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Early menopause may raise dementia risk later – UK study of 150,000 women

Compared with women who enter menopause at about 50, women who experience very early menopause (before 40) were found to be 35% more likely to develop some type of dementia later in life, according to a large study of women living in the United Kingdom.

The research also showed that women entering menopause before 45 were also 1.3 times more likely to develop dementia before 65. In addition, women who entered menopause later, at age 52 or older, had dementia risk similar to women who entered menopause at the average age for menopause onset, which is 50 to 51 years old.

Dr Wenting Hao, a PhD candidate at Shandong University in Jinan, China, said: “Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age.”

Dementia involves serious changes in the brain that impair a person’s ability to remember, make decisions and use language. Alzheimer’s disease is the most common type of dementia, while the second most common is vascular dementia, which is the result of disruptions in blood flow to brain cells caused by strokes or plaque build-up in arteries supplying blood to the brain. Both of these types of dementia are more common with age. Diseases affecting specific parts of the brain can also lead to dementia, and a person can have dementia due to more than one disease process.

In the current study, the researchers analysed the potential relationship between age at menopause onset and the diagnosis of dementia from any cause. Health data were examined for 153,291 women who were an average age of 60 when they became participants in the UK Biobank (between 2006 and 2010) and were examined. The UK Biobank is a large biomedical database that includes genetic and health information on a half million people living in the United Kingdom.

The investigators identified the diagnosis of all types of dementia including Alzheimer’s disease, vascular dementia and dementias from other causes. They calculated risk of occurrence in terms of the age at which the women reported having entered menopause, compared with the women who began menopause at average age of menopause onset, which is 50-51 (51 years is the average age for menopause onset among women in the US).

The results were adjusted for factors including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income and leisure and physical activities.

The analysis found:
• Women who entered menopause before 40 were 35% more likely to have been diagnosed with dementia.
Women who entered menopause before the age of 45 were 1.3 times more likely to have been diagnosed with dementia before they were 65 years old (called presenile or early-onset dementia).

• Women who entered menopause at 52 or older had similar rates of dementia to those women who entered menopause at average age of menopause onset, which is the age of 50-51 years.

Although post-menopausal women are at greater risk of stroke than pre- menopausal women, and stroke can disrupt blood flow to the brain and may result in vascular dementia, in this study the researchers did not find an association between age at menopause and the risk of vascular dementia.

“Dementia can be prevented, and there are various ways women who experience early menopause may be able to reduce their risk of dementia. This includes routine exercise, participation in leisure and educational activities, not smoking and not drinking alcohol, maintaining a healthy weight, getting enough vitamin D and, if recommended by their physician, possibly taking calcium supplements,” Hao said.

The researchers suggest that lowered oestrogen levels may be a factor in the possible connection between early menopause and dementia.

“We know that the lack of oestrogen over the long term enhances oxidative stress, which may increase brain ageing and lead to cognitive impairment,” Hao said.

Healthcare clinicians who care for women should be aware of a woman’s age at menopause onset and closely monitor for cognitive decline in those who reached menopause before age 45.

“Further research is needed to assess the added value of including the timing of menopause as a predictor in existing dementia models,” Hao said. “This may provide clinicians with a more accurate way to assess a woman’s risk for dementia.”

The study has several limitations. Researchers relied on women’s self- reported information about their age at menopause onset. In addition, the researchers did not analyse dementia rates in women who had a naturally occurring early menopause separate from the women with menopause induced by surgery to remove the ovaries, which may affect the results. The data used for this study included mostly white women living in the UK and may not generalise to other populations.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference, sponsored by the American Heart Association.

Study details

Early Menopause Is Linked To Increased Risk Of Presenile Dementia Before Age 65 Years

Wenting Hao, Chunying Fu, Dongshan Zhu.

Presented at Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 on 1 March 2022

Abstract

Introduction
Evidence on the association between age at menopause and risk of dementia has been inconsistent. Some studies observed that later menopause was related to lower risk of dementia, while others reported no association, or even came to the opposite.

Oestradiol plays an important role in a wide range of neurological functions in brain, so the reduction of endogenous oestrogen at menopause may aggravate brain changes related to neurodegenerative diseases, and accelerate the progression of dementia.

Hypothesis
Based on the neuroprotective effects of oestrogen, we hypothesised that earlier menopause might be related to higher risk of and earlier onset of dementia, compared with menopause at normal age or later.

Methods
We used cohort data from UK Biobank and a total of 153 291 postmenopausal women were included. Age at menopause was categorised as <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-55, and >55 years. The main outcome was all-cause dementia, a comprehensive outcome including Alzheimer’s disease (AD), vascular dementia (VD) and dementia classified elsewhere. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between menopausal age and all-cause dementia.

We also stratified the age when dementia was diagnosed into ≤65 years and >65 years to explore the association between age at menopause and timing of experiencing dementia. All HRs were adjusted for age at last follow-up, race, education level, BMI, cigarette smoking, alcohol drinking, cardiovascular disease status, diabetes status, income, leisure activities and physical activities. We also used restricted cubic splines to analyse the dose-response relationship between menopausal age and dementia.

Results
Among the 153,291 women, there were 1,688 woman suffering from all-cause dementia. The average follow-up time was 11.7 years. Compared with menopausal age of 50-51 years, the HRs (95% CI) with dementia in women with menopausal age <40, 40-44, 45-49, 52-55 and >55 years were 1.53 (1.22-1.91), 1.07 (0.89-1.28), 1.08 (0.94-1.25), 0.81 (0.70-0.94), and 0.91 (0.78-1.06) respectively. Restricted cubic spline also showed an inverse dose-response relationship between them. In addition, compared to women with menopausal age of 50-51 years, women with early menopause (<45 years) had elevated risk of experiencing all-caused dementia before age 65 years (1.31, 1.07-1.72; P<0.001).

Conclusions
Compared to women with menopausal age of 50-51 years, women with premature menopause (<40 years) had around 35% higher risk of having all-cause dementia, and women with early menopause (<45 years) were 1.3 times more likely to experience presenile dementia before age 65 years. Women with early menopause may need a close monitoring of their cognitive decline in clinical practice.

 

AHA presentation – Early Menopause Is Linked To Increased Risk Of Presenile Dementia Before Age 65 Years (Open access)

 

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