Menopause May Raise Alzheimer’s Risk Though Metabolic Changes in Brain, Study Says

Menopause triggers numerous changes in a woman’s body — and, apparently, metabolic changes in the brain as well that puts middle-age women at greater risk of Alzheimer’s disease, a study reports.

This finding provides new insights into why women have a higher incidence of this neurological disease, even when a generally longer lifespan accounted. It also may promote new ways of evaluating these people to detect early signs of Alzheimer’s and try to prevent its progression.

The study, titled “Perimenopause and emergence of an Alzheimer’s bioenergetic phenotype in brain and periphery,” was conducted by researchers at Weill Cornell Medicine and the University of Arizona Health Sciences and published in the journal PLOS One.

“This study suggests there may be a critical window of opportunity, when women are in their 40s and 50s, to detect metabolic signs of higher Alzheimer’s risk and apply strategies to reduce that risk,” Lisa Mosconi, an associate professor of neuroscience in neurology at Weill Cornell and the study’s lead author, said in a news release.

Researchers evaluated the bioenergetics status of the brains of 43 women, ages 40 to 60, who were clinically and cognitively healthy. With the use of positron emission tomography (PET) imaging, they could evaluate the consumption of glucose, the main energy source used by cells, in the brain.

Results showed that women who had undergone menopause (15 women), or were in the process of menopause (14), had lesser signs of glucose consumption (metabolism) in several brain regions compared to pre-menopausal women (14). In addition, post- or menopausal women had lower levels of activity in an important metabolic enzyme called mitochondrial cytochrome oxidase, as well as lower scores on standard memory tests.

A similar pattern of lesser brain metabolism has been reported in studies of early-stage Alzheimer’s patients and in experimental mice models of the disease.

“Our findings show that the loss of estrogen [female hormone] in menopause doesn’t just diminish fertility,” said Mosconi, who is also associate director of the Alzheimer’s Prevention Clinic at Weill Cornell and New York-Presbyterian. “It also means the loss of a key neuroprotective element in the female brain and a higher vulnerability to brain aging and Alzheimer’s disease.”

Researchers believe that declining estrogen levels caused by menopause are associated with changes in brain metabolism from an active to a more inactive state. This process may be beneficial for a short period, but can be damaging in the long term.

These findings further support the hypothesis that menopause and Alzheimer’s are linked by shared biological mechanisms. Based on this, women may benefit from exercise and foods that are rich in antioxidants, which help to increase estrogen levels and to protect the brain from such harmful metabolic changes.

“We believe that more research is needed to test efficacy and safety of hormonal-replacement therapies at the very early stages of menopause, and to correlate hormonal changes with risk of Alzheimer’s,” Mosconi said.

The research team is planning to additional studies in larger groups of patients and to follow them for longer periods. These studies may help identify neuronal and metabolic makers, which in turn can help spot people most at risk of developing Alzheimer’s disease.