Association of cholesterol and glycemic state biomarkers with phenotypic variation and Parkinson's disease progression: The Oxford Discovery cohort

• Published in: Journal of Parkinson's disease Vol. 15; no. 3; pp. 522 - 530
• Main Authors: Ho Chiu, Nicholas Kwan, Lawton, Michael, Zerenner, Tanja, Morovat, Alireza, Welch, Jessica, Razzaque, Jamil, Hu, Michele T, Ben-Shlomo, Yoav
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2025; Sage Publications Ltd
• Subjects: Activities of daily living; Aged; Behavior disorders; Biomarkers; Biomarkers - blood; Blood Glucose - metabolism; Blood levels; Cholesterol; Cholesterol - blood; Cholesterol, HDL - blood; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - blood; Cognitive Dysfunction - etiology; Cognitive Dysfunction - physiopathology; Cohort Studies; Daytime; Disease Progression; Female; Fructosamine - blood; Genetic variability; High density lipoprotein; Humans; Hypercholesterolemia; Hyperglycemia; Lipids; Male; Middle Aged; Mood; Movement disorders; Neurodegenerative diseases; Neuroprotection; Parkinson Disease - blood; Parkinson Disease - complications; Parkinson Disease - physiopathology; Parkinson's disease; Phenotype; Phenotypes; Phenotypic variations; Regression analysis; REM sleep; Sleep and wakefulness; Sleep disorders; Statistical models; Synuclein; HDL-C; cholesterol; fructosamine; prognosis; biomarkers; Parkinson’s disease
• ISSN: 1877-7171; 1877-718X
• DOI: 10.1177/1877718X251323914

Background Parkinson's disease (PD) has marked phenotypic variability. Increased lipids have been suggested as being neuroprotective whilst hyperglycemia may increase α-synuclein aggregation. Objective We have tested whether high total cholesterol and high-density lipoprotein cholesterol (HDL-C) and low levels of fructosamine are associated with better PD phenotypes and predict less rapid progression Methods Non-fasting serum HDL-C, total cholesterol, and fructosamine were measured at baseline in 866 patients with early PD (median duration, 0.96; IQR, 0.43–1.98 years) from the Oxford Discovery cohort. These biomarkers were compared against our data-derived PD subtypes using multinomial logistic regression. We used multilevel models to predict longitudinal motor and non-motor outcomes (e.g., cognition, mood). Results HDL-C and total cholesterol differed across baseline PD phenotype clusters, with reduced levels associated with the most severe motor and non-motor phenotypes (psychological well-being, cognitive impairment, REM sleep behavior disorder, and daytime sleepiness). Higher HDL-C and total cholesterol, although the latter was attenuated after adjustment for statin use, were associated with better baseline activities of daily living (e.g., UPDRS-II score with 1 SD increase in HDL-C −0.74, 95%CI −1.22 to −0.26, p = 0.002) and non-motor features. Neither predicted the rate of motor or non-motor progression. Fructosamine levels were not associated with phenotypic variability or rate of disease progression. Conclusions Hypercholesterolemia was associated with a better motor/non-motor disease subtype and daily living impairment at presentation, but did not predict longitudinal change. Future research needs to determine if these associations are causally related or secondary to disease onset by examining prodromal subjects. Plain language summary People with Parkinson's disease (PD) can have quite different features when they first present and may get worse at different rates. We wanted to test whether the levels of fats and sugar control predicted worse presentation and differences in how the disease develops, as had been suggested by past research. We used blood tests for cholesterol (total and HDL cholesterol) and fructosamine (a measure of glucose control) from 866 patients with early PD (half within a year of diagnosis) from the Oxford Discovery cohort. We used sophisticated statistical models to test if the blood levels predicted changes in motor and non-motor outcomes (e.g., cognition, mood) over time. We found lower levels of HDL and total cholesterol were associated with the most severe motor and non-motor phenotypes (psychological well-being, cognitive impairment, REM sleep behavior disorder, and daytime sleepiness). Higher HDL cholesterol was associated with slightly better baseline activities of daily living. Neither, however, predicted the rate of motor or non-motor progression. A higher fructosamine (worse control of sugar) also did not predict changes in motor function. Our results suggest that higher cholesterol is associated with a better motor/non-motor disease subtype and slight benefits in daily living impairment at presentation but does not predict longitudinal change in contrast to past research. Future research needs to determine if these associations in early disease have a causal role or are secondary to disease onset by examining subjects who are at high risk of developing PD in the future.