Hormone replacement therapy (HRT) introduced aboriginal during the menopausal modulation whitethorn support against Alzheimer's dementia successful women carrying the APOE4 gene, caller probe suggests.
Results from a cohort survey of astir 1200 women showed that usage of HRT was associated with higher delayed representation scores and larger entorhinal and hippocampal encephalon volumes ― areas that are affected aboriginal by Alzheimer's disease (AD) pathology.
HRT was besides recovered to beryllium astir effective, arsenic seen by larger hippocampal volume, erstwhile introduced during aboriginal perimenopause.
"Clinicians are precise overmuch alert of the susceptibility of women to cognitive disturbances during menopause," pb writer Rasha Saleh, MD, elder probe associate, Norwich Medical School, University of East Anglia, United Kingdom, told Medscape Medical News.
"Identifying the at-risk APOE4 women and aboriginal HRT instauration tin beryllium of benefit. Confirming our findings successful a objective proceedings would beryllium the adjacent measurement forward," Saleh said.
The findings were published online January 9 successful Alzheimer's Research and Therapy.
Personalized Approaches
Saleh noted that estrogen receptors are localized successful assorted areas of the brain, including cognition-related areas. Estrogen regulates specified things arsenic neuroinflammatory status, glucose utilization, and lipid metabolism.
"The diminution of estrogen during menopause tin pb to disturbance successful these functions, which tin accelerate AD-related pathology," she said.
HRT during the menopausal modulation and afterward is "being considered arsenic a strategy to mitigate cognitive decline," the investigators write. Early observational studies person suggested that oral estrogen "may beryllium protective against dementia," but results of objective trials person been inconsistent, and immoderate person adjacent shown "harmful effects," they add.
The existent researchers were "interested successful the personalized approaches successful the prevention of AD," Saleh said. Preclinical and aviator information from her radical person shown that women with APOE4 have "better cognitive trial scores with nutritional and hormonal interventions."
This led Saleh to hypothesize that HRT would beryllium of much cognitive payment for those with vs without APOE4, peculiarly erstwhile introduced aboriginal during the menopausal transition.
To analyse this hypothesis, the researchers analyzed baseline information from participants successful the European Prevention of Alzheimer's Dementia (EPAD) cohort. This task was initiated successful 2015 with the purpose of processing longitudinal models implicit the full people of AD anterior to dementia objective diagnosis.
Participants were recruited from 10 European countries. All were required to beryllium astatine slightest 50 years old, to person not been diagnosed with dementia astatine baseline, and to person nary aesculapian oregon psychiatric unwellness that could perchance exclude them from further research.
The existent survey included 1178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT attraction for existent oregon erstwhile users included estrogen unsocial oregon estrogen positive progestogens via oral oregon transdermal medication routes, and astatine antithetic doses.
The 4 tests utilized to measure cognition were the Mini-Mental State Examination dot counting to measure verbal moving memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) full score, the Four Mountain Test, and the supermarket trolley virtual world test.
Brain MRI information were collected. The researchers focused connected the medial temporal lobe arsenic the "main encephalon portion regulating cognition and representation processing." This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
"Critical Window"
The researchers recovered a "trend" toward an APOE-HRT enactment (P-interaction = .097) for the full RBANS score. In particular, it was important for the RBANS delayed representation index, wherever scores were consistently higher for women with APOE4 who had received HRT compared with each different groups (P-interaction = .009).
Within-genotype radical comparisons showed that HRT users had a higher RBANS full standard people and delayed representation scale (P = .045 and P = .002, respectively), but lone among APOE4 carriers. Effect size analyses showed a ample effect of HRT usage connected the Four Mountain Test score and the supermarket trolley virtual world trial people (Cohen's d =.988 and 1.2, respectively).
"This ample effect was recovered lone successful APOE4 carriers," the investigators note.
Similarly, a mean to ample effect of HRT connected the near entorhinal measurement was observed successful APOE4 carriers (Cohen's d = .63).
In members of the APOE4 radical who received HRT, the near entorhinal and near and close amygdala volumes were larger compared with some no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the close entorhinal measurement (P = .074).
In addition, among HRT users, the near entorhinal measurement was larger (P = .03); the close and near anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the near superior frontal gyrus measurement was larger (P = .009) successful examination with women who did not person HRT, independently of their APOE genotype.
Early usage of HRT among APOE4 carriers was associated with larger close and near hippocampal measurement (P = .035 and P = .028, respectively) ― an relation not recovered successful non-APOE4 carriers. The relation was besides not important erstwhile participants were not stratified by APOE genotype.
"The cardinal important constituent present is the timing, oregon the 'critical window,' erstwhile HRT tin beryllium of astir benefit," Saleh said. "This is astir beneficial erstwhile introduced early, earlier the neuropathology becomes irreversible."
Study limitations see its cross-sectional design, which precludes the constitution of a causal relationship, and the information that accusation regarding the benignant and dose of estrogen was not disposable for each participants.
HRT is not without risk, Saleh noted. She recommended that clinicians "carry retired assorted screening tests to marque definite that a pistillate is eligible for HRT and not astatine hazard of hypercoagulability, for instance."
Risk-Benefit Ratio
Commenting for Medscape Medical News, Howard Fillit, MD, cofounder and main subject serviceman astatine the Alzheimer's Drug Discovery Foundation, called the survey "exactly the benignant of enactment that needs to beryllium done."
Fillit, who was not progressive with the existent research, is simply a objective prof of geriatric medicine, palliative attraction medicine, and neuroscience astatine Mount Sinai Hospital, New York City.
He compared the process to that of osteoporosis. "We cognize that if women are treated [with HRT] astatine the clip of the menopause, you tin forestall the accelerated bony nonaccomplishment that occurs with accelerated estrogen loss. But if you hold 5, 10 years out, erstwhile the bony nonaccomplishment has occurred, the HRT doesn't truly person immoderate interaction connected osteoporosis hazard due to the fact that the equine is already retired of the barn," helium said.
Although HRT carries risks, "they tin intelligibly beryllium managed; and if it's proven that estrogen oregon hormone replacement astir the clip of the menopause tin beryllium protective [against AD], the risk-benefit ratio of HRT could beryllium successful favour of treatment," Fillit added.
The survey was conducted arsenic portion of the Medical Research Council (MRC, UK) NuBrain Consortium. The investigators and Fillit person reported nary applicable fiscal relationships.
Alzheimers Res Ther. Published online January 9, 2023. Full article
Batya Swift Yasgur MA, LSW is simply a freelance writer with a counseling signifier successful Teaneck, NJ. She is simply a regular contributor to galore aesculapian publications, including Medscape and WebMD, and is the writer of respective consumer-oriented wellness books arsenic good as Behind the Burqa: Our Lives successful Afghanistan and How We Escaped to Freedom (the memoir of 2 brave Afghan sisters who told her their story).
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