A recent study of 1,178 women found that those carrying the APOE4 gene taking Hormone Replacement Therapy (HRT) had a better delayed memory score compared to APOE4 carriers that were not taking HRT, and to non-APOE4 carriers.[1] They also had slightly larger brain volumes in certain areas. This study suggested that HRT may help to prevent Dementia. This study was an observational trial, not a clinical trial, meaning the statement remains a hypotheses and requires further randomised controlled trials to investigate further. We analysed the paper and provided our comments below.

Clinical Trials on HRT

Clinical trials to date have not shown benefit of HRT with improving cognitive function. 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) conducted 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]

The ApoE4 Gene

Roughly 1 in 5 people 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.[1]

Find out your risk for Dementia

In our Dementia Risk Index, as part of the Cognitive Function test, and COGNITION programme to reduce dementia, we excluded HRT because the evidence was not conclusive or consistent.

Have you tried our free Cognitive Function Test yet? Find out your Alzheimer’s disease risk using our evidence backed Dementia Risk Index. If your risk is high, our clever new programme COGNITION can help you make the right nutrition and lifestyle changes to help improve your score.

References

[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.

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This study investigate bilingualism & cognition. The study was a meta analysis of studies. Inclusion criteria was studies investigating bilingualism in the elderly with relation to Alzheimer’s disease risk. 6 prospective cohort studies were selected and 8 retrospective studies were selected. Of the 14 studies, only 2 had a monolingual control group. 14 studies selected for analysis. Study indicated that bilingualism may be protective against memory decline in older adults.

Results:

Meta analysis indicates that one exception, the studies support the idea that bilingualism reduces risk of memory decline. . However, only a small sample of studies included, although selected studies generally of a good sample size (>500). Only two of the studies included participants with Alzheimer’s disease diagnosis. Moreover, only two studies had a control group. Further, two of the studies included only Hispanic subjects, which may have impacted results.

A notable limitation of the meta analysis is that it did not include any statistical analysis methods (i.e p value) and this is a significant limitation. Further large scale research is required to explore effects of bilingualism on cognition, and whether bilingualism may be protective against cognitive decline.

Abstract available here

Klimova, B., Valis, M., and Kuca, K. (2017). Bilingualism as a strategy to delay the onset of Alzheimer’s disease. Clin. Interv. Aging 12, 1731–1737.

This study investigated bilingualism & cognition. Study included 28 older adult participants – 14 monolingual participants and 14 bilingual participants (who had been bilingual since before age 11). All participants were subjected to a fMRI and had no diagnosed mental health conditions.

Results indicated:

Bilingual participants performed better on tasks and had better working memory (p<0.01) and better connectivity (p=0.002), compared with the monolingual group (p=0.17)

Results observed for other types of memory were not significant

Study size was small. Further large scale warranted. Study did not specify regarding bilingualism, as to whether participants spoke more than 2 languages, or whether certain type and complexity of language afford greater protection (i.e romance languages, Germanic languages etc.). Further research merited to explore effects of bilingualism on other types of memory.

Abstract available here

Grady, C. L., Luk, G., Craik, F. I., and Bialystok, E. (2015). Brain network activity in monolingual and bilingual older adults. Neuropsychologia 66, 170–181. doi: 10.1016/j.neuropsychologia.2014.10.042

In this study memory change over 6 years was assessed using a large scale sample (16, 638 elderly individuals born <1948) from Health and Retirement Study. Growth curve models were analysed with reference to memory recall of a 10 word list and levels of social integration (i.e with family, volunteering, marital status).

Results indicated:

Socialisation demonstrated as a predictor of slower memory decline (p<.01). 

In individuals with vascular disease, socialisation observed to be protective buffer ( (p< 0.05)

Memory amongst least socialised deteriorated at twice the rate of other participants, with association greatest amongst those with <12 years of education (p<0.07)

The study indicates that socialisation and levels of education may be protective factors for memory decline. The study also suggests that socialisation may reduce risk for memory decline in individuals with vascular diseases. The study did not use a robust means of measuring memory capability, such as MMSE. Results for socialisation as a predictor of slower memory decline not statistically significant. However, socialisation in individuals with vascular disease as a protective factor was observed to be statistically significant. More research required as to the mechanisms of how socialisation reduces risk of memory decline in vascular disease. Findings for education as a protective factor were observed to be statistically significant. More research required into to what level of education is most protective against memory decline.

Abstract can be viewed here

Ertel, K. A., Glymour, M. M., & Berkman, L. F. (2008). Effects of social integration on preserving memory function in a nationally representative US elderly population. American journal of public health, 98(7), 1215–1220.