Hormone replacement therapy may help prevent Alzheimer’s disease in millions of women at risk of developing the condition, research suggests.
Dementia is one of the world’s biggest health threats. The number of people living with the condition worldwide is set to nearly triple to 153 million by 2050, and experts have warned it presents 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 are female, and about a quarter of women in the UK alone 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 Alzheimer’s disease in women carrying the APOE4 gene. The study was published in the Alzheimer’s Research & Therapy journal.
Although they stressed they could not say for sure that HRT cut the risk in women, the findings were “really important” amid limited drug options for dementia and an urgent need for novel treatments.
HRT, which helps control symptoms of the menopause, is associated with better memory, cognitive function and larger brain volumes in later life in women with the APOE4 gene, the researchers found.
Prof Michael Hornberger, of UEA’s Norwich Medical School, said: “It’s too early to say for sure that HRT reduces dementia risk in women, but our results highlight the potential importance of HRT and personalised medicine in reducing Alzheimer’s risk.
“The next stage of this research will be to carry out an intervention trial to confirm the impact of starting HRT early on cognition and brain health. It will also be important to analyse which types of HRT are most beneficial.”
In the study, researchers found that HRT was most effective when given during perimenopause – where symptoms build up months or years before periods stop – and could lead to brains that appear several years younger.
Prof Anne-Marie Minihane, also of Norwich Medical School, and the co-leader of the study, said: “We know that 25% of women in the UK are carriers of the APOE4 gene and that almost two-thirds of Alzheimer’s patients are women.
“In addition to living longer, the reason behind the higher female prevalence is thought to be related to the effects of menopause and the impact of the APOE4 genetic risk factor being greater in women.
“We wanted to find out whether HRT could prevent cognitive decline in at-risk APOE4 carriers.”
The team analysed data from 1,178 women taking part in the European Prevention of Alzheimer’s Dementia 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 50 who did not have dementia at the start of the study. For the new research, experts looked at the results of cognitive tests and brain volumes as 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 non-APOE4 carriers.
Dr Rasha Saleh, of Norwich Medical School, said: “We found that HRT use is associated with better memory and larger brain volumes among at-risk APOE4 gene carriers. 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 limited drug options for Alzheimer’s disease for 20 years and there is an urgent need for new treatments. The effects of HRT in this observation study, if confirmed in an intervention trial, would equate to a brain age that is several years younger.”
Minihane said the team did not look at dementia cases, but that cognitive performance and lower brain volumes are predictive of future dementia risk.
The risk of Alzheimer’s and other types of dementia increases with age, affecting an estimated one in 14 people over the age of 65 and one in every six over the age of 80. Inheriting APOE4 does not mean someone will definitely develop the condition.
Prof Craig Ritchie, a co-leader of the study from the University of Edinburgh, said it “highlights the need to challenge many assumptions about early Alzheimer’s disease and its treatment, especially when considering women’s brain health”.
He added: “An effect on both cognition and brain changes on MRI supports the notion that HRT has tangible benefit. These initial findings need replication, however, in other populations.”
Dr Sara Imarisio, head of strategic initiatives at Alzheimer’s Research UK, said the findings were “encouraging” but need to be confirmed in further studies.
“They provide evidence that HRT could have some cognitive benefits, particularly in women who carry the APOE4 Alzheimer’s risk gene,” she said. “The next step is to investigate this in more detail.”
Imarisio said if the new findings were subsequently confirmed, it could pave the way for clinical trials to see if HRT can eventually prevent dementia.
Dr Richard Oakley, associate director of research at the Alzheimer’s Society, said: “Studies of this kind are important as they hint at a link between HRT and the changes to the brain. We need more studies, on a larger scale, to better understand this link.”
