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Am J Geriatr Psychiatry. 2014 May;22(5):489-98. doi: 10.1016/j.jagp.2012.08.006. Epub 2013 Jan 11.

Estrogen receptor α polymorphisms and the risk of cognitive decline: A 2-year follow-up study.

Author information

  • 1Department 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.
  • 2Functional 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.
  • 3Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, China.

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.

CONCLUSION:

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.

Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

ESR1; Genetics; cognitive decline

PMID:
23567436
[PubMed - in process]
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