Alzheimer's disease is responsible for roughly half of all cases of dementia. Alzheimer's is caused by a disease process in the brain that includes a tangling of the dendritic fibers in the nerve cell bodies. This tangling contributes to a major loss of synapses, and occurs most prominently in the areas of the brain that are involved in new learning and in memory. Alzheimer's also involves a degeneration of a protein called apolipoprotein E (Apo E), which has several subvarieties. Having the gene Apo E4 triples the risk for developing Alzheimer's. Given this genetic evidence, doctors may be able to predict which patients are likely to develop Alzheimer's. But, research on estrogen-replacement therapy offers the possibility of preventing or delaying the onset for Alzheimer's disease.
Estrogen-replacement therapy, is widely prescribed for postmenopausal women as protection against osteoporosis heart disease, and stroke. Now, it appears that there is yet another way in which estrogen might prove beneficial: it might help prevent Alzheimer's disease. The possibility that estrogen could help Alzheimer's patients is one of the hottest topics in the field (Wickelgren, 676). This hormone might protect the neurons that deteriorate in Alzheimer's. Multiple studies suggest that estrogen might prevent or delay the onset of Alzheimer's disease in women.
Neurons die at a vastly increase rate in people with Alzheimer's. Estrogen promotes the growth and survival of cholinergic neurons by raising the levels of nerve growth factors (Tang, 429). In addition, estrogen may interact with a subvariety of Apo E, but it is not yet determined how. Estrogen also appears to increase the number of connections between neurons by creating more cholinergic markers, boosting levels of an enzyme needed to make neurotransmitters (specifically acetylcholine, a neurotransmitter involved in cognitive functioning), as well as improving blood flow to the brain (Tang, 432). In rats, estrogen has been found to prevent neuronal atrophy in the hippocampus, the region of the brain associated with Alzheimer's disease and involved in memory impairment (Burns, 420).
Researchers at Columbia University conducted a study on the relationship between estrogen-replacement therapy and Alzheimer's. Researchers reported that estrogen may cut the risk of Alzheimer's by up to 60 percent (Waters, 41). Sixteen percent of the women who had taken estrogen, compared with six percent of the women who had taken estrogen, developed Alzheimer's. None of the women showed any signs of Alzheimer's at the start of the study. Their five year study also found that the longer the women took estrogen, the lower their risk of developing Alzheimer's. The women in the study who took estrogen for longer than a year gained more protection against Alzheimer's than those who were on the hormone for a shorter time. In cases where estrogen did not prevent Alzheimer's, it appeared to delay the onset of the disease by several years (Waters, 42).
A study in California replicated the findings of Columbia's study. This study included over 3,700 women and is the largest study of this sort so far. This research found that women on estrogen developed Alzheimer's less frequently that nonusers. Estrogen users in this study showed a 30 percent lower risk of developing Alzheimer's disease than women who did not use the drug. Researchers also found in this study that women taking the highest doses of estrogen had the lowest risk of Alzheimer's. And, in those women who developed Alzheimer's the age at onset for the disease was significantly later in those who used estrogen (Fackelmann, 74).
In multiple studies at McGill University in Canada, estrogen users showed increases in general cognitive and memory tasks. In these studies, older and younger women were given memory tasks as well as other baseline measures prior to estrogen administration. Then estrogen-replacement therapy was given for 60 days. After re-administering the cognitive tasks, researchers found that older women performed as well on the tasks as did younger women, and that their general skills and cognitive abilities were increased. Performance correlated with the amount of estrogen: the higher the concentration of estrogen in the blood, the better the task scores (Fackelmann, 74). Estrogen users were able to recall more information when given a short-term and long-term memory task, and performed significantly better on these tasks than did their peers. This shows that estrogen-replacement therapy may provide some protection against memory loss. In addition, reaction time, verbal ability, mental alertness, and thinking abilities were found to be improved and influenced by estrogen-replacement therapy (Fackelmann, 75).
The first double-blind, controlled study in which Alzheimer's patients received the standard estrogen dose given to post-menopausal women found improvements in Alzheimer's patients taking estrogen. Five of the six women who had mild Alzheimer's disease and wore an estrogen patch for two months showed noteworthy improvements in verbal memory and attention. A direct relationship was found between the level of estrogen in the blood, and improvement in memory. This effect disappeared when the treated women went off estrogen (Wickelgren, 677).
But, it is too early to draw causal conclusions on this benefit of estrogen. There may be other differences between women who choose to take estrogen and those who do not. Women who take estrogen tend to get better medical care, and women who take estrogen may have be better educated. These attributes may stave off Alzheimer's themselves (Waters, 42). Studies demonstrating the benefits of estrogen are not conclusive in stating that estrogen prevents or delays Alzheimer's. But, a flood of work has clearly proven that estrogen has neuronal effects consistent with a role in cognition and memory.
Estrogen is believed to increase the risk of developing uterine and breast cancer. But, for women with a family history of Alzheimer's disease, the chance that estrogen could help fend off the disease may make it worth the risk. Yet, researchers are not recommending that women take estrogen for the sole purpose of preventing Alzheimer's. A study that will be completed in 2005 should settle the question of whether estrogen helps to preserve healthy brains, and whether its benefits outweigh the costs.
Burns, Alistair. (August 17, 1996). Protection against Alzheimer's disease. Lancet, 348: 9025. 420-421.
Fackelmann, Kathleen. (February 4, 1995). Forever smart: Does estrogen enhance memory. Science News, 147: 5. 74-75.
Tang, Ming Xin. (August 17, 1996). Effect of estrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet, 348: 9025. 429-432.
Waters, Rob. (January, 1997). Estrogen to prevent Alzheimer's. Health, 11: 1. 40-42.
Wickelgren, Ingrid. (May 2, 1997). Estrogen: A new weapon against Alzheimer's. Science, 276: 5313. 676-677.
Contributed by Jill Pohlman, October 1, 1997.