While many women use hormone replacement therapy (HRT) to relieve symptoms of menopause such as hot flashes, headaches or low mood, new research suggests it could also reduce the risk of Alzheimer’s disease (AD) among those women at risk.
The study published in the journal Alzheimer’s Research & Therapy found HRT use was associated with better memory, cognition and greater brain volumes later in life among women carrying the apolipoprotein E (APOE4) gene, the highest risk factor gene commonly associated with Alzheimer’s.
HRT use was associated with better memory, cognition and greater brain volumes later in life among women carrying the … gene commonly associated with Alzheimer’s.
The researchers also found that HRT was more effective when it was introduced during perimenopause, the period when your body starts transitioning to menopause, said Rasha Saleh, lead author of the study, from U.K.-based University of East Anglia.
“This study sends two important messages: Personalized or targeted therapy can mitigate the higher lifetime risk of Alzheimer’s in people who are at high risk,” she said. “The other message is that timing is important. The earlier the intervention, the better the outcome.”
Genetic risk factors for Alzheimer’s in women
The authors noted nearly 25% of women in the United Kingdom are carriers of the APOE4 gene, and more than two-thirds of Alzheimer’s patients are women, according to the 2022 Global Burden of Disease report. However, Saleh said “women are not likely to carry the APOE4 gene compared to men.”
She explained the reason why more women have a higher disease prevalence of AD despite not being likely carriers of the APOE4 gene could be related to the effects of menopause.
“Higher incident cases in women cannot even be explained by greater life expectancy in women,” Saleh said. “The neurophysiological impact of estrogen decline during menopause is emerging as the main etiological basis for the higher prevalence of Alzheimer’s disease in women than men.”
… estrogen decline during menopause is emerging as the main etiological basis for the higher prevalence of Alzheimer’s disease in women than men.
With this information in mind, the researchers wanted to know the impact HRT could have on preventing cognitive decline in at-risk patients who are carriers of the gene.
Saleh and her colleagues looked at data from more than 1,100 women, recruited from 10 different European countries, who were over age 50 and had no previous dementia diagnosis.
They found HRT use (which can come in the form of pills, lotions and creams) was associated with higher delayed memory scores and larger “entorhinal and hippocampal volumes,” which are areas of the brain affected early by Alzheimer’s pathology.
How hormone replacement therapy can prevent Alzheimer’s in at-risk women
According to Saleh, estrogen receptors are localized in different areas of the brain, including in cognition-related areas, but they also play a role in regulating brain inflammation, glucose utilization, lipid metabolism and others.
However, she said when there’s a decline in estrogen during menopause, it “can lead to disturbance in these functions, which can accelerate Alzheimer’s disease-related pathology.”
The link between the use of HRT and better cognition in women who are carriers of the APOE4 gene, she said, can be explained by the impact of blood flow to the brain (cerebral blood flow or CBF).
“Previous studies show that APOE4 carriers have higher CBF than non-carriers,” Saleh explained. “This observation was seen at a younger age, with lower CBF observed in older age.”
Furthermore, Saleh said HRT use in early menopause has also been shown to improve blood vessel function.
“It is possible that an HRT-mediated effect on CBF in APOE4 could in part underpin the impact on brain volume and associated improved memory.”
Despite these reasons, other experts not involved in the study say more research is needed to prove if HRT has a direct impact on preventing AD.
“This is an interesting study that looks at information from a large number of individuals; however, it is collecting information from their medical records/self-report and is observational in nature,” Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, told Seasons. “It is not clear if there is a direct relationship between HRT and cognition from this study.”
Snyder added other studies have suggested conflicting results, including that earlier HRT may not be beneficial.
What comes next for this research and what it means for you
Because this study is observational, Saleh said clinical trials would have to be the next step to confirm their findings. The researchers plan to recruit women according to their APOE genotype and test the effects of HRT versus placebo on various cognitive functions.
Snyder added that because the links among HRT, hormonal changes and the risk for cognitive decline and Alzheimer’s are complex, the scientific community must understand how these factors may intersect with age and other risk factors before any clinical recommendations can be made.
Even though more studies are needed, other experts say studies like this are a good step in the right direction and provide a better understanding of neurodegenerative diseases, like AD and dementia.
“Studies of this kind are important, as they hint at a link between HRT and the changes to the brain,” Richard Oakley, PhD, associate director of research at Alzheimer’s Society, told Seasons. “We need more studies, on a larger scale, to better understand this link. Through continued investment, research will beat dementia.”