Hormone Replacement Therapy could help prevent Alzheimer’s Dementia among at-risk women

Hormone replacement therapy (HRT) may help prevent Alzheimer’s dementia in women at risk of developing the disease – according to University of East Anglia research.

Research shows that HRT use is associated with better memory, cognition and larger brain volume later in life in women who carry the APOE4 gene — the strongest risk factor gene for Alzheimer’s disease.

The research team found that HRT was most effective at the start of the menopausal journey during perimenopause.

Professor Anne-Marie Minihan of UEA’s Norwich Medical School and director of the Norwich Institute for Healthy Aging at UEA, led the research in collaboration with Professor Craig Ritchie of the University of Edinburgh.

Professor Minihan said: “We know that 25 per cent of women in the UK are carriers of the APOE4 gene and almost two thirds of Alzheimer’s patients are women.

“In addition to longer survival, the reason behind the higher female trend is thought to be related to the effects of menopause and the effect of the APOE4 genetic risk factor in women.

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“We wanted to find out if HRT could prevent cognitive decline in at-risk APOE4 carriers.”

The research team studied data from 1,178 women participating in the European Prevention of Alzheimer’s Dementia Initiative – which was set to study participants’ brain health over time.

The project spanned 10 countries and tracked participants’ brains from ‘healthy’ to a diagnosis of dementia in some. Participants were included if they were over 50 years of age and dementia-free.

The research team studied their results to analyze the effect on women undergoing HRT APOE4 genotype

Dr Rasha Saleh, from UEA’s Norwich Medical School, said: “We found that HRT use was associated with better memory and larger brain volume in at-risk APOE4 gene carriers. The associations were particularly clear when HRT was started early – the transition period known as menopause, perimenopause .

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“This is really important because for 20 years there have been very limited drug options for Alzheimer’s disease and there is an urgent need for new treatments.

“The effect of HRT in this observational study, if confirmed in an interventional trial, would be equivalent to a brain age that is several years younger.”

Professor Minihan said: “Our study looked at the relationship between cognition and brain volume using MRI scans. We didn’t look at cases of dementia, but cognitive performance and lower brain volume predicted future dementia risk.

Professor Michael Hornberger, UEA’s Norwich Medical School, said: “It is too early to say for sure whether HRT reduces the risk of dementia in women, but our results highlight the potential importance of HRT and personalized medicine in reducing the risk of Alzheimer’s.

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“The next phase of this study will be an intervention trial to confirm the effect of starting HRT early on cognition and brain health. It will also be important to analyze which type of HRT is most beneficial,” he added.

Professor Craig Ritchie, of the University of Edinburgh, said: “This important finding from the EPAD cohort highlights the need to challenge many assumptions about early Alzheimer’s disease and its treatment, particularly when women’s brain health is considered. It affects both cognition and brain changes. On MRI support the idea that HRT has real benefits. These preliminary results require replication in other populations.”

‘Hormone replacement therapy is associated with improved cognition and larger brain volume in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort’ is published in the journal Alzheimer’s research and therapy.


University of East Anglia


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