Two-thirds of the people suffering from Alzheimer's disease are women, yet most research has ignored differences between the sexes.
To help fill this gap, Rice University postdoctoral fellow Hannah Ballard will look at how Alzheimer's risk, estrogen levels and menopausal status interact with memory-related brain function and behavioral outcomes in women age 35-80.
Supported by a three-year grant from the National Institutes of Health (NIH), Ballard's research could help identify the physiological factors underlying differences in Alzheimer's incidence and pathology depending on sex and improve early disease detection and preventive therapies.
Even though they tend to live longer, women don't generally age as well as men, especially when it comes to Alzheimer's disease. Two-thirds of patients with Alzheimer's disease are women, and symptomology is more severe in female patients than male patients. Nonetheless, there's still an imbalance in where we're putting our money and our efforts."
Hannah Ballard, postdoctoral fellow, Rice University
As a Rice Academy Postdoctoral Fellow, Ballard will be working alongside Stephanie Leal, an assistant professor of psychological sciences and director of the Neuroscience of Memory, Mood and Aging Lab.
"The link between menopause and Alzheimer's disease has been greatly understudied," Leal said. "Women are more likely to get Alzheimer's disease, but we don't know why. The first signs of Alzheimer's disease pathology overlap with when women go through menopause, suggesting a potential relationship there that we don't know enough about. Hannah's study will be immensely important in learning more about this time of transition and how it impacts cognitive and brain health."
Ballard will use a noninvasive, saliva-based test to assess Alzheimer's risk and estrogen levels, and high-resolution brain imaging will be used to look at neurological function both at rest and during an emotional memory task.
"Emotional memory is a type of episodic memory, which is our memory for events to which we have a personal connection, or that are emotionally charged or salient," Ballard said. "It's the type of memory primarily impacted by Alzheimer's."
Even though most people diagnosed with Alzheimer's are 65 or older, disease biomarkers can be present decades prior to symptom onset.
"What's interesting is that the same time frame in middle age when we see preclinical Alzheimer's is also when women are typically transitioning to menopause," Ballard said.
Transition to menopause, or perimenopause, lasts somewhere between 1-3 years and varies widely between individuals in terms of age of onset and manner of progression.
"The perimenopausal stage is incredibly difficult to pinpoint," Ballard said. "That's why we are including women 35-80 in our study: We are trying to grasp reproductive-aged, perimenopausal and postmenopausal women so as to be able to better hone in on this time frame."
During perimenopause, estrogen levels can fluctuate considerably, impacting brain health.
"Perimenopause is a current point of interest in the field, because it's a critical period when changes are beginning to occur and estrogen declines ensue, but there's still considerable fluctuation in hormone levels as opposed to post-menopause, when estrogen stays at a stabilized low," Ballard said. "We are thinking that this transition stage might put the brain in a vulnerable state, potentially making it more susceptible to the development of age-related disease.
"Our goal is to explore this critical period that we may be able to target with therapeutic treatments, medications, etc., in order to try to prevent or defer the onset of Alzheimer's instead of just correcting symptoms once they're already occurring."
Patient-derived organoids: Transforming cancer research and personalized medicine