Abstract
Mystery Ingredient in Coffee Boosts Protection Against Alzheimer’s Disease
Tampa, FL (June 21, 2011)—A yet unidentified component of coffee interacts with the beverage’s caffeine, which could be a surprising reason why daily coffee intake protects against Alzheimer’s disease. A new Alzheimer’s mouse study by researchers at the University of South Florida (USF) found that this interaction boosts blood levels of a critical growth factor that seems to fight off the Alzheimer’s disease process.
The findings appear in the early online version of an article to be published on June 28 in the Journal of Alzheimer’s Disease. Using mice bred to develop symptoms mimicking Alzheimer’s disease, the USF team presents the first evidence that caffeinated coffee offers protection against the memory-robbing disease that is not possible with other caffeine-containing drinks or decaffeinated coffee.
Previous observational studies in humans reported that daily coffee/caffeine intake during midlife and in older age decreases the risk of Alzheimer’s disease. The USF researchers’ earlier studies in Alzheimer’s mice indicated that caffeine was likely the ingredient in coffee that provides this protection because it decreases brain production of the abnormal protein β-amyloid, which is thought to cause the disease.
The new study does not diminish the importance of caffeine to protect against Alzheimer’s. Rather it shows that caffeinated coffee induces an increase in blood levels of a growth factor called granulocyte colony-stimulating factor (GCSF). Granulocyte colony-stimulating factor is a substance greatly decreased in patients with Alzheimer’s disease and demonstrated to improve memory in Alzheimer’s mice. A just-completed clinical trial at the USF Health Byrd Alzheimer’s Institute is investigating GCSF treatment to prevent full-blown Alzheimer’s in patients with mild-cognitive impairment, a condition preceding the disease. The results of that trial are currently being evaluated and should be known soon.
“Caffeinated coffee provides a natural increase in blood GCSF levels,” said USF neuroscientist Dr Chuanhai Cao, lead author of the study. “The exact way that this occurs is not understood. There is a synergistic interaction between caffeine and some mystery component of coffee that provides this beneficial increase in blood GCSF levels.”
The researchers would like to identify this yet unknown component so that coffee and other beverages could be enriched with it to provide long-term protection against Alzheimer’s.
In their study, the researchers compared the effects of caffeinated and decaffeinated coffee to those of caffeine alone. In both Alzheimer’s mice and normal mice, treatment with caffeinated coffee greatly increased blood levels of GCSF; neither caffeine alone or decaffeinated coffee provided this effect. The researchers caution that, since they used only “drip” coffee in their studies, they do not know whether “instant” caffeinated coffee would provide the same GCSF response.
The boost in GCSF levels is important, because the researchers also reported that long-term treatment with coffee (but not decaffeinated coffee) enhances memory in Alzheimer’s mice. Higher blood GCSF levels due to coffee intake were associated with better memory. The researchers identified three ways that GCSF seems to improve memory performance in the Alzheimer’s mice. First, GCSF recruits stem cells from bone marrow to enter the brain and remove the harmful β-amyloid protein that initiates the disease. GCSF also creates new connections between brain cells and increases the birth of new neurons in the brain.
“All three mechanisms could complement caffeine’s ability to suppress β-amyloid production in the brain” Dr Cao said, “Together these actions appear to give coffee an amazing potential to protect against Alzheimer’s—but only if you drink moderate amounts of caffeinated coffee.”
Although the present study was performed in Alzheimer’s mice, the researchers indicated that they have gathered clinical evidence of the ability of caffeine/coffee to protect humans against Alzheimer’s and will soon publish those findings.
Coffee is safe for most Americans to consume in the moderate amounts (4 to 5 cups a day) that appear necessary to protect against Alzheimer’s disease. The USF researchers previously reported this level of coffee/caffeine intake was needed to counteract the brain pathology and memory impairment in Alzheimer’s mice. The average American drinks 1½ to 2 cups of coffee a day, considerably less than the amount the researchers believe protects against Alzheimer’s.
“No synthetic drugs have yet been developed to treat the underlying Alzheimer’s disease process” said Dr Gary Arendash, the study’s other lead author. “We see no reason why an inherently natural product such as coffee cannot be more beneficial and safer than medications, especially to protect against a disease that takes decades to become apparent after it starts in the brain.”
The researchers believe that moderate daily coffee intake starting at least by middle age (30s-50s) is optimal for providing protection against Alzheimer’s disease, although starting even in older age appears protective from their studies. “We are not saying that daily moderate coffee consumption will completely protect people from getting Alzheimer’s disease,” Dr Cao said. “However, we do believe that moderate coffee consumption can appreciably reduce your risk of this dreaded disease or delay its onset.”
The researchers conclude that coffee is the best source of caffeine to counteract the cognitive decline of Alzheimer’s because its yet unidentified component synergizes with caffeine to increase blood GCSF levels. Other sources of caffeine, such as carbonated drinks, energy drinks, and tea, would not provide the same level of protection against Alzheimer’s as coffee, they said.
Coffee also contains many ingredients other than caffeine that potentially offer cognitive benefits against Alzheimer’s disease. “The average American gets most of their daily antioxidants intake through coffee,” Dr Cao said. “Coffee is high in anti-inflammatory compounds that also may provide protective benefits against Alzheimer’s disease.”
An increasing body of scientific literature indicates that moderate consumption of coffee decreases the risk of several diseases of aging, including Parkinson’s disease, type 2 diabetes, and stroke. Just within the last few months, new studies have reported that drinking coffee in moderation may also significantly reduce the risk of breast and prostate cancers.
“Now is the time to aggressively pursue the protective benefits of coffee against Alzheimer’s disease,” Dr Arendash said. “Hopefully, the coffee industry will soon become an active partner with Alzheimer’s researchers to find the protective ingredient in coffee and concentrate it in dietary sources.”
New Alzheimer’s diagnostic guidelines, now encompassing the full continuum of the disease from no overt symptoms to mild impairment to clear cognitive decline, could double the number of Americans with some form of the disease to more than 10 million. With the baby-boomer generation entering older age, these numbers will climb even more unless an effective preventive measure is identified.
“Because Alzheimer’s starts in the brain several decades before it is diagnosed, any protective therapy would obviously need to be taken for decades,” Dr Cao said. “We believe moderate daily consumption of caffeinated coffee is the best current option for long-term protection against Alzheimer’s memory loss. Coffee is inexpensive, readily available, easily gets into the brain, appears to directly attack the disease process, and has few side-effects for most of us.”
According to the researchers, no other Alzheimer’s therapy being developed comes close to meeting all these criteria.
“Aside from coffee, two other lifestyle choices—physical and cognitive activity—appear to reduce the risk of dementia. Combining regular physical and mental exercise with moderate coffee consumption would seem to be an excellent multifaceted approach to reducing risk or delaying Alzheimer’s,” Dr Arendash said. “With pharmaceutical companies spending millions of dollars trying to develop drugs against Alzheimer’s disease, there may very well be an effective preventive right under our noses every morning—caffeinated coffee.” (Source: EurekAlert! A service of AAAS and the University of South Florida [USF Health]).
Falls May be Early Sign of Alzheimer’s Disease
Falls and balance problems may be early indicators of Alzheimer’s disease, researchers at Washington University School of Medicine in St Louis report on July 17, 2011, at the Alzheimer’s Association International Conference on Alzheimer’s Disease in Paris.
Scientists found that study participants with brain changes suggestive of early Alzheimer’s disease were more likely to fall than those whose brains did not show the same changes. Until now, falls had only been associated with Alzheimer’s in the late stages of dementia.
“If you meet these people on the street, they appear healthy and have no obvious cognitive problems,” says lead author Susan Stark, PhD, assistant professor of occupational therapy and neurology. “But they have changes in their brain that look similar to Alzheimer’s disease, and they have twice the typical annual rate of falls for their age group.”
Stark and her colleagues recruited 119 volunteers from studies of aging and health at Washington University’s Knight Alzheimer’s Disease Research Center. All the participants were 65 years or older and cognitively normal.
Brain scans showed that 18 participants had high levels of amyloid plaques, a hallmark of Alzheimer’s. The other 101 volunteers had normal amyloid levels in the brain.
Participants were given a journal and asked to note any falls. When they did so, the researchers followed up with a questionnaire and a phone interview about the falls. This follow-up allowed researchers to gather information for future analyses that will compare and contrast the nature of the falls.
About 1 in 3 adults aged 65 or older typically fall each year. But in the 18 participants with high amyloid levels in the brain, two-thirds fell within the first 8 months of the study. High levels of amyloid in the brain were the best predictor of an increased risk of falls.
“Falls are a serious health concern for older adults,” Stark says. “Our study points to the notion that we may need to consider preclinical Alzheimer’s disease as a potential cause.” (Source: EurekAlert! A service of AAAS and The Washington University School of Medicine).
Study: Alzheimer’s Disease Symptoms More Subtle in People Older Than 80
St. Paul, MN—A new study suggests that the relationship between brain shrinkage and memory loss in Alzheimer’s disease changes across the age spectrum. The research is published in the August 10, 2011, online issue of Neurology, the medical journal of the American Academy of Neurology.
“Those who are aged 85 and older make up the fastest growing population in the world,” said study author Mark Bondi, PhD, with the University of California San Diego School of Medicine and VA San Diego Healthcare System. “Our study shows how age has a dramatic effect on the profile of brain atrophy and cognitive changes evident in Alzheimer’s disease.”
The study involved 105 people with Alzheimer’s disease and 125 people who were free of dementia and recruited through the Alzheimer’s Disease Neuroimaging Initiative. Participants were grouped into those who were between the ages of 60 and 75 and those aged 80 years and older. All were given tests that measured language, attention, and speed of processing information, executive function, and immediate and delayed ability to recall information.
Participants also underwent brain scans to measure the thickness of the outermost tissue layers in the cerebrum of the brain.
Even though the two groups had similar levels of overall cognitive impairment, researchers found that the pattern of changes associated with Alzheimer’s disease appeared to be less noticeable in people over the age of 80 (very-old) compared to those between the ages of 69 and 75 (young-old). When compared to their healthy counterparts, executive function, immediate memory, and attention/processing speed were less abnormal in those considered very old compared to those considered young-old. The very-old also showed less severe thinning of portions of cerebral cortex and the overall cerebrum than the young-old when compared to their healthy counterparts. This is in part because these brain areas decrease in thickness due to age, so there are fewer differences between the healthy very-old brain and the very-old brain with Alzheimer’s disease, Bondi said. (Source: EurekAlert! A service of AAAS and American Academy of Neurology).
Rhode Island Hospital Study Identifies Fish Oil’s Impact on Cognition and Brain Structure
Providence, RI—Researchers at Rhode Island Hospital’s Alzheimer’s Disease and Memory Disorders Center have found positive associations between fish oil supplements and cognitive functioning as well as differences in brain structure between users and nonusers of fish oil supplements. The findings suggest possible benefits of fish oil supplements on brain health and aging. The results were reported at the recent International Conference on Alzheimer’s Disease in Paris, France.
The study was led by Lori Daiello, PharmD, a research scientist at the Rhode Island Hospital Alzheimer’s Disease and Memory Disorders Center. Data for the analyses were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large multicenter, NIH-funded study that followed older adults with normal cognition, mild-cognitive impairment, and Alzheimer’s Disease for over 3 years with periodic memory testing and brain MRIs.
The study included 819 individuals, 117 of whom reported regular use of fish oil supplements before entry and during study follow-up. The researchers compared cognitive functioning and brain atrophy for patients who reported routinely using these supplements with those who were not using fish oil supplements.
Daiello reports that compared to nonusers, use of fish oil supplements was associated with better cognitive functioning during the study. However, this association was significant only in those individuals who had a normal baseline cognitive function and in individuals who tested negative for a genetic risk factor for Alzheimer’s disease known as APOE4. This is consistent with previous research.
The unique finding, however, is that there was a clear association between fish oil supplements and brain volume. Consistent with the cognitive outcomes, these observations were significant only for those who were APOE4 negative.
Daiello says, “In the imaging analyses for the entire study population, we found a significant positive association between fish oil supplement use and average brain volumes in two critical areas utilized in memory and thinking (cerebral cortex and hippocampus), as well as smaller brain ventricular volumes compared to non-users at any given time in the study. In other words, fish oil use was associated with less brain shrinkage in patients taking these supplements during the ADNI study compared to those who didn’t report using them.”
Daiello continues, “These observations should motivate further study of the possible effects of long-term fish oil supplementation on important markers of cognitive decline and the potential influence of genetics on these outcomes.”
The research team included Brian Ott, MD, director of the Rhode Island Hospital and Memory Disorders Center, Assawin Gongvatana, PhD, Shira Dunsiger, PhD, and Ronald Cohen, PhD, from The Miriam Hospital and the Brown University, Department of Psychiatry and Human Behavior (Gonvatana and Cohen) and Department of Behavior and Social Sciences (Dunsiger; Source: EurekAlert! A service of AAAS and Lifespan).
Even Mild Cognitive Impairment Appears to Substantially Increase Risk of Death
Indianapolis, IN—Cognitive impairment, even when detected at an early, mild stage is a significant predictor of decreased life expectancy.
According to a new, long-term study from Regenstrief Institute and Indiana University researchers, cognitive impairment, especially at the moderate-to-severe stages has an impact on life expectancy similar to chronic conditions such as diabetes or chronic heart failure. Their findings, “Cognitive Impairment: An Independent Predictor of Excess Mortality. A Cohort Study” appears in the September 6, 2011 issue of Annals of Internal Medicine.
Nearly 4000 people between the ages of 60 to 102 years, initially seen from 1991 to 1993 by primary care physicians at Wishard Health Services, a large public hospital with community health centers in Indianapolis, participated in the study. The patients were followed for 13 years.
“Previous studies have associated cognitive impairment with an increased risk of death, but most of this work focused on patients with Alzheimer disease and participants in research centers. The patients in our study better reflect the general public, displaying no indications of disease or mild, moderate, or severe cognitive impairment,” said Regenstrief investigator Greg A. Sachs, MD, professor of medicine at the Indiana University School of Medicine, where he is the division chief of general internal medicine and geriatrics. “We found that even mild-cognitive impairment, as determined by a simple screening tool in a primary care physician’s office, has a strong impact on how long individuals survive on the same order as other chronic diseases.”
The study followed 3957 patients. At screening, 3157 had no cognitive impairment, 533 had mild impairment, and 267 had moderate-to-severe impairment. During follow-up, 57% of patients with no impairment died when compared with 68% of those with mild impairment and 79% of those with moderate-to-severe impairment. Median survival time was 138 months for patients with no impairment, 106 months for those with mild impairment, and 63 months for those with moderate-to-severe impairment.
Study participants were screened for cognitive impairment using an easy-to-administer 10-question mental status questionnaire. On the basis of the number of errors patients made on this test, they were categorized as having no, mild, or moderate-to-severe cognitive impairment. The Regenstrief Medical Record System was used to obtain data on the patients’ medical conditions, results of laboratory tests, and other relevant information.
Cognitive impairment affects memory and thinking. Approximately 4 to 5 million people in the United States have dementia, and the number of individuals affected is significantly higher if individuals with milder forms of cognitive impairment are included. The prevalence of cognitive impairment at all stages is expected to increase as the population ages.
The study findings have important clinical and prognostic implications beyond dementia detection, treatment, and support for affected patients and their families. Reduced life expectancy in patients with cognitive impairment should be factored into medical decisions, such as advance care planning, cancer screening, and prescribing of medications, especially in patients with severe impairment, the authors state.
Given that the magnitude of the risk of mild and moderate-to-severe cognitive impairment is similar to that of many life-limiting diseases, and the ease of indentifying cognitive impairment by using a short screening tool, recognition of cognitive impairment in primary care practices should be given a higher priority, the study concludes. (Source: EurekAlert! A service of AAAS and the Indiana University School of Medicine).
Study Reveals Link Between High Cholesterol and Alzheimer’s Disease
Embargoed for Release Until 4 pm ET, Monday, September 12, 2011
St. Paul, MN—People with high cholesterol may have a higher risk of developing Alzheimer’s disease, according to a study published in the September 13, 2011 issue of Neurology, the medical journal of the American Academy of Neurology.
“We found that high cholesterol levels were significantly related to brain plaques associated with Alzheimer’s disease,” said study author Kensuke Sasaki, MD, PhD, of Kyushu University in Fukuoka, Japan.
For the study, the cholesterol levels were tested for 2587 people aged 40 to 79, who had no signs of Alzheimer’s disease. Then they examined 147 autopsied people who died after a long observation period (10-15 years). Of those, 50 people, or 34%, had been diagnosed with dementia before death.
The autopsies looked for plaques and tangles in the brain, both known to be trademark signs of Alzheimer’s disease. Plaques are an accumulation of a form of the protein amyloid, which occurs between nerve cells. Tangles are an accumulation of a different protein, called tau, which occurs inside nerve cells.
People with high cholesterol levels, defined by a reading of more than 5.8 mmol/L, had significantly more brain plaques when compared with those with normal or lower cholesterol levels. A total of 86 percent of people with high cholesterol had brain plaques when compared with only 62 percent of people with low cholesterol levels.
The study found no link between high cholesterol and the tangles that develop in the brain with Alzheimer’s disease.
In addition to high cholesterol increasing the risk of Alzheimer’s disease, Sasaki previously found that insulin resistance, a sign of diabetes, may be another risk factor for brain plaques associated with Alzheimer’s disease.
“Our study clearly makes the point that high cholesterol may contribute directly or indirectly to plaques in the brain,” Sasaki said, “but failed treatment trials of cholesterol-lowering drugs in Alzheimer’s disease means there is no simple link between lowering cholesterol and preventing Alzheimer’s.” (Source: EurekAlert! A service of AAAS and the American Academy of Neurology).
Safeguards Needed to Prevent Discrimination of Patients With Early Alzheimer’s in the Workplace
Policies Needed to Prepare Individuals, Society for Earlier Diagnosis and High Risk of Alzheimer’s
Philadelphia, PA—The changing tide of Alzheimer’s diagnosis presents new challenges to the public, physicians, and lawmakers: if you could find out your Alzheimer’s risk, would you want to know? How should doctors tell you your risk? And what does it mean for the many newly diagnosed Americans still in the workplace?
Despite the emergence of new tools that can diagnose Alzheimer’s earlier, no effective interventions have been identified to stop the progression of the disease. A new report from the Perelman School of Medicine at the University of Pennsylvania tackles the ethical and logistical challenges of safely and effectively communicating a diagnosis of preclinical Alzheimer’s disease in light of the gulf between diagnosis and treatment. The study appears in the October 11 print edition of Neurology.
Alzheimer’s disease is among the most feared diseases of aging. The disease has been known for its role in memory loss and other clinical symptoms. But increasingly, patients learn they have the disease before symptoms start impacting their ability to function in daily life.
“We need to develop systems now, to navigate the challenges of a pre-clinical Alzheimer’s diagnosis,” said Jason Karlawish, MD, professor of medicine and medical ethics, author of the article and leading voice on the ethics of Alzheimer’s. “It’s only a matter of time before we are able identify Alzheimer’s before the patient is ill, like we’ve done with cholesterol and heart disease. Given the unique nature of this disease, which strips people of their independence as the disease progresses, safeguards are needed to protect those at high risk or with a pre-clinical diagnosis.”
On the individual level, people strongly differ in their desire to know their risk and will react differently to a high Alzheimer’s risk score or diagnosis in the early stages of the disease. In some cases, biomarker test results can be harmful; patients may develop anxiety or serious depression. To safely and effectively communicate a diagnosis of preclinical Alzheimer’s disease, Dr Karlawish recommends that researchers and clinicians track the emotional and physical impact of a preclinical diagnosis, then develop and disseminate best practices.
When an effective Alzheimer’s therapy or intervention is found, a process will be necessary to ensure the patients who stand to benefit most are prioritized accordingly. Both prognostic and predictive evidence should be gauged against not only an individual’s risk but the entire population at risk, especially, if failure to intervene could cause large numbers of people to be impacted by any disease progression. A “National Alzheimer’s Education Program” is proposed to address how to translate research results into clinical practice for those with preclinical disease.
“The Alzheimer’s disease label does not equate to disability,” said Dr Karlawish. In order to ensure that patients’ daily lives (i.e., driving, financial planning, and work status) are not negatively or prematurely limited, laws and policies need to be revised to prevent stigma, discrimination, and when patients do suffer disability, exploitation.
“The discovery of preclinical Alzheimer’s disease may be how we prevent the tsunami of Alzheimer’s disease dementia, but we must not drown in the challenges created by our own discovery,” warned Dr Karlawish. (Source: EurekAlert! A service of AAAS and University of Pennsylvania School of Medicine).