Hormone therapy and dementia: A critical window of opportunity

Hormone therapy (HT) only protects against dementia if it is taken at a certain time in life, according to the findings of a recent observational, long-term, cohort study. The study is the first to directly compare the effect of hormone therapy status in both midlife and late life on the risk for dementia.

Researchers studied 5,504 female members of Kaiser Permanente in Northern California who participated in periodic multiphasic health check-ups as part of routine medical care in San Francisco and Oakland between 1964 and 1973, when they were 40 to 55 years old.

A total of 1,524 (27%) women were diagnosed with dementia during the follow-up period. Compared with women who never took hormones, those who took the therapy only in midlife (mean age, 48.7 years) had a 26% decreased risk for dementia (multivariate adjusted hazard ratio [aHR], 0.74; 95% CI, 0.58-0.94), while those taking HT only in late life (mean age, 76 years) had a 48% increased risk for dementia (aHR, 1.48; 95% CI, 1.10-1.98), even after adjusting for a number of sociodemographic differences, number of children, body mass index, and a number of medical conditions. Women taking HT during both midlife and late life had a risk for dementia similar to that of women who did not take HT at all (aHR, 1.02; 95% CI, 0.78-1.34).

Researchers suspect that if such a critical window of neuroprotection exists, it has to do with HT reducing the deposition of ß-amyloid in the brain; improving synapse formation in the hippocampus; increasing choline acetyltransferase activity in the basal forebrain; and/or improving cerebral blood flow and glucose metabolism.

Whitmer RA, Quesenberry CP, Zhou J, Yaffe K. Timing of hormone therapy and dementia: the critical window theory revisited. Ann Neurol. 2011;69(1):163-169.