New Target For Future Alzheimer’s Disease Blood Test Reported

May 5, 2011

A new blood test that will diagnose Alzheimer’s disease may soon hit the market, thanks to an innovative study from the Research Institute of the McGill University Health Centre (MUHC). Their findings have characterized a unique biochemical diagnosis, which identifies patients with this devastating disorder. This research, published in the month’s issue of the Journal of Alzheimer’s Disease, has implications for the half-a-million Canadian sufferers and many millions more worldwide.

“Until now, there has been no definitive diagnostic tool for Alzheimer’s, other than postmortem analysis of brain tissue,” says senior author Dr. Vassilios Papadopoulos, director of the MUHC Research Institute. “Our clinical study shows that a non-invasive blood test, based on a biochemical process, may be successfully used to diagnose Alzheimer’s at an early stage and differentiate it from other types of dementia.”

Papadopoulos and colleagues based the Alzheimer’s blood test on the production of a brain hormone called dehydroepiandrosterone (DHEA). This hormone is present at high levels in the brain where it has a wide range of biological effects.

The researchers were able to promote the production of DHEA, using a chemical process called oxidation, in blood taken from non-Alzheimer’s patients. However, oxidation of blood from Alzheimer’s patients did not result in an increase of DHEA.

“There is a clear correlation between the lack of ability to produce DHEA through oxidation in the blood and the degree of cognitive impairment found in Alzheimer’s disease,” says Papadopoulos. “We demonstrated we could accurately and repetitively detect Alzheimer’s disease, with small samples of blood. This test also allowed for differential diagnosis of early stages of Alzheimer’s disease, suggesting this can be used as a test to diagnose the disease in its infancy.”

“There are many candidate disease-modifying therapies that target the underlying development of Alzheimer’s disease, which are in clinical trials,” adds Papadopoulos. “However, the implementation of any therapy is dependent on the reliability of the diagnosis.” Currently the diagnosis of Alzheimer’s follows the sequence of family history, information, mental assessment and the physical exam, focusing on neurological signs.

“An accurate, easy and specific non-invasive biochemical test that correlates with clinical findings is vital. We believe our results demonstrate that the DHEA-oxidation blood test can be used to diagnose Alzheimer’s at a very early stage and monitor the effect of therapies and the evolution of the disease.”

Adapted from the McGill University Health Centre
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Higher Levels Of Social Activity May Decrease The Risk Of Cognitive Decline

April 26, 2011

If you want to keep your brain healthy, it turns out that visiting friends, attending parties, and even going to church might be just as good for you as crossword puzzles.

According to research conducted at Rush University Medical Center, frequent social activity may help to prevent or delay cognitive decline in old age. The study has just been posted online in the Journal of the International Neuropsychological Society. The researchers were especially careful in their analysis to try to rule out the possibility that cognitive decline precedes, or causes, social isolation, and not the reverse.

“It’s logical to think that when someone’s cognitive abilities break down, they are less likely to go out and meet friends, enjoy a camping trip, or participate in community clubs. If memory and thinking capabilities fail, socializing becomes difficult,” said lead researcher Bryan James, PhD, postdoctoral fellow in the epidemiology of aging and dementia in the Rush Alzheimer’s Disease Center. “But our findings suggest that social inactivity itself leads to cognitive impairments.”

The study included 1,138 older adults with a mean age of 80 who are participating in the Rush Memory and Aging Project, an ongoing longitudinal study of common chronic conditions of aging. They each underwent yearly evaluations that included a medical history and neuropsychological tests.

Social activity was measured based on a questionnaire that asked participants whether, and how often, in the previous year they had engaged in activities that involve social interaction—for example, whether they went to restaurants, sporting events or the teletract (off-track betting) or played bingo; went on day trips or overnight trips; did volunteer work; visited relatives or friends; participated in groups such as the Knights of Columbus; or attended religious services.

Cognitive function was assessed using a battery of 19 tests for various types of memory (episodic, semantic and working memory), as well as perceptual speed and visuospatial ability.

At the start of the investigation, all participants were free of any signs of cognitive impairment. Over an average of five years, however, those who were more socially active showed reduced rates of cognitive decline. On average, those who had the highest levels of social activity (the 90th percentile) experienced only one quarter of the rate of cognitive decline experienced by the least socially active individuals. Other variables that might have accounted for the increase in cognitive decline—such as age, physical exercise, and health—were all ruled out in the analysis.

Why social activity plays a role in the development of cognitive problems is not clear. According to James, one possibility is that “social activity challenges older adults to participate in complex interpersonal exchanges, which could promote or main efficient neural networks in a case of ‘use it or lose it.’”

Future research is needed to determine whether interventions aimed at increasing late-life social activity can play a part in delaying or preventing cognitive decline, James said.

Adapted from Rush University Medical Center
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New Guidelines for Diagnosis of Alzheimer’s Disease

Expert Panels Define Early Stages of Disease with Biomarkers and Brain Imaging

April 21, 2011

The clinical guidelines for diagnosing whether someone has Alzheimer’s disease haven’t been updated since 1984. For the past 27 years, a person had to show dramatic memory problems and in many cases “severe” cognitive decline before being diagnosed with Alzheimer’s. In most cases, this diagnosis couldn’t be confirmed until after death, when an autopsy would reveal a brain riddled with abnormal protein deposits called plaques and tangles. Now, new guidelines for Alzheimer’s disease definition and diagnosis have been put together by three expert panels and appear in a series of publications in the April 19 issue of the Alzheimer’s & Dementia journal.

The updated guidelines redefine the disease progression to include an early “preclinical” stage, a middle stage called “mild cognitive impairment (MCI) due to Alzheimer’s disease,” and a final stage of dementia due to the Alzheimer’s related changes in the brain. In particular, the guidelines have added new detection methods to define each stage and determine whether any clinical change in thinking or memory is specifically due to Alzheimer’s.

The findings are not without controversy. While all agree that medical research stands to greatly benefit from new assessment criteria, some media outlets have shrugged their shoulders, suggesting that this is more about calls for increased funding than for an immediate impact on concerned families.

Under the new guidelines, clinical definitions of cognitive decline are combined with what is known about protein biomarkers and brain imaging technologies such as MRI and PET scans. These panels clarified the difference between the presence of biological changes in the brain (beta-amyloid and tau proteins, the hallmarks of plaques and tangles, respectively) and the appearance of changes in brain function or cognitive decline. “There have been tremendous advances in biomarker research which now allow us to detect evidence of early Alzheimer’s disease pathology in the living brain, likely more than a decade before clinical dementia,” said Reisa A. Sperling, M.D., Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, Harvard Medical School, who chaired the “preclinical” panel.

Since cognitive symptoms are believed to appear long after structural or biochemical changes, the panels reasoned that evidence of these chemical or structural changes could be accepted as an indication of Alzheimer’s disease. “The Alzheimer’s disease process is long and goes on for years before the symptoms become severe,” says Bradley T. Hyman, M.D., Ph.D., Professor in the Department of Neurology, Massachusetts General Hospital and Harvard Medical School, chair of the dementia panel and contributor to the two other panels. “We hope that by diagnosing this disease in early stages, we’ll be able to develop disease-modifying treatments.”

One of the updates to the old guidelines is the definition of the middle stage, “MCI due to Alzheimer’s disease.” Previously, MCI was not necessarily specific to Alzheimer’s disease. MCI, on its own, is defined as a set of mild cognitive difficulties that can be caused by Alzheimer’s and also by a number of other conditions, like stroke, problems with blood vessels in the brain, dementia associated with Parkinson’s disease, depression, drug interactions, and others.

With the new guidelines, if someone has the clinical signs of MCI and is positive for characteristics of Alzheimer’s such as abnormal beta-amyloid and tau protein biomarkers, then there’s an increasing likelihood that this is the new classification “MCI due to Alzheimer’s disease” rather than just “MCI.” If someone is negative for both biomarkers, then the MCI is unlikely to be due to Alzheimer’s and the clinician can look for other causes that would be managed and treated differently.

Currently, there are no disease-modifying treatments for Alzheimer’s disease. Existing medications serve only to address symptoms without affecting the underlying progression of the disease. Concerned patients or family members are presented with the dilemma of whether an earlier positive diagnosis of Alzheimer’s disease might provide a benefit or cause them greater stress.

Although many of the technologies described in the new criteria are not widely available at this time and are largely limited to facilities actively involved in research, there may be some immediate benefits to clinicians and patients with access to the tools. “These new guidelines help to better define whether someone’s initial difficulties with cognition are due to Alzheimer’s disease versus another cause,” says David M. Holtzman, M.D., Professor and Chairman of the Department of Neurology at Washington University School of Medicine, and expert on the “MCI due to Alzheimer’s disease” panel. Though many dementias remain untreatable, some causes such as tumors or abnormal pressure in the brain may be treatable. “In addition,” says Holtzman, “the guidelines allow for a standardized way to diagnose Alzheimer’s disease at all stages of the illness. This will be particularly important as effective treatments are being developed to delay the onset or prevent the disease.”

The promise of early diagnosis may have benefits that are not, strictly speaking, biological. “Disease-modifying treatments are our holy grail, but we also have to focus on the idea that biological changes are not the only toll that Alzheimer’s disease has on patients and families,” says Guy Eakin, Vice President of Scientific Affairs at the American Health Assistance Foundation. “Even if we can’t yet cure Alzheimer’s, new technologies may give patients and families valuable time to prepare for life changes.” In addition, many caregivers must make career, legal and financial decisions, as they prepare to devote more and more time and resources to caring for someone with Alzheimer’s disease. Says Eakin, “For some families, even a few extra months may make a world of difference—especially if those months position the patient to have a greater voice in these decisions.”

Co-authors Bradley T. Hyman, M.D., Ph.D., Massachusetts General Hospital and Harvard Medical School, David M. Holtzman, M.D., Washington University School of Medicine, Reisa A. Sperling, M.D., Brigham and Women’s Hospital, Massachusetts General Hospital, and Harvard Medical School, and Kristine Yaffe, M.D., University of California, San Francisco, are grant recipients of by AHAF’s Alzheimer’s Disease Research program. Co-authors Dennis Dickson, M.D., Mayo Clinic, Jacksonville, David M. Holtzman, M.D., Washington University School of Medicine, and William Jagust, M.D., University of California, Berkeley, serve as scientific advisors to AHAF.

For the full press releases from the National Institute on Aging/National Institutes of Health and Alzheimer’s Association (who jointly convened the expert panels), and for copies of the original publications from the Alzheimer’s & Dementia journal, please refer to the following websites:

National Institutes on Aging/National Institutes of Health:
http://www.nia.nih.gov/NewsAndEvents/PressReleases/PR20110419guidelines.htm

Alzheimer’s Association:
http://www.alz.org/research/diagnostic_criteria/overview.asp?type=homepageflash

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Brain Starts Shrinking Nearly A Decade Before Alzheimer’s Appears

April 19, 2011

Areas of the brain affected by Alzheimer’s disease may start shrinking up to a decade before dementia is diagnosed, according to a new study published in the April 13, 2011, issue of Neurology®, the medical journal of the American Academy of Neurology.

For the study, researchers used MRI scans to measure areas of the brain in people with no memory problems or other signs of Alzheimer’s, then followed them for years to see who developed the disease. The researchers specifically focused their measurements on areas known to be involved in AD. Those with smaller brain size in the Alzheimer’s-related areas of the brain were much more likely to develop the disease than those with larger measurements.

“This measure is potentially an important imaging marker of early changes in the brain associated with Alzheimer’s disease that could help predict who might develop the dementia associated with this disease and possibly even how long it would be before dementia develops,” said study author Bradford Dickerson, M.D., of Harvard Medical School in Boston and a member of the American Academy of Neurology.

The study involved two separate groups of people with no signs of Alzheimer’s. In the first group, 33 people were followed for an average of 11 years. During that time, eight of the participants developed Alzheimer’s disease dementia. In the second group, 32 people were followed for an average of seven years, and seven of them developed the disease.

The participants were divided into three groups based on the brain scans: those with low, average and high measurements in the Alzheimer’s-related areas. Of the 11 people who had the lowest MRI measurements, 55 percent developed Alzheimer’s, while none of the nine people with the highest measurements developed dementia. Of those with average measurements, 20 percent developed the disease.

“We also found that those who express this MRI marker of the Alzheimer’s disease in the brain were three times more likely to develop dementia over the following 10 years than those with higher measurements,” Dickerson said. “These are preliminary results that are not ready to be applied outside of research studies right now, but we are optimistic that this marker will be useful in the future.”

Adapted from American Academy of Neurology

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