title: Genetic influences on cognitive decline in Parkinson's disease.
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.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvalia, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Morley
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.forename: Howard I
authors.initials: HI
authors.lastname: Hurtig
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Stern
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.forename: Stacy
authors.initials: S
authors.lastname: Horn
authors.forename: Nabila
authors.initials: N
authors.lastname: Dahodwala
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.forename: Alice S
authors.initials: AS
authors.lastname: Chen-Plotkin
authors.forename: Vivianna
authors.initials: V
authors.lastname: Van Deerlin
authors.forename: Dana
authors.initials: D
authors.lastname: Falcone
authors.forename: Andrew
authors.initials: A
authors.lastname: Siderowf
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C054369:MAPT protein, human; D016875:tau Proteins; D002394:Catechol O-Methyltransferase