Alzheimer's disease/dementia

Alzheimer's disease (AD) is a chronic disease that is poorly understood and has no known prevention or cure. Treatment is aimed at slowing its progression. It is characterized by loss of function of nerve cells in the brain leading to the loss of mental functions such as memory, learning, and reasoning. AD is a major cause of dementia, a term used to refer to the group of symptoms associated with the loss of intellectual functions. Most often dementia and AD are used interchangably. I will do this here. AD/dementia is strongly linked with age; the older a person gets, the greater the risk. There is evidence for a genetic predisposition.

Although women and men develop AD/dementia at about the same rate, (the number of new cases each year) the prevalence rate is higher for women than men (there are many more women living with this disorder). This is simply because women live significantly longer than men (about 6 years longer).

It is only very recently that AD/dementia has been constructed as primarily a woman's disease that is supposedly due to menopause and estrogen as a possible prevention strategy. Those who are doing so typically use the prevalence rate (more women living with AD/dementia than men) to suggest that this disease is due to estrogen deficiency. But there is no convincing evidence that the reduced amount of estrogen, normal for women who have completed the menopause, is linked to AD/dementia. If women died as early as men did, there would be no difference in this disorder between the sexes. Therefore, it is women's longer life, not their hormone levels, that is responsible for more women than men living with AD/dementia.

What about evidence that estrogen use decreases the risk of AD/dementia or slows its progression? There have been many studies examining this question. In 1998, Kristine Yaffe and colleagues (1) performed a literature search of the smaller, shorter term studies published through June 1997. The results were mixed. Some showed, on average, a lower level of cognitive functioning among estrogen users compared to nonusers, others showed no difference and still other studies showed an increased cognitive function. The authors concluded that substantial methodological problems are responsible for the conflicting results and there is no convincing evidence for a benefical effect of hormones. A year earlier, Beckmann (2) had reviewed the same literature and concluded that there was evidence for a beneficial effect.

The two statements given below are cogent examples of how the perspectives of the reviewers shape their conclusions. Remember, both reviewed the same studies, yet they propose opposite recommendations. The first is from the review by Beckmann, the second from the review by Yaffe and colleagues.

"Given the proven value of ERT for most women for other indications, this probable additional benefit is welcome." (1) p297.

"Given the known risks of estrogen therapy, we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed." (2) p688.

Since these two literature reviews, adequate trials have been completed. One is a large scale observational study and the other, a fairly large scale randomized clinical trial Neither of these trials showed a beneficial effect. In the Nurses Health Study, the largest on-going observational study of women in the United States, neither current nor long-term hormone users, age 70-78, performed better on an assortment of tests of reasoning and recall or on overall cognitive functioning than never users (3). In the Alzheimer's Disease Cooperative Study, the largest and longest randomized clinical trial to date examining the effects of estrogen as a treatment for women with mild to moderate Alzheimer's disease, no improvement or stability in cognition was found in estrogen users compared with the placebo group (4).

The Council on Scientific Affairs reviewed the guidelines on the diagnosis and treatment of Alzheimer's disease from various organizations and found insufficient information from which recommendation for the use of estrogen could be made (5).

In contrast to the lack of benefit of hormone use for AD/dementia, a large scale randomized clinical trial (6) examining the relationship between ginkgo biloba and AD/dementia found a slowing in the progression of AD/dementia in both women and men. Other smaller studies have also find beneficial effects. In some European countries, ginkgo biloba is currently being used to prevent or slow the progression of AD/dementia.

Heart disease and osteoporosis have been studied far more extensively than AD/dementia and there still continues to be controversy over the long-term use of estrogen to reduce the risk of these diseases. It is surprising, therefore, that advocates of medicalized menopause suggest that exogenous estrogen might benefit women's cognitive functioning. Given the evidence, it seems much more prudent to suggest the use of ginkgo biloba, a low-risk plant extract to reduce the risk of AD/dementia or slow its progression than it is to suggest high-risk hormones. I should add that the use of gingko biloba is not advised for people on blood thinning agents.

References
1. Beckmann, C.R. Alzheimer's disease: an estrogen link? Curr Opin Obstet Gynecol 1997; 9: 295-299.

2. Yaffe, K. et al. Estrogen therapy in postmenopausal women. JAMA 1998; 279: 688-695, 1998.

3. Grodstein, F. et. al. Postmenopausal hormone therapy and cognitive function in healthy older women. J Am Geriatr Soc. 2000; 48: 746-752.

4. Mulnard, R.A., et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer's disease: A randomized controlled trial. Alzheimer's disease cooperative study. JAMA 2000; 283:1007-1015.

5. Report of the Council on Scientific Affairs. Alzheimer disease: Adverse effects. Arch Fam Med. 8: 347-353, 1999.

6. Le Bars, PL et al. A placebo-controlled, double-blind, randomized trial of an extract of ginkgo biloba for dementia. JAMA 1997; 276: 1327-32.