Sex hormones, vascular factors and cognition.

After more than a century of research, we have failed to develop a pharmacological prevention or cure for dementia. There are strong indicators that sex hormones influence cognition. In this paper we discuss the role of these hormones at the intersection between vascular disease and dementia, in light of the mounting literature covering the shared risk factors, pathological features alongside the timeline of hormonal change with the evolution of vascular and neurodegenerative disease. Interactive risk factors and the role of inflammation over the duration of disease evolution are highlighted. Our summary tables assessing the impact of estrogen-based hormone therapy on cognition over the past 45 years illustrate the effort expended to determine the ideal age for intervention and the type, dose, administration, and duration of therapy that might improve or protect cognition as well as alleviate menopausal symptoms. As the prevalence of dementia is rising and is higher in women, it is crucial we advance our knowledge from the "inconclusive" position statement on menopausal hormone therapy of the US Preventive Services Task Force.