A study published last week in Neurology, “Sex-Driven Modifiers of Alzheimer Risk,” provides new insights into why women are more than twice as likely as men to develop Alzheimer’s disease. The paper, co-authored by ADDF-funded researchers Roberta Brinton, Richard Isaacson, Dawn Matthews, and Lisa Mosconi, found that menopause was associated with higher beta-amyloid loads, lower glucose metabolism, and lower gray and white matter volumes, which are all important biomarkers for Alzheimer’s disease.
For years, researchers pointed to a simple explanation for why women have a higher risk of developing Alzheimer’s: their longevity. Aging is the major risk factor for Alzheimer’s and women live longer than men. But Alzheimer’s is a complex disease and if there is one thing we have learned, it is that the answers are not simple. Longevity alone does not explain why two-thirds of Alzheimer’s patients are women.
The current study enrolled a small sample of cognitively normal participants between the ages of 40 and 65: 85 women and 36 men. They received three neuroimaging biomarker tests. PET amyloid imaging was done to detect beta amyloid plaques, which are one of the earliest signs of Alzheimer’s disease. PET glucose scans were done to look at how their brains functioned. MRI was employed to measure the degree of neurodegeneration by looking at brain atrophy.
Natural menopause or surgical menopause by bilateral hysterectomy were associated with changes in all three biomarkers, with increased amyloid deposition, brain atrophy, and decreased brain function. In fact, menopause and hysterectomy were more strongly associated with pathological changes in the neuroimaging biomarkers than any other factor the investigators examined, including age, APOE status, family history of Alzheimer’s, medical conditions such as diabetes and elevated cholesterol, and lifestyle factors such as smoking, diet, and exercise. Of great interest, those women taking estradiol hormone therapy had fewer of the changes that indicate the onset of Alzheimer’s disease.
But as I said in a recent interview with Reader’s Digest The Healthy, while findings like these may eventually tip the scale in favor of estrogen replacement therapy for some women, more research is needed. This study was small and not designed to show cause and effect, meaning we cannot know from this study alone whether declines in estrogen caused the changes in the brain, or if something else was at play. The other important caveat is that while all women who live past their early 50’s (on average) will transition through menopause, most of them will not go on to develop Alzheimer’s. So, in addition to the question of whether estrogen is a direct cause, we also need to figure out why in some women and not others?
It is a question that needs an answer. At the time of menopause, 60 to 80 percent of women complain of memory problems, irritability and depression. With an average age of onset for Alzheimer’s at around 75, this means for those who do go on to develop the disease, there may be a 20- to 25-year period during which the disease is advancing. These are decades when we need to be focused on preventing or slowing Alzheimer’s by addressing known risks, like lowering high blood pressure, quitting smoking and getting more exercise, and developing effective drug treatments.
At the ADDF, you can be assured we’ll continue to ask challenging questions like this and fund cutting edge research to find the answers. Science, especially for complex diseases like Alzheimer’s, is a long game. My research in this area began in 1985 at Rockefeller University and I am excited that research continues to advance our understanding of how hormone changes affect development of Alzheimer’s. It is also important to note the invaluable role of Alzheimer’s biomarkers in making research like this possible, which is why our Diagnostics Accelerator is such an integral part of our quest to rapidly accelerate the discovery of drugs to prevent, treat and cure Alzheimer’s.
Sincerely,
Howard Fillit, MD
Founding Executive Director and Chief Science Officer