Friday, July 31, 2009

What you should know
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Alzheimer's disease and other dementias do a number on the mind and body of the individual with the disease and can also take a major toll on the health and finances of the individual's family. The Alzheimer's Association's latest annual report, "2009 Alzheimer's Disease Facts and Figures," documents the multilevel impact of the disease that 5.3 million Americans are living with today, which translates into a new case of Alzheimer's every 70 seconds. And as the oldest baby boomers are due to reach age 65 over the next two years, that rate will balloon by midcentury, so that someone will develop Alzheimer's disease every 33 seconds.

As the burden of Alzheimer's disease grows, states' healthcare infrastructure will be strained; some states will see more than an 80 percent increase in residents with Alzheimer's by 2025. U.S. News caught up with Angela Geiger, chief strategy officer at the Alzheimer's Association, to discuss some of the finer points of the new report.

1) Alzheimer's disease is more than lost memories. Forgetfulness is a hallmark symptom, but the disease cuts deeper. "Your body forgets how to function," explains Geiger. In fact, Alzheimer's disease causes death, as its progression eventually prevents the individual from engaging innate abilities like moving and swallowing.

2) Early diagnosis may garner better care. According to 2009 research in the journal Alzheimer's and Dementia, people 70 and older who were told they had Alzheimer's or dementia by a doctor and were aware of it--or had family members who knew--tended to have more doctor contact and fewer days in the hospital. But early diagnosis, which can translate into a care plan that can have a significant impact on the quality of life of the individual and the family, is not always attained. "We know people don't know enough about early signs [of the disease]," including healthcare professionals, says Geiger. Mood and behavior changes, an early warning sign of Alzheimer's, often get misdiagnosed as depression, for example.

3) Alzheimer's patients have higher out-of-pocket costs. People 65 or older with Alzheimer's disease or dementia pay 30 percent more in out-of-pocket healthcare costs than those without such disease, according to the new annual report.

4) Total healthcare spending is radically higher in Alzheimer's families. Add up all the healthcare dollars spent by various payers--including Medicare, Medicaid, and private insurers--on people 65 or older with Alzheimer's or dementia, and you get triple the burden of people without, says the new Alzheimer's Association report. "The costs get greater and greater as the disease progresses," says Geiger, and more consistent, specialized care is needed, typically resulting in 24-hour nursing home care.

5) Additional medical conditions complicate matters. The majority of people with Alzheimer's or dementia also have at least one other serious medical condition, according to a January report by the Dartmouth Institute for Health Policy and Clinical Practice. For example, 60 percent also have hypertension, 26 percent have coronary heart disease, 23 percent have diabetes, and 18 percent have osteoporosis. The presence of Alzheimer's or other dementia only complicates the management of another chronic disease. To properly control diabetes, notes Geiger, vigilant daily maintenance is required, from checking blood sugar to taking insulin to being extremely conscientious about food choices.

6) Hospital trips become more frequent. Having Alzheimer's or another form of dementia at age 65 or older resulted in triple the likelihood of a hospital stay compared with people without such an illness, says the January Dartmouth report. And the frequency extends to caregivers, too. A 2008 Journal of General Internal Medicine study found that nearly 1 in 4 caregiver spouses of people with Alzheimer's or dementia required a trip to the emergency room or hospitalization.

7) Family caregivers take a personal health hit. Multiple studies have found that unpaid caregivers for those who have Alzheimer's or other dementia are more likely to have higher levels of stress hormones, reduced immune function, new hypertension, and new heart disease than noncaregivers. Geiger stresses the importance of caregivers' efforts to alleviate their own stress: "We want to break down that isolation." She encourages caregivers to participate in local face-to-face support groups or, if they prefer, anonymously in online message boards.

8) Family caregivers face a long haul. People with Alzheimer's and dementia typically experience a slow progression of the disease, so family caregiving is often a long-term prospect. A 2004 report by the Alzheimer's Association and the National Alliance for Caregiving found that at any one time, nearly a third of these caregivers have been at it for five years or longer and nearly 40 percent have been doing so for one to four years.

9) Family caregivers do the job free. The Alzheimer's Association estimates that in 2008, 9.9 million caregivers--from children and other family members to friends and neighbors--provided 8.5 billion hours of unpaid care, which amounts to some $94 billion in value. On top of that, these caregivers pay an average of $219 per month out of their own pockets, according to the 2004 report by the Alzheimer's Association and the National Alliance for Caregiving.

10) The states will feel an increasing burden. The annual report estimates that by 2025, the western states of Washington, Oregon, Nevada, Idaho, Utah, Montana, Wyoming, Colorado, and Alaska will experience growth in the number of residents with Alzheimer's of between 81 percent and 127 percent compared with 2000. Also by 2025, California and Florida, where more than 500,000 residents will have the disease, will lead the nation in volume.
...http://www.wtxx.com

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Thursday, July 30, 2009

Key Alzheimer's Brain Changes Observed In Unimpaired Older Humans
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New research has uncovered an early disruption in the process of memory formation in older humans who exhibit some early brain changes associated with Alzheimer's disease (AD) but show little or no memory impairment. The work, published in the July 30th issue of the journal Neuron, sheds light on the role of amyloid protein in memory impairment and may lead to development of strategies for predicting and treating cognitive decline in individuals who are at-risk for AD.
Amyloid beta-protein plays a major pathogenic role in AD, a devastating neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. In fact, one of the primary characteristics of AD is the accumulation and deposition of neuron-damaging clumps of amyloid protein. Previous studies have led to the suggestion that amyloid deposition begins many years prior to the onset of clinical symptoms. However, the exact link between amyloid deposition and memory impairment has not been clearly demonstrated in humans.
"Two recent advances in neuroimaging now allow us to explore the early, asymptomatic phase of AD, the ability to measure amyloid distribution in living humans and the identification of sensitive markers of brain dysfunction in AD," explains lead study author, Dr. Reisa Sperling from the Center for Alzheimer's Research and Treatment at Brigham and Women's Hospital in Boston. In addition to amyloid accumulation, AD has been associated with functional alterations in a specific network of brain regions that are intimately linked with memory formation.
Dr. Sperling and colleagues combined amyloid imaging with an associative memory functional brain imaging paradigm to study older humans who did not exhibit significant memory impairment. Importantly, the researchers found that a significant number of nondemented older individuals exhibited amyloid deposition and abnormal neural activity in key areas of the brain network thought to be involved in successful memory function. These results demonstrate for the first time that amyloid pathology in asymptomatic older humans is linked with aberrant neural responses during the process of memory formation.
"Longitudinal studies are certainly needed, but our findings are consistent with the premise that cognitively intact older individuals with amyloid pathology may already be in the early stages of AD," explains Dr. Sperling. "The combination of molecular and functional imaging techniques may prove useful in monitoring disease progression prior to significant clinical symptoms, as well as the response to amyloid-modifying therapeutic agents in subjects at-risk for developing AD."
...http://www.modernmedicine.com

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A daily supplement of Lactobacillus and Bifidobacterium strains may reduce the incidence of cold and 'flu-like symptoms in children by 50 per cent, says a new study from Danisco. ...http://www.nutraingredients.com


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Wednesday, July 29, 2009

Need more research to clarify dimebolin affects
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In a surprising result, acute treatment with the drug dimebolin, currently in clinical development for Alzheimer's disease, increased excreted amyloid-β (Aβ) protein levels in a study presented at the 2009 International Conference on Alzheimer's Disease, held July 11 to 16 in Vienna, Austria.

Samuel Gandy, M.D., of Mount Sinai School of Medicine in New York City, and colleagues evaluated the molecular effects of dimebolin. The investigators used preclinical models, including cultured N2a mouse neuroblastoma cells overexpressing the SweAPP gene, isolated nerve terminals from transgenic TgCRND8 mice overexpressing the Swe/Indiana-APP gene, and freely moving Tg2576 transgenic mice overexpressing the SweAPP gene.

The researchers found that acute treatment with dimebolin increased the amount of Aβ levels released from the isolated nerve terminals of TgCRND8 mice. Interstitial fluid from dimebolin-treated Tg2576 mice also exhibited increased levels of Aβ protein. In contrast, the authors note, the media conditioned by dimebolin-treated SweAPP N2a cells showed either no difference or a decrease in the amount of Aβ protein. These results were consistent regardless of the preparation of dimebolin used (obtained from two independent vendors).

"This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer's drug," Gandy said in a statement. "We need more research to further clarify how dimebolin affects Aβ levels in the brain." For example, chronic dimebolin treatment may have a different effect than observed with the acute treatment used in this study.
...http://www.modernmedicine.com

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Antioxidants from black tea may aid diabetics

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Tuesday, July 28, 2009

Alzheimer's-Causing Amyloid And Bacteria

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In a new study published today in the July issue of the journal Cell Host & Microbe, UC Davis researchers report that both amyloid plaques found in the brains of Alzheimer's patients and structures made by some gut bacteria likely elicit the same response by human immune cells.

"Alzheimer's disease may be a case of mistaken identity," said Andreas Bäumler, a professor of microbiology and medical immunology. Bäumler and his colleagues showed that the immune systems of mice injected with E. coli and salmonella are triggered by curli fibrils, fiber-like structures consisting of curli proteins that allow bacteria to stick to host tissue and to each other and form colonies.

Curli fibrils are morphologically identical to amyloid fibrils found in Alzheimer's plaques. When they presented human cells with the two kinds of fibrils, they saw the same immune response - even though the two have nothing in common in their amino acid sequences.

"Our results suggest that it's the structure of these protein aggregates that matter and that, to the innate immune system, Alzheimer's plaques may look like colonies of bacteria. This would result in the chronic inflammation we see in Alzheimer's disease that damages neurons," Bäumler explained.

Amyloid plaques are the sticky buildup of proteins that accumulate outside nerve cells. They are characteristic of several illnesses, including Alzheimer's disease, Huntington's disease, type 2 diabetes, secondary amyloidosis and prion diseases, like Creutzfeldt-Jakob (the human form of mad cow disease). These diseases all involve marked inflammation at the sites of amyloid deposition, resulting in tissue injury.

The protein forming plaques in Alzheimer's patients is normally soluble. When the protein folds improperly, it forms amyloid deposits that are associated with brain inflammation. Until now, scientists have not been able to identify what causes this destructive, chronic inflammation.

Bäumler and his colleagues did not expect to be studying Alzheimer's disease. They were studying inflammation of the gut caused by bacteria when they discovered that the innate immune system was being triggered by a structural feature of bacterial amyloids and not by the amino acids that make up the proteins in the biofilms.

"When we destroyed the ability of the proteins to aggregate, we no longer saw the same immune response," Bäumler said.

When the researchers figured out the amyloid structure was responsible for triggering the immune system, they decided to see whether the same immune response was being triggered by structurally identical amyloids associated with human disease. They chose to study the synthetic form of the proteins that make up Alzheimer's plaques because the disease has been widely studied and a lot is known about the biochemistry of these plaques.

In the current study, Bäumler and his team found that, in mice, the immune response to curli fibrils is controlled by a protein called TLR-2 (Toll-like receptor 2). TLR-2 is expressed on the surface of certain cells that recognize foreign substances and passes on appropriate signals to the cells of the immune system.

Next, the team used cultures of human immune system cells to see if synthetic versions of the major curli fibril protein (CsgA) and the major protein found in amyloid plaques, (beta-amyloid) would trigger the TLR-2 response. They used cultures of macrophage cells, immune cells that engulf and digest cellular debris and pathogens. They also used microglia, which are essentially macrophages of the brain.

The team found that the mechanism involving TLR-2 was triggered by both CsgA and beta-amyloid but only when these proteins were allowed to aggregate into amyloids.

"The CsgA peptide and beta-amyloid don't have anything genetically in common. The similarity is only in the structure of the amyloids they form. Our study indicates that there is some structural feature of amyloids that triggers the innate immune system," Bäumler said.

The current findings are only the first step in what may ultimately be a drug treatment for amyloid diseases. If researchers can find a drug that inhibits the TLR-2-dependent immune response, Bäumler said, they could potentially slow down the progression of amyloid diseases, including Alzheimer's.

"You have to know what causes the diseases in order to find the right drug target. Now we know what's causing the chronic inflammation associated with amyloids. It's a start, though we're still a long from finding a treatment," he said. ...http://www.medilexicon.com

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Wednesday, July 01, 2009






Alzheimer's disease