HRT could ward off Alzheimer’s disease in at-risk women

Hormone Replacement Therapy could help prevent Alzheimer’s among women at risk of developing the disease – according to new research.

A new study shows that HRT use is associated with better memory, cognition and larger brain volumes in later life among women carrying the APOE4 gene – the strongest risk factor gene for Alzheimer’s disease [1].

The research team found that HRT was most effective when introduced early in the menopause journey during perimenopause.

Longevity.Technology: Menopause is the natural biological process that marks the end of a woman’s reproductive years, with perimenopause being the preceding time of transition. Typically occurring between the ages of 45 and 55, menopause is characterised by the permanent cessation of menstruation, but also comes with myriad of other uncomfortable side effects symptoms including brain fog, weight gain, hot flashes, night sweats and debilitating mood swings.

The root cause of menopause is ovarian aging, and hormone replacement therapy (HRT) is often used to alleviate the symptoms of menopause. HRT replaces the estrogen and progesterone hormones that are no longer produced by the ovaries, with the goal of balancing the hormones in the body and reducing the frequency and severity of symptoms. However, HRT is not as widely used as perhaps it should be due to concerns about potential risks, such as an increased risk of breast cancer, blood clots and stroke, an issue which is causing much debate.

A new study which lends support to the HRT argument comes from Professor Anne-Marie Minihane, from UEA’s Norwich Medical School and director of the Norwich Institute for Healthy Aging at UEA, and Professor Craig Ritchie at the University of Edinburgh.

Professor Minihane said: “We know that 25 per cent 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 [2].”

The research team studied data from 1,178 women participating in the European Prevention of Alzheimer’s Dementia initiative – which was set up 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 and dementia-free.

The research team studied their results to analyse the impact of HRT on women carrying the APOE4 genotype.

Dr Rasha Saleh, also from UEA’s 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 [2].”

Professor Anne Marie Minihane said: “Our research looked at associations with cognition and brain volumes using MRI scans. We did not look at dementia cases, but cognitive performance and lower brain volumes are predictive of future dementia risk.”

Professor Michael Hornberger, from 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,” he added [2].”

Professor Craig Ritchie, from the University of Edinburgh, added: “This important finding from the EPAD Cohort highlights the need to challenge many assumptions about early Alzheimer’s disease and its treatment, especially when considering women’s brain health. 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 [2].”

This study is particularly interesting given recent news that women who suffer an early menopause are 35% more likely to develop dementia. Estrogen is already known to be a neuroprotector, with research demonstrating it can reduce oxidative damage in the cerebral cortex [3], so it further research on the relationship between the brain, dementia, hormones and the menopause is most certainly warranted.