The Impact of Cholesterol-Lowering Medication Use and Plasma Lipid Levels on Cognitive and Motor Function

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1 The Impact of Cholesterol-Lowering Medication Use and Plasma Lipid Levels on Cognitive and Motor Function Kaltra Dhima, B.A. October 26 th, 2017 National Academy of Neuropsychology PD is the second most common neurodegenerative disorder 1 Cardinal motor symptoms 2 Bradykinesia Rigidity Rest tremor Postural instability BACKGROUND Heterogeneous presentation & disease progression Age at PD onset predicts speed of disease progression 3 Young onset slow progression Older onset fast progression Risk of cognitive decline unclear MCI in 19-38% of non-demented PD patients 4 ~80% develop dementia eventually 5, 6 2 BACKGROUND OBJECTIVE Previous study found protective effect of hyperlipidemia diagnosis on memory function over time in PD Lipid levels in PD: Lower incidence of PD related to abnormal lipid levels (e.g., high LDL) 7-10 Statins in PD: Lower incidence of PD among statin users Anti-inflammatory properties Increased striatal dopamine concentration in PD animal models 21 Reduced intraneuronal aggregation of alpha-synuclein22, 23 Examine how use of cholesterol lowering medication and plasma lipid levels relate to cognitive and motor Hypothesis: Cholesterol lowering medication use and/or abnormal plasma lipid levels will demonstrate a neuroprotective effect in this PD cohort. 3 4 METHOD PD cohort De novo at enrollment Recently diagnosed (2 years) Assessed at baseline (T1) & 3 years later (T2) Demographic & medical information Neuropsychological & motor measures Baseline blood collection (fasting 12 hours) 93 subjects STATISTICAL ANALYSIS Stepwise linear regressions to predict cognitive and motor function Baseline Baseline predictors & outcome variables Longitudinal Baseline predictors & longitudinal outcome variables Change scores = T2 - T1 Bonferroni correction for multiple comparisons: (T1 & T2 measures, baseline lipid panel, fasting) 5 6

2 PREDICTOR VARIABLES Baseline cholesterol-lowering medication use (Y/N) Baseline fasting lipid levels from blood plasma (mg/dl) Triglycerides High-density lipoprotein (HDL) Low-density lipoprotein (LDL) Age at baseline as covariate Animal Fluency OUTCOME VARIABLES Benton Judgement of Line Orientation Test (JoLO) Hopkins Verbal Learning Test-Revised (HVLT-R) Trials 1-3 total Delayed recall Retention Symbol Digit Modalities Test (SDMT), written Wechsler Memory Scale-III, Letter-Number Sequencing (LNS) Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) 24 Subscale III Off state (at T2 7 8 MDS-UPDRS MDS-UPDRS SUBSCALE III Update published in 2008 Multimodal scale assesses impairment and disability in PD Subscales I-IV Subscale III: Motor Examination Administered by the investigator Measures presence and severity of motor symptoms 33 items based on 18 questions Items scored 0-4 (absent severe) Score range Speech 2. Facial expression 3. Rigidity 4. Finger tapping 5. Hand movements 6. Pronation-supination 7. Toe tapping 8. Leg agility 9. Arising from chair 10. Gait 11. Freezing 12. Postural stability 13. Posture 14. Bradykinesia 15. Postural tremor 16. Kinetic tremor 17. Rest tremor (amplitude) 18. Rest tremor (consistency) 9 10 Table 1. Baseline Demographics Table 2. Predictor Variables 11 12

3 13 Table 3. Baseline Outcome Variables Table 4. Longitudinal Outcome Variables 14 Table 5. Significant Regression Models CONCLUSIONS Cholesterol measures did not predict cognitive or motor function at baseline Higher age predicted worse memory at baseline Higher baseline triglycerides predicted slower memory decline Higher baseline LDL predicted slower motor decline Association between hyperlipidemia and better outcomes in cognitive and motor function Hyperlipidemia may slow down disease progression in PD REFERENCES 1. De Lau, L. M., & Breteler, M. M. (2006). Epidemiology of Parkinson's disease. The Lancet Neurology, 5(6), Hughes, A. J., Daniel, S. E., Kilford, L., & Lees, A. J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery & Psychiatry, 55(3), van Rooden, S. M., Heiser, W. J., Kok, J. N., Verbaan, D., van Hilten, J. J., & Marinus, J. (2010). 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4 THANK YOU! QUESTIONS? Co-authors: Nicholas Holder, BS C. Munro Cullum, PhD, ABPP-CN Laura Lacritz, PhD, ABPP-CN 19 20

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10 The views expressed herein are those of the presenter and do not reflect the official policy of the Department of the Army, Department of Defense, or DVBIC. The presenter does not intend to discuss the offlabel/investigative (unapproved) use of commercial products or devices. The presenter has no relevant financial relationships to disclose.

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