The Women’s Health Initiative Memory Study

western Europe will be over age 65 years, and up to 10% will have Alzheimer’s disease (AD).1 Furthermore, the prevalence of mild cognitive impairment, thought to be a preclinical stage of AD, is estimated to be between 20 % and 30 % in elderly people.2 The social and economic implications of this are greatest among women because their life expectancy and risk of AD are greater than for men.3 Three prospective observational studies of hormone therapy (HT) and AD each reported that HT reduced the risk of AD by 39–50%.3–5 Meta-analyses of cohort and prospective case-controlled studies of the potential protective effects of HT against dementia reported risk reductions of up to 34 % (RR 0·66; 95 % CI 0·53–0·82).6 However, these studies could be confounded. For example, a high level of education is associated with a decreased risk of AD, particularly for women,7 and women who receive HT tend be better educated and healthier than those who choose not to receive it (the “healthy-user bias”).8 Furthermore, the results from small randomised controlled studies of the effects of HT on cognition were inconsistent.6 The possibility that HT protects against age-related cognitive impairment and dementia therefore became a major public-health issue, and large placebo controlled trials of HT in patients with dementia and cognition were needed