Beta-Amyloid Clearance from Brain May Underly Alzheimer’s Disease

Alzheimer’s disease is the most common cause of dementia in older adults, and affects as many as 5.1 million Americans. In Alzheimer’s disease, a protein fragment called beta-amyloid accumulates at abnormally high levels in the brain. In the the most common type of Alzheimer’s disease, late-onset Alzheimer’s, symptoms usually appear after age 65.

Now researchers have found that in late-onset Alzheimer’s disease, beta-amyloid is produced in the brain at a normal rate but is not cleared, or removed from the brain, efficiently. [Read more…]

Elderly with Untreated Vision Problem More Likely to Develop Alzheimer’s

Elderly people with visual disorders that are left untreated are significantly more likely to develop Alzheimer’s disease — the most common form of dementia, according to a University of Michigan Health System study.

The study used Medicare data and shows that those with poor vision who visited an ophthalmologist at least once for an examination were 64 percent less likely to develop dementia.

The study appears online ahead of print in the American Journal of Epidemiology and may draw a new picture of poor vision as predictor of dementia rather than as a symptom after the diagnosis.

“Visual problems can have serious consequences and are very common among the elderly, but many of them are not seeking treatment,” says lead author Mary A.M. Rogers, Ph.D, research assistant professor of internal medicine at the U-M Medical School and research director of the Patient Safety Enhancement Program at the U-M Health System and the Ann Arbor VA Medical Center.

For the study, Rogers and her colleague Kenneth M. Langa, M.D., Ph.D., professor of internal medicine at U-M Medical School, analyzed data from the nationally representative Health and Retirement Study and records from Centers for Medicare and Medicaid Services.

”Our results indicate that it is important for elderly individuals with visual problems to seek medical attention so that the causes of the problems can be identified and treated,” Rogers says.

The types of vision treatment that were helpful in lowering the risk of dementia were surgery to correct cataracts and treatments for glaucoma, retinal disorders and other eye-related problems.

Proper vision is a requirement for many of the activities that previously have been found to lower the risk of Alzheimer’s disease. These include reading, playing board games, other mentally stimulating activities, social networking, as well as physical activity such as walking and routine exercising. A visual disorder may interfere with normal mobility and may also hinder a person’s ability to participate in such activities.

“Many elderly Americans do not have adequate health coverage for vision, and Medicare does not cover preventative vision screenings for most beneficiaries,” Rogers says. “So it’s not unusual that the elderly receive vision treatment only after a problem is severe enough to warrant a visit to the doctor when the problem is more advanced.”

According to a survey conducted by the National Eye Health Education Program, less than 11 percent of respondents understood that there are no early warning signs for eye problems such as glaucoma and diabetic retinopathy.

However, vision problems and blindness are among the top 10 disabilities among adults and can result in a greater tendency to experience other health conditions or even to die prematurely.

“While heart disease and cancer death rates are continuing to decline, mortality rates for Alzheimer’s disease are on the rise,” says Rogers. “So if we can delay the onset of dementia, we can save individuals and their families from the stress, cost and burden that are associated with Alzheimer’s disease.”

The study was based on the surveys and medical information from 625 people compiled from 1992-2005. Only 10 percent of Medicare beneficiaries who developed dementia had excellent vision at the beginning of the study, while 30 percent of those who maintained normal cognition had excellent vision at the onset of the study.

One in five Americans who are over age 50 report experiencing a visual impairment, according to the U.S. Centers for Disease Control and Prevention. Approximately 5 million Americans have Alzheimer’s disease and the number has doubled since 1980. It is expected to be as high as 13 million by 2050.

Source: American Journal of Epidemiology,/em> 2010 Feb. 11; doi:10.1093; University of Michigan

Alzheimer’s Disease Risk Different for Men and Women

Recent research suggests that the chances of developing Alzheimer’s Disease are different for men and women, with stroke in men and depression in women being key elements.

The research was conducted in France, among 7,000 people aged 65 and over, drawn from the general population. While none of the participants had dementia, some 40% had mild cognitive impairment. Four years later 6.5% of those displaying mild cognitive impairment had developed dementia, while no change was noted in just over half. About one third returned to normal cognitive ability.

The move from cognitive impairment to dementia however, was marked among subjects taking anticholinergic drugs for depression. A variation in the ApoE gene, a known risk factor for dementia, was also more common among those whose mild cognitive impairment progressed.

The results demonstrated that men with mild cognitive impairment were probably overweight and diabetic, and to have suffered a stroke. In fact, male stroke victims were three times as likely to progress from cognitive impairment to dementia.

Women with mild cognitive impairment had poorer general health, were disabled, and suffered from insomnia, besides having an inadequate support group. They were also unable to perform the daily tasks that would enable them to live alone without assistance. It was judged they were 3.5 times as likely to develop dementia, while those suffering from depression were twice as likely to do so. Stroke was not a risk factor for women, although there was similar rate of occurrence in men and women.

Source: Journal of Neurology, Neurosurgery, and Psychology, 2008; doi 10.1136/jnnp.2007.136903

Alcohol May Cause Lower Brain Volume

According to a recent report, the more you drink the smaller your brain becomes. It is estimated that 1.9 percent decrease in brain volume per decade accompanies an increase in white matter lesions.

The progression of dementia and problems with thinking, learning and memory are accompanied by lower brain volumes and larger white matter lesions. Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease; because the brain receives blood from this system, researchers have hypothesized that small amounts of alcohol may also attenuate age-related declines in brain volume. The study results were published in the October, 2008 issue of Archives of Neurology.

Members of the Framingham Offspring Study, which began in 1971 and included 1,839 adults with an average age of 60, were studied by Carol Ann Paul, M.S., of Wellesley College, Mass., and colleagues. The Study also included children of the original Framingham Heart Study participants and their spouses. Between 1999 and 2001, participants underwent magnetic resonance imaging (MRI) and a health examination. They reported the number of alcoholic drinks they consumed per week, along with their age, sex, education, height, body mass index and Framingham Stroke Risk Profile (which calculates stroke risk based on age, sex, blood pressure and other factors).

“Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers,” the authors write. “There was a significant negative linear relationship between alcohol consumption and total cerebral brain volume.”

Although men were more likely to drink alcohol, the association between drinking and brain volume was stronger in women, they note. This could be due to biological factors, including women’s smaller size and greater susceptibility to alcohol’s effects.

“The public health effect of this study gives a clear message about the possible dangers of drinking alcohol,” the authors write. “Prospective longitudinal studies are needed to confirm these results as well as to determine whether there are any functional consequences associated with increasing alcohol consumption. This study suggests that, unlike the associations with cardiovascular disease, alcohol consumption does not have any protective effect on brain volume.”

Source: Archives of Neurology,

Alzheimer’s Disease Connection to Stroke Explained

The risk of Alzheimer’s disease is nearly doubled among people who have had a stroke, and researchers at Columbia University Medical Center have found a process in the brain that explains the connection.

There is an increase in the production of the toxic amyloid beta (Aß) peptides after a stroke that are believed to cause Alzheimer’s disease. Results in this study showed that Aß production rises when there is an increase in production of a peptide called p25, which occurs in rodents and humans following a stroke. The Columbia team identified a pathway, known as p25/cdk5, whereby higher levels of p25 led to enhanced activity of a molecule called cdk5, which in turn led to a rise in the production of Aß

By reducing the activity of cdk5, by either an inhibitor or by genetic manipulation, lead author Karen found a decrease in Aß production in the brain, demonstrating that the p25/cdk5 pathway may be a treatment target for Alzheimer’s disease. Specifically, inhibitors of cdk5 are particular candidates for therapeutic development.

"This finding connects the dots between p25 and increased production of amyloid beta, and this p25/cdk5 pathway could explain why the risk of Alzheimer’s disease is significantly higher following a stroke," said Dr. Duff, professor of pathology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at Columbia University Medical Center and the New York State Psychiatric Institute. "However, we still need to verify that this pathway is actually set in motion after a stroke; right now the data is still circumstantial."

Dr. Duff’s laboratory is currently working on experiments to verify this pathway’s involvement using human post-mortem tissue of stroke patients. The specific pathway investigated was shown to be most active in young mice, as compared to older mice suggesting that p25/cdk5 may not be implicated in late-onset Alzheimer’s disease, the most common form of this neurodegenerative disease.

The research was published in the March 13, 2008 issue of Neuron.

Some Hypertension Drugs May Also Treat Alzheimer’s

Recent research points to the possibility that patients being treated with hypertension drugs may also benefit from the drug’s ability to treat or even prevent Alzheimer’s disease.

"If we can deliver certain anti-hypertensive drugs to patients at high risk to develop Alzheimer’s disease, at doses that do not affect blood pressure, these drugs could be made available for all members of the geriatric population identified as being at high
risk for developing Alzheimer’s disease", says Dr. Giulio Maria Pasinetti of Mount Sinai School of Medicine.

Under Dr. Pasinetti’s supervision, more than 1,500 drugs used to treat other disorders have been screened for their potential in treating Alzheimer’s disease, and 7 out of 55 drugs prescribed for the treatment of hypertension have been identified as significantly preventing beta-amyloid production, which plays a key role in Alzheimer’s disease pathogenesis.

Valsartan, an anti-hypertensive agent, was found to pharmacologically prevent beta-amyloid production in the brains of test mice even when administered to Alzheimer’s disease mice at 3-4 times lower than the minimal equivalent dose prescribed for the treatment of hypertension in humans.

Other hypertension drugs with positive results included Propranol HCI, Carvedilol, Losartan, Nicardipine HCI, Amiloride HCI and Hydralazine HCI.

"The use of these drugs for their potential anti-Alzheimer’s disease role is still highly experimental," said Dr. Pasinetti, "and at this stage we have no clinical data beyond phenomenological observation in humans. We need to complete preventive and therapeutic clinical trials in the near future if we are to identify certain anti-hypertensive drugs with anti beta-amyloid antiligomeric activities, which will need to be prescribed at dosages that do not interfere with blood pressure in normotensive Alzheimer’s patients."

The research was conducted by Dr.Giulio Maria Pasinetti, MD, Ph.D., Professor of Psychiatry and Neuroscience, Geriatrics and Adult Development , and Director of the Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer’s Disease at Mount Sinai School of Medicine, and published in the November, 2007 issue of the The Journal of Clinical Investigation.

Rate of Memory Loss Greater in Dementia Patients With More Education

According to a recent study in the journal Neurology, while higher education levels initially delay the onset of dementia, once dementia starts, the rate of memory loss is more rapid than in less educated individuals.

According to study author Charles B. Hall, PhD of the Albert Einstein College of Medicine, "our study showed that a person with 16 years of formal education would experience a rate of memory decline that is 50% faster than someone with just four years of education."

The study started in the 1980s, and monitored 488 people born between 1894 and 1906, with study findings based on the 117 members of the sample who eventually developed Alzheimer’s or some other form of dementia. Study participants ranged from people with postgraduate education to people with less than three years of elementary school education.

Dr. Hall believes that this rapid decline in the more educated people might be explained by their having a greater cognitive reserve, or the brain’s ability to maintain function in spite of damage. This meant that while patients are often diagnosed with dementia at a later date, once the cognitive reserve is no longer able to compensate for the damage that has occurred, then the symptoms emerge.

The study is valuable, says Dr. Hall, because it examines memory loss before a formal diagnosis of Alzheimer’s.

The study was supported by the National Institute on Aging. Other researchers from the Einstein Aging Study involved in the research included Carol Derby, PhD; Aaron LeValley, MA; Mindy J. Katz, MPH; Joe Verghese, MD; and Richard B. Lipton, MD.

Source: Neurology, October 23, 2007

Conscientiousness May Help Protect Against Alzheimer’s Disease

Results of a recent study about the link between conscientiousness and Alzheimer’s disease may provide yet another strategy for delaying the symptoms of Alzheimer’s, according to a study published in the October issue of Archives of General Psychiatry.

Conscientiousness, which generally refers to a person’s ability to be goal-directed and control impulses, has been associated with various mental and physical disorders. In the published study, which ran from 1994 to 2006 and studied nearly 1,000 older individuals, participants were evaluated for medical history, neurologic examinations and cognitive testing.

The "conscientiousness score" was determined with a 12-items evaluation where participants rated their agreement with a number of statements, such as: “I am a productive person who always gets the job done." Those who had conscientiousness scores in the top 10% had an 89% lower risk of developing Alzheimer’s disease than those whose scores ranked in the bottom 10% of the conscientiousness score.

The study’s author’s posit that conscientious people are more likely to be succesful in education and work, both of which have been associated with a reduced risk of Alzheimer’s disease. In addition, conscientiousness has been linked to resilience and to coping actively with difficulties. “These factors might lessen the adverse consequences of negative life events and chronic psychological distress, which have been associated with risk of dementia in old age,” the researchers note.

The study concludes that the "level of conscientiousness is associated with incidence of mild cognitive impairment and Alzheimer’s disease but not with the pathologic hallmarks of these conditions."


Source: Arch Gen Psychiatry. 2007;64(10):1204-1212.

Alzheimer’s and Aluminum

Aluminum is unusually abundant in the neurofibrillary tangles of Alzheimer’s disease. For years, rumors have circulated that aluminum cookware contributed to the disease. And for just as long, most scientists have scoffed at this notion because aluminum is one of the most abundant elements on earth and everyone is exposed to a great deal of it.

Over the last decade several studies have explored the issue of aluminum–especially Aluminum in drinking water–and Alzheimer’s risk. Some show that as the aluminum concentration in water increases beyond about 11 micrograms per liter, so does Alzheimer’s risk. Others show no association.

Studies showing an aluminum-Alzheimer’s link suggest that aluminum alone is not the sole culprit. Other substances, notably acids, must be present in the water to enable aluminum absorption in the gut.

Scientists who suspect that aluminum exposure may be a risk factor for Alzheimer’s warn against drinking carbonated beverages from aluminum cans. The carbonation makes the drink acidic, which increases aluminumn absorption in the gut.

The issue of aluminumn as a possible risk factor for Alzheimer’s is extremely controversial.

If you’re concerned enough about aluminum to spend about $100 to have your water tested, the National Testing Laboratory of Cleveland includes aluminum in a 74-item test of water quality.

They send you sampling test tubes. You fill them with your water, and send then to the lab in a special styrofoam-lined box. A week or so later, the lab sends you a report detailing what’s in your water. For more information, call 1-800-458-3330.

— By Matthew Naythons MD and Michael Castleman

Donepezil Shows Promise for Severe Alzheimer’s

In a study released last week published in the Journal of the American Academy of Neurology, the drug donepezil has improved the cognitive functioning and memory of individuals with severe Alzheimer’s disease.

The study, funded by Eisai Inc. and Pfizer, makers of the drug, took place over six months and studied 343 individuals.Half of the group took donepezil and the other half received a placebo.

The results showed that over 63% of the individuals demonstrated memory stabilization or increased function, compared to 39% on the placebo.