title: Vitamin D receptor gene polymorphisms and cognitive decline in Parkinson's disease.
abstract: We and others have suggested that vitamin D receptor gene (VDR) polymorphisms influence susceptibility for Parkinson's disease (PD), Alzheimer's disease (AD), mild cognitive impairment (MCI) or overall cognitive functioning. Here we examine VDR polymorphisms and cognitive decline in patients with PD. Non-Hispanic Caucasian PD patients (n=190) in the Parkinson Environment Gene (PEG) study were successfully genotyped for seven VDR polymorphisms. Cognitive function was assessed with the Mini-Mental State Exam (MMSE) at baseline and at a maximum of three follow-up exams. Using repeated-measures regression we assessed associations between VDR SNP genotypes and change in MMSE longitudinally. PD cases were on average 67.4years old at diagnosis and were followed for an average of 7.1years into disease. Each additional copy of the FokI A allele was associated with a 0.115 decrease in the total MMSE score per year of follow-up (β=-0.115, SE(β)=0.05, p=0.03) after adjusting for age, sex, education and PD duration. The effect on MMSE by the FokI A allele was comparable in absolute magnitude to the effect for disease duration in years prior to first interview (β=-0.129 per year, SE(β)=0.08, p=0.13), and years of education (β=0.118 per year, SE(β)=0.03, p<0.001). When LD/LED use and PD subtype were added to the model, the effect of the FokI A allele on total MMSE score was magnified (β=-0.141, SE(β)=0.05, p=0.005). Results point to Fokl, a functional VDR polymorphism, as being associated with cognitive decline in PD. Future studies examining the contributions of the vitamin D metabolic pathway to cognitive dysfunction in PD are needed.
authors: School of Community and Global Health, Claremont Graduate University, Claremont, CA 91711, United States. Electronic address: nicole.gatto@cgu.edu.
authors: Nicole M
authors: NM
authors: Gatto
authors: Department of Epidemiology, UCLA, Los Angeles, CA 90095, United States.
authors: Kimberly C
authors: KC
authors: Paul
authors: Department of Human Genetics, UCLA, Los Angeles, CA 90095, United States; Department of Biomathematics, UCLA, Los Angeles, CA 90095, United States; Department of Biostatistics, UCLA, Los Angeles, CA 90095, United States.
authors: Janet S
authors: JS
authors: Sinsheimer
authors: Department of Neurology, UCLA, Los Angeles, CA 90095, United States.
authors: Jeff M
authors: JM
authors: Bronstein
authors: Department of Neurology, UCLA, Los Angeles, CA 90095, United States.
authors: Yvette
authors: Y
authors: Bordelon
authors: Department of Neurology, UCLA, Los Angeles, CA 90095, United States.
authors: Rebecca
authors: R
authors: Rausch
authors: Department of Epidemiology, UCLA, Los Angeles, CA 90095, United States; Department of Environmental Health Sciences, UCLA, Los Angeles, CA 90095, United States; Department of Neurology, UCLA, Los Angeles, CA 90095, United States.
authors: Beate
authors: B
authors: Ritz
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics*; D004522:Educational Status; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012044:Regression Analysis; D044465:White People / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D018167:Receptors, Calcitriol; C579457:VDR protein, human
keywords: Cognitive decline; FokI; MMSE; Parkinson's disease; Vitamin D receptor