Longitudinal untargeted metabolomics of cognitive impairment in Parkinson's disease.
Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD), yet the mechanism remains unclear.
Longitudinal serum samples from PD patients in a community-based case-control study were profiled, with cognition assessed by the Mini-Mental State Examination at baseline and follow-up. We performed three metabolome-wide association studies: a baseline cross-sectional analysis (n = 632), a time-to-event analysis (n = 412), and a repeated measures analysis (n = 265), followed by "Mummichog" pathway analysis.
Of the 4762 metabolomic features, four reached statistical significance in the baseline analysis, 22 in the time-to-event analysis, and none in the repeated measures analysis. Dysregulated pathways included purine metabolism, the pentose phosphate pathway, fatty acid pathways, and C21-steroid hormone biosynthesis and metabolism.
Disruptions in core metabolic pathways may contribute to PD-related cognitive impairments. Disturbances in pentose and purine pathways may occur before clinical cognitive decline is observed, suggesting early metabolic markers.
Longitudinal serum samples from PD patients in a community-based case-control study were profiled, with cognition assessed by the Mini-Mental State Examination at baseline and follow-up. We performed three metabolome-wide association studies: a baseline cross-sectional analysis (n = 632), a time-to-event analysis (n = 412), and a repeated measures analysis (n = 265), followed by "Mummichog" pathway analysis.
Of the 4762 metabolomic features, four reached statistical significance in the baseline analysis, 22 in the time-to-event analysis, and none in the repeated measures analysis. Dysregulated pathways included purine metabolism, the pentose phosphate pathway, fatty acid pathways, and C21-steroid hormone biosynthesis and metabolism.
Disruptions in core metabolic pathways may contribute to PD-related cognitive impairments. Disturbances in pentose and purine pathways may occur before clinical cognitive decline is observed, suggesting early metabolic markers.
Authors
Lin Lin, Yu Yu, Zhang Zhang, Del Rosario Del Rosario, Duarte Folle Duarte Folle, Mayeda Mayeda, Jones Jones, Walker Walker, Bronstein Bronstein, Keener Keener, Paul Paul, Ritz Ritz
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