title: Estrogen receptor α polymorphisms and the risk of cognitive decline: A 2-year follow-up study.
abstract: OBJECTIVE
  The neuroprotective role of estrogen is supported by biochemical studies, but the results from clinical trials of estrogen replacement therapy on cognitive decline are controversial. One possible missing link might be the interindividual difference in estrogen receptor expression. In this study, the association of estrogen receptor α (ESR1) polymorphisms and cognitive decline was investigated.
  
  
  METHODS
  Chinese older adults (n = 284) were recruited, and the cognitive profile was follow-up over 2-year period. Twenty ESR1 polymorphisms were investigated and correlated with the cognitive decline for the subjects.
  
  
  RESULTS
  Significant association was found between ESR1 polymorphisms (rs9340799 [ESR1+351], rs1801132 [ESR1+975], rs6557171, rs9397456, and rs1884049) and subjects with no dementia (Clinical Dementia Rating, CDR 0) and very mild dementia (CDR 0.5). Several ESR1 polymorphisms were associated with cognitive decline as assessed by Chinese versions of Mini-Mental State Examination and Alzheimer Disease Association Scales-Cognitive Subscale. Different sets of ESR1 polymorphisms were associated with cognitive decline from CDR 0 to 0.5 and CDR 0.5 to 1. ESR1 polymorphisms (rs3853248, rs22334693 [ESR1+397], rs9340799 [ESR1+351], rs9397456, rs1801132 [ESR1+975], rs2179922, rs932477, and rs9341016) were associated with the deterioration of episodic memory among subjects with baseline CDR 0, indicating these polymorphisms might be markers for episodic memory decline at an earlier stage.
  
  
  CONCLUSIONS
  This study showed association between ESR polymorphisms and cognitive decline or specific areas in cognitive profile. These findings might be useful in identifying individuals at risk for early intervention, and more research is required to elucidate the underlying mechanisms.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, China; Functional Genomics and Biostatistical Computing Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, China.
authors.forename: Suk Ling
authors.initials: SL
authors.lastname: Ma
authors.affiliation: Functional Genomics and Biostatistical Computing Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, China; Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, China; Laboratory of Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, China. Electronic address: nelsontang@cuhk.edu.hk.
authors.forename: Nelson Leung Sang
authors.initials: NL
authors.lastname: Tang
authors.affiliation: Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, China.
authors.forename: Grace Tak Yu
authors.initials: GT
authors.lastname: Leung
authors.affiliation: Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, China.
authors.forename: Ada Wai Tung
authors.initials: AW
authors.lastname: Fung
authors.affiliation: Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, China.
authors.forename: Linda Chiu Wa
authors.initials: LC
authors.lastname: Lam
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha
keywords: ESR1; Genetics; cognitive decline