Female dementia: why early prevention is a challenge (and an opportunity)

Neurodegenerative diseases, and dementias in particular, represent one of the most pressing challenges for global health. They affect women most of all: around 7 out of 10 cases affect women, making the issue a real gender issue. A figure that calls for reflection on the clinical-social impact and importance of early prevention, now increasingly possible thanks to advances in research.
To understand how to intervene, we asked prof.ssa Maria Salsone, head of the Neurology and Stroke Unit and coordinator of the new Brain Health Service at the IRCCS Policlinico San Donato, the first European centre to develop a pathway dedicated to women's brain health.

A higher risk for women: between genetics and hormones
The higher incidence in women is linked to a combination of factors. "The risk of dementia arises from the interaction between genetic (non-modifiable) and environmental (modifiable) factors. In particular, the genetic variant of the APOE-ε4 gene increases the risk by up to 4-10 times in women, compared to 1-4 in men,' explains Salsone, who is also an associate professor at the Vita-Salute San Raffaele University.
Hormonal changes during the menopause are also a factor. "The fall in 17β-estradiol levels, which have neuroprotective effects, and indirect consequences such as weight gain, cardiovascular alterations and mood and anxiety disorders, modulate cognitive risk". Only recently has the focus of scientific research also shifted to the period before the menopause, the perimenopause. "In this phase of life, characterised by large hormonal fluctuations, many women report difficulty concentrating, memory problems, mental slowdown (brain fog). However, there is still a lack of sufficiently long studies to demonstrate a direct link with the risk of dementia'.
The role of Hormone Replacement Therapy (HRT) has been the subject of much scientific debate. "The issue is complex. Factors such as type of HSCT, age of onset and genetic characteristics of the patients may be decisive'.
Sleep also plays a key role: "During sleep, the so-called glymphatic system comes into operation, acting as a brain 'scavenger', eliminating proteins that accumulate physiologically and that, if present in excessive quantities, can trigger neurodegeneration processes.

Risk factors: many are modifiable
An international commission in 2024 identified the main modifiable risk factors for dementia throughout life; in middle age: hearing loss, high cholesterol, depression, head trauma, alcohol, diabetes, physical inactivity. After the age of 70: social isolation and pollution. "Intervening early on these factors can prevent up to 45% of cases", emphasises Salsone.
The lifestyle is central: physical activity, metabolic control and active social relationships. "Exercise reduces the risk of dementia by 20 per cent: up to 5 times a week (150 minutes max) is associated with better cognitive performance over time."

The early signs: recognise them to intervene
Dementias develop slowly, with initially nuanced signs. "An early symptom is the subjective memory impairment: the patient perceives a cognitive decline in the absence of a deficit that can be objectified by neuropsychological assessment".
This perception of difficulty deserves attention: although not always significant of neurodegenerative pathologies, it should not be underestimated.

Prevention: a "cognitive" lifestyle
Prevention also concerns the mind. "Stimulating the brain from a young age is crucial. Activities such as reading, art, music and socialising contribute to cognitive reserve. Interaction with pets can also encourage cognitive-emotional stimulation".

An integrated approach to brain health
In this context, the "3D - Early Diagnosis of Subjective Memory Disorder in Women" project, from the Brain Health Service (BHS) of Policlinico San Donato, a pathway dedicated to women's brain health, is set up.
The pathway considers genetic predisposition (analysis of the APOE gene), hormonal alterations linked to peri- and post-menopause, sleep and mood disorders, conditions such as osteopenia, osteoporosis, visual and auditory deficits, dyslipidaemia, periodontal pathologies and cardiovascular factors, lifestyle, diet, and physical activity.
"Today we can identify those at risk, recognise the very early stages of the disease and intervene with targeted strategies," Salsone concludes.

Looking Ahead: from Diagnosis to Awareness
Dementia is no longer an inevitable condition. Intervening before obvious symptoms appear is one of the greatest opportunities in contemporary medicine. For women, in particular, it means turning early prevention into a concrete tool for protecting brain health and improving quality of life.