New research on Alzheimer's disease

When President Ronald Reagan first designated November as Alzheimer's Disease Awareness Month in 1983, the progressive and fatal brain disease had been diagnosed in fewer than 2 million Americans. Today, an estimated 5.2 million Americans are believed to suffer from Alzheimer's disease, which is now the nation's sixth leading cause of death.

In 1994, Reagan revealed he was suffering from Alzheimer's. He died in 2003 after a decade-long struggle against the devastating disease.

Alzheimer's is as costly as it is deadly, with direct and indirect costs totaling more than $148 billion each year. Although the causes of Alzheimer's are not yet known, most experts agree that it most likely develops as a result of multiple risk factors, the greatest of which is advancing age. As the number of Americans surviving into their 80s and 90s grows because of advances in medicine and social/environmental conditions, so too will the incidence and prevalence of Alzheimer's disease.

 The blue areas in this illustration represent plaques and tangles, which tend to spread through the cortex in a predictable pattern as Alzheimer's disease progresses. (Illustration courtesy of the National Institute on Aging)

In 2008 Alzheimer's Disease Facts and Figures, the Alzheimer's Association reports that 10 million baby boomers will develop the disease during their lifetime. The number of new Alzheimer's cases reported annually is projected to increase to 454,000 by 2010 and to 615,000 by 2030. By 2050, the number of individuals age 65 and over with Alzheimer's could be as high as 16 million—unless science finds a way to prevent the disease.

In addition to age, another risk factor for Alzheimer's is heredity. Scientists have identified the apolipoprotein E-e4 gene as increasing the risk for developing Alzheimer's and tending to make symptoms appear at a younger age than usual.

Deterministic genes also have been identified that directly cause Alzheimer's in a few hundred extended families worldwide. Familial Alzheimer's disease accounts for less than 5 percent of Alzheimer's cases.

While little progress has been made in identifying a cure for Alzheimer's, recent studies have suggested promising methods for reducing the risk of developing the disease and delaying the progression of its symptoms.

Cognitive activity may delay onset

In a study published in the September 2008 issue of Alzheimer's & Dementia, the journal of the Alzheimer's Association, researchers from the Johns Hopkins Bloomberg School of Public Health and Duke University Medical Center reported that participation in a range of cognitively and socially engaging activities in midlife reduced the risk for Alzheimer's disease and other types of dementia in men, particularly those with an increased genetic risk.

The study, which followed 147 male twin pairs over 28 years, divided cognitive activities into three categories—novel, intermediate novel, and passive/receptive—to discriminate activities that involved the active processing of new information from activities that were more passive or receptive.

Researchers found that participation in intermediate novel activities—including home and family activities, visiting with friends and relatives, club activities such as attending parties and playing card games, and home hobbies—was most strongly associated with reduced dementia risk. Passive and receptive activities, including going to the movies and watching television, also were associated with reduced risk.

"Overall, these findings suggest that engaging in activities that incorporate both cognitive and social activity might confer protection against Alzheimer's and dementia, particularly among those at elevated genetic risk for the disease," said study author Michelle C. Carlson, PhD. "These results can help inform future preventive interventions, especially because they point to a range of activities that individuals are likely to maintain because they are rewarding, entertaining, and engaging."

Drug combinations delay progression

Drugs to treat Alzheimer's disease have shown only modest success in easing its symptoms. A new study by researchers at the Massachusetts General Hospital Memory Disorders Unit offers hope, however, that drug combinations may help delay progression of symptoms.

In the study, published in the July-September 2008 issue of Alzheimer Disease & Associated Disorders, researchers found that combining two types of Alzheimer's drugs worked better to slow cognitive and functional declines than one drug or no drugs.

Researchers analyzed the records of 382 patients who were treated at the Memory Disorders Unit since 1990; 144 patients did not receive any medication, 122 received a cholinesterase inhibitor, and 116 received a cholinesterase inhibitor in combination with memantine. Memantine is the first of a new class of anti-glutamatergic drugs for Alzheimer's treatment. The patients were followed for an average of two and a half years and given tests to measure cognitive abilities and capacity to carry out daily activities.

Patients who took the combination of drugs underwent a significantly smaller degree of decline than those who were taking only a cholinesterase inhibitor or no drug. The results raise the possibility that the drugs may be protecting patients' brains from further deterioration.

"Finding something that could actually modify the course of the disease is the holy grail of Alzheimer's treatment, but we really don't know if that is happening or what the mechanism behind these effects might be," said Alireza Atri, MD, the study's lead author.

"What we can say now is that providers should help patients understand that the benefits of these drugs are long-term and may not be apparent in the first months of treatment. Even if a patient's symptoms get worse, that doesn't mean the drug isn't working—since the decline probably would have been much greater without therapy."