A new long-term study from the National Institute on Aging (NIA) suggests that use of estrogen replacement therapy (ERT) by
post-menopausal women may help slow normal age-related decline in memory. By looking at estrogen use in 288 women
enrolled in the NIA's Baltimore Longitudinal Study of Aging (BLSA) between 1978 and 1994, researchers were able to
examine the relationship between estrogen therapy and short-term visual memory.
The study, in the December 1997 issue of Neurology (Vol. 49), is the first to document the effects of estrogen on age-related changes in memory over a long period of time. The investigators collected information on ERT use during visits to the NIA for
memory testing as part of the BLSA and were able to show that women who were on ERT during the memory testing period
performed better than women who had never received treatment. Furthermore, some participants who began ERT between
their regular visits to the NIA were able to maintain stable memory performance whereas women who never took ERT
showed predicted age-associated decreases in memory over a six year period, on average.
These findings may be of interest to the 36 million women in this country who have been through menopause, and may be
another factor to take into consideration when thinking about starting ERT. Estrogen replacement is not recommended for all
post-menopausal women; often, use of estrogen and an additional hormone, progestin, is advised.
This study of significant long-term effects of ERT on memory was made possible by use of health data from the BLSA, which,
now entering its 40th year, is one of the largest and longest ongoing studies of aging in existence. Using the BLSA database,
the researchers looked at 116 women on ERT and 172 who had never used any type of hormone replacement therapy.
On each visit to the NIA, the women in the BLSA were given the Benton Visual Retention Test (BVRT) where they were
shown a series of figures for 10 seconds and then asked to reproduce each figure from memory. The BVRT uses up to 10
different figures in each testing session. Dr. Susan Resnick, Ph.D, principal investigator of the study, says, "because there is no
maximum number of errors that can be scored during the BVRT, one way to evaluate performance on the test is to examine
the average difference in the number of errors between follow-up visits to the BLSA. Women who were on ERT showed an
average difference of about 2 fewer errors than women who were never treated with ERT, which is a significant difference."
Previous studies have indicated that verbal memory may be affected by ERT use, but this study is one of the first documenting
an effect on visual memory. The effects of ERT on visual memory decline are smaller than those seen in studies on verbal
memory decline and may only be evident in studies like this one that include larger numbers of subjects. These findings, in
combination with previous studies of verbal memory, suggest that ERT may influence different types of memory.
Age-associated increases in errors in the BVRT have been recorded for some participants in the BLSA since 1960. With the
help of 34 years of follow-up, NIA investigators have previously shown that BVRT performance can predict cognitive
performance as much as 16 to 22 years into the future, and that declines in BVRT performance can be seen in a six-year
interval preceding the onset of symptoms of age-associated disease including Alzheimer's disease. Earlier studies from the
BLSA and elsewhere have shown that ERT may reduce the risk for Alzheimer's disease.
Dr. Resnick states that "animal studies show that estrogen can directly influence structural characteristics of neurons in the
brain, particularly in regions that are important for new learning. These regions are also most vulnerable to neuron loss seen in
Alzheimer's disease. Thus, lessening the effects of these changes with ERT holds promise as a drug intervention." Dr. Resnick
cautions that before anyone can advocate use of ERT to slow cognitive decline or prevent Alzheimer's disease, results from
double-blind, controlled clinical trials are needed. ERT trials supported by the NIA are in the planning stages or currently in
E. Jeffery Metter, M.D. and Alan B. Zonderman, Ph.D. are the other authors of this paper. The BLSA will celebrate its 40th
anniversary in 1998 and currently has over 1,200 research participants enrolled in its studies.
The National Institute on Aging is the major Federal funding agency for Alzheimer's disease research, and leads the Federal
effort supporting basic, clinical, epidemiological, and social research on aging and the special needs of older people.
For more information on Alzheimer's disease, please contact the NIA's Alzheimer's Disease Education and Referral Center at
1-800-438-4380. B-roll of Alzheimer's disease studies is available from the NIA by calling (301) 496-1752