Practical Strategies for Reducing Your Risk for Cognitive Decline.

A new book by Ken Kosik, MD, Outsmarting Alzheimer's, lays out practical strategies for helping people reduce their risk for developing Alzheimer's disease.

Dr. Kosik recommends four activities based on solid research evidence.  He says that people who regularly do these activities have a lower risk of developing cognitive decline.

1. Get Physical
Dr. Kosik says physical activity is the most potent Alzheimer's protection agent, stating that study after study has shown that people who exercise at least three times a week for a minimum of 15 to 30 minutes a sessions were less likely to develop Alzheimers disease, even if the disease ran in their family.

2. Eat Antioxidant-Rich, Anti-Inflammatory Foods
Dr. Kosik cautions that there is no single dietary pattern, food, or supplement that leads to optimum brain health, he says that one thing those that are effective have in common is an abundance of plant-based foods and a minimum of processed food.  He cites a new diet, developed by researchers at Rush University Medical Center in Chicago, as an an example of a the kind of approach to eating that can significantly lower the risk for developing Alzheimers.

The MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet is a hybrid of two other diet regimens (the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets) previously found to reduce the risk of cardiovascular conditions, like hypertension, heart attack and stroke.  

Read more about the MIND diet Here, Here, and Here.

3. Make Time For Friends
Dr. Kosik points to a research study at Rush Alzheimer's Disease Center in Chicago that showed that adults who frequently spent time with others—being part of a book club, or a card game, having dinner dates with their friends, visiting familky had a 70 percent lower rate of cognitive decline over 12 years than did seniors with fewer interactions.

4. Exercise Your Brain
Dr. Kosik says one long-term study showed that older adults who frequently did stimulating leisure activities were less likely to develop dementia over 21 years, compared with those who did so less often. Reading, playing board games, practicing musical instruments, and working on puzzles at least several times a week may encourage the growth of new brain cells and connections between them. Even people who were carriers of a gene linked to Alzheimer's postponed the development of the disease by almost a decade by immersing in intellectually enriching activities throughout their lives.

This is not the first book to focus on ways individuals can adjust their lifestyle to reduce the risk of cognitive decline (Alzheimer's), but this book is noteworthy not only for it's research-backed guidance; it's noteworthy because of its author.

Ken Kosik, MD is one of the world's leading Alzheimer's researchers.  Dr. Kosik's work focuses on gaining an understanding of the fundamental causes, risk factors, and workings of Alzheimer's disease. 

After completing a B.A. and M.A. in English literature from Case Western Reserve University in 1972 and an M.D. from the Medical College of Pennsylvania in 1976, he served as a resident in neurology at Tufts New England Medical Center and was Chief Resident there in 1980. Beginning in 1980 he held a series of academic appointments at the Harvard Medical School and achieved the rank of full professor there in 1996. He also held appointments at McLean Hospital, Brigham and Women's Hospital, the Massachusetts General Hospital and the Dana-Farber Cancer Institute. In 2004, Kosik became the Harriman Professor of Neuroscience Research and Co-Director of the Neuroscience Research Institute at the University of California, Santa Barbara. He founded and serves as Medical Director of the non-profit center, Cottage Center for Brain Fitness (CCBF).

Dr. Kosik is probably best known for the ground-breaking research he has conducted in and around Medellin, Columbia.  JDFAF was a supporter of Dr. Kosik in his research in Columbia.

Dr. Kosik and his fellow researchers discovered an extended family, spread over this region of Colombia who have passed a particular Alzheimer gene from generation to generation, and Kosik says the family members who carry the Alzheimer's gene will definitely get the disease. The family represents the largest cluster of familial Alzheimer's disease in the world. In each generation, affected family members get the disease in their mid-40's.

Kosik explained it is possible to test people in the Colombian families for the gene, and predict who will get the disease and who will be spared. The ability to predict who and when family members will get the disease raises the possibility of developing clinical trials to find out whether or not certain drugs and other therapies are effective in delaying the disease in those family members who have the gene.

"We have the opportunity to treat this disease before it strikes," said Kosik. "We would be able to find out if drugs really work."

Clinical drug trials are now underway among this population.

Read more about Dr. Kosik's research Here and Here.

New diet shown to significantly reduce the risk for Alzheimer's.

A new study, reported in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, finds that adhering to a new diet, developed by researchers at Rush University Medical Center in Chicago, can significantly lower the risk for developing Alzheimers.

The MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet is a hybrid of two other diet regimens (the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets) previously found to reduce the risk of cardiovascular conditions, like hypertension, heart attack and stroke.  

The study shows that the MIND diet lowered the risk of AD by as much as 53 percent in participants who rigorously adhered to the diet, and by about 35 percent in those who followed it moderately well.

“One of the more exciting things about this is that people who adhered even moderately to the MIND diet had a reduction in their risk for AD,” said Martha Clare Morris, PhD, a professor, assistant provost for Community Research, and director of Nutrition and Nutritional Epidemiology at Rush. “I think that will motivate people.”

The MIND diet is also easier to follow than, say, the Mediterranean diet, which calls for daily consumption of fish and three to four daily servings of each of fruits and vegetables, Morris said.

The MIND diet has 15 dietary components, including 10 “brain-healthy food groups” — green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil and wine — and five unhealthy groups that comprise red meats, butter and stick margarine, cheese, pastries and sweets, and fried or fast food.

The MIND diet includes at least three servings of whole grains, a salad and one other vegetable every day — along with a glass of wine. It also involves snacking most days on nuts and eating beans every other day or so, poultry and berries at least twice a week and fish at least once a week. Dieters must limit eating the designated "unhealthy" foods, especially butter (less than 1 tablespoon a day), cheese, and fried or fast food (less than a serving a week for any of the three), to have a real shot at avoiding the devastating effects of Alzheimer's, according to the study.

"Even moderate adherence to the MIND diet showed a statistically significant decreased risk of developing Alzheimer's disease," says study author Martha Clare Morris, a professor of epidemiology at Rush University in Chicago. "Neither the Mediterranean diet or DASH had that benefit with moderate adherence."

Learn more about the MIND Diet here, here, and here

New Studies suggest women's brains are more vulnerable to Alzheimer's than men’s.

Two-thirds of all individuals in the US diagnosed with Alzheimer’s are women — a circumstance long explained by scientists by the fact that women live longer than men. 

Two new studies presented at the 2015 Alzheimer's Association International Conference (AAIC) in Washington, DC suggest there may be more to the story.

The studies indicate that women's brains may in fact be more vulnerable to the degenerative effects of Alzheimer's disease than men’s, and that these differences may also cause them to experience memory loss and other declines in cognitive function twice as fast as men.

The first study conducted at Duke University used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to study how the cognitive abilities of about 400 seniors (141 women, 257 men) with Mild Cognitive Impairment (MCI) changed over the course of up to eight years.

They found the cognitive abilities of the women declined twice as fast as men's.

“The bottom line is, more and more we think there are some differences,” said Kristine Yaffe, a professor of psychiatry, neurology and epidemiology at the University of California at San Francisco. “It’s not just that women are living to be older — that’s true, and that drives some of this. But there’s something else going on in terms of biology [and] environment for women compared to men that may make them at greater risk or, if they have some symptoms, may change the progression.”

Katherine Amy Lin who reported on the study said, "Our findings suggest that men and women at risk for Alzheimer's may be having two very different experiences."  "Our analyses show that women with mild memory impairments deteriorate at much faster rates than men in both cognitive and functional abilities. These results point to the possibility of as yet undiscovered gender-specific genetic or environmental risk factors that influence the speed of decline. Uncovering those factors should be a high priority for future research."

The second study conducted at University of California at San Francisco used PET (positron emission tomography) scanning to measure levels of amyloid (the substance that forms sticky plaques in the brains of Alzheimer's patients) in about 1,000 people, including many with cognitive impairment or Alzheimer's disease. 

“This study shows women have more amyloid in their brain than men in general, and especially once the women are in the late stages where they’re having dementia,” said Michael W. Weiner, a radiology professor at UC San Francisco and principal investigator of the Alzheimer’s Disease Neuroimaging Initiative.

As to why women have more amyloid in their brain, Weiner says the answer is still unclear—it may be a function of genetics, or caused by hormonal differences (women have estrogen, men have testosterone) or lifestyle differences; diet, exercise, childbearing.

Learn more about this research Here.

New study shows a form of age-related cognitive decline—tied to an immune-system molecule—can be reversed in mice.

Two studies published in 2014 and 2015 — the product of a collaboration between Saul A. Villeda, PhD, a Faculty Fellow at University of California San Francisco (UCSF) and Tony Wyss-Coray, PhD, professor of neurology at Stanford University — provide important insights into the cause of one type type of cognitive decline—and the possibility of reversing its effects. (note: Dr. Wyss-Coray has been previously funded by JDFAF. Read his profile here.)

The research teams found that a blood-borne molecule (beta-2 microglobulin, or B2M, a component of a larger molecule called MHC) which plays an important role in the adaptive immune system, greatly increases as we age, and can act adversely in the brain, in ways not related to immunity—blocking the regeneration of brain cells, thus promoting cognitive decline.

In 2014 study, Villeda and Tony Wyss-Coray showed that connecting the circulatory system of a young mouse to that of an old mouse could reverse the declines in learning ability that typically emerge as mice age.

Over the course of their research, however, the researchers noted an opposite effect—blood from older animals appears to contain the "pro-aging factors" that suppress neurogenesis--the formation of new brain cells in regions important for memory--which when introduced into younger animals can contribute to cognitive decline.

In a new study, published online on July 6, 2015 in Nature Medicine, Villeda and  Wyss-Coray followed up on these findings, as well as other studies correlating high B2M blood levels with cognitive dysfunction in Alzheimer's disease, HIV-associated dementia, and as a consequence of chronic dialysis for kidney disease.

The researchers observed that when B2M was administered to young mice, either via the circulatory system or directly into the brain, the mice performed poorly on tests of learning and memory compared to untreated mice, and neurogenesis was also suppressed in these mice.

These experiments were complemented by genetic manipulations in which some mice were engineered to lack a gene known as Tap1, which is crucial for the MHC I complex to make its way to the cell surface. In these mice, administration of B2M in young mice had no significant effect, either in tests of learning or in assessments of neurogenesis.

The group also bred mice missing the gene for B2M itself. These mice performed better than their normal counterparts on learning tests well into old age, and their brains did not exhibit the decline in neurogenesis typically seen in aged mice.

Villeda emphasized that the effects on learning observed in the B2M-administration experiments were reversible—30 days after the B2M injections, the treated mice performed as well on tests as untreated mice, indicating that B2M-induced cognitive decline in humans could potentially be treated with targeted drugs.

"From a translational perspective, we are interested in developing antibodies or small molecules to target this protein late in life," said Villeda. "Since B2M goes up with age in blood, cerebrospinal fluid (CSF), and also in the brain itself, this allows us multiple avenues in which to target this protein therapeutically."

Read more about this research.

First Alzheimer's Drug Shown in Early Stage Clinical Trial to Remove Beta Amyloid Plaque and Slow Cognitive Decline.

As of the end of last year (2014), more than two-hundred forty-four Alzheimer's drug compounds have been tested, with failure rate that exceeds 99 percent.  

But a new treatment is showing real promise in early stage clinical trials.

The results of a new early-stage trial, reported at the AD/PD 2015: International Conference on Alzheimer's and Parkinson's Diseases, and a further analysis of subgroup treatment response presented at the recent American Academy of Neurology (AAN) 67th Annual Meeting, showed that a monoclonal antibody, aducanumab (formerly known as BIIB037), developed by Biogen Inc., significantly reduced amyloid plaque in the brain over the 1 year study period and slowed cognitive decline.

"Treatment with aducanumab results in a dose-dependent and time-dependent effect that is consistent across APOE ε4 carriers and noncarriers, and among subjects with both mild and prodromal disease," lead author Jeffrey Sevigny, MD, Biogen Inc, stated.  

This is significant as more than 50 percent of people with AD are APOE ε4 carriers.

Scientists are cautiously optimistic, in light of a history of other drugs which have shown promis in early stages, only to fail in later, larger scale trials.

Based on these early-stage results, Aducanumab will now move directly to phase III trials.

Learn more about aducanumab here, here, and here

A Blood Test That Could Diagnose Alzheimer's Shows Promise.

In what might prove to be an important advance in getting treatment to Alzheimer's patients as early as possible, UCLA researchers have found that a simple blood test might be developed that could diagnose patients with Alzheimer's.

While there is currently no cure for Alzheimer's, getting treatment to patients as early as possible is important, as many treatments are most effective in the earliest stages of the disease.

At present, the only way to definitely prove the presence of Alzheimer’s is through the examination of brain tissue after death, however, to diagnose patients while they are alive, doctors rely on the presence of biomarkers (beta amyloid proteins in the brain, a hallmark of the disease) and cognitive symptoms such as memory loss.

Two methods are currently used to determine the beta-amyloid formation characteristic of Alzheimer’s disease, however, there are significant drawbacks to both. A spinal tap can be used to obtain cerebrospinal fluid, however, this is an invasive procedure that carries the risk of nerve damage and other serious side effects. Alternatively, an amyloid PET scan can be used, and while this technology is non-invasive, it exposes subjects to radiation. Moreover, amyloid PET scans are available in only few medical centers, and are not typically covered by insurance as a diagnostic test. 

For their study, the UCLA researchers developed a simple signature for predicting the presence of brain amyloidosis — the build-up of amyloid in the brain — including several blood proteins known to be associated with Alzheimer’s disease, along with information routinely obtained in the course of a clinical work-up for patients suspected to have the disease, such as results of memory testing and structural magnetic resonance imaging.

The UCLA researchers found that their method could be used to predict the presence of amyloid in the brain with modest accuracy.

"Our study suggests that blood protein panels can be used to establish the presence of Alzheimer’s-type pathology of the brain in a safe and minimally invasive manner,” said Liana Apostolova, MD, director of the neuroimaging laboratory at the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA and head of the research team. “We need to further refine and improve on the power of this signature by introducing new disease-related metrics, but this indicates that such a test is feasible and could be on the market before long.”

Results of the study appeared in the journal Neurology.

A Non-Drug Therapy May Show Promise

Axona® is a new, prescription dietary supplement (non-drug therapy) designed to support cognition and memory in individuals with Alzheimer's.

Axona is not a replacement for drug therapies that target the chemicals that brain cells need to function, instead, Axona addresses another factor influencing reduced cognition—diminished cerebral glucose metabolism (DCGM).  

To function properly, the brain needs too consume a lot of fuel, in the form of a constant supply of glucose (a kind of sugar). When glucose levels are too low, brain cells do not function properly and memory and other cognitive processes are affected.

Research has shown that Alzheimer's interferes with the brain's ability to process and use glucose. This is called diminished cerebral glucose metabolism (DCGM).

However, when glucose levels are too low, the body produces a back-up source of nutrition for the brain know as ketone bodies. Ketone bodies are naturally produced by the liver. 

Axona contains fatty acids called medium-chain triglycerides (MCTs), which the body converts into ketone bodies to help support cognition in patients with mild-to-moderate Alzheimer's disease.

Clinical studies have shown that raised ketone body levels can enhance memory and cognition in some people with mild to moderate Alzheimer’s disease.

The John Douglas French Alzheimer's Foundation is funding a study at UCLA examining the cerebral metabolic effects of AC-1202 (Axona®) treatment in mild-to-moderate Alzheimer’s disease (AD), using positron emission tomography (PET). Subjects in the study include both carriers and non-carriers of the APOE4 gene.

The John Douglas French Alzheimer's Foundation also funded an initial study of ketone ester in Alzheimer's disease in mice, conducted by Dr. Richard Veech and Dr Yoshihiro Kashiwaya at the NIH. The study found that feeding the ketone ester to mice (1) decreased amyloid accumulation in brain, (2) decreased phosphorylated tau and (3) improved cognitive performance in the mice.

Learn more about Axona by visiting the Axona website HERE and reading a report on Axona by the Mayo Clinic HERE

A tough question for parents: Considering the risks for brain damage, should you let your son play football?

In recent years there has been increasing awareness of the long-term effects of brain trauma.  Recent studies have confirmed that a history of at least one mild-traumatic brain injury increases the likelihood of dementia later in life.  

Trauma appears to predispose to not only Alzheimer’s disease, but also Parkinson’s disease and Lou Gehrig’s disease (amyotrophic lateral sclerosis).  Individuals who suffer from multiple traumatic injuries are particularly vulnerable to a disorder that has been called Chronic Traumatic Encephalopathy or CTE.  

This syndrome has also been described in wrestlers, boxers, war veterans and altheletes involved in contact sports. CTE  begins as a behavioral disorder with anxiety, anger, disinhibition, and sometimes problems with memory or multi-tasking and is followed by the development of motor problems, dementia and eventually death.  The brain shows the pathological accumulation of the tau protein and sometimes a protein called TDP-43.  No treatments exist yet for CTE, but avoiding head trauma is the best way to avoid this devastating disorder.

With that in mind, parents should carefully consider the risks for long-term brain damage when deciding whether or not to let their sons play football.

Dr. Bruce Miller, Director of the UCSF Memory and Aging Center and Chief Medical Officer of The John Douglas French Alzheimer's Foundation, heads a team involved in a study analyzing head impacts incurred by NFL players and the part it may play in future dementia.