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

Sarah Gregory^{1

2

3}, Katie Bridgeman³, Hannah Darwin³, Mariapaola Barbato⁴, Laura Booi^{5

6}, Anna Brugulat Serrat^{7

8

9}, Antonella Santuccione Chadha⁴, Francesca R Farina^{5

10}, Natalie Jenkins¹¹, Otto-Emil I Jutila¹², Audrey Low¹³, Roberta Marongiu^{4

14}, Lorina Naci^{5

15}, Polly Pulford¹⁶, Craig W Ritchie^{2

3}, Karen Ritchie^{17

18}, Chinedu Udeh-Momoh^{9

19

20

21}, Tamlyn Watermeyer^{1

22}, Miles Welstead², Graciela Muniz-Terrera^{1

23}

Affiliations

¹ Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatients Department 2, University of Edinburgh, Western General Hospital, Edinburgh, UK.
² Scottish Brain Sciences, Edinburgh, UK.
³ School of Medicine, University of St. Andrews, St. Andrews, UK.
⁴ Women's Brain Foundation, Basel, Switzerland.
⁵ Global Brain Health Institute, Trinty College Dublin, Dublin, Ireland.
⁶ Centre for Dementia Research, Leeds Beckett University, Leeds, UK.
⁷ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
⁸ Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBER-FES), Instituto de Salud Carlos III, Madrid, Spain.
⁹ Global Brain Health Institute, University of California San Francisco, San Francisco, California, USA.
¹⁰ Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
¹¹ School of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
¹² Department of Psychology, The University of Edinburgh, Edinburgh, UK.
¹³ Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
¹⁴ Department of Neurosurgery, Weill Cornell Medicine, New York, USA.
¹⁵ Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland.
¹⁶ South West London & St George's NHS Trust, Springfield University Hospital, London, UK.
¹⁷ Institut de Neurosciences de Montpelier (INM), Inserm, Montpellier, France.
¹⁸ Institut du Cerveau Trocadéro, Paris, France.
¹⁹ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
²⁰ School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
²¹ Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
²² Ellison Place, Northumbria University, Newcastle upon Tyne, UK.
²³ Ohio University Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.

PMID: 41263327
PMCID: PMC12631545
DOI: 10.1002/alz.70873

Review

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

Sarah Gregory et al. Alzheimers Dement. 2025 Nov.

. 2025 Nov;21(11):e70873.

doi: 10.1002/alz.70873.

Authors

Affiliations

¹ Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatients Department 2, University of Edinburgh, Western General Hospital, Edinburgh, UK.
² Scottish Brain Sciences, Edinburgh, UK.
³ School of Medicine, University of St. Andrews, St. Andrews, UK.
⁴ Women's Brain Foundation, Basel, Switzerland.
⁵ Global Brain Health Institute, Trinty College Dublin, Dublin, Ireland.
⁶ Centre for Dementia Research, Leeds Beckett University, Leeds, UK.
⁷ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
⁸ Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBER-FES), Instituto de Salud Carlos III, Madrid, Spain.
⁹ Global Brain Health Institute, University of California San Francisco, San Francisco, California, USA.
¹⁰ Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
¹¹ School of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
¹² Department of Psychology, The University of Edinburgh, Edinburgh, UK.
¹³ Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
¹⁴ Department of Neurosurgery, Weill Cornell Medicine, New York, USA.
¹⁵ Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland.
¹⁶ South West London & St George's NHS Trust, Springfield University Hospital, London, UK.
¹⁷ Institut de Neurosciences de Montpelier (INM), Inserm, Montpellier, France.
¹⁸ Institut du Cerveau Trocadéro, Paris, France.
¹⁹ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
²⁰ School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
²¹ Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
²² Ellison Place, Northumbria University, Newcastle upon Tyne, UK.
²³ Ohio University Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.

PMID: 41263327
PMCID: PMC12631545
DOI: 10.1002/alz.70873

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.

Keywords: contraception; dementia; estrogen; hormone therapy; menarche; menopause; pregnancy; women's health.

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Conflict of interest statement

Sarah Gregory and Miles Welstead are employees of Scottish Brain Sciences; Mariapaola Barbato is the scientific lead of the Women's Brain Foundation. Antonella Santuccione Chadha is the co‐founder and pro bono CEO of the Women's Brain Foundation, and is also the pro bono Euresearch vice president. Craig W. Ritchie is founder and CEO of Scottish Brain Sciences. All other authors have nothing to declare. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
Overview of reported associations in the synthesized literature between estrogen and 14 modifiable risk factors for dementia (early life: education; midlife: hearing loss, TBI, hypertension, alcohol, obesity, smoking, depression, exercise (physical activity), diabetes, LDL cholesterol; later life: social isolation, air pollution, vision loss. HRT, hormone replacement therapy; LDL, low‐density lipoprotein; TBI, traumatic brain injury.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Medical