A recent study has found that Hormone Replacement Therapy (HRT) could potentially prevent Alzheimer’s dementia in women who are at risk of developing the disease.
The study, conducted by the University of East Anglia (UAE), found that HRT was linked with better memory, cognition, and larger brain volumes in later life among women carrying the APOE4 gene, which is the strongest risk factor gene for Alzheimer’s disease.
The research team found that HRT was most effective when introduced early on in the menopause journey during perimenopause. However, researchers noted that more research is needed to confirm these findings and to understand the long-term risks and benefits of HRT.
Professor Anne-Marie Minihane, from UEA’s Norwich Medical School and director of the Norwich Institute for Healthy Aging at UEA, led the study in collaboration with Professor Craig Ritchie at the University of Edinburgh, to determine “whether HRT could prevent cognitive decline in at-risk APOE4 carriers”.
“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,” Minihane said.
“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.”
UEA’s researchers have found that HRT 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.
— UEA Research (@UEAResearch) January 14, 2023
The study analyzed data from 1,178 women participating in the European Prevention of Alzheimer’s Dementia initiative to examine the impact of HRT on the brain health of women who carry the APOE4 genotype.
The project was conducted across 10 countries and followed participants from a “healthy” state to a diagnosis of dementia in some cases. Participants were included in the study if they were over 50 and had no dementia at the beginning of the study.
Dr Rasha Saleh, also from UEA’s Norwich Medical School, said the study “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,” Saleh said.
“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.”
Although the findings will comes as promising news for those at risk of developing Alzheimer’s disease, Professor Michael Hornberger, from UEA’s Norwich Medical School, cautioned that “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,” Hornberger added.
The prevalence of Alzheimer’s disease among women and the high rate at which women are impacted has long been studied by researchers. In a recent study scientists discovered that an inflammatory immune protein is much more common in the brains of women with Alzheimer’s, offering a hint as to why women are more susceptible to the condition than men.
As part of the Mechanistic insight into female predominance in Alzheimer’s disease based on aberrant protein S-nitrosylation of C3 study, scientists from Scripps Research and Massachusetts Institute of Technology (MIT) used methods to detect S-nitrosylation, which can modify a protein’s function, to quantify proteins modified in 40 postmortem human brains.
Half of the brains examined were from people who had died of Alzheimer’s, while the other half were from people who hadn’t with each group divided equally between males and females.
In the brains affected by Alzheimer’s, the scientists found 1,449 different proteins that had been modified by S-nitrosylation.
Among the proteins modified the most in this manner, there were several associated with Alzheimer’s, including complement C3, with the levels of S-nitrosylated C3 (SNO-C3) more than six-fold higher in female Alzheimer’s brains compared to male Alzheimer’s brains.
Why are women at greater risk of #Alzheimers? Prof. Stuart Lipton & @MIT discover harmful form of an inflammatory immune protein called complement C3 present at higher levels in brains of women who had died with the disease compared to men https://t.co/hYz3EEwc0D @ScienceAdvances pic.twitter.com/bUdO5chxn2
— Scripps Research (@scrippsresearch) December 14, 2022
Study senior author Stuart Lipton, MD, PhD said the “new findings suggest that chemical modification of a component of the complement system helps drive Alzheimer’s, and may explain, at least in part, why the disease predominantly affects women.”
“Why women are more likely to get Alzheimer’s has long been a mystery, but I think our results represent an important piece of the puzzle that mechanistically explains the increased vulnerability of women as they age,” Lipton said.
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