealed in comprehensive studies of the general public, the Herlev-Oesterbro Study and the Oesterbro Study, involving 76,000 people.

Point of departure for the development of new drugs

The healthy brain consists of millions of interconnected nerve cells. The brain in a person suffering dementia is very different. The well-organised, structured coordination of nerve cells is intersected by, among other things, senile plaques that consist of the viscous compound, β-amyloid.

The low level of apolipoprotein E in the blood, as the researchers point out in the study, most likely reflects a low level of apolipoprotein E in the brain, and this indicates that the viscous compound, β-amyloid, is less effectively removed. Thus the study’s results underpin a biological mechanism.

“Over time, this increased biological knowledge about dementia can constitute a point of departure for the development of new drugs,” concludes Ruth Frikke-Schmidt.

Journal Reference:

  1. Katrine L. Rasmussen, Anne Tybjaerg-Hansen, Børge G. Nordestgaard, Ruth Frikke-Schmidt. Plasma levels of apolipoprotein E and risk of dementia in the general population. Annals of Neurology, 2015; 77 (2): 301 DOI: 10.1002/ana.24326

University of Copenhagen – The Faculty of Health and Medical Sciences. (2015, February 9). Simple blood test can predict risk of dementia. ScienceDaily. Retrieved February 14, 2015 from www.sciencedaily.com/releases/2015/02/150209184420.htm

Promising Results for New Alzheimer’s Therapy

(Karolinska Institutet) Scientists at Karolinska Institutet have evaluated a new Alzheimer’s therapy in which the patients receive an implant that stimulates the growth of a certain type of nerve cell. The results, which are published in the scientific journal Alzheimer’s & Dementia, suggest that the introduction of a nerve growth factor can prevent neuronal degradation in Alzheimer’s patients.

Patients with Alzheimer’s disease suffer a selective and early breakdown of so-called cholinergic nerve cells, which require a specific nerve growth factor (NGF) — essentially a group of proteins necessary for cell growth and survival — to function. As NGF levels decline, the cholinergic nerve cells begin to degrade and the patient’s condition slowly deteriorates.

In an attempt to curb the breakdown of the cholinergic nerve cells, researchers at Karolinska Institutet’s Centre for Alzheimer’s Research and their colleagues at Karolinska University Hospital’s neurosurgery clinic and the Danish biotech company NsGene introduced NGF directly into the brains of Alzheimer’s patients.

To do this, they used NGF-producing cell capsules, placing them in the basal fore-brain where the cholinergic cells reside using precision stereotactic surgery. There the capsules, which can easily be removed, release NGF to the surrounding cells in order to prevent their degradation.

The study now published in Alzheimer’s & Dementia is based on data from six Alzheimer’s patients. To gauge whether the NGF release had any effect on the cholinergic nerve cells, the researchers assayed the presence of specific markers of functioning cholinergic cells. This cell system communicates using acetylcholine, which in turn produces an enzyme called ChAT (pronounced Cat) that is found both inside and outside the cells. The team therefore developed a method enabling them to measure ChAT in the cerebral spinal fluid for the first time.

“Our results show that when the patients received NGF, there was a significant increase in ChAT in the CSF,” says Dr Taher Darreh-Shori, one of the researchers involved in the study. “The patients that exhibited this increase were also those that responded best to the treatment. Our PET scans also showed an increase in cholinergic cell activity and metabolism in the brain.”

In addition, the researchers were able to detect a retardation of memory impairment over time compared with untreated patients. While all this suggests that cholinergic functionality improved in the Alzheimer’s patients who had received NGF therapy, the team adds the caveat that far-reaching conclusions should not be drawn from the results:

“The results are promising, but must be treated with circumspection as only a few patients participated in the study,” says principal investigator Professor Maria Eriksdotter. “So our findings will have to be substantiated in a larger controlled study using more patients.”


Journal Reference:

  1. Azadeh Karami, Helga Eyjolfsdottir, Swetha Vijayaraghavan, Göran Lind, Per Almqvist, Ahmadul Kadir, Bengt Linderoth, Niels Andreasen, Kaj Blennow, Anders Wall, Eric Westman, Daniel Ferreira, Maria Kristoffersen Wiberg, Lars-Olof Wahlund, Åke Seiger, Agneta Nordberg, Lars Wahlberg, Taher Darreh-Shori, Maria Eriksdotter. Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer’s disease. Alzheimer’s & Dementia, 2015; DOI: 10.1016/j.jalz.2014.11.008

Karolinska Institutet. (2015, February 13). Promising results for new Alzheimer’s therapy. ScienceDaily. Retrieved February 14, 2015 from www.sciencedaily.com/releases/2015/02/150213081521.htm


Neurogeneticists Harness Immune Cells to Clear Alzheimer’s-Associated Plaques

(University of Southern California) New research from scientists at the Keck School of Medicine of the University of Southern California (USC) shows that the body’s immune system may be able to clear the brain of toxic plaque build-up that is the hallmark of Alzheimer’s disease, reversing memory loss and brain cell damage.

The study, which appears in the Feb. 4 edition of the peer-reviewed scientific journal Neuron, identifies a promising avenue for treating a disease that the Alzheimer’s Association projects will affect 16 million Americans over age 65 by 2050.

“Alzheimer’s disease is the public health crisis of our time, and effective treatment does not yet exist,” said Terrence Town, PhD, professor of physiology and biophysics at the Keck School of Medicine of USC and the study’s senior author.

“Our study shows that ‘rebalancing’ the immune response to wipe away toxic plaques from the brain may bring new hope for a safe and effective treatment for this devastating illness of the mind.”

Alzheimer’s disease is an irreversible, progressive brain disease that causes problems with memory, thinking and behavior. Affecting more than 5 million Americans today, Alzheimer’s is the most common type of dementia, a general term for loss of memory and other mental abilities.

Brains with Alzheimer’s disease show build-up of a sticky plaque — made of a protein called beta-amyloid — that induces memory loss. When afflicted with Alzheimer’s, the immune system, which typically rids the body of toxic substances, becomes imbalanced and inefficient at clearing those plaques.

immune-cellA 3D reconstruction of an immune cell (red) containing β-amyloid (blue) within an intracellular degradation compartment (yellow). Deletion of the anti-inflammatory cytokine, Il10, activates innate immune cells to clear the brain of toxic β-amyloid plaques. Image by Marie-Victoire Guillot-Sestier, Ph.D.

In the Neuron study, Town and his team used genetically modified mice to show that blocking a substance called interleukin-10 activates an immune response to clear the brain of the beta-amyloid plaques to restore memory loss and brain cell damage.

Alzheimer’s-afflicted mice in which the immune cells were activated behaved more like mice without the disease in various learning and memory tests. Future studies will test the effectiveness of drugs that target interleukin-10 in rats that the scientists have genetically modified to develop Alzheimer’s disease.

USC co-authors include Marie-Victoire Guillot-Sestier, Kevin R. Doty, David Gate, Javier Rodriguez, Jr., and Brian P. Leung. The study was supported in part by the National Institutes of Health (1F31NS083339-01A1, 5R00AG029726-04, 3R00AG029726-04S1, 1R01NS076794-01), American Federation of Aging Research/Ellis Medical Foundation and Zilkha Neurogenetic Institute.


Journal Reference:

  1. Marie-Victoire Guillot-Sestier, Kevin R. Doty, David Gate, Javier Rodriguez, Brian P. Leung, Kavon Rezai-Zadeh, Terrence Town. Il10 Deficiency Rebalances Innate Immunity to Mitigate Alzheimer-Like Pathology. Neuron, 2015; 85 (3): 534 DOI: 10.1016/j.neuron.2014.12.068

© 2015 Keck Medicine of USC


SuperAger Brains Yield New Clues to Their Remarkable

(Northwestern University) SuperAgers, aged 80 and above, have distinctly different looking brains than those of normal older people, according to new Northwestern Medicine® research that is beginning to reveal why the memories of these cognitively elite elders don’t suffer the usual ravages of time.

SuperAgers have memories that are as sharp as those of healthy persons decades younger.

Understanding their unique “brain signature” will enable scientists to decipher the genetic or molecular source and may foster the development of strategies to protect the memories of normal aging persons as well as treat dementia.

Published Jan. 28 in the Journal of Neuroscience, the study is the first to quantify brain differences of SuperAgers and normal older people.

Cognitive SuperAgers were first identified in 2007 by scientists at Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center at Northwestern University Feinberg School of Medicine.

Their unusual brain signature has three common components when compared with normal persons of similar ages: a thicker region of the cortex; significantly fewer tangles (a primary marker of Alzheimer’s disease) and a whopping supply of a specific neuron –von Economo — linked to higher social intelligence.

“The brains of the SuperAgers are either wired differently or have structural differences when compared to normal individuals of the same age,” said Changiz Geula, study senior author and a research professor at the Cognitive Neurology and Alzheimer’s Disease Center.

“It may be one factor, such as expression of a specific gene, or a combination of factors that offers protection.”

The Center has a new NIH grant to continue the research.

“Identifying the factors that contribute to the SuperAgers’ unusual memory capacity may allow us to offer strategies to help the growing population of ‘normal’ elderly maintain their cognitive function and guide future therapies to treat certain dementias,” said Tamar Gefen, the first study author and a clinical neuropsychology doctoral candidate at Feinberg.

MRI imaging and an analysis of the SuperAger brains after death show the following brain signature:

1) MRI imaging showed the anterior cingulate cortex of SuperAgers (31 subjects) was not only significantly thicker than the same area in aged individuals with normal cognitive performance (21 subjects), but also larger than the same area in a group of much younger, middle-aged individuals (ages 50 to 60, 18 subjects). This region is indirectly related to memory through its influence on related functions such as cognitive control, executive function, conflict resolution, motivation and perseverance.

2) Analysis of the brains of five SuperAgers showed the anterior cingulate cortex had approximately 87 percent less tangles than age-matched controls and 92 percent less tangles than individuals with mild cognitive impairment. The neurofibrillary brain tangles, twisted fibers consisting of the protein tau, strangle and eventually kill neurons.

3) The number of von Economo neurons was approximately three to five times higher in the anterior cingulate of SuperAgers compared with age-matched controls and individuals with mild cognitive impairment.

 “It’s thought that these von Economo neurons play a critical role in the rapid transmission of behaviorally relevant information related to social interactions,” Geula said, “which is how they may relate to better memory capacity.” These cells are present in such species as whales, elephants, dolphins and higher apes.

Other Northwestern authors on the study include Melanie Peterson, Steven T. Papastefan, Adam Martersteck, Kristen Whitney, Alfred Rademaker, Eileen Bigio, Sandra Weintraub, Emily Rogalski and Dr. M. Marsel Mesulam.

The research was funded by National Institute on Aging, National Institutes of Health grant AG045571, The Davee Foundation, the Northwestern University Alzheimer’s Disease Core Center grant AG13854 from the National Institute on Aging, a fellowship from the National Institute on Aging grant F31-AG043270 and others.

For more information on the SuperAger study, visit http://www.brain.northwestern.edu/research/studies/sa.html.

If you are interested in participating in research at Northwestern University, please call the NU Study line at 1-855-NU-STUDY.


by Marla Paul


Journal Reference:

  1. T. Gefen, M. Peterson, S. T. Papastefan, A. Martersteck, K. Whitney, A. Rademaker, E. H. Bigio, S. Weintraub, E. Rogalski, M.- M. Mesulam, C. Geula. Morphometric and Histologic Substrates of Cingulate Integrity in Elders with Exceptional Memory Capacity. Journal of Neuroscience, 2015; 35 (4): 1781 DOI: 10.1523/JNEUROSCI.2998-14.2015

Copyright 2015 Northwestern University