Vasomotor and Personal Characteristics Associated With Changes in Brain Glucose Metabolism in Menopause

With Alzheimer’s disease now classified as the sixth leading cause of death in the United States, there is no question that there is a need for a richer understanding of the etiology of the disease due to its current insurmountable prevalence. Related to questions regarding the etiology of the disease, the fact that two-thrids of patients with Alzheimer’s disease are women raises the question as to why women more than men. As a result, brain imaging studies have explored menopause as a sex-linked risk factor for Alzheimer’s Disease. These studies have demonstrated hypo-metabolism in both brains of women with hot flashes (HF) and those with Alzheimer's Disease. Because of these findings, estrogen-related changes in brain glucose transport and metabolism may result in an increased risk for Alzheimer's Disease. The objectives of this study are to explore blood glucose transport and metabolism during HF events using MRI brain images. This data will also be used to investigate the personal characteristics of symptomatic menopausal women who demonstrated cerebral activation as a result of cognitive stimulation during the MRI. These objectives strive to bridge the gap between the many questions that separate current knowledge of Alzheimer’s Disease from the cure.

Participants

Primary recruitment for the study was achieved using a mass email in the Texas A&M University system with additional recruitment through an ad in the Eagle newspaper. This study included 17 participants that ranged from 45 to 65 years old. The race distribution includes 11 non-Hispanic white women, 5 African American women, 1 Hispanic woman, and 1 Asian woman. Demographic inclusion criteria included women ages 45-60 years old, English speaking, no menstrual period in the last six months, and symptomatic for menopausal hot flashes with at least seven hot flashes per day. Exclusion criteria included those currently taking hormone therapy to manage menopausal symptoms, women with pacemakers or implantable defibrillators, MRI exclusion criteria, volunteers who cannot read, speak, or understand English, and men since they do not experience hot flashes under normal conditions.

Study Method

The research model for this study is based on finding that cognitive stimulation increases both glucose consumption in the brain and glucose transport across the blood-brain barrier through a neurovascular coupling response. This response leads to vasodilation in the brain as nutrient demands increase during neuron activation. An essential element of this response is mediated by GLUT 1, a carrier protein that relies on estrogen to efficiently and rapidly increase the production of this protein in the cerebral cortex during times of glucose decline, such as in times of cognitive stimulation. It is proposed that as estrogen declines during menopause, the upregulation of GLUT 1 is inhibited resulting in an inefficient response that leads to the vasomotor symptoms experienced during menopause. This alteration in brain glucose metabolism and transport mirrors changes that have been demonstrated in brains with Alzheimer’s Disease.

This study is designed to answer three questions. The first is whether pre-MRI glucose is associated with HF events during the MRI. The second is exploring individual characteristics, such as age, ethnicity, marital status, Utian Quality of Life scale, menarche, gravida, para, years since LMP, and type of menopause, that differentiate women who demonstrate cerebral activation during HF compared to those who do not. The third question is whether the time of day that the MRI occurred relates to HF stimulation, in order to more accurately study glucose transport and metabolism in future studies.

Participants in the study fasted for 4 hours before brain imaging using MRI. During the imaging scans, participants simultaneously performed cognitive tasks that reliably stimulated HF responses that were imaged. The participants were scanned for 5 minutes during the performance of the Stroop and N-back cognitive tasks at both easy and hard difficulties. The participants were also scanned during a 3-minute resting period that separated each of the tasks. Blood glucose measurements were obtained before and directly preceded the MRI brain imaging scan.

Results

Data collection is complete, and data analysis is in progress. The association between pre-MRI glucose reading and HF events during the MRI will be analyzed using logistic regression. Individual characteristics (age, ethnicity, education, marital status, Utian Quality of life scale, menarche, gravida, para, years since LMP, and type of menopause) that differentiate women who demonstrated cerebral activation during HF stimulation compared to those who did not will be analyzed using logistic regression. Also, the correlation between the time of day of the MRI and HF stimulation will be analyzed using logistic regression.

Conclusion and Implications

This study has several key implications for women's health including a more thorough understanding of HF physiology that can be used to prevent and treat VMS. By treating VMS, women can prevent alterations in brain glucose metabolism and transport that reflect brain alterations in Alzheimer's Disease. This significant implications for the prevention of Alzheimer's Disease in women have the potential to save countless lives and salvage millions of families from the damaging effects of Alzheimer's disease. Implications for future studies using this research model are critical. Future studies with a larger sample size and a more effective recruitment strategy for Hispanic women is necessary to explore the trends presented in this study and to formulate causative relationships between the factors explored in this study.