NIH grant funds study into why dementia symptoms fluctuate
By John Battiston
A new, federally funded VCU Parkinson’s and Movement Disorders Center (PMDC) research project is exploring why some patients with dementia experience dramatic shifts in cognition throughout the day – and how understanding those swings could open the door to better treatment.
VCU neurology professor Matthew Barrett, M.D., recently secured a five-year R01 grant from the National Institute on Aging, part of the National Institutes of Health. The grant will fund a study of cognitive fluctuations in patients with dementia with Lewy bodies and Parkinson’s disease dementia.
“These are fluctuations in alertness, attention and cognition that vary widely over the course of the day, sometimes minute to minute,” says Barrett, who serves as the PMDC’s Lewy Body Dementia Association Research Center of Excellence director. “What causes them? If patients have the capacity to be more lucid and engaged some of the time, why can’t we keep them there more often?”
Barrett is a movement disorders-trained neurologist whose research focuses on the overlap between motor and cognitive decline. He has spent years examining how degeneration in neurons that produce acetylcholine – a chemical crucial to focus and attention – may underlie cognitive impairment in Parkinson’s and related diseases.
The new project brings those studies together with recent findings from electroencephalogram (EEG) studies showing that patients with Lewy body dementia have distinct patterns of brain activity that appear to correlate with their moment-to-moment lucidity. “We’re going to look at the part of the brain that produces acetylcholine and how that impacts dementia, then link it to the EEG changes that seem to be related to cognitive fluctuations.”
The study will focus on patients with Parkinson’s disease, Lewy body dementia and mild cognitive impairment, many of whom will be recruited through the PMDC’s clinics. Participants will undergo brain MRI scans, biomarker testing and 48 hours of EEG and cognitive monitoring to track how their alertness and brain activity change over time.
Some patients will return for annual follow-ups, and others will receive a standard acetylcholine-boosting medication to observe its effects on fluctuations. Barrett and his team – including research coordinators, a postdoctoral fellow and collaborators from neuropsychology, neurology and engineering – hope the results will do more than describe a phenomenon.
“If we can establish that acetylcholine-related dysfunction is really involved in cognitive fluctuations, we can focus on therapy that targets the cholinergic system, which heavily uses acetylcholine,” Barrett says. He adds that such findings could help to hone future drug intervention studies.
The project also aligns with the PMDC’s mission to translate scientific discoveries into real-world treatments that help patients and families “live their best lives possible.” As Barrett and his colleagues look ahead to the next five years of data collection and analysis, their goal is clear: to turn an enigmatic symptom into an actionable pathway for care.