World Alzheimer’s Day: What Menopause, Oestrogen, And Heart Health Tell Us

A 2025 analysis of Global Burden of Disease data estimated 7.75 million cases of early-onset Alzheimer’s disease and other dementias among people aged 40–64 globally in 2021, including 4.28 million women versus 3.46 million men. The data for India (covering 1990-2021) found that women had higher age-standardised mortality rates from Alzheimer’s disease and other dementias than men. Why is the difference so striking? Researchers are investigating several overlapping explanations ranging from longevity, cardiovascular and metabolic health to genetics, reproductive history, hormonal changes, sleep, depression and anxiety, education and cognitive reserve, and differences in how the ageing brain responds to disease. Increasingly, menopause is becoming an important part of this conversation.

The Longevity Factor

At the outset, is important to note that women generally live longer. Because Alzheimer’s risk rises sharply with age, having more women survive into their 80s and 90s naturally produces more women living with the disease. The latest Alzheimer’s Association data specifically caution that it is still unclear whether women and men of the same age have different overall risks of developing Alzheimer’s. But longevity may not explain everything. Researchers are examining whether biological differences between male and female brains, sex hormones, genetics, vascular health and life-course exposures might alter the trajectory of brain ageing. Recent findings identified possible contributions from APOE ε4, depression and insomnia, pregnancy-related complications such as pre-eclampsia and gestational hypertension.

What Happens During Perimenopause?

Perimenopause is not simply a reproductive transition, but also a period of major hormonal and neurological change. As ovarian function changes, oestradiol levels fluctuate and eventually fall. The brain is highly responsive to oestrogen and receptors are found in areas involved in memory, learning, mood, sleep and executive function, including the hippocampus and prefrontal cortex. During the menopausal transition, some women report problems with concentration, word-finding, memory and mental clarity, commonly described as ‘brain fog’. Research suggests that cognitive changes during this period can be subtle and may overlap with changes in sleep and mood. But this doesn’t mean that a woman has Alzheimer’s disease.

Menopause-related cognitive symptoms can include forgetting names or words temporarily, difficulty concentrating, feeling mentally slower, losing track of a thought, trouble multitasking, reduced attention after a poor night's sleep and feeling less mentally sharp than before. Sleep can be a particularly important piece of the puzzle. Sleep disruption becomes more common around menopause. Sleep problems themselves are associated with impaired cognition and are being investigated as potential contributors to Alzheimer’s disease. Mood, anxiety and depression can affect attention, memory, motivation and executive functioning.

Dr Heena Sujoy, a Bengaluru-based psychiatrist says, ‘Brain fog is a very real experience, but it is not a diagnosis. During perimenopause and menopause, women may notice difficulty concentrating, forgetfulness or feeling mentally slower. These symptoms can be amplified by poor sleep, hot flashes, anxiety, depression and the stress of managing multiple responsibilities. In many cases, the underlying problem is attention rather than memory. If you're exhausted or anxious, information may not be encoded properly in the first place.’ She adds, ‘What concerns me is when patients don’t have an occasional lapse, but a pattern that is persistent and gets increasingly worse. If someone is repeatedly forgetting conversations, getting lost in familiar places, struggling to manage finances or medications, or having difficulty performing tasks they previously handled easily, or if family members are noticing a clear change, I would not simply attribute that to menopause. That warrants a proper cognitive and medical evaluation.’

Dr Heena believes that menopause can make a woman feel cognitively different without necessarily indicating neurodegeneration. ‘The clinical red flag is a persistent, progressive decline that begins to affect how she functions. Don't dismiss brain fog, but you don’t have to equate it with Alzheimer's either. In Alzheimer's, there can be deeper underlying symptoms. Sometimes, when the brain loses the ability to process new information and make sense of its environment, situations that were previously routine can become confusing or threatening. What looks like irrational anxiety or agitation may actually be the person's response to a world that no longer makes sense to them.’

Does Falling Oestrogen Harm The Brain?

Oestrogen influences brain energy metabolism and the activity of several neurotransmitter systems. Researchers are also studying its relationship with amyloid and tau, the proteins most closely associated with Alzheimer’s pathology. This has led to the ‘oestrogen hypothesis’. The loss of ovarian oestrogen during menopause could represent a period when the brain becomes more vulnerable to ageing and neurodegenerative processes. But this again is not proof that menopause accelerates Alzheimer’s, nor does it mean that replacing oestrogen will prevent Alzheimer’s.

The Menopause Society currently does not recommend hormone therapy specifically to improve cognition or to prevent dementia. Nor is oestrogen-containing hormone therapy recommended as a strategy for the primary prevention of cardiovascular disease or dementia in women going through menopause at the usual age.

Dr Heena says, ‘However, for appropriately selected women, hormone therapy remains an important treatment for troublesome vasomotor (blood vessels) and genitourinary (reproductive and urinary organ-related) symptoms, and may have other established benefits. The benefit-risk balance is generally considered more favourable for healthy women who begin treatment before age 60 or within 10 years of menopause, after individual assessment.’

APOE ε4: The Genetic Risk Factor

The APOE gene helps transport fats and cholesterol. One version, APOE ε4, is the best-established common genetic risk factor for late-onset Alzheimer’s disease. Having one copy increases risk, while having two copies increases it further. But APOE ε4 is a risk factor, not a diagnosis or destiny. Some carriers never develop Alzheimer’s, while many people who develop the disease do not carry two copies or APOE ε4 at all. There has been particular interest in whether APOE ε4 affects women and men differently. Some studies have reported stronger associations between APOE ε4 and Alzheimer’s in women, particularly during certain age ranges. Other large analyses have challenged the idea that female APOE ε4 carriers universally have greater risk than male carriers.

A 2023 analysis of more than 31,000 people found that the relationship varied by age and ancestry. In some groups, female APOE ε4 carriers showed greater risk at particular ages, while the overall sex difference was not consistent across all groups. A 2025 study using Health and Retirement Study data likewise found that APOE ε4 was associated with cognitive decline and dementia onset but did not find that the relationship differed by sex.

The Heart-Brain Connection

High blood pressure, diabetes, high cholesterol, obesity, smoking and physical inactivity can damage blood vessels and are associated with dementia risk. Some of these risk factors become more common or change around midlife and menopause. This makes cardiovascular health particularly relevant when discussing women's brain health.

Pregnancy-related complications such as pre-eclampsia and gestational hypertension are also being investigated as possible markers of later-life vascular and cognitive risk. Protecting cardiovascular health may also be protecting brain health. That means monitoring blood pressure, cholesterol and blood glucose, staying physically active, avoiding smoking, maintaining a healthy weight, getting adequate sleep, eating a balanced diet and treating other health conditions.

What Women Can Do

There is no guaranteed way to prevent Alzheimer’s disease, but several factors associated with brain health are modifiable. That includes:

- Controlling blood pressure, cholesterol and diabetes

- Regular physical activity

- Not smoking

- Maintaining social connections

- Getting adequate, good-quality sleep

- Treating depression and anxiety

- Maintaining a healthy diet

- Staying intellectually and socially engaged

- Addressing hearing and vision problems

- Discussing troublesome menopause symptoms with a healthcare professional

The Menopause Society specifically highlights physical and mental activity, social connection, a Mediterranean-style diet, smoking avoidance and management of cardiovascular risk factors as measures that may support brain health. For women in midlife, forgetfulness and brain fog during the menopausal transition are common and do not automatically signal Alzheimer’s disease. What matters is recognising persistent or progressive changes, treating reversible contributors such as sleep disorders, depression, anxiety and cardiovascular risk factors, and seeking assessment when cognitive problems begin to interfere with everyday life.