Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women.
BACKGROUND
Several genes associated with sporadic Alzheimer's disease have been identified; however, approximately 50% of genetic factors remain unidentified. We investigated whether estrogen receptor 1 (ESR1) polymorphisms are associated with risk of developing cognitive impairment in older women.


METHODS
A total of 2625 women > or = 65 years of age completed a modified Mini-Mental Status Exam (mMMSE) at baseline and at 6-8 years of follow-up. We defined cognitive impairment as a mMMSE decline of > or = 3 points, follow-up score < or = 20, or a history of physician-diagnosed dementia. The ESR1 polymorphisms, PvuII (P or p) and XbaI (X or x), were coded so that the capital letter signifies the absence of the restriction site.


RESULTS
Women with a p allele had a greater age, education, and baseline-score adjusted decline in mMMSE (for PP, Pp, and pp, respectively:.6 +/-.1,.8 +/-.1, and.9 +/-.1 points, p for trend =.01); women with at least one x allele also had greater score decline (XX, Xx, and xx:.7 +/-.1,.7 +/-.1, and.9 +/-.1 points, p for trend =.02). Six percent (n = 166) of the women developed cognitive impairment. Compared to those who did not develop impairment, more women who developed cognitive impairment had a p allele (62% vs. 56%, p =.03; adjusted odds ration (OR) = 1.33; 95% confidence interval [CI], 1.03-1.72) or an x allele (70% vs. 64%, p =.03; adjusted OR = 1.38; 95% CI, 1.06-1.81). There was no interaction with current estrogen use, or with serum estradiol level and ESR1 polymorphisms (p >.10).


CONCLUSIONS
Estrogen receptor 1 polymorphisms are associated with risk of developing cognitive impairment. More research is needed to determine the mechanism whereby ESR1 polymorphisms or linked genes influence cognitive function in older women.
Yaffe
Kristine
K
Department of Psychiatry, University of California-San Francisco, Box 111G, 4150 Clement Street, San Francisco, CA 94121, USA.
Lui
Li Yung
LY
Grady
Deborah
D
Stone
Katie
K
Morin
Philip
P
D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004522:Educational Status; D004958:Estradiol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008609:Mental Status Schedule; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*; D012307:Risk Factors
D011960:Receptors, Estrogen; D004958:Estradiol