Emerging evidence has linked higher rates of hot flashes with cognitive decline. However, the underlying mechanism that differentiates women at risk for this decline is not known. It is vital to understand the connection between hot flashes and their long-term effects to prevent the cognitive decline and provide adequate treatment if it has developed.
Research Model
Impaired Glucose Delivery Model of Vasomotor Symptoms
Activation of CNS neurons from resting states generates both increased glucose consumption in the brain and glucose transport at the blood brain barrier (BBB) since glucose is not stored (Chih & Roberts, 2003).
Neuron activation leads a neurovascular coupling response to increases in blood vessel diameter and blood flow to provide adequate blood supply to meet the nutrient needs (Harder, et al. 1998).
Neurobarrier coupling then upregulates GLUT 1, a carrier protein for facilitated diffusion in the endothelial cells of the blood brain barrier (Leybaert, 2005). This process, however, is estrogen dependent: estrogen augments GLUT 1 in the cerebral cortex (Cheng 2001), enabling rapid response to changing glucose needs that are associated with brain activation.
In an effort to keep brain glucose levels stable, GLUT 1 responds to glucose concentrations in the blood with down-regulation during periods of increased glucose concentrations, and with enhanced production in response to glucose decline (Rydzewski, Wozniak, & Raizada,1991).
As estrogen declines during the menopausal transition, neurobarrier coupling with upregulation of GLUT 1 is limited and the hot flash is proposed to be the result of an exaggerated response of the neurovascular coupling system (Dormire, 2009).
Objectives
The purpose of this study is to identify cognitive stressors that reliably stimulate a hot flash in symptomatic women. This will allow further studies to effectively stimulate a hot flash.
Design
The research was designed to answer the following questions:
- Is stressor difficulty related to HF stimulus effectiveness in symptomatic women?
- Does blood glucose mediate the relationship between cognitive stimulation of HF?
- Is time of day of the experiment related to HF stimulus effectiveness?
- Do individual characteristics mediate the relationship between hot flash and cognitive stress? (age, education, ethnicity, marital status, and years since LMP)
To answer these questions, we used a quasi-experimental time series design. We gave four cognitive tasks in a random order to each participant.
Participants
Participants were primarily recruited using a bulk email in the Texas A&M University system. For additional recruitment, an advertisement was placed in a local newspaper, The Eagle. The sample consisted of 29 women, ranging from ages 45-65.
Inclusion criteria consisted of being 45-60 years old, English speaking, and symptomatic for menopausal hot flashes with at least 7 hot flashes per day. A woman's most recent menstrual period must have been over 6 months ago. The women must be Non-Hispanic Black, Non-Hispanic White, or Hispanic.
Exclusion criteria consisted of currently taking hormone therapy, having a pacemaker or implantable defibrillator, and being allergic to adhesive or tape. Other exclusion criteria included planning to travel by air during the study period and women who cannot read, speak, or understand English. Also, men were excluded from the study.
Method
volunteers meeting inclusion criteria were scheduled for the initial study visit. After completion of the informed consent, a skin conductance and continuous glucose monitor were each applied to obtain 5 days of assessment data in the ambulatory setting.
On day 5 participants were scheduled for cognitive testing. Participants completed four cognitive tasks in random order - the Stroop task (hard and easy) and the n-back task (1-back and 3-back) - with a three-minute music interludes as a washout period between testing scenarios. Upon completion of the testing, participants were fed a standard meal, provided compensation for participation, and the monitors removed. All data were downloaded to a secure website using monitor specific software. Data were stored in RedCap for security purposes.
Results
Data collection is complete and analysis using Chi-Square and logistic regression is in process. In this presentation we will report the results of testing these research questions.
Implications
This can have significant implications for management of menopause in long term. This study will increase our understanding of this phenomena, which has had limited amounts of research in the past.
This study can be improved in many ways. For example, there could be a better recruitment strategy for Hispanic women. Despite their high population in the area, a small percentage of the study’s participants were Hispanic. Also, a future study with a larger sample size is needed.
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