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Abstract
Objective: We aimed to investigate the impact of endogenous estradiol (E2) on dementia and to evaluate the contribution of vascular risk factors and inflammatory and blood coagulation markers to this association.
Methods: Using data from a French population-based prospective study (the Three-City Study) including 5,644 postmenopausal women aged 65 years or older, we investigated the association of endogenous total-E2 and bioavailable-E2 and total-testosterone with the 4-year incidence of all-cause dementia. We further focused on the role of dementia and cardiovascular risk factors as well as inflammation (C-reactive protein, fibrinogen) and hypercoagulability (fibrin d-dimers, thrombin generation) in these associations. We used a case-cohort design consisting of a random subcohort of 562 women not using hormone therapy and 132 incident dementia cases.
Results: Adjusted Cox proportional hazards models showed a J-shaped relationship between total-E2 and risk of dementia (p = 0.001). Total-E2 values in the lower and upper quartiles were associated with an increased dementia risk (adjusted hazard ratio [HR] [95% confidence interval] = 2.2 [1.1–4.5] and HR = 2.4 [1.2–5.2], respectively). Importantly, the risk associated with higher E2 levels was dramatically increased in women with diabetes compared with nondiabetic women (adjusted HR associated with the upper E2 quartile = 14.2 [1.60–123] and HR = 3.4 [0.1–147], respectively, p interaction <0.05). Similar results were found for bioavailable-E2. Adjustment for inflammatory and blood coagulation markers did not modify our results. No significant association was found for total-testosterone.
Conclusion: High E2 level is an independent predictor of incident dementia, particularly in postmenopausal women with diabetes.
GLOSSARY
- AD=
- Alzheimer disease;
- BMI=
- body mass index;
- DSM-IV-R=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised;
- DVC=
- dementia with vascular component;
- E2=
- estradiol;
- GM=
- geometric mean;
- HDL-C=
- high-density lipoprotein cholesterol;
- HR=
- hazard ratio;
- hs-CRP=
- high-sensitivity C-reactive protein;
- SSH=
- steroid sex hormone;
- T=
- testosterone;
- WHR=
- waist-to-hip ratio
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received July 1, 2013.
- Accepted in final form November 1, 2013.
- © 2014 American Academy of Neurology
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