Thyroid Drugs May Raise Fracture Risk in Elderly

30 april 2011-- Many seniors may be at increased risk for fractures because they take "excessive" doses of drugs used to treat thyroid problems, a new study says.

The findings suggest that treatment targets may have to be modified in elderly patients with thyroid problems and that regular dose monitoring of thyroid drugs is essential into older age, the researchers said.

Reporting in the online April 28 edition of the BMJ, they examined the link between fractures and levothyroxine, a synthetic form of thyroid hormone, which is widely used to treat an underactive thyroid gland (hypothyroidism).

Many patients with hypothyroidism are diagnosed in early or middle adulthood. Even though their treatment requirements change as they age, many patients remain on the same drug dose. This can lead to excess levels of thyroid hormone, which increases the risk of fractures, especially in older women, the study authors explained.

They analyzed data from over 213,500 patients, aged 70 or older, in the province of Ontario, Canada, who filled at least one prescription for levothyroxine between April 1, 2002 and March 31, 2007. During the study period, more than 22,000 (10.4 percent) of the patients suffered at least one fracture.

Current and recent past users (who had discontinued the drug 15 to 180 days before the start of the study) had a significantly higher fracture risk than "remote" users (who had discontinued use of the drug more than 180 days before the start of the study).

Among current users, those who took high or medium doses of the drug were much more likely to suffer a fracture than those who took a low dose.

"Our findings provide evidence that levothyroxine treatment may increase the risk of fragility fractures in older people even at conventional dosages, suggesting that closer monitoring and modification of treatment targets may be warranted in this vulnerable population," concluded Lorraine Lipscombe, a scientist at the Women's College Research Institute in Toronto, and colleagues.

One expert wasn't surprised by the findings.

"It has long been known that high or excessive doses of levothyroxine usage predispose [people] to increases in osteoporosis and the risk of fracture," said Dr. Irwin Klein, director of the thyroid unit and associate chairman of the department of medicine at the North Shore-LIJ Health System in Manhasset, N.Y. "This study further confirms this finding in an elderly population of women who are inherently at risk for this occurrence."

Klein also noted that the study underscores the need for preventive action.

"As the authors conclude, it is important to monitor thyroid blood tests -- especially TSH levels -- to prevent this potential adverse health burden," he said.

Increased metabolic rate may lead to accelerated aging

A recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM) found that higher metabolic rates predict early natural mortality, indicating that higher energy turnover may accelerate aging in humans.

29 april 2011--Higher energy turnover is associated with shorter lifespan in animals, but evidence for this association in humans is limited. To investigate whether higher metabolic rate is associated with aging in humans, this study examined whether energy expenditure, measured in a metabolic chamber over 24 hours and during rest predicts natural mortality.

"We found that higher endogenous metabolic rate, that is how much energy the body uses for normal body functions, is a risk factor for earlier mortality," said Reiner Jumpertz, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, Ariz., and lead author of the study. "This increased metabolic rate may lead to earlier organ damage (in effect accelerated aging) possibly by accumulation of toxic substances produced with the increase in energy turnover."

"It is important to note that these data do not apply to exercise-related energy expenditure," added Jumpertz. "This activity clearly has beneficial effects on human health."

In this study, researchers evaluated 652 non-diabetic healthy Pima Indian volunteers. Twenty four hour energy expenditure (24EE) was measured in 508 individuals, resting metabolic rate (RMR) was measured in 384 individuals and 240 underwent both measurements on separate days. Data for 24EE were collected in a respiratory chamber between 1985 and 2006 with a mean follow-up time of 11.1 years. RMR was evaluated using an open-circuit respiratory hood system between 1982 and 2006 with a mean follow-up time of 15.4 years.

During the study period, 27 study participants died of natural causes. Researchers found that as energy expenditure increased, there was also an increase in risk for natural mortality.

"The results of this study may help us understand some of the underlying mechanisms of human aging and indicate why reductions in metabolic rate, for instance via low calorie diets, appear to be beneficial for human health," said Jumpertz.

More information: The article, "Higher energy expenditure in humans predicts natural mortality," appears in the June 2011 issue of JCEM.

Provided by The Endocrine Society

WHO warns of enormous burden of chronic disease

28 april 2011– Chronic illnesses like cancer, heart disease and diabetes have reached global epidemic proportions and now cause more deaths than all other diseases combined, the World Health Organization (WHO) said on Wednesday.

In its first worldwide report on so-called non-communicable diseases, or NCDs, the United Nations health body said the conditions caused more than half of all deaths in 2008 and pose a greater threat than infectious diseases such as malaria, HIV and tuberculosis (TB) -- even in many poorer countries.

"The rise of chronic noncommunicable diseases presents an enormous challenge," WHO Director-General Dr Margaret Chan, who launched the report at a meeting in Moscow, said in a statement.

"For some countries, it is no exaggeration to describe the situation as an impending disaster; a disaster for health, for society, and most of all for national economies," she said.

NCDs, which include heart disease, lung diseases, cancer and diabetes, accounted for 36 million, or 63 percent, of the 57 million deaths worldwide in 2008. Millions of lives could be saved and much suffering avoided if people did more to avoid risk factors like smoking, drinking and being overweight, the WHO said.

It found that almost 6 million people die from tobacco use every year -- both directly from smoking, and indirectly from second-hand smoke. By 2020, this will increase to 7.5 million, 10 percent of all deaths by disease worldwide.

On top of this, 3.2 million people die each year as a result of a lack of physical activity, at least 2.8 million as a result of being overweight or obese, and 2.5 million as a result of drinking harmful levels of alcohol.

"The NCD epidemic exacts an enormous toll in terms of human suffering and inflicts serious damage to human development in both the social and economic realms," the WHO report said.

"This state of affairs cannot continue ... Unless serious action is taken, the burden of NCDs will reach levels that are beyond the capacity of all stakeholders to manage."

A special meeting of the United Nations General Assembly is scheduled for September in New York to talk about the rising threat of NCDs, and the WHO's global status report set out ways to map the epidemic, reduce its major risk factors and improve healthcare for those who already suffer from NCDs.

It said the epidemic was already beyond the capacity of poorer countries to cope, which is why death and disability are rising disproportionately in these countries.

"As the impact of NCDs increases and as populations age, annual NCD deaths are projected to continue to rise worldwide, and the greatest increase is expected to be seen in low- and middle-income regions," it added.

In many developing countries where the health focus is often on infectious diseases, chronic illnesses are often detected late, when patients need extensive and expensive hospital care.

Most of this care is unaffordable or unavailable, or is covered with out-of-pocket payments which can drive patients and their families into poverty, further risking their health.

Nearly 80 percent of NCD deaths occur in low- and middle-income countries and NCDs are the most frequent causes of death in most countries, except in Africa, the WHO said. Even in Africa, NCDs are rising rapidly and are expected to exceed other diseases as the most common killers by 2020.

The WHO said three priorities for action were surveillance -- to monitor chronic diseases; prevention -- to tell people about the risks and help them adapt their lifestyle; and healthcare -- to improve treatment of those who are sick.

It listed 10 action points, including banning smoking in public places, enforcing tobacco advertising bans, restricting access to alcohol and cutting salt in food, and said taking these steps now would save lives, prevent diseases and avoid heavy costs.

Fitness and frailty in adults linked to health outcomes

The prevalence of frailty, which is linked to earlier death, increases throughout adulthood as people age and not just after age 65, found an article in CMAJ (Canadian Medical Association Journal). Relatively good fitness levels at all ages were predictive of lower mortality and less reliance on health care services.

27 april 2011--Frailty in medical terms refers to a person's health status and the risk of adverse events related to various health conditions. It is usually associated with older adults.

The researchers sought to understand the impact of age on fitness and frailty, the profile of relatively fit people aged 15 to 102 compared with frail adults and the impact of fitness and frailty related to age and sex on mortality. They looked at data on 14 713 people, of whom 54% were women, over a 12 year period from 1994-95 to 2006-07 with two-year monitoring intervals. A Frailty Index, used to grade risk, rated people's health levels and the accumulation of health deficits. These included diseases, disabilities (e.g. needed help with meal preparation), symptoms (e.g. hearing impairment), allergies and other conditions.

Most participants (7183) reported fairly high relative fitness at the start of the study compared with 1019 who were frail. These relatively fit people generally stayed healthy and those who were frail at the start were most likely to die. As participants aged, their frailty level increased.

"We found that the prevalence of frailty increased exponentially with age throughout the adult life span and not just after age 65, where the sharpest inflection of the curve occurred," writes Dr. Kenneth Rockwood, Dalhousie University, and the Centre for Health Care of the Elderly, Halifax, Nova Scotia, with coauthors. "At all ages, relatively fit people had a lower mortality and used fewer health care services."

People with higher frailty levels used more health care services and the risk of institutionalization increased for the frailest.

"That deficits accumulate with age is not surprising; indeed, at the subcellular level, this is said to be how aging occurs," write the authors. "Our data suggest that deficit accumulation is a fact of aging, not age, and that the antecedents of frailty in late life manifest at least by middle age."

The authors suggest a more integrated approach to managing frail patients is required given the complex nature of frailty.

Provided by Canadian Medical Association Journal

ACC/AHA issue first clinical guidance for controlling high blood pressure in the elderly

Hypertension is very common among older adults. 64 percent of older men and 78 percent of older women have high blood pressure, placing them at heightened risk for heart disease including heart failure, stroke, coronary artery disease and atrial fibrillation, as well as chronic kidney disease and diabetes mellitus. Despite its prevalence, rates of blood pressure control remain substantially lower in the elderly than in younger patients. In fact, over age 80, only one in three men and one in four women have adequate control of their blood pressure. Faced with an aging patient population and compelling data that confirm the benefits of blood pressure-lowering medications in the elderly (≥80 years), the American College of Cardiology (ACC) and the American Heart Association (AHA) today released the first expert consensus document to help clinicians reduce the risks for developing and effectively manage hypertension in older adults.

26 april 2011--"Adequate control of high blood pressure in the elderly can significantly reduce cardiovascular events and mortality, and is much more cost-effective than treating heart problems that result from uncontrolled hypertension," said Wilbert S. Aronow, M.D., clinical professor of medicine at New York Medical College/Westchester Medical Center and one of the chairs of the ACC/AHA writing committee. "The real concern is that a majority of elderly people have suboptimal control of their blood pressure and – until recently – many clinicians didn't treat hypertension in octogenarians because they worried that doing so would increase mortality."

Moreover, most hypertension trials had upper age limits or failed to present age-specific results. But in 2008, results from the Hypertension in the Very Elderly Trial (HYVET) – the largest clinical trial in very elderly patients with hypertension to date – began to shift this thinking. According to Dr. Aronow, this was the first study to show clear benefits for using anti-hypertensive therapy in people 80 years and older, including a 30 percent reduction in stroke, 23 percent reduction in cardiac death, 64 percent reduction in heart failure and 21 percent reduction in all-cause mortality.

"HYVET was the main impetus for developing this consensus document, which is designed to provide the medical community with systematic recommendations to lower blood pressure in older adults," said. Dr. Aronow. "Treating hypertension in the elderly is particularly challenging because they usually have several health problems and a greater prevalence of cardiovascular risk factors and cardiac events. There also needs to be greater vigilance to avoid treatment-related side effects such as electrolyte disturbances, renal dysfunction, and excessive orthostatic blood pressure decline."

Some of the consensus recommendations addressed in the new ACC/AHA consensus document include:

• There has been uncertainty about the appropriate therapeutic target for patients ≥80 years of age. Levels of less than 140/90 mm Hg in persons 65-79 years and a systolic blood pressure between 140 and 145 mmHg in persons 80 years and older if tolerated were discussed; hypertension in older adults is usually characterized by an elevated systolic blood pressure and a normal or low diastolic BP due to age-associated stiffening of the large arteries.
  
• Use of medications as appropriate. Angiotensin converting enzyme (ACE) inhibitors, beta blockers, angiotensin receptor blockers, diuretics and calcium channel blockers are all effective in lowering blood pressure and reducing cardiovascular outcomes among the elderly; clinicians should select medications based on efficacy, tolerability, specific comorbidities, and cost. For example, if someone has had a heart attack, they should be started on a beta blocker and an ACE inhibitor.
  
• Initiation of antihypertensive drugs in this population should generally be at the lowest dose with gradual increments as tolerated.
  
• Routine monitoring of blood pressure, including taking blood pressure measures in the standing position.
  
• Encouragement of lifestyle changes to prevent and treat hypertension among older adults; these include regular physical activity, restriction of salt, weight control, smoking cessation and avoiding excessive alcohol intake (more than two drinks for men and one drink for women)

Experts say the high cost of blood pressure lowering medications also contributes to low rates of blood pressure control in the elderly and should be discussed with patients.
Provided by American College of Cardiology

Kidney disease coupled with heart disease common problem in elderly

Chronic kidney disease (CKD) is common and linked with heart disease in the very elderly, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN).

25 april 2011--CKD is a major public health problem that disproportionately affects the elderly. Shani Shastri, MD, Mark Sarnak, MD (Tufts Medical Center), and their colleagues examined kidney and heart disease in octogenarians. The researchers assessed the prevalence of CKD by using different formulas based on different kidney function markers (serum creatinine and cystatin C) in 1,028 octogenarians enrolled in the Cardiovascular Health Study All Stars, a study of adults aged 65 years and older that examined subclinical and clinical risk factors for cardiovascular disease.

The prevalence of CKD was very high in the elderly individuals in this study. However, the study revealed that different formulas used to assess prevalence provide different pictures of CKD in the elderly. Prevalence differed from 33% to 51% depending on the equation used, even though there is a strong correlation between creatinine- and cystatin C-based estimates of kidney function. According to Dr. Sarnak, the study emphasizes that using different formulas to estimate kidney function in octogenarians results in different estimates of the prevalence of CKD. "Unfortunately, there is no gold standard estimating equation that has been developed or validated in octogenarians," he said.

Regardless of which equation researchers used to estimate kidney function, CKD in the elderly was associated with cardiovascular disease. Elderly individuals with CKD were approximately one-and-a-half to two times as likely to suffer from coronary heart disease, heart failure, or stroke as those without CKD. "Therefore, even in the very old, kidney function appears to be a marker of vascular disease," said Dr. Sarnak.

More information: The article entitled, "Chronic Kidney Disease in Octogenarians" will appear online at doi 10.2215/CJN.08801010

Provided by American Society of Nephrology

Moderate exercise improves brain blood flow in elderly women

Research conducted at Texas Health Presbyterian Hospital's Institute for Exercise and Environmental Medicine in Dallas suggests that it's never too late for women to reap the benefits of moderate aerobic exercise. In a 3-month study of 16 women age 60 and older, brisk walking for 30-50 minutes three or four times per week improved blood flow through to the brain as much as 15%.

24 april 2011--Rong Zhang, the lead researcher in the study, will discuss the team's findings in a presentation titled, "Aerobic exercise training increases brain perfusion in elderly women" at the Experimental Biology meeting (EB 2011), being held April 9-13, 2011 at the Walter E. Washington Convention Center, Washington, DC.

The Study

At the beginning of the study, the researchers used Doppler ultrasonography to measure blood flow in the women's internal carotid arteries, which are located in the neck and supply the brain with necessary glucose and oxygen-rich blood. After assessing the women's physical health and maximal oxygen consumption (VO2 max), which is the body's maximum capacity to transport and use oxygen during exercise, the team tailored training programs for each woman according to her fitness level.

Training started at a base pace of 50-60% of the participants' VO2 max for 30 minutes per session, three times per week. By the third month, the team had increased the sessions to 50 minutes each, four times per week, and added two more sessions at 70-80% of the women's VO2 max for 30 minutes.

At study's end, the team measured blood flow in the women's carotid arteries again and found that cerebral blood flow increased an average of 15% and 11% in the women's left and right internal carotid arteries, respectively. The women's VO2 max increased roughly 13%, their blood pressure dropped an average of 4%, and their heart rates decreased approximately 5%.

According to Dr. Zhang, the results provide insight into how vascular health affects brain health. "There are many studies that suggest that exercise improves brain function in older adults, but we don't know exactly why the brain improves. Our study indicates it might be tied to an improvement in the supply of blood flow to the brain."

Blood Flow and the Brain

A steady, healthy flow of blood to the brain achieves two things. First, the blood brings oxygen, glucose and other nutrients to the brain, which are vital for the brain's health. Second, the blood washes away brain metabolic wastes such as amyloid-beta protein released into the brain's blood vessels. Amyloid-beta protein has been implicated in the development of Alzheimer's disease.

Whether the increased blood flow to the brain improves learning and reasoning has yet to be determined, says Dr. Zhang. "I don't have the data to suggest a correlation between brain perfusion and cognitive function, but this is something we eventually will see after this study is completed," he says. "We do know there is strong evidence to suggest that cardiovascular risk is tied to the risk for Alzheimer's disease. We want to see how we can fight that."

Dr. Zhang stresses the importance of the finding that improvement in brain blood flow is possible in one's senior years. "We often start to see a decline in brain perfusion and cognitive function in the 60s and 70s. That's when the downward trajectory starts. We want to see how much we can do to reverse or delay that process."

Provided by Federation of American Societies for Experimental Biology

Physical activity improves walking capacity in Chilean elderly

Policies to promote healthy ageing often emphasize a healthy diet and maintaining physical activity. But currently there is little good evidence to support the benefits of improved nutrition and increased physical activity levels for older adults from low-income or transition economies.

23 april 2011--Alan Dangour from the London School of Hygiene & Tropical Medicine, United Kingdom, and colleagues report this week in PLoS Medicine the outcomes of the Cost-effectiveness Evaluation of a Nutritional supplement and EXercise program for older people — CENEX — which evaluated whether Chile's national nutritional supplementation and physical exercise program prevented pneumonia and physical functional decline in older people in Santiago, and whether these interventions were cost-effective.

Using a cluster randomized trial design they found that during the 2-year trial the incidence rate of pneumonia did not differ between intervention and control groups but, at the end of the study period, there was a significant difference in walking capacity between the intervention and control clusters. Therefore, the provision of locally-available physical activity classes to older people could be of clinical benefit, especially in urban settings.

More information: Dangour AD, Albala C, Allen E, Grundy E, Walker DG, et al. (2011) Effect of a Nutrition Supplement and Physical Activity Program on Pneumonia and Walking Capacity in Chilean Older People: A Factorial Cluster Randomized Trial. PLoS Med 8(4): e1001023. doi:10.1371/journal.pmed.1001023

Provided by Public Library of Science

Study adds weight to link between calcium supplements and heart problems

New research published in the British Medical Journal today adds to mounting evidence that calcium supplements increase the risk of cardiovascular events, particularly heart attacks, in older women.

The findings suggest that their use in managing osteoporosis should be re-assessed.

22 april 2011--Calcium supplements are often prescribed to older (postmenopausal) women to maintain bone health. Sometimes they are combined with vitamin D, but it's still unclear whether taking calcium supplements, with or without vitamin D, can affect the heart.

The Women's Health Initiative (WHI) study - a seven-year trial of over 36,000 women – found no cardiovascular effect of taking combined calcium and vitamin D supplements, but the majority of participants were already taking personal calcium supplements, which may have obscured any adverse effects.

So a team of researchers, led by Professor Ian Reid at the University of Auckland, re-analysed the WHI results to provide the best current estimate of the effects of calcium supplements, with or without vitamin D, on the risk of cardiovascular events.

They analysed data from 16,718 women who were not taking personal calcium supplements at the start of the trial and found that those allocated to combined calcium and vitamin D supplements were at an increased risk of cardiovascular events, especially heart attack.

By contrast, in women who were taking personal calcium supplements at the start of the trial, combined calcium and vitamin D supplements did not alter their cardiovascular risk.

The authors suspect that the abrupt change in blood calcium levels after taking a supplement causes the adverse effect, rather than it being related to the total amount of calcium consumed. High blood calcium levels are linked to calcification (hardening) of the arteries, which may also help to explain these results.

Further analyses - adding data from 13 other trials, involving 29,000 people altogether - also found consistent increases in the risk of heart attack and stroke associated with taking calcium supplements, with or without vitamin D, leading the authors to conclude that these data justify a reassessment of the use of calcium supplements in older people.

But in an accompanying editorial, Professors Bo Abrahamsen and Opinder Sahota argue that there is insufficient evidence available to support or refute the association.

Because of study limitations, they say "it is not possible to provide reassurance that calcium supplements given with vitamin D do not cause adverse cardiovascular events or to link them with certainty to increased cardiovascular risk. Clearly further studies are needed and the debate remains ongoing."

Provided by British Medical Journal

Older adults doing better than younger when it comes to phytonutrient

Although only one in 10 American adults eats enough fruits and vegetables, new research being presented at the Experimental Biology meeting this week in Washington, D.C., finds older adults are consuming higher levels of carotenoids, flavonoids and other phytonutrients found in fruits and vegetables that are thought to support healthy aging. Specifically, the new findings suggest that, calorie for calorie, intakes of carotenoids are 20 percent higher, flavonoids 40 percent higher, and ellagic acid is 80 percent higher among older compared to younger adults.

21 april 2011-Phytonutrients, which are plant-based compounds found naturally in fruits and vegetables, may be associated with protective health benefits. For example, carotenoids such as lycopene and beta-carotene may offer breast, ovarian and other health benefits for women, while flavonoids such as quercetin and anthocyanidins may support brain health. Ellagic acid, found in foods like pomegranates, strawberries and walnuts, may help ward off some cancers, including breast and prostate.

This new phase of ongoing research, funded by Nutrilite Health Institute, the world's leading brand of vitamin, mineral, and dietary supplements based on 2008 sales, compares energy-adjusted phytonutrient intakes between younger (19-44 years), middle aged (45-64 years) and older adults (65+ years) to better understand if and how intakes vary by age. In addition to the carotenoid and flavonoid shortfalls observed among younger adults, the new data indicate that energy adjusted resveratrol intake (excluding wine) is 50 percent higher in older adults versus younger adults, while adjusted intakes of lycopene are similar between age groups, and allicin intake (found in garlic) by older adults is lower.

"We know that Americans of all ages are missing out on the protective benefits of phytonutrients, but most troubling is our new finding that shortfalls are greatest among younger adults – the very ones who could most benefit from a lifetime of consumption," said Keith Randolph, Ph.D., Technology Strategist for Nutrilite. Previous related research also supported by the Nutrilite Health Institute found that eight in 10 Americans have a "phytonutrient gap," meaning they fall short in consuming key phytonutrients from foods including fruits and vegetables that could benefit their health. Additional findings from that research showed that while most Americans do not meet recommended intakes of fruits and vegetables, women 65 years and older were doing the best with a mere 12 percent meeting intake recommendations.

Food Sources of Phytonutrients

To help uncover which foods Americans are eating that provide these important nutrients, top ranked food sources for each of the phytonutrients were identified (3). Results showed that the top food source was not necessarily among the most phytonutrient-rich options, and that there may be opportunities for Americans to increase phytonutrient intakes by selecting more nutrient-rich options, such as the ones mentioned below:

• Carotenoids: While carrots are the number one source of the beta-carotene in the average American's diet, baked sweet potatoes have nearly double the beta-carotene per serving.
  
• Flavonoids: Grapes are the number one source of anthocyanidins in the American diet, but cherries and blueberries deliver three to four times as much anthocyanidins per serving.
  
• Ellagic Acid: The top food source of ellagic acid is strawberries, yet per serving, raspberries have three times the ellagic acid.

"Our data hit home the point that we need to increase accessibility to, and awareness of the quality of fruits and vegetables, not just the quantity. "It's eating the most phytonutrient-rich foods every day that likely translates into healthier aging, so getting the younger generations to choose the most phytonutrient-rich options whenever possible can make a big difference to the nation's health," continues Dr. Randolph.

Closing the Gap

The overall goal should be to encourage Americans to close their "phytonutrient gap" by selecting a greater variety of nutrient dense fruits and vegetables to "power up" their produce selection, and help increase phytonutrient intakes. A reasonable target for most individuals is to consume a combined total of 10 servings of fruits and vegetables daily. For those having trouble getting enough fruits and vegetables into their daily diet, plant-based supplements containing phytonutrients are an option.

Study Details

The analyses supporting this body of research were conducted by Exponent for Nutrilite Health Institute. The dataset comes from National Health and Nutrition Examination Surveys (NHANES), surveys that capture what Americans eat daily, supplemental nutrient concentration data from the United States Department of Agriculture (USDA) and the published literature. Fourteen phytonutrients were analyzed including carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin lutein/zeaxanthin, lycopene); flavonoids (anthocyanidins, epigallocatechin 3-gallate [EGCG], hesperitin, isoflavones, quercetin); phenolics (ellagic acid, resveratrol); allicin and isothiocyanates. The study population includes non-pregnant, non-lactating NHANES respondents ages 19 years and older with two complete and reliable 24-hour dietary recalls based on NHANES criteria. MyPyramid guidance for fruit and vegetable intake recommendations, which is based on the 2005 Dietary Guidelines for Americans, was used to assess the percent of adults consuming recommended intakes of fruits and vegetables.

More information: Kimmons J, Gillespie C, Seymour J, Serdula M, Blanck HM. Fruit and vegetable intake among adolescents and adults in the United States: percentage meeting individualized recommendations. Medscape J Med. 2009;11:26.

Provided by Weber Shandwick Worldwide

Alzheimer's diagnostic guidelines updated for first time in decades

For the first time in 27 years, clinical diagnostic criteria for Alzheimer's disease dementia have been revised, and research guidelines for earlier stages of the disease have been characterized to reflect a deeper understanding of the disorder. The National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Alzheimer's Disease outline some new approaches for clinicians and provides scientists with more advanced guidelines for moving forward with research on diagnosis and treatments. They mark a major change in how experts think about and study Alzheimer's disease. Development of the new guidelines was led by the National Institutes of Health and the Alzheimer's Association.

20 april 2011--The original criteria were the first to address the disease and described only later stages, when symptoms of dementia are already evident. The updated guidelines announced today cover the full spectrum of the disease as it gradually changes over many years. They describe the earliest preclinical stages of the disease, mild cognitive impairment, and dementia due to Alzheimer's pathology. Importantly, the guidelines now address the use of imaging and biomarkers in blood and spinal fluid that may help determine whether changes in the brain and those in body fluids are due to Alzheimer's disease. Biomarkers are increasingly employed in the research setting to detect onset of the disease and to track progression, but cannot yet be used routinely in clinical diagnosis without further testing and validation.

"Alzheimer's research has greatly evolved over the past quarter of a century. Bringing the diagnostic guidelines up to speed with those advances is both a necessary and rewarding effort that will benefit patients and accelerate the pace of research," said National Institute on Aging Director Richard J. Hodes, M.D.

"We believe that the publication of these articles is a major milestone for the field," said William Thies, Ph.D., chief medical and scientific officer at the Alzheimer's Association. "Our vision is that this process will result in improved diagnosis and treatment of Alzheimer's, and will drive research that ultimately will enable us to detect and treat the disease earlier and more effectively. This would allow more people to live full, rich lives without—or with a minimum of—Alzheimer's symptoms."

The new guidelines appear online April 19, 2011 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. They were developed by expert panels convened last year by the National Institute on Aging (NIA), part of the NIH, and the Alzheimer's Association. Preliminary recommendations were announced at the Association's International Conference on Alzheimer's Disease in July 2010, followed by a comment period.

Guy M. McKhann, M.D., Johns Hopkins University School of Medicine, Baltimore, and David S. Knopman, M.D., Mayo Clinic, Rochester, Minn., co-chaired the panel that revised the 1984 clinical Alzheimer's dementia criteria. Marilyn Albert, Ph.D., Johns Hopkins University School of Medicine, headed the panel refining the MCI criteria. Reisa A. Sperling, M.D, Brigham and Women's Hospital, Harvard Medical School, Boston, led the panel tasked with defining the preclinical stage. The journal also includes a paper by Clifford Jack, M.D., Mayo Clinic, Rochester, Minn., as senior author, on the need for and concept behind the new guidelines.

The original 1984 clinical criteria for Alzheimer's disease, reflecting the limited knowledge of the day, defined Alzheimer's as having a single stage, dementia, and based diagnosis solely on clinical symptoms. It assumed that people free of dementia symptoms were disease-free. Diagnosis was confirmed only at autopsy, when the hallmarks of the disease, abnormal amounts of amyloid proteins forming plaques and tau proteins forming tangles, were found in the brain.

Since then, research has determined that Alzheimer's may cause changes in the brain a decade or more before symptoms appear and that symptoms do not always directly relate to abnormal changes in the brain caused by Alzheimer's. For example, some older people are found to have abnormal levels of amyloid plaques in the brain at autopsy yet never showed signs of dementia during life. It also appears that amyloid deposits begin early in the disease process but that tangle formation and loss of neurons occur later and may accelerate just before clinical symptoms appear.

To reflect what has been learned, the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Alzheimer's Disease cover three distinct stages of Alzheimer's disease:

• Preclinical – The preclinical stage, for which the guidelines only apply in a research setting, describes a phase in which brain changes, including amyloid buildup and other early nerve cell changes, may already be in process. At this point, significant clinical symptoms are not yet evident. In some people, amyloid buildup can be detected with positron emission tomography (PET) scans and cerebrospinal fluid (CSF) analysis, but it is unknown what the risk for progression to Alzheimer's dementia is for these individuals. However, use of these imaging and biomarker tests at this stage are recommended only for research. These biomarkers are still being developed and standardized and are not ready for use by clinicians in general practice.
  
• Mild Cognitive Impairment (MCI) – The guidelines for the MCI stage are also largely for research, although they clarify existing guidelines for MCI for use in a clinical setting. The MCI stage is marked by symptoms of memory problems, enough to be noticed and measured, but not compromising a person's independence. People with MCI may or may not progress to Alzheimer's dementia. Researchers will particularly focus on standardizing biomarkers for amyloid and for other possible signs of injury to the brain. Currently, biomarkers include elevated levels of tau or decreased levels of beta-amyloid in the CSF, reduced glucose uptake in the brain as determined by PET, and atrophy of certain areas of the brain as seen with structural magnetic resonance imaging (MRI). These tests will be used primarily by researchers, but may be applied in specialized clinical settings to supplement standard clinical tests to help determine possible causes of MCI symptoms.
  
• Alzheimer's Dementia – These criteria apply to the final stage of the disease, and are most relevant for doctors and patients. They outline ways clinicians should approach evaluating causes and progression of cognitive decline. The guidelines also expand the concept of Alzheimer's dementia beyond memory loss as its most central characteristic. A decline in other aspects of cognition, such as word-finding, vision/spatial issues, and impaired reasoning or judgment may be the first symptom to be noticed. At this stage, biomarker test results may be used in some cases to increase or decrease the level of certainty about a diagnosis of Alzheimer's dementia and to distinguish Alzheimer's dementia from other dementias, even as the validity of such tests is still under study for application and value in everyday clinical practice.

The panels purposefully left the guidelines flexible to allow for changes that could come from emerging technologies and advances in understanding of biomarkers and the disease process itself.

"The guidelines discuss biomarkers currently known, and mention others that may have future applications," said Creighton H. Phelps, Ph.D., of the NIA Alzheimer's Disease Centers Program. "With researchers worldwide striving to develop, validate and standardize the application of biomarkers at every stage of Alzheimer's disease, we devised a framework flexible enough to incorporate new findings."

Provided by National Institutes of Health

Weight loss improves memory: research

John Gunstad, an associate professor in Kent State University's Department of Psychology, and a team of researchers have discovered a link between weight loss and improved memory and concentration. The study shows that bariatric surgery patients exhibited improved memory function 12 weeks after their operations.

19 april 2011--The findings will be published in an upcoming issue of Surgery for Obesity and Related Diseases, the Official Journal of the American Society for Metabolic and Bariatric Surgery. The research report is also available online at www.soard.org/article/S1550-7289(10)00688-X/abstract.

"The initial idea came from our clinical work," Gunstad said. "I was working at Brown Medical School in Rhode Island at the time and had the chance to work with a large number of people who were looking to lose weight through either behavioral means or weight loss surgery."

Gunstad said he kept noticing that these patients would make similar mistakes. "As a neuropsychologist who is focused on how the brain functions, I look for these little mental errors all the time," Gunstad explained.

The research team studied 150 participants (109 bariatric surgery patients and 41 obese control subjects) at Cornell Medical College and Weill Columbia University Medical Center, both in New York City, and the Neuropsychiatric Research Institute in Fargo, N.D. Many bariatric surgery patients exhibited impaired performance on cognitive testing, according to the study's report.

The researchers discovered that bariatric surgery patients demonstrated improved memory and concentration 12 weeks after surgery, improving from the slightly impaired range to the normal range.

"The primary motivation for looking at surgery patients is that we know they lose a lot of weight in a short amount of time, so it was a good group to study," Gunstad said. "This is the first evidence to show that by going through this surgery, individuals might improve their memory, concentration and problem solving."

Gunstad thinks the study is reason for optimism. "One of the things about obesity, relative to other medical conditions, is that something can be done to fix it," Gunstad said. "Our thought was, if some of these effects are reversible, then we're really on to something - that it might be an opportunity for individuals who have memory or concentration problems to make those things better in a short amount of time. And that's what we found."

The team is following study participants for two years. They tested subjects before surgery, 12 weeks after surgery and one year after surgery, and will also test at the two-year mark.

Gunstad was the principal investigator for the team, which included Gladys Strain, Ph.D., of Cornell Medical College in New York City; Michael Devlin, M.D., of Weill Columbia University Medical Center in New York City; Rena Wing, Ph.D., and Ronald Cohen, Ph.D., of the Warren Albert Medical School of Brown University in Providence, R.I.; Robert Paul, Ph.D., of the University of Missouri-St. Louis in St. Louis, Miss.; and Ross Crosby, Ph.D., and James Mitchell, M.D., of the Neuropsychiatric Research Institute in Fargo, N.D.

Gunstad wasn't surprised by the study's findings. "A lot of the factors that come with obesity – things such as high blood pressure, type 2 diabetes and sleep apnea - that might damage the brain are somewhat reversible," Gunstad said. "As those problems go away, memory function gets better."

The team's next project will examine whether people who experience behavioral weight loss see the same effects as those who have had bariatric surgery. Gunstad said he expects to see similar results.

"One of the things we know is that as individuals become more cardiovascular fit and their heart health gets better, their brain health also improves," Gunstad added. "Even if we take young adults and put them through an exercise program, their memory and their concentration get better by the end of the program."

Provided by Kent State University

AAN issues new guideline on best treatments for diabetic nerve pain

The American Academy of Neurology has issued a new guideline on the most effective treatments for diabetic nerve pain, the burning or tingling pain in the hands and feet that affects millions of people with diabetes. The guideline is published in the April 11, 2011, online issue of Neurology, the medical journal of the American Academy of Neurology, and will be presented April 11, 2011, at the American Academy of Neurology's Annual Meeting in Honolulu.

18 april 2011--This guideline was developed in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation.

Diabetic nerve pain, or neuropathy, is caused by nerve damage. "When neuropathy strikes, it is painful and can disrupt sleep; because of this it can also lead to mood changes and lower quality of life," said lead guideline author Vera Bril, MD, FRCP, with the University of Toronto and a member of the American Academy of Neurology. "It is estimated that diabetic nerve pain affects 16 percent of the more than 25 million people living with diabetes in the United States and is often unreported and more often untreated, with an estimated two out of five cases not receiving care."

According to the guideline, strong evidence shows the seizure drug pregabalin is effective in treating diabetic nerve pain and can improve quality of life; however, doctors should determine if it is appropriate for their patients on a case-by-case basis.

In addition, the guideline found that several other treatments are probably effective and should be considered, including the seizure drugs gabapentin and valproate, antidepressants such as venlafaxine, duloxetine and amitriptyline and painkillers such as opioids and capsaicin. Transcutaneous electric nerve stimulation (TENS), a widely used pain therapy involving a portable device, was also found to be probably effective for treating diabetic nerve pain.

"We were pleased to see that so many of these pain treatments had high-quality studies that support their use," said Bril. "Still, it is important that more research be done to show how well these treatments can be tolerated over time since diabetic nerve pain is a chronic condition that affects a person's quality of life and ability to function."

The recommendations of this guideline will serve as the foundation for a new set of tools the AAN is creating for doctors to measure the quality of care they provide people with nerve pain. The measures will be released in 2012.

The guidelines will also appear in the April edition of the journal Muscle and Nerve from the American Association of Neuromuscular and Electrodiagnostic Medicine as well as the April issue of PM&R, the American Academy of Physical Medicine and Rehabilitation's scientific journal.

Provided by American Academy of Neurology

Inability to detect sarcasm, lies may be early sign of dementia, study shows

16 april 2011-- By asking a group of older adults to analyze videos of other people conversing -- some talking truthfully, some insincerely -- a group of scientists at the University of California, San Francisco has determined which areas of the brain govern a person's ability to detect sarcasm and lies.

Some of the adults in the group were healthy, but many of the test subjects had neurodegenerative diseases that cause certain parts of the brain to deteriorate. The UCSF team mapped their brains using magnetic resonance imaging, MRI, which showed associations between the deteriorations of particular parts of the brain and the inability to detect insincere speech.

"These patients cannot detect lies," said UCSF neuropsychologist Katherine Rankin, PhD, a member of the UCSF Memory and Aging Center and the senior author of the study. "This fact can help them be diagnosed earlier."

The finding was presented today, Thursday, April 14, 2011, at the 63rd Annual Meeting of the American Academy of Neurology in Hawaii, by Rankin and her postdoctoral fellow Tal Shany-Ur, PhD. The title of their presentation was, "Divergent Neuroanatomic Correlates of Sarcasm and Lie Comprehension in Neurodegenerative Disease."

In a presentation today at the 63rd Annual Meeting of the American Academy of Neurology in Hawaii, Rankin and her postdoctoral fellow Tal Shany-Ur, PhD, will show the data, which suggests that it may be possible to spot people with particular neurodegenerative diseases early just by looking for the telltale sign of their inability to detect lies.

"We have to find these people early," said Rankin. In general scientists believe that catching people early in the disease will provide the best opportunity for intervention when drugs become available.

The study is part of a larger body of work at UCSF's Memory and Aging Center examining emotion and social behavior in neurodegenerative diseases as tools for better predicting, preventing, and diagnosing these conditions.

Dementia and Disbelief

The ability to detect lies resides in the brain's frontal lobe. In diseases like frontotemporal dementia, this is one of the areas that progressively degenerates because of the accumulation of damaged proteins known as tau and the death of neurons in those areas.

Because the frontal lobes play a significant role in complex, higher-order human behaviors, losing the ability to detect lies is only one of several ways the disease may manifest. The first signs of the disease may be any number of severe behavioral changes. People sometimes behave in socially inappropriate ways or undergoing fundamental shifts in outlook -- switching political affiliations or changing religions, for instance.

Ironically, these signs are often missed because they are misattributed to depression or an extreme form of midlife crisis.

Hoping to increase the tools available for doctors and caregivers to recognize the early signs of the disease, the UCSF team focused on the fact that people with frontotemporal dementia often lose the ability to detect sarcasm and lies. Doctors have observed evidence of this fact for years because people suffering from the disease sometimes lose significant amounts of money to online scams and telemarketers because of their blind trust.

People who age normally without suffering neurodegeneration, on the other hand, generally do not suffer a significant decline in their ability to understand sarcasm and deception.

But the question was how solid this association is. Would the inability to detect sarcasm and lies actually match the brain regions hit early in these diseases?

Assess, Lies, and Videotape

In order to answer this question, the UCSF team worked with 175 people, more than half of whom had some form of neurodegeneration. They showed them videos of two people talking, one of whom would occasionally tell lies or use sarcasm -- a fact that was apparent in the videos from verbal and non-verbal cues. Then the test subjects were asked yes/no questions about videos.

Healthy older subjects in the study could easily distinguish sincere from insincere speech. However, the subjects who had frontotemporal dementia were less able to discern among lies, sarcasm, and fact. Patients with other forms of dementia, such as Alzheimer's disease, did better.

To associate the detection inability with neurodegeneration, the UCSF team used MRI to make extremely accurate maps of the brains of the subjects in the study. This allowed them to measure the volumes of different regions of the brain showing that the sizes of those regions correlated with the inability to detect sarcasm or lying.

According to Rankin, the work should help raise awareness of the fact that this extreme form of gullibility can actually be a warning sign of dementia -- something that could help more patients be correctly diagnosed and receive treatment earlier in the long run.

"If somebody has strange behavior and they stop understanding things like sarcasm and lies, they should see a specialist who can make sure this is not the start of one of these diseases," said Rankin.

Provided by University of California, San Francisco

Green tea and tai chi enhance bone health, reduce inflammation in postmenopausal women

C.S. Lewis, the famous author and Oxford academic, once proclaimed "You can't get a cup of tea big enough or a book long enough to suit me." We sip it with toast in the morning, enjoy it with sweets and biscuits in the afternoon, and relax with it at the end of the day. Tea has for generations been an integral infusion worldwide, carrying both epicurean and economic significance. But, does it impart honest-to-goodness health benefits? In other words, is its persistence in the human diet perhaps coincident with enhanced quality (or quantity) of life?

15 april 2011--Dr. Chwan-Li (Leslie) Shen, an associate professor and a researcher at the Laura W. Bush Institute for Women's Health at the Texas Tech University Health Sciences Center, is convinced that the answer to this question is a resounding yes – especially if the tea is of the "green" variety. Green tea, historically consumed in the Orient and now an international mainstay, is chock full of compounds called polyphenols known for their potent antioxidant activity. Dozens of epidemiological (observational) studies have shown that people who consume the highest levels of green tea polyphenols (GTP) tend to have lower risks of several chronic degenerative diseases such as cardiovascular disease and osteoporosis. These findings have been followed up with animal studies, including some conducted by Shen, suggesting that the mechanism behind this correlation may have to do with lowering chronic levels of inflammation.

Originally from Taiwan, Dr. Shen has now spent over 2 decades studying how and why some Eastern lifestyle norms (such as drinking green tea) might be beneficial for Westerners as well. For instance, she has developed an animal model (the ovariectomized, middle-aged female rat). With this model Dr. Shen and her team can effectively study the effects of green tea consumption on protection against breakdown of the bone's microarchitecture. In humans, this can lead to osteoporosis, a condition common to older women. It is Dr Shen's hope that what she learns from her animal models might also be applicable to postmenopausal women.

In Shen's most recent research, she focused on postmenopausal women and investigated the potential for green tea to work synergistically with tai chi – a traditional Chinese form of moderately intense aerobic fitness activity grounded in mind-body philosophy – in enhancing bone strength. The results of this work, which was funded by the National Institutes of Health/National Center for Complementary and Alternative Medicine, will be presented as a poster at the Experimental Biology meetings on April 10. Carried out as a double-blind, placebo-controlled, intervention trial (the "holy grail" of scientific studies), this experiment involved 171 postmenopausal women (mean age: ~57 y) who had weak bones but not full-fledged osteoporosis. Subjects were divided into 4 groups:

• Placebo: starch pill (placebo) and no tai chi
  
• GTP: green tea polyphenols (500 mg/day) and no tai chi
  
• Placebo+TC: starch pill and tai chi (3 times/week)
  
• GTP+TC: green tea polyphenols and tai chi

The study lasted for 6 months, during which time blood and urine samples were collected and muscle strength assessed.

The results show that consumption of GTP (at a level equivalent to about 4-6 cups of steeped green tea daily) and participation in tai chi independently enhanced markers of bone health by 3 and 6 months, respectively. A similar effect was found for muscle strength at the 6-month time point. Participants taking tai chi classes also reported significant beneficial effects in quality of life in terms of improving their emotional and mental health. Perhaps most remarkable, however, was the substantial effect that both GTP and tai chi had on biological markers of oxidative stress. Because oxidative stress is a main precursor to inflammation, this finding suggests that green tea and tai chi may help reduce the underlying etiology of not only osteoporosis, but other inflammatory diseases as well.

Dr. Shen and colleagues concluded that there is a "favorable effect of modest green tea consumption on bone remodeling in this pre-osteoporotic population" and hope to soon complete a more long-term study utilizing more technically savvy measures of bone density.

Perhaps C.S. Lewis was correct – it's tea time!

Provided by Federation of American Societies for Experimental Biology

Brain starts shrinking nearly a decade before Alzheimer's appears

ST. PAUL, Minn.–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.

14 april 2011--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, MD, 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."

Provided by American Academy of Neurology

Vitamin D levels associated with age-related macular degeneration

Women under the age of 75 with high vitamin D status were less likely to have early age-related macular degeneration (AMD), the leading cause of irreversible vision loss in adults, a University at Buffalo study has shown. The disease affects approximately 9 percent of Americans aged 40 and older.

The paper is published in the April issue of "Archives of Ophthalmology," one of the JAMA/Archives journals.

13 april 2011--Vitamin D status was assessed using the blood measure of 25-hydroxyvitamin D or 25 (OH) D. The 25 (OH) D level is generally considered the means by which nutritional vitamin D status is defined.

"In women younger than 75, those who had 25-hydroxyvitamin D concentrations lower than 38 nanomoles per liter were more likely to have age-related macular degeneration than women with concentrations greater than 38 nanomoles per liter," says Amy E. Millen, PhD, assistant professor in the UB School of Public Health and Health Professions and lead author. "Blood concentrations above 38 nanomoles per liter were associated with at least a 44 percent decreased odds of having AMD."

She notes that the Institute of Medicine considers an adult with a blood 25 hydroxyvitamin D concentration of lower than 30 nanomoles per liter to be at increased risk of vitamin D deficiency and a person with a concentration of less than 50 nanomoles per liter to be at increased risk for vitamin D inadequacy.

Millen's "Carotenoids in Age-Related Eye Disease Study (CAREDS)" involved data from 1,313 women. The purpose of the study was to investigate if serum 25 hydroxyvitamin D levels in the blood, the preferred biomarker for vitamin D, were associated with early age-related macular degeneration. CAREDS is an ancillary study within the Women's Health Initiative (WHI) Observational Study, which was conducted at WHI clinic centers in Oregon, Iowa and Wisconsin. UB is a major participating center in the WHI.

"The take- home message from this study is that having very low vitamin D status (25-hydroxyvitamin D blood concentrations lower than 38 nanomoles per liter) may be associated with increasing your odds of developing age-related macular degeneration," says Millen. "But based on these study findings, being at a higher vitamin D level than 38 nanomoles per liter does not appear to be more protective," she cautions.

Vitamin D status may be increased by spending moderate amounts of time outside, and eating foods rich in vitamin D, such as fatty fish from cold waters, and foods fortified with vitamin D, such as milk and fortified cereal, or by taking supplements.

"This is a promising study, but more still needs to be done," says Millen. "We still don't understand all of the effects of Vitamin D on health."

Provided by University at Buffalo

Evidence lacking for efficacy of memantine in treating mild Alzheimer's disease

An analysis of studies involving the drug memantine finds a lack of evidence for benefit when the drug is used to treat patients with mild Alzheimer disease, according to a report posted online today that will appear in the August print issue of Archives of Neurology.

12 april 2011--"Memantine, indicated for moderate to severe Alzheimer disease (AD), is frequently prescribed off-label [for uses other than those approved by the FDA] either alone or with a cholinesterase inhibitor for mild AD and mild cognitive impairment," the authors write as background information in the article. Cholinesterase inhibitors are drugs that increase levels of a brain chemical called acetylcholine. Increasing acetylcholine levels appears to slow mental decline in people with AD.

Lon S. Schneider, M.D., M.S., of the University of Southern California Keck School of Medicine, Los Angeles, and colleagues systematically searched manufacturer-sponsored meta-analyses, registries, presentations, and publications for randomized, placebo-controlled, parallel-group clinical trials of memantine in patients with mild to moderate AD. Three trials were identified that included 431 patients with mild AD and 697 patients with moderate AD. Using several different scales, the researchers assessed cognition, global change, functional activities, and behavior.

"There were no significant differences between memantine and placebo on any outcome for patients with mild AD, either within any trial or when data were combined," the authors report.

Among patients with moderate AD, there was no significant difference between memantine and placebo in any individual trial, although there was a significant effect when the three trials were statistically combined.

"Despite its frequent off-label use, evidence is lacking for a benefit of memantine in mild AD, and there is meager evidence for its efficacy in moderate AD," the authors conclude. "Prospective trials are needed to further assess the potential for efficacy of memantine either alone or added to cholinesterase inhibitors in mild and moderate AD."

More information: Arch Neurol. Published online April 11, 2011. doi:10.1001/archneurol.2011.69

Provided by JAMA and Archives Journals

Chronic stress of cancer causes accelerated telomere shortening

Results of a study presented at the AACR 102nd Annual Meeting 2011, held here April 2-6, lend credence to the idea that improving quality of life affects stress-related biological markers and possibly the health of people with cancer.

Researchers know that telomeres shorten and deteriorate with aging, but they are learning that stress also affects telomere length.

10 april 2010--"We are trying to understand the interconnections between the mind and the body; that is, how does the diagnosis and treatment of cancer impact patients not only psychologically, but also physiologically and how can we improve their outcome. Cancer drives a chronic stress response in some patients," said Edward Nelson, M.D., division chief of hematology/oncology at the University of California, Irvine.

Just as aglets prevent a shoelace from unraveling or fraying, telomeres are structures on the ends of chromosomes that protect the chromosome from deteriorating, breaking apart or joining with other chromosomes, which can lead to mutations. Chromosomal rearrangements are seen in cancers and provided a biological reason to investigate this link, according Nelson.

"For this study, we wanted to know if chronic stress was associated with accelerated telomere shortening in cancer patients, and if a psychosocial intervention that modulates the stress response could also modulate telomere length," he said.

In this retrospective study, the researchers took biological samples from 31 women with cervical cancer who had been randomized to one of two groups — those who received six counseling sessions by telephone and those who received usual care without counseling.

The six sessions consisted of a quality of life and psychosocial profile, managing stress and emotions, enhancing health and wellness, addressing relational and sexual concerns, and integrating and summarizing the information. At enrollment and after four months, the researchers obtained biological samples from both groups and investigated changes over time to see if psychological counseling had any physical effects.

"Improved quality of life and reduced stress response was associated with changes in telomere length," Nelson said.

"It is important to recognize that this was an exploratory and preliminary analysis. We embarked on the first study of telomere length and chronic stress in a cancer population and the first longitudinal analysis in whether changes in quality of life and changes in the stress response would be associated with modulating the telomere length," he said.

Still, he added, "there is no doubt that offering psychological services has the potential to improve quality of life and outcomes of patients. After all, making patients feel better should be an outcome that a cancer team should want to have, but whether we can draw conclusions or make recommendations about the capacity of a behavioral intervention to modulate telomere length remains an open question."

Provided by American Association for Cancer Research

New research published finds clear link between height and longevity

08 april 2011---- New research shows that the way we live directly affects the length of our bodies – and our lives. The research, which is published today in a new book ‘The Changing Body’ (Cambridge University Press), has been conducted over the past 30 years and confirms that there is a clear link between height and longevity.

By exploring the links between nutrition and economic development in Europe and North America since the early-1700s, the researchers linked the changing size, shape and capability of the human body to economic and demographic change.

The research found that 200 years ago there were substantial differences in height between working-class and upper-class people. For example, in nineteenth-century Europe, there were dramatic differences between the heights of poor London boys and boys attending the Royal Military Academy at Sandhurst, between army recruits and students attending the École Polytechnique in France and between the sons of ‘elite’ families and those who grew up in unskilled manual households in the Netherlands.

In the 1780s, the average height of a 14-year-old working-class child was 1.3m, while an upper class child was "significantly taller" at 1.55m. Today however, as health services, nutrition, sanitation and education have become universal, upper-class children have continued to grow taller, but at a slower rate than working-class children. The difference between the upper- and working-class adults has narrowed to less than 0.06m.

One of the book’s authors, Professor Bernard Harris from the University of Southampton, whose work focused on developments in height, health and mortality in Britain and in Continental Europe, says: “The aim is to describe, analyse and explain changes in height and health in different countries over time. However, we also want to emphasise the ways in which the changes may affect patterns of human development in the future.

“Our work shows that there have been dramatic changes in child health (as reflected in achieved adult height) over the last 100 years, and other researchers have highlighted the existence of close links between improvements in child health and health in later life. These changes have profound implications for developments in later-life health, longevity and economic performance over the coming century.

“The investments we make in the health of today’s children can play a pivotal role in determining the economic wellbeing of future generations.”

Regional variation also plays its part. Two centuries ago, people in Scotland were 2.3cm taller than those living in southern England, while Norwegians were among the shortest nations in Europe. Today the Scottish, averaging 1.73m for an adult male, are shorter than those living in south-east England at 1.75m, while the Norwegians are the second tallest nation in Europe, surpassed only by the Dutch.

Professor Harris says: "Improvements in diet and sanitation in the South-east have outstripped improvements in Scotland, reflecting the broad pattern of economic and social change over the last 200 years."

Provided by University of Southampton

Using MRI, researchers may predict which adults will develop Alzheimer's

Using MRI, researchers may be able to predict which adults with mild cognitive impairment are more likely to progress to Alzheimer's disease, according to the results of a study published online and in the June issue of Radiology.

07 april 2011--Mild cognitive impairment (MCI) is an intermediate stage between the decline in mental abilities that occurs in normal aging and the more pronounced deterioration associated with dementia, a group of brain disorders that includes Alzheimer's disease (AD).

Individuals with MCI develop AD at a rate of 15 to 20 percent per year, which is significantly higher than the one to two percent rate for the general population. Some people with MCI remain stable while others gradually decline and some quickly deteriorate.

"Being able to better predict which individuals with MCI are at greatest risk for developing Alzheimer's would provide critical information if disease-modifying therapies become available," said the study's lead author, Linda K. McEvoy, Ph.D., assistant professor in the Department of Radiology at the University of California, San Diego School of Medicine.

Dr. McEvoy and a team of researchers analyzed MRI exams from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large publicly and privately sponsored study, which performed imaging and other tests on hundreds of healthy individuals and others with MCI and early AD between 2005 and 2010 in hopes of identifying valuable biomarkers of the disease process.

Included in the study were a baseline MRI exam, serving as an initial point of measurement, and a second MRI performed a year later on 203 healthy adults, 317 patients with MCI and 164 patients with late-onset AD. The average age of the study participants was 75.

Using MRI, the researchers measured the thickness of the cerebral cortex — the outermost layer of the cerebral hemispheres of the brain that plays a key role in memory, attention, thought and language — and observed the pattern of thinning to compute a risk score. One of the characteristics of AD is a loss of brain cells, called atrophy, in specific areas of the cortex.

"MRI is very sensitive to brain atrophy," Dr. McEvoy said. "There's a pattern of cortical thinning associated with AD that indicates the patient is more likely to progress to AD."

Using the baseline MRI, the researchers calculated that the patients with MCI had a one-year risk of conversion to AD ranging from three to 40 percent.

"Compared to estimating a patient's risk of conversion based on a clinical diagnosis only, MRI provides substantially more informative, patient-specific risk estimates," Dr. McEvoy said. "The baseline MRI helped identify which patients were at very low risk of progressing to Alzheimer's and those whose risk was doubled."

By combining results of the baseline MRI and the MRI exam performed one year later, the researchers were able to calculate a rate of change in brain atrophy that was even more informative. The MCI patients' risk of disease progression based on the serial MR exams ranged from 3 to 69 percent.

"Rapid thinning of the cortex is reflective of a degenerative disorder," Dr. McEvoy explained.

Although no treatments currently exist that slow or prevent the neurodegeneration associated with AD, Dr. McEvoy said patients at high risk of progressing to AD might want to enroll in clinical trials of disease-modifying therapies. She said the information would also help ensure patients receive optimal care and allow families more time for planning.

More information: "Mild Cognitive Impairment: Baseline and Longitudinal Structural MR Imaging Measures Improve Predictive Prognosis." Collaborating with Dr. McEvoy were Dominic Holland, Ph.D., Donald J. Hagler, Jr., Ph.D., Christine Fennema-Notestine, Ph.D., James B. Brewer, M.D., Ph.D., and Anders M. Dale, Ph.D. http://radiology.rsna.org/

Provided by Radiological Society of North America

Blood biomarker associated with prevalence, severity of Alzheimer's, but not risk of development

Higher levels in blood of the protein clusterin, also known as apolipoprotein J, are significantly associated with the prevalence and severity of Alzheimer's disease, but not with the risk of onset of new disease, according to a study in the April 6 issue of JAMA.

06 april 2011--Clusterin levels have been found to be increased in brain and cerebrospinal fluid of patients with Alzheimer disease (AD), and have been suggested to be involved in the pathogenesis of AD. "Plasma clusterin was reported to be associated with brain atrophy, baseline disease severity, and rapid clinical progression in AD, suggesting its possible use as a biomarker of AD," according to background information in the article.

Elisabeth M. C. Schrijvers, M.D., of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and colleagues examined the associations between plasma levels of clusterin and the prevalence, severity, and risk of AD. The study included analysis of data on plasma levels of clusterin measured at baseline (1997-1999) in 60 individuals with prevalent AD, a random sub-group of 926 participants, and an additional 156 participants diagnosed with AD during follow-up (average, 7.2 years) until January 2007.

The researchers found that the likelihood of prevalent AD increased with increasing plasma levels of clusterin, with the odds increased by 63 percent for every standard deviation increase in clusterin levels, after adjusting for age, sex, education level, apolipoprotein E status, diabetes, smoking, coronary heart disease, and hypertension. Among patients with AD, higher clusterin levels were associated with more severe disease.

There was no statistically significant association of plasma clusterin levels with new AD during total follow-up or with new AD within or after 3 years of baseline. Results for all-cause dementia and vascular dementia were similar.

"In conclusion, our data from the general population show that increased plasma clusterin levels are associated with prevalent AD and are higher in more severe cases of AD. However, increased levels of clusterin do not precede development of AD and therefore are not a potential early marker of subclinical disease," the authors write.

More information: JAMA. 2011;305[13]1322-1326.

Provided by JAMA and Archives Journals

Five new genes linked to Alzheimer's

Scientists said Sunday they had uncovered five genes linked to the onset of Alzheimer's disease, doubling the number of genetic variants known to favour the commonest form of dementia.

05 april 2011--The findings, published in the journal Nature Genetics, may provide clues on the causes of this incurable and complex disease and help doctors predict who is most at risk, they said.

In the largest such studies to date, some 300 scientists in two consortia combed the genomes of 54,000 people -- some afflicted, others not -- to tease out the newly identified genetic variations.

The two projects started out independently but later swapped their data, enabling each group to confirm the overall findings.

"Prior to these studies, there were five accepted late-onset genes," said Gerard Schellenberg, a researcher at the University of Pennsylvania School of Medicine and the main architect of one of the studies.

"Now there are five more -- MS4A, ABCA7, CD33, EPHA1 and CD2AP," he said in an email exchange.

Identifying which snippets of DNA contribute to Alzheimer's boosts our understanding of the role of inheritance in its onset, Schellenberg said, adding that others surely remained to be found.

But, he added, "the biggest contribution will be in helping to understand the underlying mechanism that causes Alzheimer's. These genes highlight new pathways that are critical to the disease process."

Over the course of the illness, unwanted proteins form plaque in some areas of the brain, ultimately destroying neurons and leading to irreversible brain damage. Typically, symptoms include memory loss, erratic behaviour and eventually full-on dementia.

The ultimate aim, said Schellenberg, is creating drugs that can stop or even prevent this progression.

Toward that goal, "molecular biologists who work on disease mechanisms now need to figure out exactly how these new genes plug into the Alzheimer's process," he said.

Current treatments, he added, are only "marginally effective" in masking symptoms or slowing the disease's inexorable advance.

Alzheimer's affects 13 percent of people over 65, and up to 50 percent of those over 85.

As populations in rich countries age, the number of sufferers worldwide is set to double to more than 65 million by 2030, placing a huge burden on health care systems, experts forecast.

Ninety percent of Alzheimer's cases are so-called "late-onset", affecting people over the age of 65. The likelihood of developing this form doubles every five years.

More information: 'Common Variant at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease' is published in Nature Genetics.

(c) 2011 AFP

Vitamin D levels linked with health of blood vessels

A lack of vitamin D, even in generally healthy people, is linked with stiffer arteries and an inability of blood vessels to relax, research from the Emory/Georgia Tech Predictive Health Institute has found.

04 april 2011--The results add to evidence that lack of vitamin D can lead to impaired vascular health, contributing to high blood pressure and the risk of cardiovascular disease. Study participants who increased their vitamin D levels were able to improve vascular health and lower their blood pressure.

The data is being presented on Sunday by Ibhar Al Mheid, MD, a cardiovascular researcher at Emory University School of Medicine, at the annual American College of Cardiology meeting in New Orleans. Al Mheid is one of five finalists for the ACC's Young Investigators Award competition in physiology, pharmacology and pathology. He is working with Arshed Quyyumi, MD, professor of medicine and director of the Emory Cardiovascular Research Institute.

The 554 participants in the study were Emory or Georgia Tech employees –average age 47 and generally healthy -- who are taking part in the Center for Health Discovery and Well Being, part of the Emory/Georgia Tech Predictive Health Institute.

The average level of 25-hydroxyvitamin D (a stable form of the vitamin reflecting diet as well as production in the skin) in participants' blood was 31.8 nanograms per milliliter. In this group, 14 percent had 25-hydroxyvitamin D levels considered deficient, or less than 20 nanograms per milliliter, and 33 percent had levels considered insufficient, less than 30 nanograms per milliliter.

The researchers monitored the ability of participants' blood vessels to relax by inflating and then removing a blood pressure cuff on their arms. To allow blood to flow back into the arm, blood vessels must relax and enlarge – a change that can be measured by ultrasound. The researchers also made other measurements of smaller blood vessels and examined the resistance to blood flow imposed by the arteries.

Even after controlling for factors such as age, weight and cholesterol, people with lower vitamin D levels still had stiffer arteries and impaired vascular function, Al Mheid says.

"We found that people with vitamin D deficiency had vascular dysfunction comparable to those with diabetes or hypertension," he says.

Throughout the body, a layer of endothelial cells lines the blood vessels, controlling whether the blood vessels constrict or relax and helping to prevent clots that lead to strokes and heart attacks.

"There is already a lot known about how vitamin D could be acting here," Al Mheid says. "It could be strengthening endothelial cells and the muscles surrounding the blood vessels. It could also be reducing the level of angiotensin, a hormone that drives increased blood pressure, or regulating inflammation."

Most Americans generally get the majority of their vitamin D from exposure to sunlight or from dietary supplements; fortified foods such as milk or cereals are a minor source. A few foods, such as oily fish, naturally contain substantial amounts of vitamin D.

Participants whose vitamin D levels increased over the next six months, either from dietary supplements or ample sun exposure, tended to improve their measures of vascular health and had lower blood pressure. Forty-two study participants with vitamin D insufficiency whose levels later went back to normal had an average drop in blood pressure of 4.6 millimeters mercury.

"This was an observational study, rather than an interventional one, and it was difficult to tease out how the people who restored their vitamin D levels got there," Al Mheid says. "We are hoping to conduct a study where we have participants take a defined regimen of vitamin D."

"With his findings showing the relationship between vitamin D deficiency and vascular dysfunction, Dr. Mheid has helped advance our understanding of the importance of Vitamin D in preventing a common health problem in aging adults," says Kenneth Brigham, MD, medical director of the Emory/Georgia Tech Center for Health Discovery and Well Being. "Additionally, ongoing health studies based on the Center's collection of health information from participants will yield more discovery as the Center continues to develop."

The Emory-Georgia Tech Predictive Health Institute is a national leader in moving the practice of medicine from a reactive, disease-focused system to a proactive health-focused system. The initiative integrates research, scholarship and education in an innovative effort aimed at revolutionizing care of people to define, preserve and prolong the health of individuals and of society.

Key areas of the Initiative include defining and measuring health using optimal biomarkers of health and understand their interrelationships, determining the best interventions to optimize health throughout an individual's or a population's lifetime.

Provided by Emory University

Antidepressants linked to thicker arteries

Antidepressant use has been linked to thicker arteries, possibly contributing to the risk of heart disease and stroke, in a study of twin veterans. The data is being presented Tuesday, April 5 at the American College of Cardiology meeting in New Orleans.

03 april 2011--Depression can heighten the risk for heart disease, but the effect of antidepressant use revealed by the study is separate and independent from depression itself, says first author Amit Shah, MD, a cardiology fellow at Emory University School of Medicine. The data suggest that antidepressants may combine with depression for a negative effect on blood vessels, he says. Shah is a researcher working with Viola Vaccarino, MD, PhD, chair of the Department of Epidemiology at Emory's Rollins School of Public Health.

The study included 513 middle-aged male twins who both served in the U.S. military during the Vietnam War. Twins are genetically the same but may be different when it comes to other risk factors such as diet, smoking and exercise, so studying them is a good way to distill out the effects of genetics, Shah says.

Researchers measured carotid intima-media thickness – the thickness of the lining of the main arteries in the neck -- by ultrasound. Among the 59 pairs of twins where only one brother took antidepressants, the one taking the drugs tended to have higher carotid intima-media thickness (IMT), even when standard heart disease risk factors were taken into account. The effect was seen both in twins with or without a previous heart attack or stroke. A higher level of depressive symptoms was associated with higher IMT only in those taking antidepressants.

"One of the strongest and best-studied factors that thickens someone's arteries is age, and that happens at around 10 microns per year," Shah says. "In our study, users of antidepressants see an average 40 micron increase in IMT, so their carotid arteries are in effect four years older."

Antidepressants' effects on blood vessels may come from changes in serotonin, a chemical that helps some brain cells communicate but also functions outside the brain, Shah says. The most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), which increase the level of serotonin in the brain. Other types of antidepressants also affect serotonin levels, and antidepressants can act on other multi-functional brain chemicals such as norepinephrine.

In the study, researchers saw higher carotid IMT in both participants who used SSRIs (60 percent of those who took antidepressants) and those who used other types of antidepressants.

Most of the serotonin in the body is found outside the brain, especially in the intestines, Shah notes. In addition, serotonin is stored by platelets, the cells that promote blood clotting, and is released when they bind to a clot. However, serotonin's effects on blood vessels are complex and act in multiple ways. It can either constrict or relax blood vessels, depending on whether the vessels are damaged or not.

"I think we have to keep an open mind about the effects of antidepressants on neurochemicals like serotonin in places outside the brain, such as the vasculature. The body often compensates over time for drugs' immediate effects," Shah says. "Antidepressants have a clinical benefit that has been established, so nobody taking these medications should stop based only on these results. This isn't the kind of study where we can know cause and effect, let alone mechanism, and we need to see whether this holds up in other population groups."

Provided by Emory University