Genetic influences on cognitive decline in Parkinson's disease

James F. Morley, Sharon X. Xie, Howard I. Hurtig, Matthew B. Stern, Amy Colcher, Stacy Horn, Nabila Dahodwala, John E. Duda, Daniel Weintraub, Alice S. Chen-Plotkin, Vivianna Van Deerlin, Dana Falcone, Andrew Siderowf

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)512-518
Number of pages7
JournalMovement Disorders
Volume27
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

Keywords

  • Apolipoprotein e
  • Cognitive symptoms
  • Genetics
  • Microtubule-associated protein tau
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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