Early menopause linked to dementia risk

Women who enter menopause at an earlier age are more likely to develop dementia later in life, a new study suggests.

Researchers explored the association between reproductive and hormonal factors across a woman’s lifespan and the risk of brain ageing.

The findings show that being older at menopause, having higher blood oestrogen levels and having more children all correlated with better cognition test scores.

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A greater exposure to oestrogen throughout a woman’s reproductive lifespan was associated with enhanced cognitive performance and larger brain volumes, suggesting that hormone replacement therapy (HRT) could be protective against dementia.

The results, published in the Journal for Alzheimer’s Disease, from the University of Galway, come from the analysis of data from nearly 1,500 cognitively healthy women who were part of the Framingham Heart Study, the world’s longest-running longitudinal cohort study.

Women have a higher risk of dementia than men, making up nearly two-thirds of people living with Alzheimer’s disease. To analyse the association between reproductive factors and markers of brain ageing, the researchers carried out the study with 1,329 women who did not have dementia. The average age of the women was 60, and the data was collected between 1998 and 2001.

The researchers examined age at menarche and menopause, the number of biological children and the use of HRT. They analysed a range of neurocognitive and neuroimaging markers from MRI brain scans, as well as cognitive test performance, assessing memory, reasoning and visuospatial skills and determined the future risk of dementia in relation to these reproductive factors.

Protective effect of HRT

The researchers found that the use of HRT after menopause, higher oestrogen levels and an earlier age at menarche were each linked to better abstract reasoning skills, including the ability to problem solve.

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An older age at menopause, higher oestrogen levels, and having one or more children were linked to better visuospatial performance. Women who had children were found to have a larger total brain volume.

Professor Emer McGrath, lead author from the University of Galway, and consultant neurologist, Galway University Hospital, said: ‘When we explored signs of brain ageing on MRI brain scans, we also found that having more children was associated with larger brain volumes, including in the areas we tend to see shrinkage in Alzheimer’s disease.’

In contrast, reaching menopause before the age of 50 was linked to a smaller hippocampal volume, the part of the brain used in memory and learning, suggesting a potential vulnerability to cognitive decline.

Professor McGrath added: ‘We found that entering menopause at an earlier age appears to be associated with an increased risk of dementia, while post-menopause hormone replacement therapy appears to be associated with a lower risk of dementia. Although our results suggest positive cognitive benefits of greater lifetime estrogen exposure, they do require further validation.’

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The researchers suggest that sex-specific biological factors, such as hormonal changes and reproductive history, are linked to a greater risk of dementia in women and are calling for a greater focus on sex-specific differences in the progression and development of Alzheimer’s disease.