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Genetic influences on cognitive decline in Parkinson's disease§

Authors

  • James F. Morley MD, PhD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Parkinson's Disease Research, Education and Clinical Center. Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
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  • Sharon X. Xie PhD,

    1. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Howard I. Hurtig MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Matthew B. Stern MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Amy Colcher MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Stacy Horn DO,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Nabila Dahodwala MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • John E. Duda MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    3. Parkinson's Disease Research, Education and Clinical Center. Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
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  • Daniel Weintraub MD,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    3. Parkinson's Disease Research, Education and Clinical Center. Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
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  • Alice S. Chen-Plotkin MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Vivianna Van Deerlin MD, PhD,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Dana Falcone MS,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
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  • Andrew Siderowf MD, MSCE

    Corresponding author
    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    2. Morris K Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA
    • Department of Neurology, 330 South 9th Street, Second Floor, Philadelphia, PA 19107, USA

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  • Funding agencies: This work was supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from the National Institute for Neurological Disorders and Stroke (NS-053488) and by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

The role of genetic factors in cognitive decline associated with Parkinson's disease (PD) is unclear. We examined whether variations in apolipoprotein E (APOE), microtubule-associated protein tau (MAPT), or catechol-O-methytransferase (COMT) genotypes are associated with cognitive decline in PD. We performed a prospective cohort study of 212 patients with a clinical diagnosis of PD. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. The ε4 allele of APOE was associated with more rapid decline (loss of 2.9; 95% confidence interval [CI]: 1.7–4.1) of more points per year; P < 0.001) in total score and an increased risk of a ≥10 point drop during the follow-up period (hazard ratio, 2.8; 95% CI: 1.4–5.4; P = 0.003). MAPT haplotype and COMT genotype were associated with measures of memory and attention, respectively, over the entire follow-up period, but not with the overall rate of cognitive decline. These results confirm and extend previously described genetic associations with cognitive decline in PD and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one APOE ε4 allele is associated with more rapid cognitive decline in PD, supporting the idea of a component of shared etiology between PD dementia and Alzheimer's disease. Clinically, these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients. © 2012 Movement Disorder Society

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