michael mullan

Michael Mullan: Sex Differences in Alzheimer’s Disease

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Illustration to go with the review of the book, "Brainstorm: The Flaws in the Science of Sex Differences" by Rebecca Jordan-Young
Illustration to go with the review of the book, “Brainstorm: The Flaws in the Science of Sex Differences” by Rebecca Jordan-Young

Article Written by Dr. Michael Mullan

There has long been controversy over whether women or men are most affected by Alzheimer’s disease. Decades ago the perceived wisdom was that Alzheimer’s affected women more than men because women live longer than men and Alzheimer’s is a disease of aging. However, this apparent sex discrimination was challenged in subsequent studies and more recent investigations suggest that women may be at greater risk than men on an age matched basis. However, even this is controversial and may differ between populations.

For instance, some American studies report equal rates between men and women whereas European ones report a sex difference with more women than men being affected. However, several incidence studies looking at new cases of Alzheimer’s suggests that women are more readily affected than men.

Many reasons have been offered as to why there may be sex discrimination by Alzheimer pathology. One idea is that loss of sex hormones after menopause is particularly detrimental to the human brain. It’s known, for instance, that sex hormones can regulate Beta amyloid production. Cell culture studies show that estrogen and testosterone can mitigate the production of amyloid, one of the central features of Alzheimer’s.

Sex hormones may play other roles as well as regulating the amount of amyloid produced. They may have a role for instance in the breakdown of amyloid and the clearance of amyloid by other mechanisms in the brain. It’s also possible that progesterone have a protective role in the brain. Evidence suggests that after difference insults to the brain, progesterone can be protective.

While all of these observations on the sex differences have been very valuable, no therapy has yet emerged based on hormone replacement. In fact, key studies looking at hormone replacement in post-menapausal women have not shown any beneficial reduction in the risk for Alzheimer’s disease. At best, hormone replacement therapy has shown mixed results in relation to any protection against Alzheimer’s disease. Interestingly, any evidence that sex hormones are helpful in Alzheimer’s are restricted to prevention strategies rather than treatment strategies. In other words, it looks as if prolonged exposure to sex hormones may influence the rate of Alzheimer’s disease; but, once the disease is established, sex hormone therapy is not clearly protective.
So, although there is evidence that Alzheimer’s disease does indeed discriminate against women, the underlying causes are still uncertain and simple hormone replacement therapy may not be the best answer. However, more broadly, Alzheimer’s discriminates against both genders once natural hormone levels start to fall in the later decades of life.

Much more work needs to be done to understand these effects and to ask whether any of these findings can be turned into new clinical treatments for the disease.


Michael Mullan – A leader in Alzheimer’s disease research

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Michael MullanDr. Michael Mullan is CEO of the Roskamp Institute, a Sarasota, Florida based research facility. The institute conducts research on Alzheimer’s disease and other neurodegenerative disorders, as well as traumatic brain injury aftermath and potential biological markers for substance abuse. Mullan specifically works in the Roskamp Memory Disorder Clinic, where he focuses on finding treatments, and hopefully a cure, for Alzheimer’s disease, which affects approximately 5 million Americans, mostly ages 60-80.

Mullan’s inspiration for studying Alzheimer’s

On one of his blogs, Michael Mullan discusses why he focuses on Alzheimer’s in his research. He points to the amazing history of many sufferers of the disease; they have long memories over the course of lives consisting of many interesting experiences, either in the military, in business or otherwise. One of the expressions of Alzheimer’s is that short term memory deteriorates, while older memories seem more present and clear. The tendency to nostalgia for Alzheimer’s patients, he believes, is fascinating; while the short-term memory loss causes agony for the patient, as well as their families. Mullan takes pride in the fact that he has the ability to offer these people a treatment for their disease. Although it is not yet a cure, his ability to offer FDA approved drugs and treatments, as well as experimental methods the Roskamp Institute is exploring, gives hope to many people who are suffering from their loved ones’ memory loss. Being able to give people hope in dealing with such a difficult disease, which affects the entire family, is one of Mullan’s main inspirations for continuing steadfastly in his research.

The institute

The Roskamp Institute is funded by its namesake, as well as the National Institutes of Health, the U.S. Department of Defense, the Veteran’s Administration and CTAC. Their research is not just into Alzheimer’s, however; the Memory Disorder Clinic also deals with post-trauma patients, especially those with head trauma. This is the reason for many military veterans participating in the institute’s research. Mullan and his partner, Dr. Fiona Crawford, lead a team aiming to develop therapeutic methods and specific targets to achieve a deeper understanding of Alzheimer’s and its etiology. Mullan’s team discovered a genetic error which causes an excessive production of beta-amaloid. The mutation is what forms the basis for Alzheimer’s disease; it proves that there is a genetic propensity for the disease and lead this research team to begin searching for a way of understanding its presentation. Not only is Mullan’s Roskamp team searching for potential treatments for Alzheimer’s; they hope to find a cure and potentially also find ways to treat and cure some types of cancer.

The medical training of Michael Mullan

Originally trained as a medical professional at the London University, Mullan has received many awards throughout his career. His first was the Ethel Williams Scholarship for postgraduate research; already at this early point in his career, he was focused on Alzheimer’s research, which he conducted also at the Royal Free Hospital. He also earned a PhD from London University, studying molecular genetics.