Estradiol and Alzheimer/Dementia Disease

This study examined whether estrogen replacement therapy affected risk for Alzheimer’s disease in 971 postmenopausal women. We found that estrogen therapy used during early postmenopause may reduce Alzheimer’s risk.

This study looked at women ages 50-63. This is consistent with other studies in showing that you have to start estrogen within approximately eight years of menopause to get significant reduction of Alzheimer’s risk. The risk reduction in this study was rather incredible: The odds ratio for estrogen users was? 0.35, (a 65% reduction in risk!) with a 95% confidence interval?of?0.19 to 0.66? statistically highly significant.

J Neurol Neurosurg Psychiatry. 2005 Jan;76(1):103-5. Postmenopausal hormone therapy and Alzheimer’s disease risk: interaction with age.

Researchers at the Mayo Clinic assessed the risk of neurologic disease among several thousand Midwestern women. They found that having had even one ovary removed before menopause, especially in women younger than 38 years, was associated with a significantly increased risk of cognitive impairment and dementia. However, when estrogen therapy was used after [ovary removal], and taken until at least age 50, no increase in cognitive impairment was found.

Rocca WA, Bower JH, Maraganore DM, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology. 2007;69:1074?1083.

This prospective study followed 472 post- or perimenopausal women for up to 16 years in the Baltimore Longitudinal Study of Aging. The relative risk for Alzheimer’s Disease in Estrogen Replacement Therapy users as compared with nonusers was 0.46 (95% CI, 0.209-0.997), indicating a reduced risk of AD for women who had reported the use of estrogen.

Our finding offers additional support for a protective influence of estrogen in Alzheimer’s Disease.

Kawas C, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology. 1997;48:1517-1521.

“We studied 1124 elderly women who were initially free of Alzheimer’s disease, Parkinson’s disease, and stroke, and who were taking part in a longitudinal study of aging and health in a New York City community. Onset of Alzheimer’s disease was significantly later in women who had taken estrogen than in those who did not and the relative risk of the disease was significantly reduced (5.8% of estrogen users vs 16.3% of nonusers; RR= 0.40 [95% CI 0.22-0.85], p < 0.01), even after adjustment for differences in education, ethnic origin, and apolipoprotein-E genotype. Women who had used estrogen for longer than 1 year had a greater reduction in risk; none of the women who were taking estrogen at study enrollment has developed Alzheimer’s disease.

Tang MX et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet. 1996;348:429-432.

In this study of hormones, memory, and mood in a healthy elderly population, 14 women who use estrogen and 41 women who do not use estrogen, whose average age was 72.1 years, were given a battery of psychological tests measuring verbal memory, visual memory, concentration and attention, language fluency and semantic memory, and mood.

Estrogen-users had higher total (p < .01) and forward (p < .001) digit span scores compared with non-users, and also had higher backward digit span scores than non-users (p < .05).

Psychoneuroendocrinology. 1998 Aug;23(6):583-603.

Studies on hormone replacement therapy and cognitive function are complicated by differences in how the studies are done.

Is it a preventative study or an interventional study? Did they use estrogen alone or estrogen with a synthetic progestin? How far post-menopause were the women when they started estrogen? But one thing all the studies had in common was that almost none of them used bio-identical estrogen. They all used Premarin (or its’ generic equivalent, conjugated equine estrogen). However, last year a study finally came out comparing the effect of Premarin and bioidentical estrogen on memory. As you might suspect, our brain seems to respond better to the natural human version.

Results: Women receiving 17-beta-Estradiol (i.e. bio-identical estrogen) showed significantly better verbal memory performance compared to women receiving conjugated equine estrogens (i.e. Premarin), regardless of age, IQ, years of education, risk factors for Alzheimer’s Disease (including APOE-4 carriership), duration of endogenous and exogenous estrogen exposure, concurrent progesterone use, or natural or surgical menopause status.

Conclusions: Verbal memory performance was better in menopausal women receiving [bio-identical estrogen] compared to [Premarin] in women with risk factors for Alzheimer’s Didease. Genetic risk for AD as well as other confounders did not affect this finding. The results suggest a differential effect of the type of Hormone Therapy on verbal memory, with [bio-identical estrogen] being a preferential compound.

Differences in verbal memory performance in postmenopausal women receiving hormone therapy: 17beta-estradiol versus conjugated equine estrogens. Am J Geriatr Psychiatry. 2011 September ; 19(9): 792?802.

What is surprising about those results is that only 43 women in their study group were taking bioidentical estrogen? and seven of those women were also taking Provera. There is strong evidence to suggest that Provera worsens verbal memory1,2, and so it’s rather remarkable that they nevertheless got statistically significant results. I suspect a larger trial using just bioidenticals would produce even stronger results.