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Aging and disease    2016, Vol. 7 Issue (3) : 237-245     DOI: 10.14336/AD.2015.1030
Original Article |
Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease
Sterling Nicholas W.1, Lichtenstein Maya1, Lee Eun-Young1, Lewis Mechelle M.1,2, Evans Alicia1, Eslinger Paul J.1,3,4, Du Guangwei1, Gao Xiang7, Chen Honglei8, Kong Lan3, Huang Xuemei1,2,4,5,6,*
1Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA 17033, USA.
3Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA 17033, USA.
2Public Health Sciences, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA 17033, USA.
4Radiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA 17033, USA.
5Neurosurgery, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA 17033, USA.
6Kinesiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey PA 17033, USA.
7Department of Nutritional Sciences, the Pennsylvania State University, University Park, PA 16802, USA.
8Epidemiology Branch/Aging & Neuroepidemiology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
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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.

Keywords Parkinson’s disease      cholesterol      low density lipoprotein cholesterol (LDL-cholesterol)      cognition      neuroprotection      executive function     
Corresponding Authors: Huang Xuemei   
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These authors equally contribute this work

Issue Date: 09 January 2016
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Sterling Nicholas W.
Lichtenstein Maya
Lee Eun-Young
Lewis Mechelle M.
Evans Alicia
Eslinger Paul J.
Du Guangwei
Gao Xiang
Chen Honglei
Kong Lan
Huang Xuemei
Cite this article:   
Sterling Nicholas W.,Lichtenstein Maya,Lee Eun-Young, et al. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease[J]. Aging and disease, 2016, 7(3): 237-245.
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PD, n=64Control, n=64P-values
n, Female : n, Male26 : 3832 : 320.374
Statin Use (No : Yes)46 : 1849 : 150.686
Smoker (No : Yes)48 : 1649 : 151.000
Age (years)62.7 ± 7.961.3 ± 6.80.268
Education (years)15.6 ± 2.816.9 ± 2.60.008
LDL-cholesterol (mg/dL)127.3 ± 33.0126.5 ± 41.30.616
MMSE29.3 ± 1.029.5 ± 0.90.698
Hamilton Depression Scale7.7 ± 4.84.0 ± 2.6<0.0001
LEDD (mg)709 ± 481NA-
Disease duration (years)4.4 ± 4.4NA-
Hoehn & Yahr Score1.7 ± 0.7NA
Table 1  Demographics of study subjects at baseline (averages presented as mean ± SD)
Cognitive DomainIndividual Tests
Fine motor speedGrooved Pegboard Test
MemoryBrief Visuospatial Memory Test-Revised (BVMT-R)
Hopkins Verbal Learning Test-Revised (HVLT-R)
Executive function: Spontaneous flexibilityDKEFS Design Fluency Test (DesFlu)
Verbal Fluency Test (VerbFlu)
Executive function:
CWInt-Switch and CWInt-Inhibition subtests, including error scores
Attention//Working memoryDigit Span
Spatial Span
Letter-Number Sequencing Test
Processing speedCWInt color
Symbol search
LanguageBoston Naming Test (BNT)
CWInt-Word subtest
Spatial cognitionBenton’s Judgment of Line Orientation (JoLO)
Table 2  Individual cognitive tests comprising cognitive domains
Baseline Visit
Fine Motor Speed-2.03 ± 1.11-0.46 ± 1.08<0.001
Memory-0.59 ± 0.91-0.45 ± 0.920.403
Executive Function: SF0.11 ± 0.780.43 ± 0.700.090
Executive Function: SS-0.01 ± 0.940.44 ± 0.470.018
Attention0.29 ± 0.6610.37 ± 0.530.803
Processing Speed0.08 ± 0.570.29 ± 0.320.049
Language0.29 ± 0.800.51 ± 0.490.246
Spatial Cognition-0.27 ± 0.93-0.19 ± 0.770.787
18-Months Visit
Fine Motor Speed-2.03 ± 1.06-0.31 ± 0.98<0.001
Memory-0.60 ± 0.81-0.24 ± 0.800.067
Executive Function: SF0.00 ± 0.870.27 ± 0.730.095
Executive Function: SS0.01 ± 0.880.46 ± 0.410.008
Attention0.19 ± 0.750.36 ± 0.550.456
Processing Speed-0.02 ± 0.590.23 ± 0.310.022
Language0.19 ± 0.760.54 ± 0.480.015
Spatial Cognition-0.18 ± 0.91-0.15 ± 1.000.610
36-Months Visit
Fine Motor Speed-2.09 ± 1.09-0.19 ± 0.97<0.001
Memory-0.45 ± 0.92-0.05 ± 0.740.098
Executive Function: SF-0.08 ± 0.730.37 ± 0.760.022
Executive Function: SS0.21 ± 0.740.52 ± 0.470.059
Attention0.33 ± 0.590.34 ± 0.560.949
Processing Speed0.08 ± 0.560.21 ± 0.380.300
Language0.32 ± 0.860.64 ± 0.440.053
Spatial Cognition-0.11 ± 0.59-0.13 ± 0.830.952
Table 3  Association of baseline LDL-cholesterol levels with change in cognitive function over time (using baseline, 18-month, and 36-month scores)
Figure 1.  Annual rates of changes in cognitive function over time associated with baseline plasma LDL-cholesterol levels

Annual rates of change estimated using linear regression of baseline, 18-month, and 36-month cognitive z-scores.

PDControlsGroup Difference
Fine motor speed0.0020.0300.0000.8010.0020.104
Executive function: SF0.0000.7410.0000.4820.0000.900
Executive function: SS0.003<0.001*0.0000.9050.0030.005*
Processing speed0.0000.7420.0000.8110.0000.889
Spatial cognition0.0010.5630.0000.8750.0010.705
Table 4  Association of baseline LDL-cholesterol levels with change in cognitive function over time (using baseline, 18-month, and 36-month scores)
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