Associations of estrogen with modifiable and non-modifiable risk factors for dementia: A narrative review.

Sarah Gregory, Katie Bridgeman, Hannah Darwin, Mariapaola Barbato, Laura Booi, Anna Brugulat Serrat, Antonella Santuccione Chadha, Francesca R Farina, Natalie Jenkins, Otto-Emil I Jutila, Audrey Low, Roberta Marongiu, Lorina Naci, Polly Pulford, Craig W Ritchie, Karen Ritchie, Chinedu Udeh-Momoh, Tamlyn Watermeyer, Miles Welstead, Graciela Muniz-Terrera

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association 2025;21(11):e70873

PMID: 41263327

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Abstract

Female sex is associated with higher incidence and risk of dementia. Estrogen may represent one important mechanism contributing to the increase in incidence rates. In this review, we synthesize narratively the evidence for associations between estrogen-across the life course from menarche to menopause, estrogen-containing hormonal contraception and hormone replacement therapies, and pregnancy-with potential modifiable risk factors for dementia. These include education, hearing loss, traumatic brain injury, hypertension, alcohol use, obesity, smoking, depression, physical inactivity, diabetes, low-density lipoprotein (LDL) cholesterol, social isolation, air pollution, and untreated visual loss, as well as apolipoprotein E ε4. In addition, evidence is summarized for associations with sleep, diet, and stress. Evidence suggests that estrogen is associated with some of these modifiable risk factors for dementia, particularly LDL cholesterol, smoking, and depression. Research needs to further define these associations and understand whether interventions targeting estrogen levels at key life stages could offer intervention opportunities to reduce future risk of dementia in women. HIGHLIGHTS: Higher dementia risk in women may be associated with estrogen. Estrogen is associated with some of the modifiable risk factors for dementia. However, significant gaps exist in the literature for most risk factors.

Address: Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatients Department 2, University of Edinburgh, Western General Hospital, Edinburgh, UK.; Scottish Brain Sciences, Edinburgh, UK.; School of Medicine, University of St. Andrews, St. Andrews, UK.; School of Medicine, University of St. Andrews, St. Andrews, UK.; Women's Brain Foundation, Basel, Switzerland.; Global Brain Health Institute, Trinty College Dublin, Dublin, Ireland.; Centre for Dementia Research, Leeds Beckett University, Leeds, UK.; Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBER-FES), Instituto de Salud Carlos III, Madrid, Spain.; Global Brain Health Institute, University of California San Francisco, San Francisco, California, USA.; Global Brain Health Institute, Trinty College Dublin, Dublin, Ireland.; Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.; School of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.; Department of Psychology, The University of Edinburgh, Edinburgh, UK.; Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK.; Women's Brain Foundation, Basel, Switzerland.; Department of Neurosurgery, Weill Cornell Medicine, New York, USA.; Global Brain Health Institute, Trinty College Dublin, Dublin, Ireland.; Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland.; South West London & St George's NHS Trust, Springfield University Hospital, London, UK.; Scottish Brain Sciences, Edinburgh, UK.; School of Medicine, University of St. Andrews, St. Andrews, UK.; Institut de Neurosciences de Montpelier (INM), Inserm, Montpellier, France.; Institut du Cerveau Trocadéro, Paris, France.; Global Brain Health Institute, University of California San Francisco, San Francisco, California, USA.; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.; School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.; Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatients Department 2, University of Edinburgh, Western General Hospital, Edinburgh, UK.; Ellison Place, Northumbria University, Newcastle upon Tyne, UK.; Scottish Brain Sciences, Edinburgh, UK.; Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatients Department 2, University of Edinburgh, Western General Hospital, Edinburgh, UK.; Ohio University Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.

DOI: 10.1002/alz.70873

MeSH Terms: Humans, Dementia, Risk Factors, Estrogens, Female, Estrogen Replacement Therapy