Jan 132014
 

In this first blog of 2014, I would like to review some of the highlights from the world of Alzheimer’s disease research in 2013, as well as the new directions that we will likely be heading in 2014.Driving on an empty road towards the setting sun 2014

Advances in Brain Imaging 

Advances in brain imaging, specifically amyloid PET scans, have led the way towards earlier identification of Alzheimer’s. Their widespread use in larger studies has made it possible to visualize the presence of beta-amyloid deposition in individuals with no symptoms.

The year began with the publication of additional data showing that amyloid deposition in the brain leads to atrophy, or shrinkage, of specific brain areas, even before patients develop memory loss. Research groups in France, Australia and the United States reported longitudinal studies of amyloid deposition in the brain, demonstrating that its presence predicts subsequent brain atrophy and cognitive decline.

Additional developments in brain imaging were made with results of Avid’s Tau tracers, both of which allow for visualization of the abnormal Tau protein that contributes to the formation of the neurofibrillary tangles of Alzheimer’s. Tau PET scans will undoubtedly become a critical tool in Alzheimer’s research during the next few years, much like amyloid imaging has been so important since the first papers were published on its use nine years ago.

Understanding Alzheimer’s in People with Down Syndrome

In the spring of 2013, the National Institutes of Health held a meeting focusing on Alzheimer’s disease among people with Down syndrome, bringing researchers together to discuss ways to develop a consortium with an aim to understand Alzheimer’s in this highly susceptible population.

- Every person with Down syndrome (DS) will develop AD pathology by age 40

- Half of the Down Syndrome population develops dementia by age 60

The Down Syndrome Biomarker Initiative (DSBI) pilot study was launched this year as a feasibility study of a planned large-scale study to discover indicators of Alzheimer’s disease in Down syndrome, with the ultimate goal of better understanding brain aging and Alzheimer’s in adults with Down syndrome.

Economic Impact of Dementia

A major publication in the New England Journal of Medicine by the RAND Corporation estimated the economic cost of dementia to the United States was approximately $203 billion in 2010. This paper garnered major attention, as it was a well conducted analysis of the economic impact of dementia. The sheer dollar amount is greater than the cost of any other disease faced by our society and is expected to rapidly increase in the next decade.

Trials and Tribulations

2013 was also the year when the long awaited results of the phase III IGIV study were presented, which were unfortunately, negative. Additionally, researchers studying the drug Bexarotene were able to replicate some, but not all of the previously reported effects of this drug on memory and beta-amyloid in mouse models of Alzheimer’s disease. Nonetheless, a placebo controlled clinical trial of Bexarotene was launched this year for the treatment of Alzheimer’s. Results are expected mid-year in 2014.

Prevention and Early Intervention

Perhaps one of the biggest events in the Alzheimer’s research world this year was the launch of the first clinical trial to prevent Alzheimer’s dementia in the general population. The trial, Anti-Amyloid in Asymptomatic Alzheimer’s Disease, or A4, is a three-year study looking at the effectiveness of a drug given to subjects who have absolutely no outward symptoms of memory loss but have positive amyloid scans of the brain. Much will be learned when this study is completed about how soon intervention can be offered in efforts to prevent Alzheimer’s disease.

G8 on Dementia

And finally, global focus on dementia was raised at this year’s G8 summit. All G8 nations made commitments to develop an international action plan for research, share information and data across the G8 countries and to provide unprecedented collaboration. The G8 plan includes open access to all publically-funded dementia research, the introduction of a new global envoy for dementia innovation, and the ambitious aim to “find a cure or disease-altering therapy by 2025.” This plan parallels the U.S. National Alzheimer’s Project Act (NAPA), with a goal of “preventing or effectively treating Alzheimer’s” by 2025.

What Is on the Horizon in 2014?

There are an unprecedented number of clinical trials now running with the aim of preventing Alzheimer’s. As data from recent studies suggest, it may only be through early intervention, before the symptomatic stage, that we can truly affect the course of AD and even consider preventing its dementia stage.

We anticipate more discoveries this upcoming year with Tau imaging, as well as the use of biomarkers in asymptomatic individuals. New data is also expected from large-scale whole-genome studies, which are revealing other Alzheimer’s susceptibility genes. We also look forward to data from some of the new mouse models created with these newly discovered mutations to understand how they contribute to the development of Alzheimer’s, and perhaps represent treatment targets.

We look forward to keeping you updated on the world of Alzheimer’s research in the upcoming year and are optimistic that there will be great developments in 2014.  Stay tuned.

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

 

Sep 252013
 

British scientists recently reported finding signs of the gum-disease bacterium toothbrush (P. gingivalis) in the brains of Alzheimer’s patients. The new study is being widely reported as adding to a growing body of evidence linking periodontal (gum) disease to an increased risk for Alzheimer’s disease.

However, such data needs to be considered very carefully.

In fact, what the study found was that substances on the surface of the bacterium (lipopolysaccharides) were present in the brain tissue of four out of 10 recently deceased people who had Alzheimer’s. It was found in zero out of 10 age-matched patients who did not have Alzheimer’s. The bacteria itself was not found in the brain tissue of any people.

The theory behind linking gum disease with Alzheimer’s is that the presence of gum bacteria lipopolysaccharides in the brain may cause inflammation. This in turn could trigger a biological cascade that may be linked to the brain changes associated with Alzheimer’s disease.

We already know that P. gingivalis is commonly found in chronic periodontal (gum) disease, and, if there is significant dental disease, it can enter the bloodstream through such everyday activities as eating, brushing teeth and invasive dental treatments. While in the bloodstream, the bacteria can settle on heart valves and damage them. Hence, patients with mitral valve prolapse and other heart anomalies often take an antibiotic before dental procedures to prevent the bacteria from depositing within the heart. However, no bacteria have been reported in the brains of patients with gum disease, as the brain is an immunologically, well-protected organ, more so than any other.

It is important for readers to know that these types of studies show an association between gum disease and Alzheimer’s disease, but do not prove causation. For example:

  • The number of subjects is extremely small to make a definitive conclusion, and the finding could have occurred simply by statistical chance.
  • Only four out of 10 subjects with Alzheimer’s had such changes, not 10 out of 10. If the gum disease was causative, one would expect more than just a minority of patients exhibiting the lipopolysaccharides.
  • Finally, what if very early stage dementia caused people to actually brush their teeth less often, or altered their dietary intake? They would be at risk of developing gum disease. But the gum disease would have resulted from the early dementia, not vice versa.

It is also important to note that previous studies have shown links between gum disease and other illnesses, including heart disease and certain forms of cancer; these findings are not specific to Alzheimer’s.

The study is important and should be followed up with larger sample sizes, but given the above limitations, the study does not show that “brushing teeth reduces the risk of dementia” or that “gum disease can lead to dementia.”

Thanks for reading.

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

Learn More

 

Feb 152013
 
goldie_byrd

During February, Black History Month, the Alzheimer’s Association sat down for a one-on-one talk with Dr. Goldie Byrd, an African-American scientist who has spent more than a decade researching the genetics of Alzheimer’s disease. Early in her career, Dr. Byrd recognized the impact of studying the nature of Alzheimer’s disease on a genomic level. Here are some of her thoughts on her observations and her motivations for continuing her research.

“I decided to focus my research on Alzheimer’s because it’s a disease of disparity, affecting some populations far more than others; its genetics aren’t well understood; and it had an impact on my family.

There’s a tremendous stigma about Alzheimer’s. People perceive it as affecting their social standing, their professional opportunities … they don’t want be associated with that kind of stigma, especially coming from a community that’s had an historical struggle to integrate.

I remember when people wouldn’t talk about cancer — it was taboo. Now people are proud to say they’re survivors. I want to create a buzz about Alzheimer’s so that people feel free to talk about it. I want more information out there and more literacy about the disease.

We need to do a better job educating people about how to care for those with Alzheimer’s — that will help with the embarrassment. And we need to provide resources to help caregivers who have an extraordinary challenge. This disease can strip a family of so many things, including their finances.

People also need to understand that the healthier we are, the healthier the brain will be. We need to increase physical activity, reduce stress, control high blood pressure and cholesterol, reduce obesity and eat a healthy diet. Often, these things are related to socioeconomics. But where we can make changes, we should. Education really is key.”

Dr. Byrd and her team were recently recognized with a $1 million grant for outreach activities. It will be used in part to support “Keeping Memories Alive” a project to bring better understanding about Alzheimer’s to all those with the disease, caregivers and policy makers.

Learn More:

 

Know the 10 warning signs of Alzheimer’s (PDF) Caregiver stress brochure (PDF)

Jul 242012
 
researcher_testube

This post originally appeared on the ChicagoNow blog, “Ask Dr. Chill: Practical Answers to the Toughest Caregiving Questions.” It is being reposted here with the author’s permission.

Alas, I was not able to attend the Alzheimer’s Association International Conference in Vancouver this month, but I did follow it closely on the organization’s website. The event attracted over 4,300 scientists, physicians and other professionals in the Alzheimer’s community who gathered to discuss findings from their most recent batches of research.

If your eyes tend to glaze over when you read news blurbs about complicated research, I don’t blame you. The sheer amount of news these days certainly can induce medical information overload.

As an antidote, I offer my Cliff Notes version of the Alzheimer’s Association International Conference:

  • A couple of risk factors emerged, including  late-life binge drinking, changes in gait (walking patterns) and sleep changes(Note: A risk factor implies a correlation between the factor and eventual onset of the disease — it does not imply causality. Just because something is associated with something else does not mean that one causes the other.)
  • Several treatments showed promise, including experimental drug EVP-6124, intravenous immunoglobulin, medical food Souvenaid, dietary supplement citicoline, and home-based care coordination. (Note: Treatment studies focus on treating the symptoms of Alzheimer’s after the disease process is already underway. There is no evidence that any of these treatments are useful for prevention.)
  • But on the upside, four different studies indicated that targeted exercise training could reduce the risk of developing dementia among older adults who were either cognitively healthy or only had mild cognitive impairment. (Get moving, folks!)
  • Diagnostic advances now allow researchers to better identify people with Alzheimer’s when they are still presymptomatic. That’s right  early brain changes and subtle cognitive problems can now be detected so that a diagnosis of “preclinical” or “presymptomatic” Alzheimer’s disease can be made. Granted, this type of diagnostic accuracy is seen mostly in research settings and has yet to become evident in general medical practice. But what this means is that researchers can now test new drugs among presymptomatic individuals to see if the progression to symptomatic Alzheimer’s can actually be prevented.

As I scoured the event’s press releases, I felt a combination of hope, pride and sadness wash over me. My hope emerges from the incredible strides taken by the Alzheimer’s community that have revealed more about the disease in the past 20 to 30 years than we learned during most of the 20thcentury (Alzheimer’s was first identified in 1906). My pride is rooted in the many years I worked for the organization and my first-hand knowledge of its dedication to ultimately finding an end to this wretched disease.

I didn’t want to feel sadness, but it’s best not to suppress such honest parts of the human experience. My sadness stemmed from my long journey with this disease  both professionally and personally  which has taught me that any measure of hope must be balanced with a healthy dose of realism.

Note that the conference highlighted causes, treatments and prevention  but not cures. We’re simply not there yet. We’re closer to a cure than ever before, but using that emotionally-laden word more than sparingly is still premature. I applaud the organization for always putting out balanced, accurate reports with no spin or pretense.

So be hopeful, but be realistic, too. And remember that the greatest barrier to the development of better treatments is the shortage of participants in Alzheimer’s clinical trials. If you want to add a dose of activism to your mixture of hope and realism, check out the Alzheimer’s Association’s TrialMatch program and find out whether there’s a clinical trial near you.

About Guest Blog Author Carrie Steckl, Ph.D.

Carrie Steckl, Ph.D. is a freelance writer specializing in caregiving, psychology, and aging. Her blog, “Ask Dr. Chill,” provides practical answers to the toughest caregiving questions.

 

Jul 152011
 

The use of positron emission tomography (PET) imaging to diagnose Alzheimer’s disease (AD) appears to be closer to becoming a clinical tool, based on results from two articles published online in the Archives of Neurology.

In one study, Adam S. Fleisher, M.D., from Banner Alzheimer’s Institute in Phoenix, and colleagues, evaluated PET imaging using the tracer florbetapir F 18. The study population included 68 individuals with probable Alzheimer’s disease, 60 individuals with mild cognitive impairment, and 82 healthy individuals who served as controls. PET scanning was used to monitor activity of the agent being studied. Dr. Fleisher and colleagues found differences in the brain uptake of florbetapir F 18, between the three groups, and in the detection of amyloid plaque; the differences may be large enough to help distinguish between the conditions, and between impaired versus unimpaired brains.

In another study, David A. Wolk, M.D., from the Penn Memory Center in Philadelphia, and colleagues, evaluated use of a tracer called fluorine 18-labeled flutemetamol for imaging the brain. The study involved conducting PET scans on seven patients who were given the tracer. All had previously undergone a biopsy for normal pressure hydrocephalus, a progressive condition that includes dementia and can be difficult to distinguish from Alzheimer’s disease. Researchers found correspondence between readings of the PET scans and evidence of amyloid lesions the plaque associated with Alzheimer’s disease (provided by microscopic evaluation of the biopsied tissue).

    The greatest use of such scans may ultimately be to help rule out Alzheimer’s disease, instead of rule it in. That is, in the physician’s office, having a negative scan (meaning no detectable amyloid buildup in the brain) may be helpful to clinicians in ruling out Alzheimer’s disease as the cause of the memory and thinking changes a person is experiencing. However, a positive scan (showing that there is amyloid buildup in the brain) has limited utility at this point.

    Having amyloid buildup does not mean for certain that one has Alzheimer’s dementia, especially in a patient who may not have symptoms. About 30 percent of elderly people have plaque, but not Alzheimer’s dementia. It is believed that having a positive amyloid scan may reflect the early stages of Alzheimer’s disease (prior to the dementia phase) and increase one’s risk of developing Alzheimer’s dementia in the future.

    1. D. A. Wolk, I. D. Grachev, C. Buckley, H. Kazi, M. S. Grady, J. Q. Trojanowski, R. H. Hamilton, P. Sherwin, R. McLain, S. E. Arnold. Association Between In Vivo Fluorine 18-Labeled Flutemetamol Amyloid Positron Emission Tomography Imaging and In Vivo Cerebral Cortical Histopathology. Archives of Neurology, 2011

    2. A. S. Fleisher, K. Chen, X. Liu, A. Roontiva, P. Thiyyagura, N. Ayutyanont, A. D. Joshi, C. M. Clark, M. A. Mintun, M. J. Pontecorvo, P. M. Doraiswamy, K. A. Johnson, D. M. Skovronsky, E. M. Reiman. Using Positron Emission Tomography and Florbetapir F 18 to Image Cortical Amyloid in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer Disease. Archives of Neurology, 2011.

    Michael S. Rafii, M.D., Ph.D.

    Director, Memory Disorders Clinic
    Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
    University of California San Diego

    This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

    Learn More

    May 052011
     

    Congress has created a new Peer-Reviewed Alzheimer’s Research program at the Department of Defense.  The program was included in the federal spending bill signed by the president on April 15, 2011.  While countless programs received funding reductions, including a $260 million cut for the National Institutes of Health, the Alzheimer’s community secured a significant victory for Alzheimer’s research in the finalized spending bill.

    The Peer-Reviewed Alzheimer’s Research program created by Congress at the Department of Defense has been funded at $15 million for its inaugural year.  This newly created program will fund innovative and outcome-oriented research that is relevant to both the Alzheimer’s community and the military.  It will provide a vital source of new funding for Alzheimer’s researchers.

    The Alzheimer’s Association worked closely with Congress on the inclusion of this provision in the bill and looks forward to working with the Department of Defense to accelerate the development of treatments that would prevent, cure, or slow the progression of Alzheimer’s disease.  Read our full statement here.


    Oct 182010
     

    Dear Readers,

    Many of our patients and their physicians are aware that physical inactivity and obesity are at epidemic proportions in the United States, which has resulted in an increased prevalence of chronic diseases. Relatively few, however, realize that both these conditions may be associated with poor memory function.

    Let’s consider the issue of obesity. Over the years, obesity has truly become a woman’s issue. Sixty five million of the 72 million American adults who are considered obese or overweight are women. In addition African American and Hispanic women are much more likely to be obese than white women. So what does being obese or overweight have to do with cognition in women?

    Well, recent findings from the Women’s Health Initiative, suggest that the more an older woman weighs, the poorer her memory will be. In this study, a total of 8,745 cognitively normal, post-menopausal women ages 65 to 79 underwent baseline cognitive testing as part of their routine evaluation. This study used the Modified MMSE examination ( a 100 point memory test) as the measure of cognitive function. The 3MSE has been widely used in large population based studies as a cognitive tool and has demonstrated good consistency, reliability, sensitivity and specificity for detecting cognitive impairment and dementia. For all women, both waist and hip measurements in addition to body mass index ( BMI) calculations were obtained. All the women were classified into BMI categories that corresponded to the standard World Health Organization classifications for normal weight, underweight, overweight and obesity.

    The majority of women in this sample ( 86.6% white) were classified as overweight or obese ( 70%). For every one-point increase in a woman’s BMI, her memory score dropped by one point.( p<0.001). These findings were adjusted for age and educational level and remained unchanged after controlling for common chronic conditions such as diabetes, heart disease and stroke.

    When the analyses included waist-hip ratio, BMI and 3MSE, the 3MSE scores for women with low waist-hip ratio decreased as the BMI category increased, although this relationship reversed for women with the highest waist-hip ratios. The 3MSE score increased (i.e. better cognition) with increasing BMI in the highest waist-hip ratio category. These results suggest that women who have a “pear shaped” body type (fat deposited around the hips) have poorer cognitive function compared to “apple shaped” body type women (fat deposited around the waist).

    One explanation for these findings is that the production of endogenous estrogen (i.e. “natural” estrogen produced by the body) by abdominal adipocytes ( fat cells) may play a protective role for cognitive function and may be less detrimental than fat in other areas. Further research in this area, and whether any notable differences in the strength and nature of these associations across diverse ethnic groups, will need to be explored.

    Check out the articles and links below to learn more:

    Thanks for reading.

    Neelum T. Aggarwal, M.D.
    Steering Committee Member, ADCS
    This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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