Science, sex and Alzheimer’s

It is time to face the facts about Alzheimer’s; some old and some new.

Alzheimer’s is much more deadly than we previously thought - more than 503,000 annual deaths from the disease, according to two new reports issued last month out of Rush Alzheimer’s Disease Center in Chicago. This means that Alzheimer’s now rivals cancer as one of our nation’s most cruel and pervasive killers.

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We know, too, that women are disproportionally affected by Alzheimer’s; two-thirds of Alzheimer’s patients in the U.S. are women, and they make up nearly two-thirds of unpaid caregivers. This is not a new finding in the 2014 Fact and Figures as released by the Alzheimer’s Association.  What's new is the long overdue focus on research into sex-based differences that has become of increased interest to the scientific and research communities.

It has long been assumed that the disparity on why women are more at risk is because statistically we outlive men. Now studies are accumulating that show distinct male/female differences in the onset, course and presentation of Alzheimer’s. 

The Mayo Clinic Study of Aging reported that incidence rates for mild cognitive impairment (MCI) were higher in men than women and suggested that risk factors for MCI should be investigated separately in men and women.

The recently concluded Geoffrey Beene Global NeuroDiscovery Challenge in collaboration with the Foundation for the National Institutes of Health and in support of WomenAgainstAlzheimer’s, elicited over 800 open project rooms from 65 countries on this topic of sex-based differences in AD.

Dr. Jill Goldstein, Professor of Psychiatry and Medicine at Harvard Medical School and Director of Research for the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, who is investigating sex differences in early cognitive decline (between ages 48-65), says,  “We need to capitalize on our knowledge of sex differences in the development and aging of the memory circuitry in order to provide insights into risk factors for Alzheimer’s disease using a ‘sex-dependent lens’, which will be key for early intervention to  attenuate disability, and, ultimately, prevention.”

Studies have already demonstrated sex differences in pathology and genes associated with Alzheimer’s disease.  For example, one study reported that increased Alzheimer’s pathology was associated with a nearly 3-fold increase of  clinical Alzheimer’s in men, compared with a more than 20-fold increase in women. These data are suggesting that it takes less structural damage in women to result in the same level of cognitive impairment as men.

In an Alzheimer’s Disease NeuroImaging Initiative (ADNI ) study of brain atrophy rates, statistical mapping revealed significant age and sex differences, with rates of brain atrophy being about 1.0%-1.5% faster in women than men.

Genetic studies are also revealing AD differences between women and men.  Female carriers of APOE Ɛ4, a strong AD risk factor, have significantly more AD brain atrophy and memory disruption than men. Studies have reported evidence for greater inheritance of AD from the maternal lineage.

Reisa Sperling, M.D., Professor of Neurology at Harvard Medical School and Brigham and Women’s Hospital and Director of Harvard’s ADCS A-4 intervention (pre-symptomatic) clinical trial (launching this November) has said that “It is critical to understand the interaction of gender, genetic risk factors, and biological markers of disease pathology as we move forward with earlier interventions.”

As a benchmark, the history of heart disease research has demonstrated the importance and relevance of elucidating biologic sex differences for better-tailored detection, treatment and prevention interventions. The research focus benefited both women and men, and transformed the body politic.  It is overdue for such a concerted focus on Alzheimer’s.

Denial when faced with the facts is not only dangerous to our health; it masks our personal fears even as we look into the vacant stare in our loved ones eyes. 

How many more proof points are required for urgent political action? Five million Americans and more than 44 million people worldwide are estimated to have Alzheimer’s or dementia, and the growth trajectory of victims is one every 68 seconds. By any mindful measure, we are, indeed, a generation out of time.

Freireis is president and executive director of the Foundation for the National Institutes of Health. Comer is president of the Geoffrey Beene Foundation Alzheimer's Initiative and co-founder of  WomenAgainstAlzheimers.