Abstract
Hyperlipidemia has been proposed as a risk factor of dementia and cognitive decline. However, the findings of the relationship between cholesterol level and cognitive/brain function have been inconsistent. Here, using a well-controlled sample from the Parkinson’s Progression Markers Initiative (PPMI), we investigated the probable non-linear relationship between plasma total cholesterol (TC) level, gray matter volume (GMv), and cognitive performance in 117 non-demented subjects (mean age, 61.5 ± 8.9 years), including 67 Parkinson’s disease (PD) patients and 50 demographically matched controls. A quadratic relationship between semantic fluency (SF) performance and TC levels was identified. Within the subjects with a desirable TC level (TC < 200 mg/dl), low TC (lTC) levels were associated with reduced SF performance, as well as reduced GMv in three medial temporal regions [including bilateral anterior hippocampus (HIP)]. In contrast, no significant relationship between TC and cognition performance/GMv was found in individuals with a high cholesterol level (i.e., TC ≥ 200 mg/dl). Further region of interest (ROI)-based analysis showed that individuals with TC levels ranging from 100 to 160 mg/dl had the lowest GMv in the medial temporal regions. These findings suggest that low-normal TC level may be associated with reduced cognitive function and brain atrophy in regions implicated in neurodegenerative diseases, adding to a growing body of literature supporting a probable non-linear relationship between cholesterol level and brain health. However, this finding needs to be verified with other large public cohort data that do not include PD patients.
Highlights
Dyslipidemia, especially hyperlipidemia, is highly prevalent in adults worldwide (World Health Organization, 2014)
All data were downloaded from the Parkinson’s Progression Markers Initiative (PPMI) website, and a total of 117 participants were included in the present study [44 female, 73 male; 67 Parkinson’s disease (PD) patients, 50 control participants]
In all data analyses, participants were divided into two groups: low TC (lTC) group, total cholesterol (TC) < 200 mg/dl (n = 69); and high TC (hTC) group, TC ≥ 200 mg/dl (n = 48)
Summary
Dyslipidemia, especially hyperlipidemia, is highly prevalent in adults worldwide (World Health Organization, 2014). In the United States, the prevalence of hyperlipidemia is even more alarming: 39.7% of adults have borderline high (>200 mg/dl) or high (>240 mg/dl) total cholesterol (TC) level (Mackey et al, 2017). This is worrisome as hyperlipidemia [high TC (hTC)] has been shown to be a strong predictor of cardiovascular disease (CVD) and is a core metric in most CVD risk. One potentially important factor is that there may be a non-linear relationship (e.g., a quadratic function) between cholesterol levels and cognitive functions, as suggested by several recent studies (Wendell et al, 2014, 2016; Lu et al, 2017; Marcum et al, 2018)
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