Nicole Licking1, Charles Murchison2, Brenna Cholerton3, Cyrus P Zabetian4, Shu-Ching Hu4, Thomas J Montine5, Amie L Peterson-Hiller1, Kathryn A Chung1, Karen Edwards6, James B Leverenz7, Joseph F Quinn8. 1. Department of Neurology, Oregon Health and Science University, Portland, OR, United States; Parkinson's Disease Research, Education, and Clinical Center, Portland Veterans Affairs Medical Center, Portland, OR, United States. 2. Department of Neurology, Oregon Health and Science University, Portland, OR, United States. 3. Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, United States. 4. Parkinson's Disease Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States; Department of Neurology, University of Washington, Seattle, WA, United States. 5. Department of Pathology, Stanford University, Palo Alto, CA, United States. 6. Department of Epidemiology, University of California at Irvine, United States. 7. Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States. 8. Department of Neurology, Oregon Health and Science University, Portland, OR, United States; Parkinson's Disease Research, Education, and Clinical Center, Portland Veterans Affairs Medical Center, Portland, OR, United States. Electronic address: quinnj@ohsu.edu.
Abstract
INTRODUCTION: Increased plasma homocysteine (HC) is a risk factor for dementia in the general population. Levodopa therapy causes increased plasma HC, but it remains unclear whether elevated plasma HC is associated with cognitive impairment in Parkinson's disease (PD). METHODS: The study population includes all participants in the Pacific Northwest Udall Center (PANUC) Clinical cohort at the time of the study, consisting of 294 individuals with PD who had a standardized neuropsychological assessment and plasma collection for HC measurement. We tested the hypothesis that elevated plasma HC is inversely related to cognitive function in patients with PD. RESULTS: As expected, plasma HC was positively associated with age, disease duration, disease severity, and levodopa usage, while cognitive function was associated with age, education, gender, and APOE genotype, so subsequent analyses controlled for these covariates. When plasma HC was dichotomized as normal (<14 μmol/L) or elevated (≥14 μmol/L), subjects with hyper-homocysteinemia had lower scores on Digit Symbol (p = 0.031), Hopkins Verbal Learning Task (HVLT) Delayed Recall (p = 0.004), and semantic verbal fluency (p = 0.049). When examined as a continuous variable, plasma HC was inversely associated with HVLT Delayed Recall (p = 0.009)) and semantic verbal fluency (p = 0.004), but was not significantly related to Digit symbol, Trail-making test, Judgment of Line Orientation, phonemic verbal fluency, MMSE, or MOCA. When analysis was restricted to non-demented subjects (n = 231), the findings were unchanged. CONCLUSIONS: We conclude that plasma HC is significantly associated with some aspects of cognitive function in PD, and may represent a treatable risk factor for cognitive decline in PD.
INTRODUCTION: Increased plasma homocysteine (HC) is a risk factor for dementia in the general population. Levodopa therapy causes increased plasma HC, but it remains unclear whether elevated plasma HC is associated with cognitive impairment in Parkinson's disease (PD). METHODS: The study population includes all participants in the Pacific Northwest Udall Center (PANUC) Clinical cohort at the time of the study, consisting of 294 individuals with PD who had a standardized neuropsychological assessment and plasma collection for HC measurement. We tested the hypothesis that elevated plasma HC is inversely related to cognitive function in patients with PD. RESULTS: As expected, plasma HC was positively associated with age, disease duration, disease severity, and levodopa usage, while cognitive function was associated with age, education, gender, and APOE genotype, so subsequent analyses controlled for these covariates. When plasma HC was dichotomized as normal (<14 μmol/L) or elevated (≥14 μmol/L), subjects with hyper-homocysteinemia had lower scores on Digit Symbol (p = 0.031), Hopkins Verbal Learning Task (HVLT) Delayed Recall (p = 0.004), and semantic verbal fluency (p = 0.049). When examined as a continuous variable, plasma HC was inversely associated with HVLT Delayed Recall (p = 0.009)) and semantic verbal fluency (p = 0.004), but was not significantly related to Digit symbol, Trail-making test, Judgment of Line Orientation, phonemic verbal fluency, MMSE, or MOCA. When analysis was restricted to non-demented subjects (n = 231), the findings were unchanged. CONCLUSIONS: We conclude that plasma HC is significantly associated with some aspects of cognitive function in PD, and may represent a treatable risk factor for cognitive decline in PD.
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