“It’s very clear from clinical experience that Parkinson’s patients are not a uniform population,” says Roger Albin, M.D. (Residency 1988), the Anne B. Young Collegiate Professor of Neurology who is also the chief of neuroscience research for the Geriatrics Research, Education and Clinical Center at the VA Ann Arbor Healthcare System. “We think there may be subtypes of Parkinson’s disease and different subtypes may require different treatments.”
“If you have the more benign subtype — tremor-predominant disease — the symptoms may be more visible, but actually these people are not that impaired or disabled,” adds Bohnen. “They are still walking well, they aren’t falling and they don’t have dementia. On the other hand, patients with balance-predominant disease who fall often may not have much visible tremor, but they actually have much greater disability.”
Biomarkers and Early Diagnosis
The nuclei of dopamine-producing neural cells are packed together in a small structure located deep within the brain. Projecting arms called axons extend from cell nuclei into the striatum — the part of the brain that uses dopamine to control motor nerves in the body. In Parkinson’s disease, something causes these axons to degenerate, cutting off the vital supply of dopamine and killing the neural cell.
A dead neuron is gone forever, so the best time to begin treating Parkinson’s disease would be before symptoms appear and too many brain cells have been lost. But there are two problems: First, doctors have no way to stop the neurons from dying. Current treatments help control motor symptoms, but do nothing to prevent or slow down progression of the disease. Second, even if preventive treatments were available, there’s no simple screening test to identify those who are at risk for developing Parkinson’s disease.
That’s why scientists at the U-M and other research institutions are searching for Parkinson’s disease biomarkers — signs of early neural degeneration that can be detected long before clinical symptoms develop.
“We believe this prodromal period can last for 7 to 10 years,” says Bohnen. “When we see someone in clinic with a tremor, the tremor may be just two months old, but biologically speaking, this person may already be halfway through the disease course.”
Parkinson’s disease can be diagnosed in its early stages using a PET scanning technique to detect the level of dopamine in the brain. However, these scans cost thousands of dollars and require specialized equipment and expertise not available outside major academic medical centers like the U-M Health System. For use in the general population, a screening test must be inexpensive and easy to administer in a doctor’s office.
An impaired sense of smell, caused by degeneration of olfactory neurons in the brain, is an early biomarker present in 95 percent of Parkinson’s patients during the prodromal period. It also is common in people who later develop Alzheimer’s disease. Loss of smell develops so gradually, many people aren’t even aware of it.
“A smell test is probably the closest thing to an inexpensive screening biomarker for use in large populations of patients,” says Bohnen. “Just like you have a screening colonoscopy at age 50, I would envision that once you reach 50, you’d need a smell test every year.”
Martijn Müller, Ph.D., assistant professor of radiology, is planning a future U-M research study with 200 older adults who will be asked to identify different odors in simple scratch-and-sniff tests. The study’s main goal is to determine if older adults who have lost their sense of smell, but have no symptoms of either Parkinson’s or Alzheimer’s disease, show brain changes indicative of either disease on PET scans.
Loss of smell isn’t always a sign of disease, however; it’s also part of the normal aging process. Determining the cut-off for a normal age-related loss of smell will be another important goal of the study.
Because there are no treatments to slow the progression of Parkinson’s disease, early diagnosis won’t change how the disease is treated, according to Albin. But identifying people in the prodromal stage of disease is important, so they can take part in clinical trials of experimental drugs to help prevent or postpone neural degeneration.