WASHINGTON -- More than a century after German psychiatrist and neuropathologist Alois Alzheimer identified the cognitively devastating disease that affects as many as 5.3 million people in the U.S. alone, an expert panel has issued a decidedly bleak report on the state of the science of Alzheimer's disease.
The independent panel -- brought together by the National Institutes of Health (NIH) this week -- determined that the causes of Alzheimer's disease are still unknown and that no reliable evidence has shown that anything can prevent the disease or stop it from progressing.
"There are no modifiable issues or variables that are going to prevent Alzheimer's or cognitive decline, and people should know that," Carl Bell, MD, professor of psychiatry at the School of Public Health at the University of Illinois at Chicago and a panel member, told reporters during a Wednesday afternoon press call.
The panel -- made up of experts in psychiatry, gerontology, genetics, nutrition, drugs, neurology, and oncology -- released its report, "Preventing Alzheimer's Disease and Cognitive Decline," on Wednesday.
After reviewing relevant studies on how nutrition, medical conditions, medication, and social, economic, behavioral, environmental and genetic factors relate to mild cognitive impairment and/or Alzheimer's, the panel concluded that the science is inconclusive on the causes of cognitive decline, which can range from mild age-related memory loss to Alzheimer's.
In the past century, Alzheimer's has gone from a rarely-reported disease to one of the most common disabling diseases, accounting for 60% to 80% of all cases of dementia, according to the report.
It is the fifth leading cause of death in the U.S., and mortality from the disease has increased 47% from 2000 to 2006, as a result of a decline in death rates from other chronic diseases.
The panel examined available clinical trials in order to accurately summarize the state of the science on the disease. In order to be considered, trials had to have been performed in humans ages 50 and older who live in developed countries. Sample size needed to reach 50 patients for randomized trials and 300 for observational studies, with a minimum study duration of one year. The studies included participants of both genders and of all racial and ethnic populations.
The first question the panel had to answer: What causes Alzheimer's disease?
The answer in the final report: We don't really know.
"There is currently no evidence considered to be of even moderate scientific quality supporting the association of any modifiable factor (nutritional supplements, herbal preparations, dietary factors, prescription or nonprescription drugs, social or economic factors, medical conditions, toxins, environmental exposures) with reduced risk of Alzheimer's disease," the report authors said.
One factor is strongly linked to Alzheimer's, however, but people don't have any control over it. That is presence of the apolipoprotein E (apoE) DNA variation, which studies show is strongly associated with the risk of Alzheimer's disease.
Studies do indicate that some factors might increase the risk of developing Alzheimer's disease or the broader category of "cognitive decline," the report noted. Those include diabetes, elevated blood cholesterol in midlife, depression, smoking, loss of a spouse or never being married, and having a limited social support system.
However, the report authors cautioned, those factors were all supported by very weak data.
Factors that appear to be associated with a reduced risk of Alzheimer's disease -- but that are also supported by very weak evidence -- include:
- Getting adequate levels of folic acid
- Adhering to a diet low in saturated fats and high in fruits, vegetables, grains, nuts, fish, and olive oil (think: Mediterranean diet)
- Use of statins
- Consumption of alcohol, although not heavy consumption
- More years of education
- Higher levels of mental engagement
- Physical activity
The most consistent evidence for how to prevent cognitive decline (although not necessarily Alzheimer's) is in support of omega-3 fatty acids, the panelists said.
Several longitudinal studies have shown that omega-3 fatty acids derived from eating fish reduce the risk of cognitive decline, but another study found fish oil supplements did not improve memory or concentration among nearly 900 septuagenarians.
There is some, albeit inconsistent, evidence to suggest that increased involvement later in life in activities that exercise the brain and body, as well as social engagements, can keep the brain sharper for longer, the report said.
The data on the use of supplements, including vitamin E and Ginkgo biloba do not indicate a link to Alzheimer's, the panelists said, nor did data on fatty acids, metabolic syndrome, blood pressure, homocysteine, obesity, antihypertensive medications, electromagnetic fields, solvents, gonadal steroids, lead, or aluminum.
The report authors said there are no studies to confirm that people can ward off Alzheimer's.
"Although numerous interventions have been suggested to delay Alzheimer's disease, the evidence is inadequate to conclude that any are effective," wrote the report authors.
Vitamins, nutrients, dietary supplements, a Mediterranean diet, not even cholinesterase inhibitors, such as donepezil (Aricept), which is the most common treatment for mild to moderate Alzheimer's disease, can prevent Alzheimer's, the report said.
"Although there is some disagreement in the literature, the entire body of evidence led us to conclude that this class of drugs is not effective in preventing Alzheimer's disease," the report authors said.
Several randomized clinical trials showed that some drugs, including the nonsteroidal anti-inflammatory drugs rofecoxib (Vioxx), naproxen (Aleve, Naprosyn), and celecoxib (Celebrex), as well as conjugated equine estrogen, have an opposite effect and may increase the incidence of Alzheimer's disease, the panelists reported.
Although the report addresses prevention, and not necessarily treatment, panel member and report author Bell said he hopes the findings will convince doctors not to prescribe unnecessary treatments for Alzheimer's patients.
"We ... hope physicians will dissuade some of the folks who have [Alzheimer's] and their caregivers who are spending an extraordinary amount of money on stuff that doesn't work," said Bell.
Another panel member and report author agreed.
"We don't have sufficient evidence to say that these modalities can prevent cognitive decline or dementia," said Dinesh Patel, MD, a geriatrician and professor at George Washington University School of Medicine.
"Patients and public should also remember that there is a cost of all these modalities -- pharmaceuticals and dietary supplements -- and for some of them we don't even know the side effects," he said.
The committee members said the lack of definitive research on cognitive decline and Alzheimer's underscores the need for further study.
There are ongoing trials testing the effects of Ginkgo biloba, vitamin E, and antihypertensives, and the panelists said they hope those trials will show promise. Several members also pointed to the need to study biomarkers that may signal the future onset of Alzheimer's in younger people.
At the end of the two-day meeting at the NIH's campus in Bethesda, many audience members expressed frustration and disappointment over the overall negative tone of the report. One audience member suggested that people might eat poorly, not exercises, and not stay mentally engaged as they age because the top cognitive experts -- under the umbrella of the nation's top research institute -- said these things don't stave off mental decline.
But the panel defended itself, and said it was tasked with examining the current state of evidence, not with making actionable public health guidelines.
"We don't want it to be so pessimistic," said Martha Daviglus, MD, PhD, MPH, professor of preventive medicine at Feinberg School of Medicine at Northwestern University in Chicago.
"We're not trying to take anyone's hope away or make anyone feel helpless," Bell said. But "we have to go with the hard science."
In order to serve on the all-volunteer panel, the members had to be free of financial conflicts of interest.