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Alzheimer’s Disease (AD) is a devastating neurodegenerative disease. It affects over 50 million patients worldwide. People living with dementia experience at first mild symptoms, with loss of cognitive functions and behavioral alterations, but eventually find themselves unable to cope with their everyday life (a stage called MCI, short for Mild Cognitive Impairment). Finally, they lose their independence.

With 99.6% of failures of clinical trials in the past 15 years, there is no cure for AD, and symptomatic treatment can only delay, but not stop, the progression of the disease. This is largely because the causes of the disease remain elusive.

While this picture is quite worrying, there are reasons for optimism. Biomarkers, prevention, and women are contributing to solve the puzzle of AD.

Biomarkers

Until a decade ago, the diagnosis of AD was exclusively done post-mortem. While living, the patient could only be classified as a ‘probable’ or ‘possible’ case of AD, after excluding all other possible causes of dementia. A definite post-mortem diagnosis relied on the observation of the signature features of AD – amyloid plaques and tangles in brains.

In terms of clinical diagnosis, as many as 50% of MCI patients and 30% of dementia cases are wrongly diagnosed, and in fact have no amyloid plaques in their brains. We know this because in the past ten years, biomarkers became available to track the pathology in living patients. These new tools allow clinicians to spot amyloid plaques, tau, and neurodegeneration via brain scans or via an analysis of the CSF (cerebro spinal fluid, which fills your spine). This means that we can identify patients at their earliest stages of AD – and act immediately.

Prevention

A recent report from the Lancet Commission has concluded that as much as 1/3 of AD risk is preventable with lifestyle changes throughout the lifespan. Modifiable risk factors include education in early life, hypertension, and obesity in midlife, and smoking and physical inactivity in late life. Indeed, a multi-intervention study conducted in Scandinavia – the FINGER study – has scientifically proved that lifestyle changes and specific training can significantly delay cognitive decline in the elderly.

This study is now being reproduced in the rest of the world. The good news? Even though we cannot fully prevent AD, we can definitely act on a daily basis to invest in our health and delay its progression.

Women’s brains

Sixty to seventy percent of patients diagnosed with AD are women. Whether women are at higher risk is a matter of debate in the scientific community. However, a mounting body of evidence indicates that female and male brains react differently to the same neuropathology. The Women’s Brain Project (WBP), a non-profit organization based in Switzerland, has recently pushed this subject area forward by reviewing the scientific evidence in the field. In their paper, published by the prestigious journal Nature Reviews Neurology, the authors identified several trends in the literature indicating significant sex-effects in AD. For instance, women with MCI were found to be declining faster than men with a similar diagnosis, with faster brain atrophy. “Similar levels of biomarkers might have different prognostic values for men and women says WBP co-founder, Dr Antonella Santuccione Chadha.

Beyond that, a number of potential risk factors related to reproductive life are specific to women, such as ovariectomy and hypertensive complications during pregnancies, or the number of pregnancies. These results suggest that the current ‘one size fits all’ approach to AD might not be appropriate. Instead, doctors should start tailoring prevention, diagnosis, and treatment, to the sex of the patient.

For Dr Annemarie Schumacher Dimech, co-founder and President of WBP, this is a priority not just in AD, but in general in brain and mental diseases: “It is critical for us to advocate for more awareness on sex and gender differences, and for a sex- and gender-sensitive precision medicine approach to AD and other mental diseases.”

The importance of sex and gender in research

Not only is considering sex differences crucial for the implementation of precision medicine; studying women’s brains might help us uncover disease mechanisms. For example, a mounting body of evidence indicates that microglial cells, the immune cells of the brain, are different in men and women. Identifying the factors that predispose women to fast AD progression might help us understand the general mechanism of the disease.

Finally, in recently launched studies to prevent AD in its preclinical stages, women were overwhelmingly overrepresented – they simply poured to these trials. Mobilization of women and their participation in clinical studies, both as participants as well as study directors, indicates a dramatic shift in society. Inspiring advocates for women’s brain health, like actress Cheri Ballinger, are calling global attention to these topics. Women’s brains, whether they belong to patients, caregivers, study directors, nurses, or advocates, will be key for winning the fight against AD.

Maria Teresa Ferretti Ph.D.
Maria Teresa Ferretti Ph.D. is a neuroimmunologist and science advocate with 10+ years of international experience in the field of Alzheimer’s Disease. In 2016 Maria Teresa co-founded a non-profit organization called Women’s Brain Project (WBP), advocating for sex-sensitive precision medicine for brain and mental diseases (www.womensbrainproject.com). WBP engages and collaborates with academic and clinical groups, pharma industry and regulators in events, symposia and scientific writing on the topic, promoting data stratification by sex in the neuroscience/neurology community. More than 20 new papers (including primary research papers, reviews and position papers) have now been written thanks to this campaign, documenting the occurrence and importance of sex-effects in clinical and preclinical datasets, in particular in Alzheimer’s.   Interested in finding out more about what we do? Follow us on Twitter @womensbrainpro, listen to the Setting the Pace podcast featuring WBP ambassador, actress Cheri Ballinger, or sign up to get updates about our upcoming Forum taking place in Switzerland in June 2019.

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