November 2006 — Life expectancy in the U.S. has reached an all-time high, with the average American expected to live to age 77.6, 2.2 years longer than in 1990. But as we achieve longer lives, we also face serious health concerns. One of the greatest is Alzheimer’s disease (AD).

The projections for the continued growth of Alzheimer’s disease are stunning. By 2020, a 27 percent increase in the number of Americans with AD is projected; by 2050, a 300 percent increase is forecast.

New clues shed light on the causes of AD
While the definitive cause of AD has not been pinpointed, one hypothesis held by many experts is that the excessive build-up of fragments of a protein called beta-amyloid in the brain may disrupt cell communication, triggering inflammation that destroys brain cells.

New genetic research examines the body’s ability to dispose of excess beta-amyloid. At California’s Salk Institute for Biological Studies, Dr. Andrew Dillin’s experiments with the roundworm C. elegans, a common subject for age-related genetic studies, showed that when researchers altered genes in the insulin/IGF-1 pathway, they were able to slow normal aging. The alterations also slowed the build-up of beta-amyloid. Two proteins in the gene pathway, HSF-1 and DAF-16, detoxify beta-amyloid. But as we age, the production of these proteins slows.

“Every pathway we discover that modifies amyloid provides us with new drug targets,” notes Dr. Sam Gandy, a neuroscientist at Thomas Jefferson University.

Genetic keys
Other researchers have focused their attention on a gene that indicates an increased risk for developing AD. The apolipoprotein e4 (APOE4) gene has been found to be a risk factor gene for the development of late-onset (after age 65) AD, the most common form of the disease. While the presence of this gene indicates a greater risk, it does not mean the carrier will develop AD.

Researchers at the University of California-Davis recently announced that they had uncovered a link between the development of AD and variations in the tumor necrosis factor (TNF) alpha molecule. “We studied the genetic variations of subjects from a community-based population; and our data suggest that the genetic modulation of a prominent inflammation mediator, TNF-alpha, is related to Alzheimer’s disease risk,” explains Dr. Lee-Way Jin, senior investigator.

On another front, alterations in the mechanism that transmits nerve growth factor signals in the cholinergic system, a genetic pathway in the brain, were found by Stanford researchers to decrease the survival of neurons. Explains study co-author Dr. Ralph A. Nixon, Professor of Psychiatry and Cell Biology at New York University, “Most of the treatments currently available for Alzheimer’s target and attempt to make the cholinergic system more effective. We have not known much about why, in Alzheimer’s disease, these (nerve growth factor signal) neurons are vulnerable. This study identifies the gene that is related to the survival of neurons. So, it links a genetic cause of Alzheimer’s disease to a specific biochemical mechanism.”

Brain changes may sound early warning
Loss of brain density seen on MRI scans has been cited as an early indicator of decreased brain health. Investigators at Dartmouth Medical School found people who complained of significant memory problems but still scored normally on memory tests had a 3% reduction in gray matter density. People diagnosed with mild cognitive impairment had only a slighter larger reduction of 4%. Tracking brain density reduction may eventually allow physicians to diagnose AD earlier.

“Our data suggest these individuals, who were previously dismissed by many clinicians as the ‘worried well,’ are actually detecting changes within themselves and that what we thought were quite sensitive tests are not able to detect these subtle changes,” says principal investigator Andrew Saykin, PsyD.

The diabetes-Alzheimer’s link: a 70% increase in risk
Recent research has found that even borderline diabetes can boost your risk of developing Alzheimer’s disease and other types of dementia by 70 percent. The nine-year study, undertaken by Dr. Weili Zu and colleagues from Karolinska Institutet and the Stockholm Gerontology Research Center in Sweden found that borderline diabetes was linked to a 70 percent increase in the risk for developing AD or dementia. The risk was highest for those who also had severe high blood pressure. Equally significant was the fact that the increased risk affected only participants who did not carry a gene that increases the risk of developing the most common form of AD.

Other recent studies have found that when people with diabetes fail to effectively control their blood sugar levels, they significantly increase their risk of developing dementia and AD. When study participants’ glycosylated hemoglobin level rose to 12 or above, their risk of developing dementia increased 22 percent. When the level was over 15, the increase in risk jumped to 78 percent.

Can AD be prevented?
While there is no definitive answer to that intriguing question yet, physicians and researchers are exploring proactive measures that may help prevent the onset of AD.

A good deal of attention is currently focused on the diabetes-AD link. “Our findings (linking diabetes and AD) have significant implications for public health because some studies show that impaired glucose regulation can be improved by lifestyle changes,” notes Dr. Weili Xu. “Our findings also highlight the need to detect borderline diabetes in order to proactively address both type 2 diabetes and dementia.”

“To try to prevent the onset of dementia, you should reduce your vascular risk factors by maintaining a healthy body weight, eating a low fat diet, and receiving good medical care to screen for high blood pressure and cholesterol and diabetes,” explains Dr. Patricia A. Bloom, Associate Clinical Professor of Geriatrics and Internal Medicine at the Mount Sinai Medical Center and a member of PinnacleCare’s Medical Advisory Board. “Research also suggests that moderate alcohol use and antioxidants in food may be helpful. In addition, recent studies have found that regular exercise may have a neuro-protective effect.”

Controlling diet may ward off AD
While some foods have demonstrated a potentially protective effect against AD, others may increase your risk. A study at Rush University Medical Center found that older people whose diets are high in saturated and trans fats who also have a high copper (found in organ meats, shellfish, nuts, seeds, legumes, whole grains, potatoes, chocolate, and some fruits) intake may be at risk for accelerated cognitive decline.

“The increase in rate for the high-fat consumers whose total copper intake was in the top 20 percent was equivalent to 19 more years of age,” note the study’s authors. They caution, however, that their findings are preliminary and require further investigation.

On the other side of the food-AD equation, researchers at the Columbia University Medical Center recently investigated the effect of a Mediterranean diet on AD. They found that a diet rich in fruits, vegetables, olive oil, legumes, cereals, and fish appears to lower the likelihood of developing the disease. Participants whose food intake was closest to the Mediterranean diet were 68 percent less likely to have Alzheimer’s than those whose diets strayed far from that model.

Keeping the brain active may increase vitality of mind
Another frontier in the preservation of cognitive functioning has been dubbed “brain fitness.” Based on research by the National Institutes of Health and the National Institute of Aging that uncovered the concept of a cognitive reserve which allows our brains to continue to operate effectively even when function is disrupted or impaired, brain fitness strives to enhance the cognitive reserve through intellectual activities and behavioral enrichment.

Dr. L. Michael Hinds, PhD, explains, “Challenging, varied cognitive activities create a neuro-chemical reaction and increase blood flow in the brain. This can help enhance the cognitive reserve and delay cognitive decline.”

There are several tools now available to help you achieve this goal, including one developed by some of Dr. Hinds’ colleagues in Israel. The interactive computer software called MindfitTM assesses the user’s cognitive skills, then creates a user-specific computer-based training program to build cognitive skills. The program continually assesses and adapts itself to the user’s strengths and weaknesses. The time investment is minimal—20 minutes three times a week.

“People should be concerned about revitalizing the health of their brain,” Dr. Hinds adds. “Our culture is focused on maintaining the body, but the brain is the most important organ. We should take proactive actions to enhance and protect its ability to function well.”

New treatments in development
A host of potential treatments are currently being investigated. Studies are gauging the efficacy of currently available diabetes medications including thiazolidinediones (TZDs) and pioglitazone to fight Alzheimer’s.

Researchers are also investigating other new ways to reduce beta-amyloid accumulation. A University of California at San Francisco is studying ways to increase the activity of the enzyme cathepsin B to counteract beta-amyloid build-up. Research is also concentrating on the enzyme Uch-L1 which helps cells rid themselves of beta-amyloid.

Experts at the University of California, Los Angles have turned their attention to the neurofibrillary tangles associated with AD. They’re trying to see if the enzyme puromycin-sensitive aminopeptidase can destroy the tangles and prevent the decline of brain cells.

Researchers are trying to determine if inhibiting tumor necrosis factor-alpha (TNF-alpha) can slow the progression of AD. The small pilot study involved perispinal administration of etanercept and researchers feel it holds promise and warrants larger studies.

At the 10th International Conference on Alzheimer’s Disease and Related Disorders, several other exciting treatments on the horizon were unveiled including the use of leuprolide acetate, currently used to treat prostate cancer and uterine fibroids, a vaccine which boosts the body’s ability to fight the build-up of beta-amyloid, and the use of the antibiotic PBT2 to help the brain properly process copper, iron, and zinc and avoid beta-amyloid formation.

A dedicated Advocate can help you manage the challenges of AD
A PinnacleCare Advocate, with the assistance of the Medical Director and PinnacleCare’s Medical Advisory Board, can be an essential resource when dealing with AD. They first review the Member’s medical records to consider other causes for cognitive deficits such as medication reactions, dehydration, and depression. If needed, the Advocate will suggest a thorough evaluation by a qualified geriatrician and/or neuropsychologist to confirm or refute the diagnosis of AD.

“For Members dealing with Alzheimer’s Disease or any form of dementia, the Advocates are working not only for the Members but also their families,” notes Nuran Saydam, Vice President, Member Services. “Typically, the patient’s children are adults in the prime of their life – working hard and at a point where they don’t necessarily have the luxury of spending large amounts of time managing their parent’s day-to-day needs. The Advocate takes much of that burden off the family, keeping track of medical follow-up, staying in touch with the Member to make sure they have the services to support them, and thinking ahead to identify what services may be needed next.”

Be proactive. Protect the health of your brain.
“With new research pointing to areas where we can proactively protect the health of brain, now is the time to take an aggressive, active role,” believes Dr. Miles J. Varn, Chief Medical Officer of PinnacleCare.

PinnacleCare For My Parents
Whether your parents are dealing with serious health issues or interested in preserving their healthy, active life, the PinnacleCare For My Parents membership can help. Not only does the Advocate help ensure your parents fast access to the top physicians and hospitals, he or she also provides you with peace-of-mind, especially if you live in another city or state.

The For My Parents membership includes:

A personal Advocate available 24/7 to coordinate physicians visits and treatment, monitor care, expedite access to the finest medical specialists, and ensure communication among all physicians at home or when traveling
Complete health assessment, tailored for seniors, including medical record collection, physician case review, detailed evaluation by geriatric specialisT
Access to a 24/7 Registered Nurse Hotline