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Alzheimer’s Dementia: Peri-menopausal Estrogen Is a Preventative Strategy for Women

Date: January 14,2021 |Hits: 135 Download PDF How to cite this paper

Joseph Loze Onwude

The Croft, Warley Road, Great Warley, Brentwood CM13 3HT, UK.

*Corresponding author: Joseph Loze Onwude


Alzheimer’s dementia (AD) predominantly affects women, and it has no cure when it becomes established. As the current biggest killer of women in the United Kingdom, it became incumbent to explore all preventive strategies. Based on the knowledge that Alzheimer’s dementia is homed in the hippo-campus and that this area is suffused with estrogen receptors, we explored whether there was a link that might suggest therapeutic or preventive strategies. We found that there was evidence that the hippocampus, the primary area of the brain that we used for declarative memory became deplete with estrogen receptors in the menopause. We also found other pointers which included that hippocampal pathology is central to the development of AD and that the hippocampal shape and volume can predict the onset of AD. There were further of in-vitro and in-vivo support that peri-menopausal estrogens could reduce the incidence of AD in women by up to 35%.


[1] Office of National Statistics. (2016). https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsregisteredinenglandandwalesseriesdr/20152.

[2] Mahoney, R., Regan, C., Katona, C., and Livingston, G. (2005). Anxiety and depression in family caregivers of people with Alzheimer disease: the LASER-AD study. Am J Geriatr Psychiatry, 13:795-801.

[3] Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, G. C., Huntley, J., Ames, D., et al. (2017). Dementia prevention, inter-vention, and care. www.thelancet.com. Published online July 20, 2017.

[4] Erickson, K. I., Prakash, R. S., Voss, M. W., Chaddock, L., Hu, L., Morris, K. S., et al. (2009). Aerobic Fitness is Associated with Hippocampal Volume in Elderly Humans. Hippocampus, 19(10): 1030-1039. 

[5] Mehra, R. D., Sharma, K., Nyakas, C., Vij, U. (2005). Estrogen receptor α and β immunoreactive neurons in normal adult and aged female rat hippocampus: a qualitative and quantitative study. Brain Res., 1056: 22-35.

[6] Wnuk, A., Korol, D. L., Erickson, K. I. (2012). Estrogens, hormone therapy, and hippocampal volume in postmenopausal women. Maturitas, 73: 186-190.

[7] Braak, H., Braak, E. (1990). Neuropathological staging of Alzheimer-related changes. Acta Neuropathol., 182: 239-259.

[8] Csernansky, J. G., Wang, L., Swank, J. J. G., Miller, J. P., Gado, M., McKeel, D., et al. (2005). Preclinical detection of Alz-heimer’s disease: hippocampal shape and volume predict dementia onset in the elderly. Neuroimage, 25: 783-792.

[9] Hackert, V. H., den Heijer, T., Oudkerk, M., Koudstaal, M., Hofman, A., Breteler, M. M. B. (2002). Hippocampal head size associated with verbal memory performance in nondemented elderly. Neuroimage, 17: 1365-1372.

[10] O’Driscoll, G. A., Florencio, P. S., Gagnon, D., Wolff, D., Anne-Lise, V., Benkelfat, C. M., et al. (2001). Amyg-dala-hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients. Psychiatry Res., 107: 75-85.

[11] Pike, C. J., Carroll, J. C., Rosario, E. R., Barron, A. (2009). Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinology, 30(2): 239-258.

[12] Bean, L. A., Lanov, L., Foster, T. C. M. (2014). Estrogen Receptors, the Hippocampus, and Memory. Neuroscientist, 20(5): 534-545. 

[13] Eberling, J. L., Wu, C., Haan, M. N., Mungas, D., Buonocore, M., Jagust, W. J. (2003). Preliminary evidence that estrogen protects against age-related hippocampal atrophy. Neurobiol Aging, 24(5): 725-32.

[14] Epperson, C. N., Sammel, M. D., Freeman, E. W. (2013). Menopause Effects on Verbal Memory: Findings From a Longitudinal Community Cohort. J Clinical Endocrinol Metab., 98(9): 3829-3838.

[15] Braak, H., Braak, E. (1990). Alzheimer’s disease: striatal amyloid deposits and neurofibrillary changes. J Neuropathol Exp Neurol., 49: 215-224.

[16] Goodman, Y., Bruce, A. J., Cheng, B., Mattson, M. B. (1996). Estrogens Attenuate and Corticosterone Exacerbates Excitotox-icity, Oxidative Injury, and Amyloid β-Peptide Toxicity in Hippocampal Neurons. J of Neurochemistry, 66: 1836-1844.

[17] Gouldm E,, Woolley, S. W., Frankfurt, M., McEwen, B. S. (1990). Gonadal Steroids Regulate Dendritic Spine Density in Hip-pocampal Pyramidal Cells in Adulthood. J of Neuroscience, 10(4): 1286-91. 

[18] Packard, M. G., Teather, L. A. (1997). Intra-hippocampal estradiol infusion enhances memory in ovariectomized rats. Neuroreport, 29: 8(14): 3009-13.

[19] Barouk, S., Hintz, T., Ping, L., MacLusky, N. J., Scharfman, H. E. (2011). 17β-Estradiol Increases Astrocytic Vascular Endo-thelial Growth Factor (VEGF) in Adult Female Rat Hippocampus. Endocrinology, 152(5): 1745-1751. 

[20] Frankish, H., Horton, R. (2017). Prevention and management of dementia: a priority for public health. The Lancet, July 20, 2017. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31756-7/fulltext.

[21] Shao, H., Breitner, J. C. S., Whitmer, R. A.,Wang, J., Hayden, K., Wengreen, H., et al. (2012). For the Cache County Investi-gators. Hormone therapy and Alzheimer disease dementia. New findings from the Cache County Study. Neurology, 79(18): 1846-1852.

[22] Kawas, S., Resnick, A., Morrison, R., Brookmeyer, M., Corrada, A., Zonderman, C., et al. (1997). A prospective study of es-trogen replacement therapy and the risk of developing Alzheimer’s disease. The Baltimore Longitudinal Study of Aging, https://doi.org/10.1212/WNL.48.6.1517.

[23] Whitmer, R. A., Quesenberry, Jr C. P., Zhou, J., Yaffe, K. (2011). Timing of hormone therapy and dementia: the critical window theory revisited. Annals Neurology, 69(1): 163-169.

[24] Craig, C. M., Maki, P. M., Murphy, D. G. M. (2005). The Women’s Health Initiative Memory Study: findings and implications for treatment. Lancet Neurol., 4: 190-194.

[25] Wang, P. N., Liao, S. Q., Liu, R. S., Liu, C. Y., Chao, H. T., Lu, S. R., et al. (2000). Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology, 54(11): 2061-6. 

[26] Mulnard, R. A., Cotman, C. W., Kawas, C., van Dyck, C. H., Sano, M., Doody, R., et al. (2000). Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer’s Disease Cooperative Study. JAMA, 283(8): 1007-15. 

[27] Henderson, V. W., Paganini-Hill, A., Miller, B. L., Elble, P. F., Reyes, D., Shoupe, C. A., et al. (2000). Estrogen for Alzheimer’s disease in women: randomized, double-blind, placebo-controlled trial. Neurology, 54(2): 295-301. 

[28] Pintzka, C. W. S. and Håberg, A. K. (015). Perimenopausal hormone therapy is associated with regional sparing of the CA1 subfield: a HUNT MRI study. Neurobiology of Aging, 36: 2555-2562.

[29] Hill, A. B. (1965). The environment and disease: association or causation? Proc Royal Soc Med., 58: 295-300.

[30] Maki, P. M. (2013). The Critical Window Hypothesis of Hormone Therapy and Cognition: A Scientific Update on Clinical Studies. Menopause, 20(6): 695-709. 

[31] Henderson, V. W., Benke, K. S., Green, R. C., Cupples, L. A., Farrer, L. A. (2005). Postmenopausal hormone therapy and Alzheimer’s disease risk: interaction with age. J Neurol Neurosurg Psychiatry, 76(1): 103-5.

[32] Lord, C., Buss, C., Lupien, S. J., Pruessner, J. C. (2008). Hippocampal volumes are larger in postmenopausal women using estrogen therapy compared to past users, never users and men: A possible window of opportunity effect. Neurobiology of Aging, 29(1): 95-101.

[33] Majumdar, S. R., Almasi, E. A., Stafford, R. S. (2004). Promotion and prescribing of hormone therapy after report of harm by the Women’s Health Initiative. JAMA, 292(16): 1983-1988.

[34] Anderson, G. L., Chlebowski, R. T., Aragaki, A. K., Kuller, L. H., Manson, J. E., Margery, G., et al. (2012). Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. The Lancet, 13: 476-86.

[35] Zhang, S. M., Manson, J. E., Rexrode, K. M., Cook, N. R., Buring, J. E., Lee, I. M. (2007). Use of oral conjugated estrogen alone and risk of breast cancer. Am J Epidemiol., 165(5): 524-9.

[36] Tabori, N. E., Stewart, L. S., Znamensky, V., Romeo, R. D., Alves, R. E., McEwen, B. S., et al. (2005). Ultrastructural evidence that androgen receptors are located at extranuclear sites in the rat hippocampal formation. Neuroscience, 130: 151-163.

[37] Pike, C. J. (2001). Testosterone attenuates b-amyloid toxicity in cultured hippocampal neurons. Brain Research, 919: 160-165.

[38] Lv, W., Du, N., Liu, Y., Fan, X., Wang, Y., Jia, X., et al. (2016). Low Testosterone Level and Risk of Alzheimer’s Disease in the Elderly Men: A Systematic Review and Meta-Analysis. Mol Neurobiol., 53(4): 2679-84.

[39] Public Health England. (2018). Prevention must be the heart of the NHS long-term plan. September 6. https://www.gov.uk/government/news/prevention-must-be-the-heart-of-the-nhs-long-term-plan.

How to cite this paper

Alzheimer’s Dementia: Peri-menopausal Estrogen Is a Preventative Strategy for Women

How to cite this paper: Joseph Loze Onwude. (2021) Alzheimer’s Dementia: Peri-menopausal Estrogen Is a Preventative Strategy for Women. International Journal of Clinical and Experimental Medicine Research5(1), 25-32.

DOI: http://dx.doi.org/10.26855/ijcemr.2021.01.006

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