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Hormone replacement therapy may protect against Alzheimer’s disease among women at risk

Hormone replacement therapy may protect against Alzheimer’s disease among women at risk

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Summary: Hormone replacement therapy (HRT) use is associated with better cognition, memory and larger brain volume in women who carry the Alzheimer’s-linked APOE4 genetic variant.

source: University of East Anglia

Hormone replacement therapy (HRT) may help prevent Alzheimer’s dementia among women at risk of developing the disease – according to research from the University of East Anglia.

The study shows that HRT use is associated with better memory, cognition and larger brain volumes in later life among women who carry the APOE4 gene, the strongest risk factor gene for Alzheimer’s disease.

The research team found that HRT was most effective when introduced at the onset of menopause during perimenopause.

Prof Anne-Marie Minihane, from UEA’s Norwich School of Medicine and Director of the Norwich Institute for Healthy Aging at UEA, led the study in collaboration with Prof Craig Ritchie from the University of Edinburgh.

Prof Minihane said: “We know that 25 per cent of women in the UK carry the APOE4 gene and that almost two-thirds of Alzheimer’s patients are women.

“In addition to longer life, the reason for the higher prevalence in women is thought to be related to the effects of menopause and the influence of the genetic risk factor APOE4, which is greater in women.

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

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

The project spanned 10 countries and followed participants’ brains from “healthy” to a diagnosis of dementia in some. Participants were included if they were over 50 years of age and without dementia.

The research team examined their results to analyze the impact of HRT on women who are carriers of APOE4 genotype.

Dr Rasha Saleh, also from UEA’s Norwich Medical School, said: “We found that HRT use was associated with better memory and larger brain volumes among at-risk carriers of the APOE4 gene. The links 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 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 interventional trial, would equate to a brain age that is several years younger.”

The study shows that HRT use is associated with better memory, cognition and larger brain volumes in later life among women who carry the APOE4 gene, the gene with the strongest risk factor for Alzheimer’s disease. Image is in the public domain

Professor Anne-Marie Minihane said: “Our study looked at associations with cognitive ability and brain volume using MRI scans. We did not look at cases of dementia, but cognitive performance and lower brain volumes predicted future risk of dementia.

Professor Michael Hornberger, from UEA’s Norwich Medical School, said: “It is too early to say for sure 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 stage of this research will be to conduct an intervention trial to confirm the impact of early initiation of HRT on cognitive ability and brain health.” It will also be important to analyze which types of HRT are most beneficial,” he added.

Prof Craig Ritchie, from the University of Edinburgh, said: “This important finding from the EPAD cohort highlights the need to challenge many assumptions about early Alzheimer’s disease and its treatment, particularly when considering women’s brain health.

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Hormone replacement therapy may protect against Alzheimer’s disease among women at risk

“The effect on both cognition and MRI brain changes supports the idea that HRT has a tangible benefit. However, these initial findings need replication in other populations.

For this research news on genetics and Alzheimer’s disease

Author: Press office
source: University of East Anglia
Contact: Press Office – University of East Anglia
Image: Image is in the public domain

Original research: Free access.
Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort.” by Anne Marie Minihane et al. Alzheimer’s research and therapy


Summary

Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort.

Background

The risk of dementia is higher in women than in men. Metabolic consequences of estrogen decline during menopause accelerate neuropathology in women. The use of hormone replacement therapy (HRT) for the prevention of cognitive decline has shown conflicting results. Here we investigate the modulatory role of APOE genotype and age at initiation of HRT on heterogeneity in cognitive response to HRT.

Methods

The analysis used baseline data from participants in the European Group for the Prevention of Alzheimer’s Dementia (EPAD) (total n= 1906, women = 1178, 61.8%). Analysis of covariance models (ANCOVA) were used to test the independent and interactive effects of APOE genotype and HRT in selected cognitive tests, such as MMSE, RBANS, dot counting, Four Mountain Test (FMT) and supermarket trolley test (SMT), along with volumes of medial temporal lobe (MTL) regions by MRI. Multiple linear regression models were used to examine the influence of age of HRT initiation according to APOE4 carrier status on these cognitive and MRI outcomes.

Results

APOE4 HRT users had the highest RBANS delayed memory index (P-APOE*HRT interaction = 0.009) compared to APOE4 non-users and non-APOE4 carriers, with 6–10% larger entorhinal (left) and amygdala (right and left) volumes (P-interaction = 0.002, 0.003, and 0.005, respectively). Earlier introduction of HRT was associated with greater right (standardized b= −0.555, p=0.035) and the left hippocampal volume (standardized b= −0.577, p=0.028) only in APOE4 carriers.

Conclusion

HRT administration was associated with improved delayed memory and larger entorhinal and amygdala volumes in APOE4 carriers only. This may represent an effective targeted strategy to mitigate the higher lifetime risk of AD in this high-risk population subgroup. Confirmation of findings in a fit-for-purpose RCT with prospective recruitment based on APOE genotype is needed to establish causation.


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