A recent groundbreaking study has shed light on why women are disproportionately affected by Alzheimer's Disease (AD) and Multiple Sclerosis (MS), pointing to sex chromosomes as a key factor. With an estimated 944,000 people living with dementia in the UK and around 7 million in the US, Alzheimer's Disease, the most common form of dementia and Britain's biggest killer, affects approximately six in ten diagnosed individuals. Notably, two-thirds of all AD diagnoses are in women, prompting a deep investigation into this significant discrepancy.

Researchers from UCLA Health identified a specific gene on the female X chromosome that drives inflammation in the brain, potentially explaining women's higher susceptibility to AD and MS. Through studies on mice genetically bred to exhibit characteristics of MS, the UCLA team pinpointed the Kdm6a gene. This gene was found to fuel inflammation within the brain's immune cells, known as microglia. When researchers successfully 'deactivated' the Kdm6a gene, both the multiple sclerosis-like disease and neuropathology showed marked improvement, with the most significant positive outcomes observed in female mice compared to their male counterparts.

The study, published in the journal Science Translational Medicine, concluded that females, possessing two X chromosomes, receive a 'double dose' of this harmful inflammation, in contrast to males who have XY chromosomes. This genetic difference appears to be a critical determinant in the higher prevalence of these neurological conditions among women.

Adding a promising dimension to their findings, the researchers discovered that Metformin, a widely prescribed diabetes medication (with over 26.4 million prescriptions in England in 2024), could serve as a potential treatment. They demonstrated that Metformin was effective in stifling the Kdm6a gene and its associated inflammatory molecules.

Dr. Rhonda Voskuhl, lead author of the study and director of the Multiple Sclerosis Program at UCLA Health, commented on the findings: "It has long been known that there are sex differences in the brain. These can impact both health and neurological diseases. Multiple sclerosis and Alzheimer's disease each affect women more often than men, about two to three times as often. Also, two-thirds of healthy women have 'brain fog' during menopause. These new findings explain why and point to a new treatment to target this." Dr. Voskuhl further explained that the more significant impact of their interventions in female mice aligns with the concept of "more to block" in females due to their two copies of the X-linked gene, reinforcing the reason women are more prone to MS and AD.

The implications for clinical practice are significant, suggesting that women may respond differently to Metformin treatment than men. While there is currently no cure for dementia, early diagnosis allows for personalized treatment plans and the prescription of drugs to prolong disease onset. Beyond genetic factors, a landmark study published in The Lancet last year proposed that nearly half of all Alzheimer's cases could potentially be prevented by addressing 14 specific lifestyle factors.

Dementia continues to be a major public health concern, with Alzheimer's Research UK analysis indicating 74,261 dementia-related deaths in the UK in 2022, up from 69,178 a year prior, solidifying its status as the country's biggest killer. Sedentary lifestyles, characterized by prolonged sitting at work and during commutes, followed by leisure activities like watching TV, contribute significantly to health issues. A 2019 estimate attributed 70,000 annual deaths in the UK to health problems caused by physical inactivity, costing the NHS £700 million each year. Globally, the WHO estimates approximately 2 million annual deaths due to physical inactivity, making it one of the top ten leading causes of global death and disability.