High plasma estradiol interacts with diabetes on risk of dementia in older postmenopausal women.

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.

• Authors: Laure Carcaillon, Sylvie Brailly-Tabard, Marie-Laure Ancelin, Olivier Rouaud, Jean-François Dartigues, Anne Guiochon-Mantel, Pierre-Yves Scarabin
• Journal: Neurology (Neurology) Vol. 82 Issue 6 Pg. 504-11 (Feb 11 2014) ISSN: 1526-632X [Electronic] United States
• PMID: 24477111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Fibrin Fibrinogen Degradation Products
• fibrin fragment D
• Testosterone
• Estradiol
• Fibrinogen
• C-Reactive Protein
• Thrombin

Topics

• Aged
• Aged, 80 and over
• Biomarkers
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Cohort Studies
• Dementia (epidemiology)
• Diabetes Mellitus (epidemiology)
• Estradiol (blood)
• Female
• Fibrin Fibrinogen Degradation Products (metabolism)
• Fibrinogen (metabolism)
• France (epidemiology)
• Humans
• Inflammation (blood, epidemiology)
• Multivariate Analysis
• Postmenopause (blood, immunology)
• Proportional Hazards Models
• Risk
• Risk Factors
• Testosterone (blood)
• Thrombin (biosynthesis)
• Thrombophilia (blood, epidemiology)