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Biomarkers provide early clues to Parkinson's disease

Research projects explore ways to stop the progressive disease

Parkinson's disease, a progressive disorder of the nervous system, gained a great deal of attention when heavyweight fighter Muhammad Ali received a diagnosis in 1984 and actor Michael J. Fox was diagnosed in 1991. However, the only definitive way to diagnose Parkinson's disease is by autopsy of brain tissue. Scientists at Mayo Clinic are working with living patients in hopes of finding disease biomarkers that will help guide earlier diagnoses and potentially reveal opportunities for slowing or halting the disease.

Wayne Puckett, and his wife, Margarita
Wayne Puckett, and his wife, Margarita. Puckett was diagnosed with a form of parkinsonism in 2012. Parkinsonism is the label for a broad spectrum of movement disorders that includes Parkinson's disease.

Collaborating to speed research

Charles H. Adler, M.D., Ph.D., a Mayo Clinic professor of neurology, founded the Arizona Parkinson's Disease Consortium (APDC), a collection of researchers from multiple institutions throughout Arizona, including Mayo Clinic Arizona, Banner Sun Health Research Institute, Banner Good Samaritan Medical Center, and the Translational Genomics Research Institute. Collaboration within this group means scientists can work faster to find answers for Parkinson's patients.

Combining clinical and pathological analysis

Currently, Dr. Adler is leading clinical research funded by the Arizona Biomedical Research Commission and the National Institute of Neurological Disorders and Stroke. The research study assesses motor and cognitive function as well as smell and nervous system-related problems experienced by patients who have enrolled in the study. All enrollees have agreed to donate their brains and other organs to research at the time of death.

Studying living patients will help develop predictive models of risk for the development of Parkinson's disease. Other study partners will perform autopsies to look for pathological markers, and a bioinformatics group maintains and shares a database of all the gathered information.

Assessing the non-motor feature of Parkinson's disease

Dr. Adler and his colleagues also published findings related to multiple non-motor features of Parkinson's disease. "Many patients with Parkinson's disease have a loss of the sense of smell well before they have tremor or slowness of movement," says Dr. Adler. The group also identified sleep disturbances and autonomic difficulties, such as lightheadedness upon standing, as non-motor features of Parkinson's disease. Dr. Adler's hope is that non-motor feature will help identify people at increased risk of developing Parkinson's disease.

Finding clues to dementia

John N. Caviness, M.D., a professor of neurology at Mayo Clinic, works with Dr. Adler and others to learn why 30 to 75 percent of Parkinson's disease patients also develop dementia later in the disease's progression. Tremors and other motor symptoms of Parkinson's disease can be treated with medications and surgical procedures, but there are no treatments for dementia.

Speaking about his research, Dr. Caviness says, "The purpose of the study was to see if we could use the measurement of brain waves to predict with higher certainty who with Parkinson's disease would develop memory problems, concentration problems and other cognitive difficulties."

Results of the study "Quantitative EEG as a predictive biomarker for Parkinson disease dementia" are published in the scientific journal Neurology.

Discovering new biomarkers

"Certain types of brainwave abnormalities could predict who was at subsequent risk for dementia and other cognitive problems," says Dr. Caviness. The study shows that the results of QEEG tests, which collect electrical patterns from the surface of the scalp, are potential predictive biomarkers for incidence of dementia in people with Parkinson's disease.

Another study found that certain changes in the electric currents in muscles can cause small tremors. "Individuals with early tendency toward tremor often don't even notice this activity in their muscles," says Dr. Caviness. These tremors were found in individuals with early pathology changes similar to those of Parkinson's disease patients, and Dr. Caviness and his colleagues think it may be another predictive biomarker.

Giving hope to patients

The primary goal of these studies is to find the earliest clinical markers for the onset of Parkinson's disease and for the onset of dementia in people with Parkinson's disease. Identifying the earliest possible biological indicators of Parkinson's in living patients will make the development and testing of potential treatments faster and less expensive. Ultimately, scientists hope to counteract those biochemical changes and subsequently prevent disease onset or progression.