Could oestrogen explain why women are more at risk of dementia?

According to Alzheimer’s Research UK, 65% of people living with dementia are female. There are a range of differences between men and women that could help explain this, including increased lifespan and increased risk of stroke for women (both age and stroke are risk factors for dementia).

Another area being investigated is the link between the hormone oestrogen and dementia. Contrary to popular belief, both men and women have oestrogen in their bodies, but because it is a female sex hormone, women usually have more of it.

So if oestrogen is a female sex hormone, why do men produce it? Although oestrogen does play an intrinsic role in reproduction, it actually contributes to a wide range of functions across the body. Crucially, oestrogen plays a major role in the hippocampus and the prefrontal cortex (PFC) – key brain areas for memory which are often damaged in dementia.

Oestrogen is vital for memory formation through a process called synaptic plasticity. Synapses are the gaps between neurones (brain cells) through which they communicate via chemical messengers. Synaptic plasticity refers to these synapses changing depending on how active the adjacent neurones are, and these changes are regulated by oestrogen. If two neighbouring brain cells are very active, the synapse will adapt to send messages between them more quickly than in less active brain cells.

Oestrogen is therefore essential for effective communication between neurones in the parts of the brain that are involved in memory. But, due to oestrogen’s role in female reproduction, this memory function can be affected by the reproductive system.

When women reach a certain age – usually in their 40s or 50s – they stop having periods and become infertile in a process called menopause. During menopause, oestrogen levels drop significantly, which affects its functions throughout the whole body. This leads to symptoms including difficulty sleeping, anxiety and depression, hot flushes, and memory problems.

Unfortunately, some of these symptoms – like mood changes and memory loss – overlap with dementia, which can cause menopause to be misdiagnosed as dementia (and vice versa). In menopause, these symptoms generally only last for four years, whereas in dementia the symptoms will gradually get worse over time. But the link between menopause and dementia extends beyond misdiagnosis.

Several research papers have discovered a link between menopause and dementia. One study published in 2020 found that women who had their periods for a shorter length of time had a greater risk of developing dementia. A shorter reproductive span – for example, due to late period onset or younger age of menopause – suggests a shorter period of exposure to oestrogen. Furthermore, another group of researchers found that women who had experienced menopause had reduced brain tissue and more amyloid-beta proteins (an indicator of Alzheimer’s disease) in their brains than men and pre-menopausal women.

It is important to note that the evidence suggests that menopause and the reduction of oestrogen it causes are linked to an increased risk of dementia, rather than that reduced oestrogen causes dementia. Even so, the establishment of an association between menopause and dementia suggests that interventions to prevent dementia in women may benefit from focusing on the time window before menopause.