University Times

While there is no cure for Alzheimer’s disease, science has made inroads in slowing its progression, so early diagnosis is helpful, Alzheimer Disease Research Center (ADRC) experts said.

According to the National Institute on Aging, several medications approved by the U.S. Food and Drug Administration may delay memory decline temporarily and slow AD symptoms for some individuals for a limited period of time.

Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) are used to treat mild to moderate Alzheimer’s; memantine (Namenda) is used to treat moderate to severe Alzheimer’s.

Scientists currently are investigating associations between cognitive decline and vascular and metabolic conditions such as heart disease, stroke, high blood pressure, diabetes and obesity. By understanding these relationships and testing them in clinical trials, researchers hope to discover whether reducing risk factors for these diseases may help with Alzheimer’s as well.

According to the Alzheimer’s Association, preliminary evidence suggests that strategies for general healthy aging may help reduce the risk of developing Alzheimer’s. These measures include controlling blood pressure, weight and cholesterol levels; exercising, including mental exercises; eating a diet that is low in fat and includes fruits and vegetables, and staying socially active.

One of the great mysteries of late-onset Alzheimer’s disease, the most common form of AD, is why it occurs in older adults almost exclusively.

Research on how the brain changes normally with age may be shedding light on this question. Scientists are learning how age-related changes in the brain may harm neurons and contribute to Alzheimer’s damage. These age-related changes include shrinking of certain parts of the brain, inflammation and the production of unstable molecules called free radicals.

Several studies have linked a gene called APOE to late-onset Alzheimer’s. One form of the gene, APOE e4, increases a person’s risk of getting the disease. About 40 percent of all people who develop late-onset Alzheimer’s carry this form of the gene.

However, carrying APOE e4 does not necessarily mean that a person will develop Alzheimer’s disease; conversely, people without APOE e4 can develop the disease.

Most experts believe that additional genes may influence the development of late-onset Alzheimer’s in some way. Scientists around the world are searching for these genes.

Both ADRC’s director, Oscar Lopez, and co-director, William Klunk, are at the forefront of Alzheimer’s research.

Lopez’s primary research has focused on the distribution (incidence and prevalence), behavioral symptoms, risks and long-term outcomes of dementia, especially Alzheimer’s disease. He has attempted to identify clinical or genetic factors that modify the natural history of dementing illnesses, and has published widely on the patterns of progression of all clinical forms of AD. He also has demonstrated the effects of psychiatric drugs and dementia medications on the progression of AD.

Currently, Lopez, who also is a professor of neurology and psychiatry, is conducting a large-scale investigation on the clinical diagnosis of mild cognitive impairment, and is the principal or co-principal investigator of seven National Institutes of Health-funded dementia-related grants.

Klunk, professor of psychiatry and director of the Laboratory of Molecular Neuropharmacology at Western Psychiatric Institute and Clinic, is a pioneer in the field of amyloid imaging.

Klunk and fellow Pitt researcher Chester Mathis discovered and developed an imaging agent, known as Pittsburgh Compound-B (PiB), that binds to the telltale beta-amyloid deposits found in the brains of AD patients.

ADRC co-director William Klunk, left, and director Oscar Lopez

PiB is a radioactive compound that, when coupled with positron emission tomography imaging, can be injected into the bloodstream to enable researchers to see the location and distribution of the beta-amyloid plaque deposits associated with Alzheimer’s.

The finding, reported in the journal Brain in 2008, is a significant step toward enabling clinicians to provide a definitive diagnosis of Alzheimer’s disease in living patients, can help clinicians monitor the progression of the disease and may further the development of potential treatments.

Klunk’s research group’s 2004 paper, “Imaging Brain Amyloid in Alzheimer’s Disease With Pittsburgh Compound-B,” was named by Nature Medicine as the most highly cited research paper published on AD since 2004. The efforts of Klunk and Mathis have resulted in the 2004 MetLife Foundation Award for Medical Research in Alzheimer’s Disease; the 2008 Potamkin Prize for Research in Pick’s, Alzheimer’s and Related Diseases, and the 2009 Ronald and Nancy Reagan Research Institute Award for outstanding contributions to the research, care and advocacy of AD patients and their caregivers.

Klunk also recently received a $400,000 grant from the Cure Alzheimer’s Fund for a joint Pitt-Harvard project to search for new drugs to slow AD. The Pitt-Harvard grant will allow Klunk to produce new compounds and then have co-investigator Rudolph Tanzi of Harvard test the compounds for viability.

For some time, Klunk has been creating markers to track the accumulation of amyloid beta, which forms the plaque that builds up in the brain of people with AD.

Curcumin, commonly known as the spice turmeric, has been shown to aid patients with Alzheimer’s disease by stimulating the immune system to clear the brain of amyloid beta.

Unfortunately, nearly 100 percent of the spice is broken down by the body before it gets to the brain, Klunk said. A person would have to consume more than 20 pounds daily to have any meaningful effect.

“What we’re trying to do is find that .0001 percent of curcumin that would get to the brain … from taking one little pill. So that’s the whole idea here: to make a curcumin derivative that’s stable in the body but still does the same thing that curcumin does,” Klunk explained when he accepted the research grant last fall.

—Peter Hart