HRT ‘potentially important’ to reduce risk of dementia in women | Health

Hormone replacement therapy may help prevent Alzheimer’s disease in millions of women at risk of developing the disease, research shows.

Dementia is one of the biggest health threats in the world. The number of people living with the disease globally is expected to nearly triple to 153 million by 2050, and experts have warned it poses a major and rapidly growing threat to future health and social care systems in every community, country and continent.

Almost two in three people with Alzheimer’s disease are women and around a quarter of women in the UK carry a gene called APOE4, which is the strongest risk factor gene for the disease.

A team of researchers from the University of East Anglia (UEA) and the University of Edinburgh have found evidence of the “potential importance” of hormone replacement therapy (HRT) in reducing the risk of heart disease. Alzheimer’s in women carrying the APOE4 gene. The study was published in the journal Alzheimer’s Research & Therapy.

Although they stressed they could not say for sure that HRT reduced the risk in women, the results were “really important” amid limited drug options for dementia and an urgent need for new treatments.

HRT, which helps control menopausal symptoms, is associated with better memory, cognitive function and larger brain volumes later in life in women with the APOE4 gene, the researchers found.

Professor Michael Hornberger, from UEA’s Norwich Medical School, said: “It is too early to say with certainty that 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.

“The next step in this research will be to perform an intervention trial to confirm the impact of early initiation of HRT on cognition and brain health. It will also be important to analyze which types of HRT are most beneficial.

In the study, the researchers found that HRT was most effective when given during perimenopause – when symptoms accumulate months or years before periods stop – and could rejuvenate the brain by several years.

Professor Anne-Marie Minihane, also from Norwich Medical School, and co-lead on the study, said: “We know that 25% of women in the UK carry the APOE4 gene and that almost two-thirds of Alzheimer’s patients are women.

“In addition to living longer, the reason for the higher female prevalence is thought to be related to the effects of menopause and the impact of the genetic risk factor APOE4 being greater in women.

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

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

The project, which involves 10 countries, tracked the brains of 1,906 people over the age of 50 who did not have dementia at the start of the study. For the new research, experts looked at cognitive test results and brain volumes recorded by MRI scans.

The results showed that APOE4 carriers who also used HRT had better cognition and higher brain volumes than people not on HRT and not APOE4 carriers.

Dr Rasha Saleh, from Norwich Medical School, said: ‘We found that HRT use is associated with better memory and larger brain volumes in carriers of the at-risk APOE4 gene. The associations were particularly evident when HRT was introduced early – during the transition to menopause, known as perimenopause.

“This is really important because there have been very few treatment options for Alzheimer’s disease for 20 years and there is an urgent need for new treatments. The effects of HRT in this observational study, if confirmed in an intervention trial, would equate to years of younger brain age.

Minihane said the team did not look at cases of dementia, but lower cognitive performance and brain volumes are predictive of future dementia risk.

The risk of Alzheimer’s disease and other types of dementia increases with age, affecting around one in 14 people over the age of 65 and one in six people over the age of 80. Inheriting APOE4 does not mean that someone will permanently develop the disease.

Professor Craig Ritchie, co-lead of the University of Edinburgh study, said it “highlights the need to challenge many assumptions about early Alzheimer’s disease and its treatment, particularly when considering women’s brain health”.

He added: ‘An effect on cognition and brain changes on MRI supports the notion that HRT has a tangible benefit. These initial findings, however, need to be replicated in other populations.

Dr Sara Imarisio, head of strategic initiatives at Alzheimer’s Research UK, said the results were “encouraging” but need to be confirmed in further studies.
“They provide evidence that HRT might have some cognitive benefits, especially in women who carry the Alzheimer’s risk gene APOE4,” she said. “The next step is to investigate this in more detail.”

Imarisio said if the new findings are later confirmed, it could pave the way for clinical trials to see if HRT can possibly prevent dementia.

Dr Richard Oakley, Associate Director of Research at the Alzheimer Society, said: “Studies like this are important because they suggest a link between HRT and brain changes. We need more studies, on a larger scale, to better understand this link.

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