ArticleAlzheimer's research & therapy2023
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.
Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.
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Who cites it
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- Male- and female-specific reproductive risk factors across the lifespan for dementia or cognitive decline: a systematic review and meta-analysis.BMC medicine · 2023Pooled it
- Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.Frontiers in aging neuroscience · 2023Pooled it
- Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.Neurology · 2026Article
- Associations between serum estradiol and estrone and Alzheimer's disease biomarkers: An analysis in female participants from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS).Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Targeting hormone treatment for the brain in menopause.Scientific reports · 2026Article
- A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.Nature genetics · 2026Article
- Estrogen Withdrawal-Induced Cognitive Impairment in Menopausal Women: Mechanisms and Prospects for Integrated Interventions.International journal of molecular sciences · 2026Review
- Menopausal insomnia as a modifiable node of dementia risk: Mechanistic insights and intervention strategies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Hormone replacement therapy and dementia risk among postmenopausal women: Identifying responsive subgroups in the UK Biobank.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Hormone replacement therapy and its association with LATE-NC in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Steroid hormones in Alzheimer's disease: a molecular analysis of blood and cerebrospinal fluid.Alzheimer's research & therapy · 2026Article
- Evidence of APOE4-related brain vulnerabilities in verbal memory systems in midlife women.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE4 negates the effects of ovarian hormones on cerebrovascular endothelial and mitochondrial function.The Journal of physiology · 2026Article
- Hormone Therapy is Associated with Better Cognitive Performance in Postmenopausal Women: Insights from the National Health and Nutrition Examination Survey (NHANES).Annals of geriatric medicine and research · 2026Article
- Estren prevents beta-amyloid-induced basal forebrain cholinergic loss and long-term spatial memory deficits in aged female mice.Scientific reports · 2026Article
- Associations of oral contraceptives and hormone replacement therapy with incident dementia risk: a population-based cohort study.Translational psychiatry · 2026Article
- Incidence of venous thromboembolism in women receiving transdermal oestradiol/testosterone with micronised progesterone in accordance with NICE guidelines.Translational andrology and urology · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Reproductive lifespan and hormonal therapy in relation to later-life neurovascular health: A population-based study of women in the Gothenburg H70-1944 Birth Cohort.medRxiv : the preprint server for health sciences · 2026Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe risk of dementia is higher in women than men. The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women. The use of hormone replacement therapy (HRT) in the prevention of cognitive decline has shown conflicting results. Here we investigate the modulating role of APOE genotype and age at HRT initiation on the heterogeneity in cognitive response to HRT.
methodsThe analysis used baseline data from participants in the European Prevention of Alzheimer's Dementia (EPAD) cohort (total n= 1906, women= 1178, 61.8%). Analysis of covariate (ANCOVA) models were employed to test the independent and interactive impact of APOE genotype and HRT on select cognitive tests, such as MMSE, RBANS, dot counting, Four Mountain Test (FMT), and the supermarket trolley test (SMT), together with volumes of the 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 outcomes.
resultsAPOE4 HRT users had the highest RBANS delayed memory index score (P-APOE*HRT interaction = 0.009) compared to APOE4 non-users and to 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 larger right (standardized β= -0.555, p=0.035) and left hippocampal volumes (standardized β= -0.577, p=0.028) only in APOE4 carriers.
conclusionHRT introduction is 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 life-time risk of AD in this large at-risk population subgroup. Confirmation of findings in a fit for purpose RCT with prospective recruitment based on APOE genotype is needed to establish causality.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.