A detailed new brain imaging study, examining a number of cognitively healthy middle-aged subjects, is suggesting lower levels of estrogen in women post-menopause could play a role in triggering brain changes linked to Alzheimer’s disease. The research hypothesizes this mechanism may be one of the reasons why women suffer from Alzheimer’s at greater rates than men.
"About two-thirds of people living with Alzheimer's are women, and the general thinking has been it's because women tend to live longer," says Lisa Mosconi, an author on the new study from Weill Cornell Medicine.
However, over recent years many researchers have started exploring potential physiological reasons why there is such stark sex-specific differences in Alzheimer’s cases. One novel study last year, for example, pointed to a number of sex-specific genes that could heighten Alzheimer’s risk in women, while another suggested structural and functional differences in female brains may accelerate the spread of toxic proteins.
This new study builds on what researchers have dubbed the “estrogen hypothesis." This hypothesis posits that women appear to show a heightened susceptibility to Alzheimer’s because the drop in estrogen levels following menopause may exacerbate a predisposition to the brain changes associated with the neurodegenerative disease.
Based on this nascent hypothesis, the new research recruited 85 women and 36 men aged between 40 and 65. All subjects were cognitively healthy and participated in detailed MRI and PET scans to measure four Alzheimer’s-related biomarkers, including levels of amyloid protein accumulations and rates of glucose metabolism.
Compared to the male control group, the women on average had 30 percent more amyloid accumulation, 22 percent lower glucose metabolism, and around 11 percent less gray and white matter volume. Controlling for variables, the study found menopausal status was the most consistent predictor for these Alzheimer’s biomarkers, adding some weight to the estrogen hypothesis.
"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,” says Mosconi. “The pattern of gray matter loss in particular shows anatomical overlap with the brain estrogen network."
The researchers say more work is needed before any conclusive recommendation is made regarding hormone replacement therapy for Alzheimer’s risk reduction. It is also important to remember that Alzheimer’s is a significantly heterogeneous disease, involving a complex volume of genetic and environmental factors. So obviously an estrogen decline following menopause cannot be considered a sole trigger for Alzheimer’s in women.
However, Mosconi does note her team’s research points to hormonal factors and menopausal status as potentially valuable indicators of early Alzheimer’s risk in some women.
"Our findings suggest that hormonal factors may predict who will have changes in the brain,” says Mosconi. “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."
The new study was published in the journal Neurology.
Source: American Academy of Neurology via Medicalxpress