A Look at the Connection Between Menopause and Alzheimer’s

A connection has been made between menopause in women and Alzheimer’s disease. Studies have been conducted to determine the role estrogen plays in this apparent connection.

Statistically, twice as many women as men suffer from Alzheimer’s in the U.S. Current estimates suggest 5.7 million Americans are afflicted. Predictions for 2050 set the potential number at 14 million. Currently, about two-thirds of Alzheimer’s patients are women. It might be wise for researchers studying women’s health to focus less on breast cancer and reproductive matters and more on factors affecting the brain.

Studies Linking Menopause with Alzheimer’s Disease

Dr. Lisa Mosconi of Weill Cornell Medicine at Cornell University in New York and Dr. Roberta Brinton of Tucson’s University of Arizona Health Sciences, with their colleagues, performed tests to explore the link between menopause and Alzheimer’s disease in women. Their hypothesis was that metabolic alteration in the brain caused by menopause could increase the likelihood of women developing Alzheimer’s.

Researchers hoped to uncover relational factors between menopause and Alzheimer’s that would lead to diagnostic testing and interventional methods to slow down or reverse the metabolic alterations of Alzheimer’s. This, in turn, would answer the question of why women are twice as likely as men to suffer from Alzheimer’s disease in later years.

One fact that makes following the progress of Alzheimer’s disease difficult is that the neurodegeneration begins several decades before any outward symptoms are manifested.

During the study, researchers used a test called positron-emission tomography (PET) to calculate the amount of glucose, which is a catalyst for action on a cellular level, that was present in the brains of a group of women between 40 and 60 years old. The women, all in apparent good health, fit into three categories: 15 of the subjects were premenopausal, 14 were menopausal and 14 were perimenopausal (early phase menopause).

Significantly lower levels of glucose metabolism were evident in crucial areas of the brains of women who were perimenopausal or fully menopausal. Previous studies had revealed comparable findings of “hypometabolism” affecting the brains of people in Alzheimer’s earliest phases.

This group of women exhibited decreased levels of mitochondrial cytochrome oxidase, an enzyme affecting metabolism. Estrogen was also found to be deficient in menopausal and perimenopausal women.

It was noted that younger women who had undergone total oophorectomies were prone to developing Alzheimer’s earlier, which strengthens the case for low estrogen levels being a factor in the debilitating and fatal disease.

Estrogen has been found to have a neuroprotective effect on brain cells, so the lack of estrogen makes women more vulnerable to brain anomalies and dementia conditions.

Interventions to Prevent or Delay the Onset of Alzheimer’s

Studies have explored the use of hormone replacement therapy (HRT) and estrogen replacement therapy (ERT) by observing women aged 40 to 60. One group had a trial of taking conjugated equine estrogen (CEE) along with medroxyprogesterone (MPA) and the other group had a placebo ().

The study had to be discontinued early because women who received the CCE and MPA combination experienced an accelerated rate of decline compared to the placebo group. It was determined that the main type of estrogen in CEE (estrone), especially when combined with progestin, doubled the rate of mental decline when compared to placebo participants.

The study further determined that the best form of estrogen replacement is 17β-estradiol (beta-estradiol). Indeed, careful testing revealed that this substance restored the hormone balance to a range closely simulating that of the premenopausal patient.

Use of 17β-estradiol diminished forgetfulness and improved processing of verbal information and memory. It lessened the damage done by β-amyloid and tau proteins, which are active in the fundamental brain changes that preclude the pathology of Alzheimer’s. It increases the amount of transthyretin, which blocks the formation of β-amyloid that leads to plaque.

The study also identified a “window of opportunity” when the estradiol is most effective in the first five years of menopause. It needs to be taken while the brain is still intact before the breakdown process begins. At this point, the incidence of developing the disease is reduced by nearly one-third.