Conference Coverage
PORTLAND, OR —A large-scale analysis has identified several new putative susceptibility genes that may affect cognitive impairment in Parkinson's disease, researchers reported at the Fourth World Parkinson Congress.
Cognitive impairment is a common and disabling nonmotor feature of Parkinson's disease. Identifying genetic variants that influence cognitive deficits could clarify the pathophysiology of cognitive impairment, help identify potential therapies, and be useful when considering patient prognosis, said Ignacio F. Mata, PhD, Research Biologist at the Veterans Affairs Puget Sound Health Care System and Acting Assistant Professor of Neurology at the University of Washington in Seattle. Rate of cognitive decline in Parkinson's disease varies. "We are trying to understand why," Dr. Mata said.
Ignacio F. Mata, PhD
Dr. Mata and colleagues conducted a genome-wide exploratory analysis of genetic risk factors for cognitive impairment in a multisite cohort. The investigators genotyped 1,105 patients from the Parkinson's Disease Cognitive Genetics Consortium for 249,336 variants using the NeuroX array, which includes variants that have been linked to neurologic diseases.
Participants completed tests of learning and memory (Hopkins Verbal Learning Test-Revised), working memory and executive function (Letter-Number Sequencing and Trail Making Test Parts A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (Montreal Cognitive Assessment).
The researchers used linear regression to test for associations between common variants and cognitive performance, with adjustment for important covariates (eg, age, sex, disease duration, and years of education). They analyzed rare variants using the optimal unified sequence kernel association test.
Participants' mean age was 68.8, 67.8% were male, and 17.5% had dementia. Mean disease duration was 8.4 years. Participants had 15.5 years of education on average.
The researchers identified 17 common genetic variants associated with cognitive performance. Three variants were associated with total recall, and two variants were associated with delayed recall on the revised Hopkins Verbal Learning Test. Five variants were associated with performance on the Trail Making Test, and seven variants were associated with performance on the Benton Judgment of Line Orientation test.
The researchers aim to perform a similar analysis using longitudinal data. They also plan to see if these findings can be replicated in an independent cohort.
—Jake Remaly
