Does HRT Help Prevent Dementia?

A recent study of 1,178 women found that those carrying the APOE4 gene taking HRT had a better delayed memory score compared to APOE4 not taking HRT and to non-APOE4 carriers.[1] They also had slightly larger brain volumes in certain areas. This was an observational trial, not a clinical trial.

Clinical trials to date have not shown benefit. A systematic review of the clinical trial evidence for the effect of HRT on cognitive outcomes did not find benefit.[2] The Women’s Health Initiative Memory Study (WHIMS), a double-blind, placebo-controlled clinical trial examining 8300 women 65 years of age or older over a 2- year period to observe the effects of HRTs and dementia progression. The trial failed to find a beneficial effect for HRT in reducing dementia risk, instead finding an increase in all types of dementia.[3]

About one in five carry the ApoE4 gene, which accounts for 4 to 6% of risk for dementia and can be modified, downregulating the gene, with positive diet, nutritional supplement and lifestyle changes.

In Food for the Brain’s Dementia Risk Index and COGNITION programme to reduce dementia they excluded HRT because the evidence didn’t stack up.


[1] Saleh RNM, Hornberger M, Ritchie CW, Minihane AM. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimers Res Ther. 2023 Jan 9;15(1):10. doi: 10.1186/s13195-022-01121-5. PMID: 36624497; PMCID: PMC9830747.

[2] Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1(1):CD004143.

[3] Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in post- menopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651-2662.