Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease

Abstract

Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson’s disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p<0.0001), executive set shifting (p=0.018), and mental processing speed (p=0.049) compared to Controls. Longitudinally, Controls demonstrated improved fine motor and memory test scores (p=0.044, and p=0.003), whereas PD patients demonstrated significantly accelerated loss in fine motor skill (p=0.002) compared to Controls. Within the PD group, however, higher LDL-cholesterol levels were associated with improved executive set shifting (β=0.003, p<0.001) and fine motor scores (β=0.002, p=0.030) over time. These associations were absent in Controls (p>0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p=0.005), whereas the cholesterol - fine motor association difference did not reach significance (interaction, p=0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies.

Higher serum cholesterol and decreased Parkinson's disease risk: A statin‐free cohort study

“…These findings were similar for non‐HDL‐C levels and across all applied sensitivity analyses. Our results are in line with other studies that have also found an inverse association of hypercholesteremia, TC, and LDL‐C with PD risk, with earlier PD onset, and with modestly slower progression of PD symptoms and improved fine motor speed skill over time …”

“…First, although the exclusion of statin users enabled us to carefully evaluate cholesterol‐PD risk, it also excluded individuals with the highest cholesterol levels. However, 30% of the entire statin‐free cohort had borderline high LDL‐C (≥140 mg/dL) and TC (≥210 mg/dL) levels similar to the other studies that included individuals who were statin and nonstain users . In addition, it is possible to characterize these individuals with a tendency to avoid or delay pharmacotherapy in general and who choose other methods to treat chronic conditions.…”

“…Our results are in line with other studies that have also found an inverse association of hypercholesteremia, 9 TC,7,8,18,19 and LDL-C 6,7,[18][19][20] with PD risk, with earlier PD onset, 21 and with modestly slower progression of PD symptoms 22 and improved fine motor speed skill over time. 23 Our study provides additional support for the controversial relationship between cholesterol and PD in the literature by making a useful innovative contribution to the full assessment of multiple serum cholesterol measurements as a time-dependent variable. It is the first study that has a large cohort in which there are no confounding effects of statin use.…”

“…However, 30% of the entire statin-free cohort had borderline high LDL-C (140 mg/dL) and TC (210 mg/dL) levels similar to the other studies that included individuals who were statin and nonstain users. 8,21,23 In addition, it is possible to characterize these individuals with a tendency to avoid or delay pharmacotherapy in general and who choose other methods to treat chronic conditions. Because PD assessment in this study was detected using a drug tracer algorithm, this may lead to selection bias.…”

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

“…Despite the literature linking serum/plasma total and LDL cholesterol to PD, the cause of the association is not known and further complicated by the compartmentalization of the brain and peripheral cholesterol. An investigation of a potential causal relationship between circulating cholesterol levels and PD took into consideration age, gender, APOE polymorphisms, smoking history, statin, and several related gene single nucleotide polymorphisms.…”