Dementia: how brain resilience, immune health and the menopause play a role in women’s risk

Women are more likely than men to be diagnosed with dementia. While researchers have some idea of the factors that elevate risk, it’s still not entirely clear why this happens. But a recent study suggests that the menopause could play a key role in increased vulnerability to Alzheimer’s disease.

Researchers at the University of Cambridge analysed brain scans from nearly nearly 125,000 women. They found the menopause is associated with measurable reductions in grey matter (brain areas where information is processed and analysed). They also identified volume reductions in brain regions involved in memory, emotion, attention and decision-making.

These changes were also linked to poorer sleep, increased anxiety and depression and slower reaction times. Importantly, the affected regions overlap with those most vulnerable in Alzheimer’s disease (the most common form of dementia).

This does not mean, however, that menopause causes dementia. But it does suggest that menopause may represent a critical neurological transition – one that can influence brain health trajectories for years or even decades afterwards.

These findings have brought the influence of biological sex on brain health into sharper focus. These findings may also bring us closer to understanding why women are not only at greater risk of Alzheimer’s disease, but a range of other neurological conditions – including multiple sclerosis and depression.

Factors affecting women’s dementia risk

Although women face a higher risk of dementia, their brains often show remarkable resilience.

Throughout much of life, women tend to outperform men on certain verbal memory tasks, and often show greater resistance to early cognitive decline.

But this resilience could be a double-edged sword, masking underlying brain changes for longer.

In Alzheimer’s disease, women often show fewer symptoms early on, despite accumulating signs of the disease in the brain. When symptoms do emerge, decline can appear faster and more dramatic – partly because the brain has already been compensating for damage for years.

There are many other crucial social and biological differences between men and women that may explain why brain health outcomes can vary so broadly, as well.

Cognitive reserve, for instance. This is the brain’s ability to adapt and maintain a certain level of function, even when faced with damage (including that caused by dementia and Alzheimer’s). Education, intellectually demanding work, being socially and physically active and lifelong learning all help build cognitive reserve.

Not only is cognitive reserve shaped by biology, it’s also shaped by social realities. For instance, many women have experienced interrupted education, chronic stress or limited access to healthcare. These factors can quietly erode cognitive reserve over time – even while women continue to function at a high level.

At the same time, strong social networks, emotional intelligence and adaptability, qualities often reinforced in women, may enhance resilience and delay the appearance of symptoms.

Another key factor in dementia risk lies in immune function differences between sexes.

Women generally have stronger immune responses than men. While this protects against infections, it can also increase vulnerability to autoimmune conditions (where the immune system becomes overactive). The immune response can particularly become overactive as women age or during periods of hormonal change.

This heightened immune activity extends to the brain. Chronic neuroinflammation, often caused by a dysregulated immune system, is increasingly recognised as a contributor to Alzheimer’s disease, as well as multiple sclerosis and mood disorders. Women’s stronger immune activation may therefore raise risk for certain brain conditions, especially during periods of hormonal instability – such as menopause.

Chromosomes also matter.

Women have two X chromosomes, while men have one X and one Y in most cases. Many immune-related genes are located on the X chromosome. But some of these genes are able to escape the usual process that switches off their activity in women.

This can lead to higher expression of immune system and inflammatory genes – potentially increasing susceptibility to autoimmune and neuroinflammatory disorders.

The menopause link

One of the most important insights from the recent Cambridge study concerns brain metabolism.

The brain is an energy-hungry organ. It primarily uses glucose (sugar) as it’s main source of energy.

Oestrogen plays a significant role in how brain cells use glucose. Oestrogen helps brain cells use glucose efficiently, supporting the energy needed for thinking and memory.

But when oestrogen levels fall during the menopause, the brain may become less efficient at generating energy from glucose. This can create a mild, chronic energy shortfall in vulnerable brain regions. Over time, this metabolic stress may increase susceptibility to processes linked to Alzheimer’s.

This metabolic aspect could also help explain why symptoms such as brain fog, fatigue, mood changes and sleep disruption are common during the menopause.

It also offers a possible biological bridge between menopause and later-life neurological conditions, including Alzheimer’s.

Alzheimer’s and other brain disorders develop under different biological conditions in women and men. Studies on brain health, as well as tests, treatments and prevention strategies, must reflect that reality.

Factors such as hormones, metabolism, lifestyle and immune function not only affect how Alzheimer’s and other brain disorders develop, but also how they interact with and affect each other.

But for decades, research has ignored women, with studies investigating women’s issues being underfunded. Clinical trials on brain health have also failed to acknowledge sex as a potential modifying factor.

Some studies have completely excluded women – with peri- and post-menopausal women particularly overlooked. As a result, many of the treatments available (including those which slow dementia) are developed and prescribed without considering how hormonal changes may alter drug metabolism.

The result is a healthcare system poorly equipped to recognise early brain changes in women or to intervene at the most effective time.

Everything we currently know is pointing towards an important message: women’s brains are complex, adaptive and shaped by forces (such as hormonal transitions throughout the lifespan) that medicine is only beginning to acknowledge. Recognising both the risks women face and the resilience they carry is the first step toward more equitable, effective brain care.

The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.