summary: Use of hormone replacement therapy (HRT) has been associated with improved cognition, memory and larger brain volume in women who carry the APOE4 genetic variant associated with Alzheimer’s disease.
Source: University of East Anglia
Hormone replacement therapy (HRT) can help prevent Alzheimer’s dementia among women at risk of developing the disease – according to University of East Anglia research.
The study showed that use of HRT is associated with better memory, cognition and larger brain volume later in 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 given early in the menopause journey during menopause.
Professor Anne-Marie Minihan, of the Norwich Medical School at UEA and Director of the Norwich Institute of Healthy Aging at UEA, led the study in collaboration with Professor Craig Ritchie at the University of Edinburgh.
Professor Minihan said: “We know that 25 per cent of women in the UK carry the APOE4 gene and that nearly two-thirds of Alzheimer’s patients are women.
In addition to living longer, the reason for the higher female prevalence 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 whether HRT could prevent cognitive decline in APOE4 carriers at risk.”
The research team studied data from 1,178 women who took part in the European Initiative for the Prevention of Alzheimer’s Disease Dementia – 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 free of dementia.
The research team studied their findings to analyze the effect of HRT on women who become pregnant APOE4 Genotype.
Dr Rasha Saleh, from UEA’s Norwich Medical School, said: “We found that use of HRT is associated with better memory and greater brain volume among APOE4-risk gene carriers. The associations were particularly clear when HRT was introduced early – during transition.” to menopause, known as amenorrhea.
“This is really important because there have been very limited drug options for Alzheimer’s disease for 20 years and new treatments are desperately needed.
“The effects of HRT in this observational study, if confirmed in an intervention trial, would equate to a brain lifespan several years younger.”
Professor Anne-Marie Minihan said: “We looked at associations with cognition and brain volumes using MRI scans. We didn’t look at cases of dementia, but cognitive performance and reduced 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 findings highlight the potential importance of HRT and personalized medicine in reducing the risk of dementia.” Alzheimer’s disease.
The next phase of this research will be an intervention trial to confirm the effect of starting HRT early on cognition and brain health. It will also be important to analyze which types of HRT are most beneficial.”
Professor Craig Ritchie, from the University of Edinburgh, said: “This important finding from the EPAD group highlights the need to challenge many assumptions about early-onset Alzheimer’s disease and its treatment, particularly when looking at women’s brain health.
“The effect on cognitive and brain changes on MRI supports the idea that HRT has a measurable benefit. However, these initial findings need to be replicated in other populations.”
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“Hormone replacement therapy is associated with improved cognition and larger brain volume in women at risk of APOE4: results from the European Alzheimer’s Disease (EPAD) Prevention Group.Written by Anne Marie Minihan et al. Alzheimer’s disease research and treatment
Hormone replacement therapy is associated with improved cognition and larger brain volume in women at risk of APOE4: results from the European Alzheimer’s Disease (EPAD) Prevention Group.
The risk of dementia is higher in women than in men. The metabolic consequences of decreased estrogen during menopause accelerate neurodegenerative diseases in women. The use of hormone replacement therapy (HRT) in preventing cognitive decline has shown conflicting results. Here we investigate the role of the modification of APOE Genotype and age at initiation of HRT depend on heterogeneity in cognitive response to HRT.
The analysis used primary data from participants in the European Group for Alzheimer’s Dementia Prevention (EPAD) (overall n= 1906, women = 1178, 61.8%). An analysis of covariate models (ANCOVA) was used to test the independent and interactive effect of APOE Genotype and HRT on selected cognitive tests, such as the MMSE, the RBANS, point counting, the Four Mountains test (FMT), and the supermarket trolley test (SMT), along with volumes of medial temporal lobe (MTL) regions by magnetic resonance imaging. Multiple linear regression models were used to examine the effect of age at initiation of HRT according to APOE4 Carrier status on these cognitive and magnetic resonance imaging findings.
APOE4 HRT users scored highest on the RBANS index of delayed memory (P-APOE*HRT reaction = 0.009) compared to APOE4 non-users and othersAPOE4 Vectors, with a 6–10% larger internal volume (left) and an amygdala (right and left) (s– interaction = 0.002, 0.003, and 0.005, respectively). Early presentation of HRT was associated with greater right (Consolidated B= 0.555, s= 0.035) and left hippocampal volumes (standardized B= −0.577, s= 0.028) only at APOE4 vectors.
Introduction of HRT is associated with improvement of delayed memory and increase in amygdala and interneuron volumes APOE4 carriers only. This may represent an effective targeted strategy to mitigate the elevated lifetime risk of Alzheimer’s disease in this large subgroup of the population at risk. Confirm results in a fit-for-purpose randomized controlled trial with prospective recruitment on a basis APOE Genotype is needed to determine causation.