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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Dr Wendy Suzuki – The Brain Changing Benefits of Exercise (TED).

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.

This study explored fasting & cognitive performance. It identified that biological ageing is a process which is accelerated and exacerbated by excessive calories and a sedentary lifestyle. Further, these factors combined may increase the risk of developing neurodegenerative diseases. This systematic review explored the role of different types of IF (intermittent fasting) on cognitive function, with specific focus on BDNF (brain derived neurotrophic factor) as a marker. Reduction of levels of BDNF has been associated with cognitive decline and increased risk of Alzheimer’s disease. Moreover, reductions in BDNF may result in a reduction in synaptic plasticity, memory and learning.

The study accepted and appraised 82 papers. Key findings were:

IF modulated BDNF supporting synaptic maturation and function

Primary evidence demonstrates pro-cognitive and neuroprotective effects of IF and BDNF

Sex specific differences were observed in response to IF

IF was suggested to be supportive for brain health and sustaining cognitive performance into old age, although it was identified further research is required into this area

The abstract is available here:

Seidler, K., & Barrow, M. (2021). Intermittent fasting and cognitive performance – Targeting BDNF as potential strategy to optimise brain health. Frontiers in neuroendocrinology, 65, 100971. Advance online publication. https://doi.org/10.1016/j.yfrne.2021.100971

Results suggest that higher adherence to the Mediterranean, DASH, or MIND diets is associated with less cognitive decline ans well as a lower risk of Alzheimer’s Disease (AD). Evidence for an association with dementia was inconsistent.

The MIND diet may be more protective against cognitive decline and AD than the Mediterranean and DASH diets, based on observational studies. However, more evidence on the MIND diet is required to draw a firm conclusion. Furthermore, the Mediterranean diet seems more protective against AD than the DASH diet.

Based on the studies included in the review, olive oil consumption seems to be an important component underlying these associations.

The full text can be accessed here.

The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less Cognitive Decline and a Lower Risk of Alzheimer’s Disease – A Review. van den Brink, A.C., Brouwer-Brolsma, E.M., Berendsen, A.A.M. et al. (2019). Advanced Nutrition. 10(6), pp1040-1065

The evidence for the relationship between alcohol, coffee and tea and cognitive deficits/benefits
has been confounding to date. This meta-analysis aimed to assess the current evidence
available in terms of the dose–response relationship between alcohol, coffee or tea
consumption and cognitive deficits.
Interestingly, it concluded that, based on the studies and data reviewed, whilst excessive
consumption of alcohol is known to have adverse health effects, light consumption of alcohol
(<11 g/day) and of coffee (<2.8 cups/day) are associated with reduced risk of cognitive deficits.
It also concludes that the cognitive benefits of green tea consumption increase with its daily
consumption.

The full text can be accessed here.

Alcohol, coffee and tea intake and the risk of cognitive deficits: a dose-response meta-analysis. Ran, L.S., Liu, W.H., Fang, Y.Y. et al. (2021) Epidemiology & Psychiatric Sciences. 30 (e13).