Summary: The use of hormone replacement therapy (HRT) was associated with better cognition, better memory and larger brain volume in women carrying the APOE4 genetic variant associated with Alzheimer’s disease.
Source: University of East Anglia
Hormone replacement therapy (HTS) could help prevent Alzheimer’s dementia in women at risk of developing the disease, according to a study from the University of East Anglia.
The study shows that HRT use is associated with better memory, better cognition and larger brain volumes later in life in women carrying the APOE4 gene, the strongest risk factor gene for Alzheimer’s disease.
The research team found that HRT was most effective when introduced early in the menopausal journey during perimenopause.
Professor Anne-Marie Minihane, from UEA’s Norwich Medical School and director of UEA’s Norwich Institute for Healthy Aging, led the study together with Professor Craig Ritchie from the University of Edinburgh.
Professor Minihane said: “We know that 25% of women in the UK carry the APOE4 gene and that almost two thirds of Alzheimer’s patients are female.
“In addition to living longer, the reason for the higher female prevalence is thought to be related to the effects of menopause and the impact of the genetic risk factor APOE4 being greater in women.
“We wanted to know if HRT could prevent cognitive decline in at-risk APOE4 carriers.”
The research team studied data from 1,178 women participating in the European Alzheimer’s Dementia Prevention Initiative, which was set up to study participants’ brain health over time.
The project spanned 10 countries and tracked participants’ brains from “healthy” to diagnosed with dementia in some. Participants were included if they were over 50 and did not have dementia.
The research team studied their results to analyze 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 in carriers of the at-risk APOE4 gene. . 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 few 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 intervention trial, would equate to years of younger brain age.”
Professor Anne Marie Minihane said: ‘Our research examined associations with cognition and brain volumes using MRI scans. We did not examine cases of dementia, but lower cognitive performance and brain volumes are predictive of future dementia risk.
Professor Michael Hornberger, from UEA’s Norwich Medical School, said: “It is too early to say with certainty 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 disease.
“The next step in this research will be to perform an intervention trial to confirm the impact of early initiation of HRT on cognition and brain health. It will also be important to analyze which types of HRT are most beneficial” , he added.
Professor Craig Ritchie, 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 the women’s brain health is considered.
“An effect on cognition and brain changes on MRI support the notion that HRT has a tangible benefit. These initial findings, however, need to be replicated in other populations.
About this genetics and Alzheimer’s disease research news
Author: Press office
Source: University of East Anglia
Contact: Press Office – University of East Anglia
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Original research: Free access.
“Hormone replacement therapy is associated with improved cognition and larger brain volumes in APOE4 women at risk: results from the European cohort for the prevention of Alzheimer’s disease (EPAD)” by Anne Marie Minihane and para. Alzheimer’s disease research and therapy
Hormone replacement therapy is associated with better cognition and larger brain volumes in APOE4 women at risk: results from the European Cohort for the Prevention of Alzheimer’s Disease (EPAD)
The risk of dementia is higher in women than in men. The metabolic consequences of declining estrogen during menopause accelerate neuropathology in women. The use of hormone replacement therapy (HRT) in the prevention of cognitive decline has yielded conflicting results. We study here the modulating role of APOE genotype and age at onset of HRT on heterogeneity of cognitive response to HRT.
The analysis used baseline data from participants in the European Cohort for the Prevention of Alzheimer’s Dementia (EPAD) (total not= 1906, women = 1178, 61.8%). Covariate analysis models (ANCOVA) were used to test the independent and interactive impact of APOE genotype and THS on certain cognitive tests, such as MMSE, RBANS, point count, Four Mountain test (FMT), and shopping cart test (SMT), as well as volumes of medial temporal lobe (MTL) regions by MRI . Multiple linear regression models were used to examine the impact of age of HRT initiation according to APOE4 carrier status on these cognitive and MRI results.
APOE4 HRT users had the highest RBANS Delayed Memory Index score (P-APOE*THS interaction = 0.009) compared to APOE4 non-users and to non-APOE4 carriers, with entorhinal (left) and tonsil (right and left) volumes 6 to 10% larger (P-interaction = 0.002, 0.003 and 0.005 respectively). Earlier introduction of HRT was associated with greater right (normalized β= −0.555, p=0.035) and the volumes of the left hippocampus (normalized β= −0.577, p=0.028) only in APOE4 carriers.
The introduction of HRT is associated with delayed memory improvement and larger entorhinal and tonsillar volumes in APOE4 carriers only. This may represent an effective targeted strategy to mitigate the higher lifetime risk of Alzheimer’s disease in this large at-risk population subgroup. Confirmation of results from a fit-for-purpose RCT with prospective recruitment based on APOE The genotype is necessary to establish causation.
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