The findings, published Oct. 10 in PLoS One, could help solve a longstanding mystery about Alzheimer’s, namely, why women get this fatal neurodegenerative disorder more often than men—even accounting for the fact that women on average live longer. The investigators say the results also eventually may lead to the development of screening tests and early interventions to reverse or slow the observed metabolic changes.
Using positron emission tomography (PET) imaging to measure the brain's use of glucose in healthy women ages 40 to 60, researchers noted significant differences:
The tests revealed the women who had undergone menopause or were peri-menopausal had markedly lower levels of glucose metabolism in several key brain regions than those who were pre-menopausal. Scientists in prior studies have seen a similar pattern of “hypometabolism” in the brains of patients in the earliest stages of Alzheimer’s — and even in mice that model the disease.
In addition, menopausal and peri-menopausal patients showed lower levels of activity for an important metabolic enzyme called mitochondrial cytochrome oxidase, as well as lower scores on standard memory tests. The strong contrast with pre-menopausal patients remained even when accounting that the menopausal and peri-menopausal women were older.
While the link between menopause and brain-related ailments is well known, this new research suggests "that the menopausal fall in estrogen may trigger a shift to a 'starvation reaction' in brain cells — a metabolic state that is beneficial in the short term but can be harmful in the long term."
“Our work indicates that women may need antioxidants to protect their brain activity and mitochondria in combination with strategies to maintain estrogen levels,” Dr. Mosconi said, noting that exercise and foods that are rich in antioxidants, such as flaxseeds, also may help boost estrogen production. “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. This is a major priority at our Alzheimer’s Prevention Clinic.”
"Our studies demonstrate," Dr. Mosconi says, "that women need medical attention in their 40s, well in advance of any endocrine or neurological symptoms."