Her Grey Matter Matters™
by Women's Brain Health Initiative:
Alzheimer’s disease (AD) affects more women than men, and not just because women tend to live longer. Almost 70% of Canadians and Americans living with the disease are women. What is unique about women that makes their brains more vulnerable to AD?Dr. Lisa Mosconi, Director of the Women’s Brain Initiative and Associate Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College/NewYork-Presbyterian Hospital, has been investigating this question for some time and has made various discoveries that are informing the search for interventions targeting AD.
Changes in Women’s Brains During the Menopause Transition that Affect AD Risk
Using brain-imaging techniques, Dr. Mosconi and colleagues have made several important findings about what transpires in women’s brains during the menopause transition.
Perimenopausal and post-menopausal women show signs of changes in their brains that are consistent with what happens during the course of AD.
These changes are highest in the brains of post-menopausal women and intermediate in peri-menopausal women, and include:
A decline in glucose metabolism (i.e. hypometabolism). Glucose is the primary fuel source for cellular activity in the brain;
Increased accumulation of amyloid beta (Aβ). The amount of Aβ accumulation is most pronounced in menopausal women who are APOE4-positive. APOE4 is the primary genetic risk factor for late-onset AD; and
Reduced volumes of grey and white matter in AD-vulnerable regions of the brain.
Collectively, these findings indicate that AD-related changes in the brain begin early in the endocrine aging process for women, coinciding with the perimenopausal transition period. This is an important finding because it is known that AD develops over a long period of time and the outward symptoms of cognitive and memory problems do not become evident until much damage has already occurred in the brain.
These early physical changes discovered in the brains of middle-aged women will provide something for researchers to look for to indicate potential AD risk, rather than having to wait for symptoms of AD to become evident (at which time it may be too late for treatments to work effectively).“Our results suggest there may be a critical window of opportunity, when women are beginning the menopause transition, to detect signs of higher Alzheimer’s risk and apply interventions to help reduce the risk,” noted Dr. Mosconi.
The Role of Estrogen
What might be causing these changes in women’s brains at this time in their lives? Estrogen plays an important role. “All hormones are involved, but estrogen is key to regulating the entire system for energy transformation in the brain,” explained Dr. Mosconi.“
Estrogen levels decrease as women go through the menopause transition. So it’s not surprising that as estrogen levels fall, brain cells become more vulnerable to aging and disease.
If declining estrogen levels result in dysfunction in the brain, it would seem that treatments to boost estrogen levels during perimenopause and postmenopause could be beneficial for the brain. Yet, clinical trials of hormone replacement therapies (HRT) have reported mixed findings about the effects on dementia risk.This may be because of differences in the type of estrogens used, as well as the timing and length of administration. Additional research is needed to determine whether there are situations in which HRT is consistently effective, and to address concerns about safety. (Some research has found links between HRT and increased risk of heart disease, blood clots, and breast cancer.)
The Role of Genetics
As previously mentioned, APOE4 is a known genetic risk factor for AD. Dr. Roberta Brinton and colleagues investigated how the presence of APOE4 combines with poor metabolic profile (i.e. impaired glucose metabolism) and affects cognitive performance in postmenopausal women. The researchers found that the association between poor metabolic profile and a reduction in cognitive performance was more apparent in women with an APOE4 allele.
These findings – published in January 2019 in Menopause – suggest that APOE4 plays a role in cognitive function as women age in a complex way.
Not every individual who has an APOE4 allele develops AD.
Accordingly, it is likely that there are other factors that interact with this genetic factor to influence AD risk.
The Role of Inflammation
Dr. Brinton and Dr. Aarti Mishra examined the role of inflammation in an academic review published in 2018 in Frontiers in Aging Neuroscience, concluding that the inflammatory immune response might be a unifying factor that “bridges” across other risk factors for AD – in particular, age, menopause, and APOE4 genetics.It is known that inflammation is evident in the brain early in the AD process and worsens during the course of the disease. However, treatments targeting inflammation have failed in clinical trials. The complex relationship between inflammation, age, menopause, and genetics suggests a need for greater refinement when selecting patient populations to try anti-inflammatory therapies. In other words, it is possible that the effectiveness of anti-inflammatory therapies varies depending on the underlying cause of an individual’s chronic inflammation.
The Search for AD Treatments
Earlier this year, the U.S. National Institute on Aging awarded Dr. Brinton’s research lab US$5.9 million over five years to study the sex differences that influence the prevalence of AD and to search for treatments. Dr. Mosconi is Co-Principal Investigator on the grant, focusing on the brain-imaging aspects of the research. The research team is looking for therapeutic targets for precision medicine interventions for both women and men during the early stage of AD, when there is the best potential for preventing, delaying, and reversing disease progression.
Because AD is a multifactorial disease (meaning, it is a disease caused by many contributing factors), individual responses to interventions will vary. Women and men will likely require different interventions, and there may be further refinement needed even among women as a group, and men as a group.
Individuals who are at an increased genetic risk of AD may require different treatment strategies than those who have an increased risk due to certain lifestyle factors.
All of this makes the search for treatments very complex.
How to Reduce Your Risk of AD Now
It is important to keep in mind that while all women go through the menopause transition, not all women will develop AD. In fact, most women will transition through perimenopause “without experiencing any long-term adverse effects,” emphasized Dr. Mosconi. “However, a substantial proportion of women do emerge from the transition with an increased risk of neurological symptoms.”It is reassuring to know that research is currently underway seeking targeted treatments for AD.
In the meantime, there are steps that you can take now to improve your odds of not developing AD.
Scientists have estimated that one in three cases of AD are the result of modifiable risk factors. For example, there is evidence that a healthy diet can help with some of the symptoms of menopause and minimize the risk of AD. Many foods (such as soy, flax seeds, chickpeas, and garlic) naturally boost estrogen production.Antioxidants are important, too, and can be found in berries, citrus fruits, some nuts, and many leafy green vegetables. Other healthy lifestyle choices can help as well, including being physically active, participating in intellectually-stimulating activities, being social, and addressing hypertension and diabetes (if you have either of these conditions).
Source: MIND OVER MATTER V9