What are the earliest biomarkers for Parkinson's disease (PD), and when do subclinical changes in movement, cognition, sleep, sense of smell and other signs of PD begin?
These questions serve as the focus of PD research conducted by Charles H. Adler, M.D., Ph.D., a neurologist and movement disorders specialist at Mayo Clinic in Arizona. They are particularly important questions because, as Dr. Adler notes, in PD, "By the time of clinical diagnosis, we know that anywhere from 60 percent to 80 percent of a patient's dopamine-producing neurons have degenerated."
One of the best ways to address early detection is to investigate the relationship between postmortem pathology and behavioral and biological markers in a population sample studied longitudinally. In 2011, the National Institutes of Health awarded an $8 million, five-year grant to Banner Sun Health Research Institute (BSHRI) and Mayo Clinic in Arizona to support the National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. This brain and tissue bank is a unique resource and the largest of its kind with more than 1,300 autopsy cases, of which more than 100 are PD, and a continuously maintained enrollment of 1,000 living participants, of whom more than 100 have a diagnosis of PD. Equally important, the research team can draw on the long-term clinical study of individuals enrolled in the brain and tissue donation program.
Thomas G. Beach, M.D., Ph.D., from BSHRI is the principal investigator and will direct the neuropathology aspects of the project. Dr. Adler will direct the clinical aspects. The two physicians also serve as co-principal investigators of the Arizona Parkinson's Disease Consortium, funded by the state of Arizona and The Michael J. Fox Foundation for Parkinson's Research. Their work has led to improved PD classification and advances in risk prediction and understanding of the pathogenesis of PD.
A major focus in the group's investigation is the progression from normal cognition to mild cognitive impairment and dementia. In addition to annual physical examinations and biomarker tests, Dr. Adler conducts in-depth testing of cognition, as well as measures of olfaction, autonomic function and sleep disorders in healthy control subjects and patients with PD enrolled in the program.
Discussing the importance of the PD brain and tissue resource, Dr. Adler says, "Advances made in the diagnosis and treatment of Parkinson's disease have come mainly from pathologic and neurochemical samples at autopsy. The creation of a bank for cerebrospinal fluid, brain and other organ tissue in individuals studied over time represents a significant step in moving the field toward better treatments and an eventual cure."