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Why do more women have Alzheimer's than men? It may be linked to hormonal changes and estrogen loss, says study

The study says changes in brain imaging features, or biomarkers in the brain, suggesting menopausal status may be the best predictor of Alzheimer's related brain changes in women. 
UPDATED JUN 25, 2020
(Getty Images)
(Getty Images)

Why do more women have Alzheimer's than men? It is not just from living longer, say researchers in a new study. Middle-aged women are more likely than men to have changes in the brain related to Alzheimer's disease, as detected by imaging, even when there are no differences in thinking and memory. This may be associated with hormonal changes due to menopause, specifically the loss of estrogen, according to experts from Weill Cornell Medicine, ADM Diagnostics, and the University of Arizona.

"Alzheimer's disease affects more women than men. About two-thirds of people living with Alzheimer's are women. For a long time, the general mindset was that women lived longer than men, and Alzheimer's was a disease of old age, and that was why the prevalence was higher in women. However, Alzheimer's is not a disease of the old. Rather, it starts with negative changes in the brain years, if not decades, before clinical symptoms emerge,” study author Dr Lisa Mosconi from Weill Cornell Medicine, told MEA WorldWide (MEAWW). She said, “In this study, we show for the first time that women develop Alzheimer's related changes in their brains at a younger age than men. So it isn't just that women live longer -- women also start showing the tell tale signs of Alzheimer's earlier in life. Even more specifically, this seems to happen during the transition to menopause, which is in our 40s and 50s."

According to Dr Mosconi, the study is important because usually, when health experts discuss Alzheimer's prevention, they talk about managing things like high cholesterol and high blood pressure. But they do not talk about managing menopause, or female hormones. Dr Mosconi told MEAWW the study findings indicate that hormonal factors need to become a strong focus of Alzheimer's prevention strategies in women. “Our findings suggest that hormonal factors may predict who will have changes in the brain. Our results show changes in brain imaging features, or biomarkers in the brain, suggesting menopausal status may be the best predictor of Alzheimer's related brain changes in women,” says Dr Mosconi. The study was supported by the National Institutes of Health, the National Institute on Aging, the Cure Alzheimer's Fund, and the Women's Alzheimer's Movement. The findings have been published in Neurology, the medical journal of the American Academy of Neurology.

Alzheimer’s disease is the most common type of dementia. Globally, around 50 million people have dementia, and Alzheimer's disease may contribute to 60-70% of cases. It is a progressive disease that begins with mild memory loss possibly leading to loss of the ability to carry on a conversation and respond to the environment. Alzheimer’s disease involves parts of the brain that control thought, memory, and language, and, over time, can seriously affect a person’s ability to carry out daily activities. About 5.7 million Americans are estimated to be living with Alzheimer’s disease in 2018, says the US Centers for Disease Control and Prevention (CDC). It is the fifth leading cause of death for adults aged 65 years and older, and the sixth leading cause of death for all adults. 

While Alzheimer's disease is not unique to women, women constitute roughly two-thirds of patients living with Alzheimer's disease dementia, with postmenopausal women accounting for greater than 60% of all those affected, says the study. (Getty Images)

According to the research team, after advanced age, female sex is the major risk factor for late-onset Alzheimer's disease. “Population-attributable risk models estimate that 1 in every 3 Alzheimer’s disease cases may be preventable, especially if addressed in midlife. Identification of sex-specific risks is, therefore, pivotal in the development of targeted Alzheimer disease risk reduction strategies,” explain the authors. The research involved 85 women and 36 men, with an average age of 52, who had no cognitive impairment. The men and women had similar scores on thinking and memory tests and measures such as blood pressure and family history of Alzheimer's. Participants underwent positron emission tomography (PET) scans to see if they had amyloid-beta plaques in the brain, a biomarker associated with Alzheimer's disease. They also had detailed brain magnetic resonance imaging scans (MRI).

For the analysis, the research team compared the women and men in key areas of brain health to assess their risk of having Alzheimer's biomarkers: the volumes of both gray and white matter in the brain, levels of amyloid-beta plaques, and the rate at which the brain metabolizes glucose, an indication of brain activity. According to the team, the women scored worse on all four of those measures. On average, the women had 30% more beta-amyloid plaques in the brain, and 22% lower glucose metabolism than the men did. “When measuring average gray matter volume, the women had 0.73 cubic centimeters (cc/cm3) compared to men who had 0.8 cm3, a difference of 11%. For average white matter volume, the women had 0.74 cm3 compared to men who had 0.82 cm3, a difference of 11%,” says the study.

The findings suggest that middle-aged women may be more at risk for the disease, perhaps because of lower levels of the hormone estrogen during and after menopause, say researchers. The analysis indicates that the window of opportunity for Alzheimer’s preventive interventions in women is early in the “endocrine aging process,” they add. “While all sex hormones are likely involved, our findings suggest that declines in estrogen are involved in the Alzheimer's biomarker abnormalities in women we observed. The pattern of gray matter loss, in particular, shows anatomical overlap with the brain estrogen network,” says Dr Mosconi.

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