Alzheimer’s Cure on the Horizon?
By Athan Bezaitis, MA

Can the increasing numbers of elders diagnosed with AD influence lawmakers to earmark additional funds for Alzheimer’s research?

The key to eradicating Alzheimer’s disease (AD) by 2020, says Harvard Medical School’s Rudy Tanzi, PhD, “is to never let it strike.” The Potamkin Prize-winning neurologist, who co-discovered three of the four known genes that can carry mutations associated with AD, believes that with a national research strategy focused on early detection and prevention, a cure is possible in the near future. Tanzi estimates that developing an effective prevention strategy will cost the federal government $5 billion per year in research costs. That’s a modest investment today, in relative terms, of $50 billion spread over the next 10 years, especially when many billions more in public expenses related to future health and long-term care expenses may be avoided. It’s also modest when considering the possibility of overcoming an incurable, degenerative, and terminal brain disease that currently affects 5.3 million Americans and 35.6 million people worldwide. 

To put his request in a budgetary perspective, Tanzi is seeking a research investment to support scientists studying AD that roughly approximates the money we invest in cancer research through the National Cancer Institute ($4.8 billion). This doesn’t sound completely unreasonable considering AD “is the most costly disease in terms of Medicare and Medicaid expenses,” as reported by the Cure Alzheimer’s Fund.  In fact, while AD-diagnosed beneficiaries make up less than 13% of the Medicare population, they account for 34% of the spending—an estimated $91 billion in 2005, according to a Lewin Group report commissioned by the Alzheimer’s Association. The same study predicted a more than $1 trillion increase in costs by 2050 when 13 million Americans are likely to be stricken with the disease. 

Though the country is already paying billions to care for AD patients, the United States is slated to spend just $430 million on government-sponsored AD research in 2010, according to the National Institutes of Health (NIH). What's more, research dollars for AD have declined in recent years, down from $640 million in 2006. Researchers claim the need for additional funding to analyze genes that contribute to risk of the disease, figure out which genetic traits have the best prospects for treatment, and find drug therapies that can prevent the disease from ever occurring. Tanzi remains optimistic as decision makers recognize the increasing body of evidence that the growing epidemic threatens to eventually bankrupt the healthcare system. He has taken his call for a 10-fold increase in funding to Congress and claims that “nobody even batted an eye” when he made the same appeal at a 2009 White House conference on the future of healthcare.

While discussions about future research are valuable, the needs of those who currently suffer from AD and their caregivers are more pressing. It’s important to keep aspirations of finding a cure in perspective as caregivers tend to their loved ones, knowing that available drugs can, at best, only help delay symptoms or prevent them from becoming worse for a limited time. The reality is that the cause of the disease continues to baffle researchers, and caregivers recognize the prospects for continuing cognitive decline in AD patients.

Making Progress
Scientists have made great strides in understanding the mechanisms behind AD.  Posthumous examinations of AD patients’ brains show deposits of a sticky protein called amyloid beta peptide, commonly referred to as plaques. The other sign of the disease noted during an autopsy is the accumulation of neurofibrillary “tangles,” or warped forms of the protein tau found in the neurons. As the condition progresses, the earliest damage occurs in the entorhinal cortex, hippocampus, and basal forebrain—parts of the brain involved with memory, according to the Alzheimer Research Forum’s Web site. Eventually, entire regions of the brain are devastated, leaving victims with little or no cognitive abilities and unable to care for themselves. On average, the research forum reports, the illness lasts seven years, although people have been known to survive up to 20 years before succumbing to death from pneumonia or lack of nutrition. 

Adding to the complexity of AD’s etiology, some autopsies of AD patients show only plaque buildup, while others reveal only the development of tangles. Remarkably, there are individuals who showed no signs of dementia during their lives whose autopsies reveal both plaques and tangles. A 2009 editorial in The New England Journal of Medicine by Douglas Ewbank, PhD, and Steven Arnold, MD, “Cool with Plaques and Tangles” gave a possible explanation why people aged 95 and older can be cognitively intact despite having these neurodegenerative lesions. They explain that the buildup of plaques and tangles over a long period of time might allow the brain to develop alternate means of functioning: “For example, with slow accumulation, cell-repair mechanisms may be able to limit the damage. Also cognitive compensation might have a better chance of minimizing the effects of neuron loss.”

Metabolic Risk Factors
Healthful living minimizes metabolic risk factors such as obesity, diabetes, hypertension, and elevated cholesterol in midlife, all of which have been linked with brain disorders in a smattering of new research. Celebrated for her studies on AD in Swedish twins, Margaret Gatz, PhD, a professor of psychology at USC and codirector of the USC Memory and Aging Center, tests for modifiable risk factors by controlling for genetic influences when looking at identical twins who have either similar to dissimilar dementia profiles in old age. “Particularly valuable for scientific studies are identical twins where one twin has developed Alzheimer’s disease but the twin sibling has not,” says Gatz. Her research allows her to assess differences in the life of the twin without the disease that may offer clues to prevention. 

“Undoubtedly, Alzheimer’s disease results from a complex combination of many genes and many environmental factors, each exerting an influence on disease risk,” Gatz says.  “Like other complex chronic diseases, certain genes contribute to putting people at higher risk than others.” Only very rarely, she adds, are there genes that completely determine the chance of developing a disease. “There is real possibility to change one’s personal risk for Alzheimer’s disease through modifications in behavior,” she says. “Consider heart disease: Family history is important, yet diet and exercise can alter any individual’s possibility to remain healthy.”

Also published in Archives of Neurology, a study from the University of California, San Francisco (UCSF) examined the relationship between obesity and cognitive decline. Researchers examined 3,000 enrollees of the NIA-funded Health ABC Study. Researchers measured body fat from various sources, including body mass index, waist size, the diameter from the highest point of the abdomen to the back, total fat, subcutaneous fat, and fat between the organs, or visceral fat. “Having greater fat in men predicted greater cognitive decline,” said lead researcher Alka M. Kanaya, MD. Men with increased levels of fat performed worse in cognitive function tests taken at the start of the study and after three, five, and eight years.

Surprisingly, obesity levels did not affect cognitive functioning in women. “In old age, fat serves more of a protective role for women so maybe higher levels are not as harmful,” Kanaya says. “Women tend to put fat in different places than men such as under their skin rather than visceral fat. Maybe it’s where you put the fat that makes the difference.”  

Research conducted by Christian Pike, PhD, associate professor at the USC Davis School of Gerontology, indicates mice on a high-fat diet show obesity, metabolic features of type 2 diabetes, and accelerated beta-amyloid accumulation. “A high-fat diet also reduces testosterone function in these mice, which our research shows accelerates AD,” Pike says. Another clue linking obesity to AD, Finch suggests, associates overweight with elevated levels of cholesterol, which “influences the production of the toxic amyloid beta peptide.” He has found that restricting caloric intake of a mouse with a genetic predisposition to AD reduces the chance of beta amyloid plaque buildup by 50%. Finch says, “They may not like to miss lunch, but they end up healthier.” As for whether people should be skipping lunch to prevent AD, he says, “Humans are different than mice. I’ve never been able skip lunch when it’s available.” 

While obesity may affect women differently from men, the presence of multiple metabolic syndromes has been shown to increase the risk of cognitive impairment. Another study from the March 2009 issue of the Archives of Neurology, also conducted at UCSF, for four years followed nearly 5,000 older women with no cognitive impairments. The study defined metabolic syndrome as the presence of three or more of five symptoms: abdominal obesity, elevated blood triglycerides (fatty acids), reduced high-density lipoprotein or good cholesterol, elevated blood pressure, and type 2 diabetes. They found a 66% increased risk of developing a cognitive impairment in those women who were classified as having the metabolic syndrome. Each additional symptom added a 23% greater risk of cognitive impairment. “This means that it is important for older patients with the metabolic syndrome to be screened early for cognitive impairment, and that the component symptoms of the syndrome should be treated early,” says lead author Kristine Yaffe, MD, in a statement from UCSF. “This is especially critical in light of the fact that almost 45% of American adults between the ages of 60 and 70 have the metabolic syndrome.”

What’s encouraging is that many of these metabolic conditions are controllable, and some can even be reversed. Pike recommends exercise and a diet low in fat and rich in antioxidants. In addition, he suggests,  “it is important to engage in highly stimulating cognitive activities and maintain diverse and supportive social networks.” Controlling stress is important, too. “Chemicals released in connection with stress have adverse effects on brain function, especially memory,” Gatz says, adding that sleep may also be a preventive measure.

“Loneliness is also a risk factor,” says Tanzi. “It’s probably more important to stay socially engaged than it is to do crossword puzzles.” Taking action to minimize the risk factors for AD improves overall health and lowers the risk of other diseases. It saves money, too. The Alzheimer’s Association reports delaying the onset of Alzheimer’s disease by just five years could save $50 billion per year. With such high stakes, Tanzi wants this country to pursue eradication of AD as aggressively as it worked toward putting a man on the moon. “I find this disease to be a totally unacceptable part of aging,” he says. “I won’t stop until we cure it—and it can be cured.”

— Athan Bezaitis, MA, is a freelance writer based in southern California.