New research from the University of Cambridge suggests that the menopause is associated with changes in the brain including a reduction in grey matter, in important regions in the brain. The menopause is also linked to higher levels of anxiety and depression, along with sleep problems.

How is this linked to dementia?

Alzheimer’s disease, the most common type of dementia, causes grey matter to shrink due to brain cell damage.

Furthermore, poor sleep or not getting enough sleep is also linked to an increased risk of developing dementia this is because the brain ‘cleans’ itself during sleep.

The menopause and HRT

Menopause occurs when a woman’s periods stop because hormone levels fall, usually between the ages of 45 and 55. During this time, many women experience symptoms such as hot flushes, low mood, and difficulty sleeping. Previous research has also connected menopause to changes in thinking abilities, including memory, attention, and language.

HRT is often prescribed to help manage symptoms, particularly depression and sleep difficulties. In England, about 15% of women were prescribed HRT in 2023. Even so, there is still limited knowledge about how menopause and HRT affect the brain, mental health, and cognitive function.

Research approach

To investigate this, researchers analysed data from nearly 125,000 women in the UK Biobank. The participants were grouped into three categories: women who had not yet reached menopause, women who were post-menopausal and had never used HRT, and women who were post-menopausal and had used HRT.

Participants completed questionnaires about their menopause experience, mental health, sleep patterns, and general health. Some also took part in cognitive tests measuring memory and reaction time. Around 11,000 women underwent MRI scans, allowing researchers to examine brain structure.

On average, menopause began at about 49.5 years of age among the participants. Women who used HRT typically started treatment around age 49.

Post-menopausal women were more likely than pre-menopausal women to have sought medical help for anxiety, nervousness, or depression. They were also more likely to score higher on depression questionnaires and to have been prescribed antidepressants.

Women in the HRT group showed higher levels of anxiety and depression than those who did not use HRT. However, further analysis revealed that these differences were already present before menopause. Researchers suggest that in some cases, doctors may have prescribed HRT because they expected symptoms to worsen during menopause.

Sleep issues were also more common after menopause. Post-menopausal women reported more insomnia, shorter sleep duration, and greater fatigue. Those taking HRT reported feeling the most tired, even though their total sleep time was similar to that of post-menopausal women not using HRT.

Menopause also appeared to affect thinking speed. Post-menopausal women who were not using HRT had slower reaction times compared with women who had not yet reached menopause and those using HRT. However, there were no major differences between the groups in memory performance.

Brain scans revealed noticeable reductions in grey matter volume in post-menopausal women, regardless of HRT use. Grey matter plays a key role in processing information, controlling movement, and managing memory and emotions.

The reductions were especially evident in the hippocampus, which supports memory formation; the entorhinal cortex, which helps relay information between the hippocampus and the rest of the brain; and the anterior cingulate cortex, which is involved in emotional regulation, decision-making, and attention.

These brain regions are also known to be affected in Alzheimer’s disease. The researchers suggest that menopause may increase women’s vulnerability to dementia later in life. While menopause alone does not fully explain why dementia is more common in women, it may be one contributing factor.

Women are twice as likely to be affected by dementia than men and this research could shine a light on the reason why.

BRACE research into the menopause

BRACE is currently funding PhD student Sophie Alderman, who is looking into this link between menopause and dementia. Sophie says:

“Thank you BRACE for giving me the opportunity to study this much needed area of the menopause and dementia risk. By researching the effects of the menopause, which is a significant change that most women go through, I hope to provide new understanding of the role menopausal symptoms may play in the development of Alzheimer’s disease. If successful, this improved understanding could lead to different medical approaches and help to reduce the risk of dementia in millions of women.”