New research has found hormone replacement therapy (HRT) can be linked with better brain health and cognition among women with a high genetic risk of developing Alzheimer's disease. The findings are observational, and cannot determine causality, but they do build on a body of study trying to understand why women are generally more likely to develop Alzheimer's compared to men.
“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," explained Anne-Marie Minihane, lead researcher on the new study. “We wanted to find out whether HRT could prevent cognitive decline in at-risk APOE4 carriers.”
Around one in four women carry the APOE4 gene, which can significantly raise a person's risk of developing Alzheimer's disease. This new study looked at data from an ongoing brain health study, allowing researchers unique insights into the effects of HRT on women with the APOE4 genotype.
The findings revealed HRT was associated with larger entorhinal and amygdala volumes and better responses to memory tests. Rasha Saleh, another researcher working on the study, said the benefits of HRT were most evident in women with the APOE4 genotype who started hormone therapy at a young age.
“We found that HRT use is associated with better memory and larger brain volumes among at-risk APOE4 gene carriers," said Saleh. "The associations were particularly evident when HRT was introduced early – during the transition to menopause, known as perimenopause."
This particular finding backs up an increasingly prominent idea known as the "critical window hypothesis." Prior studies looking into the effects of HRT on later-life cognition have delivered mixed results and some researchers have suggested the timing of the treatment could be key to its neuroprotective effects.
One 2011 study, for example, pulled data from a number of health care databases to compare the cognitive effects of HRT between women who started the therapy in their late 40s and women who started it in their 70s. That research found HRT only reduced dementia risk when started early.
Sara Imarisio, from Alzheimer's Research UK, said there were limitations to these new findings. According to Imarisio, because this research didn't actually focus on the clinical development of dementia there needs to be further study to understand whether HRT actually prevents cognitive decline over longer periods of time.
"The next step is to investigate this in more detail," said Imarisio. "Importantly, this study didn't measure whether women went on to develop dementia. So, its findings need to be confirmed, first in trials that directly test whether giving HRT affects women's cognitive abilities and changes in their brain, particularly carriers of the APOE4 gene."
Michael Hornberger, co-author on the new study, agrees with Imarisio. He said the next phase for the research will be to investigate which populations could benefit most from HRT and what kinds of HRT could be most effective at preventing dementia.
“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 personalized medicine in reducing Alzheimer’s risk," said Hornberger. “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."
The new study was published in Alzheimer's Research & Therapy.
Source: University of East Anglia
