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Intellectual Disability and Dementia
Is there a relationship between menopause and dementia?

The Alzheimer's Society notes that women are more at risk of dementia than men with women making up 65% of people who currently have dementia. Some explanation lies in the level of the hormone estrogen. As Alzheimer's disease is more common in women after the menopause, it is possible that estrogen plays a role in protecting the brain from the damage caused by Alzheimer’s, and that this protective effect is lost when estrogen levels are decreased after menopause.


See: Hormones and dementia

See: Menopause and dementia risk

Managing the menopause in women with Down’s syndrome – a review of the literature

View a PowerPoint presentation from Edinburgh Napier University in Scotland by Dr Diane Willis, Isla McGlade, and Christine Bickers.   To access presentation

The Harvard Women Health Watch noted that 'experiencing very early menopause - before age 40 - may more likely lead to later developing dementia than among women who enter menopause around age 50'. This finding emerged from a study reported at the 2022 conference of the American Heart Association (health data were drawn from 153,291 women, age 60+, in the United Kingdom). Data included information on which women later developed any type of dementia — including Alzheimer’s disease and vascular dementia. The researchers calculated how dementia risk related to age at menopause. The findings show that women who entered menopause around age 45 were 30% more likely to be diagnosed with dementia before age 65 compared with those whose periods ceased at 50 (the average age at which menstrual periods stop in American and British women).

Relevant Articles

Age at onset of dementia and age of menopause in women with Down’s syndrome

Menstrual status and the age of menopause were investigated in 143 Irish females with Down syndrome (DS). The average age of menopause in 42 subjects (44.7 years) was younger than in the general population. The age at onset of dementia correlated with the age of menopause. This finding may be a manifestation of accelerated aging in DS or point to estrogen deficiency being an independent risk factor for the development of Alzheimer’s dementia in DS. There are implications of this finding for possible treatments.

Source: M. P. Cosgrave, J. Tyrrell, M. McCarron, M. Gill, B. A. Lawlor. Age at onset of dementia and age of menopause in women with Down’s syndrome. Journal of Intellectual Disability Research, 1999, 43(6), 461-465.

HRT and its effect on normal ageing of the brain and dementia

There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD.

Source: Compton, J., Van Amelsvoort, T., Murphy, D. HRT and its effect on normal ageing of the brain and dementia. British Journal of Clinical Pharmacology, 2001, Dec., 52(6), 647-653.

Menopause and cognitive impairment: A narrative review of current knowledge

A severe impairment of cognitive function characterizes dementia. Mild cognitive impairment represents a transition between normal cognition and dementia. The frequency of cognitive changes is higher in women than in men. Based on this fact, hormonal factors likely contribute to cognitive decline. In this sense, cognitive complaints are more common near menopause, a phase marked by a decrease in hormone levels, especially estrogen. Additionally, a tendency toward worsened cognitive performance has been reported in women during menopause. Vasomotor symptoms (hot flashes, sweating, and dizziness), vaginal dryness, irritability and forgetfulness are common and associated with a progressive decrease in ovarian function and a subsequent reduction in the serum estrogen concentration. Hormone therapy (HT), based on estrogen with or without progestogen, is the treatment of choice to relieve menopausal symptoms. The studies conducted to date have reported conflicting results regarding the effects of HT on cognition. This article reviews the main aspects of menopause and cognition, including the neuroprotective role of estrogen and the relationship between menopausal symptoms and cognitive function. We present and discuss the findings of the central observational and interventional studies on HT and cognition.

Source: Conde DM, Verdade RC, Valadares ALR, Mella LFB, Pedro AO, Costa-Paiva L. Menopause and cognitive impairment: A narrative review of current knowledge. World J Psychiatry. 2021 Aug 19;11(8):412-428. doi: 10.5498/wjp.v11.i8.412.

Onset of dementia is associated with age at menopause in women with Down's syndrome

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.

Source: Schupf N, Pang D, Patel BN, Silverman W, Schubert R, Lai F, Kline JK, Stern Y, Ferin M, Tycko B, Mayeux R. Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann Neurol. 2003 Oct;54(4):433-8. doi: 10.1002/ana.10677.

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