“Seeing people who have encountered these difficulties, and working with them and their families, is a constant motivator to find ways to treat or prevent cognitive decline.”
Jennifer G. Goldman, M.D., M.S. (Photo Credit: Joshua Sears Photography)
Many people with Parkinson’s disease (PD) experience slowed thinking and have trouble concentrating or planning and carrying out activities. Increasingly, doctors have come to recognize that these and other cognitive difficulties are part of the disease. And some of them are asking: what if we were able to identify the brain changes that underlie these cognitive problems, to predict who is at risk of encountering them, and to address them early on in Parkinson’s?
These are questions being raised by Jennifer G. Goldman, M.D., M.S., Associate Professor at the PDF Research Center at Rush University Medical Center in Chicago, IL. In research that Dr. Goldman has been conducting since 2008, she has successfully identified evidence of cognitive difficulties among people with Parkinson’s through brain scans done with magnetic resonance imaging (MRI), and through clinical observations. Not only might such biomarkers be used to track cognitive changes; they might also provide a tool to help doctors evaluate the effectiveness of potential therapies.
Parkinson’s disease research at Rush is supported in part by an annual Center Grant from PDF (read more here). Dr. Goldman has been able to use a portion of the grant to study a small group of people with PD and collect pilot data for her project.
“We initially scanned about 30 people with PD using MRI, and looked for differences between those with dementia and those who were cognitively normal,” says Dr. Goldman. “The scans give a beautiful and detailed display of the anatomy of the brain.”
Later on, she added a group of people who did not have PD, permitting a comparison between those two groups. She found that among the study participants who had PD and dementia, a brain structure called the entorhinal cortex was substantially smaller than it was among people with PD who were cognitively normal. These findings suggest to her that changes in the entorhinal cortex may serve as a “biomarker” — a kind of milestone that can show how a disease develops — for dementia in PD. The entorhinal cortex is involved with the function of memory in PD as well as in Alzheimer’s.
On the strength of these results, Dr. Goldman secured a five-year grant from the National Institutes of Health to expand her search for biomarkers. At the same time, she chose to pursue a Master of Science degree in clinical research at Rush, working with Christopher G. Goetz, M.D., principal investigator of the PDF Research Center. Her goal was to develop her research skills and to learn more about imaging techniques. Her study now follows 100 people with Parkinson’s who have differing degrees of cognitive impairment, as well as about 25 healthy people who do not have PD. All have received brain MRI scans, as well as detailed clinical, neurological and psychological exams. This allows Dr. Goldman to track changes in subgroups and individuals over time. “PDF support has been vital to my work all along the way,” she says.
Already, Dr. Goldman has found additional clues about cognitive difficulties. For example, she found a feature on MRI scans — entities known as “white matter hyperintensities,” which increase in number as cognitive difficulties progress. She also found that people with PD who had trouble with daytime sleepiness showed
the most serious difficulties with cognition. Interestingly, she also found that quality of nighttime sleep was not related to cognition. Says Dr. Goldman, “This raises the question of whether daytime sleepiness is the tip of the iceberg — a warning sign for cognitive decline.
She continues to evaluate study participants once a year, repeating MRI scans and other exams, paying attention to what changes and what stays stable. Reflecting on how her work in this area has affected her philosophy, she says: “Seeing people who have encountered these difficulties, and working with them and their families, is a constant motivator to find ways to treat or prevent cognitive decline.”
Dr. Goldman’s research was funded through PDF’s Center Grants Program. In 2014, PDF is supporting the program with $2.36 million.