Greater Focus on Sex, Gender Differences in Alzheimer's Needed

Megan Brooks

June 14, 2018

Mounting evidence suggests sex and gender differentially affect the risk, clinical presentation, and progression of Alzheimer's disease (AD), and these differences should be considered in the planning and analyses of AD studies and development of AD therapeutics, researchers advise in a new report. 

The Society for Women's Health Research Interdisciplinary Network on Alzheimer's Disease, comprising an expert panel of scientists and clinicians, reviewed ongoing research and published literature related to sex and gender differences in AD.

"There is a lack of research looking at sex and gender differences in Alzheimer's disease," Michelle Mielke, PhD, network co-chair from the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News. "There are some studies coming out showing that there may be different risk factors for men and women, but there are a lot of things that we still need to do and don't know," said Mielke.

The report was published online June 12 in Alzheimer's & Dementia.

Research Priorities

The panel identified several research priorities in sex and gender differences in AD clinical research:

  • The extent to which findings of sex and gender differences in AD are due to longevity, survival bias, and comorbidities;

  • Potential sex-specific risk factors for AD across the lifespan, including oophorectomy, menopause, pregnancy, androgen deprivation therapy, and testosterone loss;

  • The influence of estrogens and hormone therapy on brain function and AD risk in light of discrepancies in the clinical literature;

  • Potential sex differences in genetic risk factors for AD;

  • Sex differences in AD progression and the trajectory of change in cognitive function, neuroimaging, cerebrospinal fluid, and blood-based biomarkers of AD;

  • Gender differences in caregiving and how the burden of caregiving influences AD risk; and

  • Sex and gender differences in development of AD therapeutics, from preclinical to clinical studies, and in the design of clinical trials.

"The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes," the panel concludes.

More Than a Covariant

In prior studies, researchers have included sex has a covariant, "but they haven't actually looked to see if a risk factor is more important for women than men, or if there are different presentations, different rates of progression," Mielke told Medscape Medical News.

She noted that the National Institutes of Health now has a requirement where grants that are submitted are supposed to consider sex as a biological variable. "That means going beyond just adjusting for sex. We are trying to continue to promote that," Mielke said.

Heather Snyder, PhD, senior director of medical and scientific operations for the Alzheimer's Association, said, "This is a topic that we, at the Alzheimer's Association, have been heavily focused on. We know that more women than men are living with this disease and the question is, Why? Is it that they are at greater risk than men? I think that is still an outstanding question. What we do know is the underlying biology and the experience with the disease is different between women and men, and I think this paper adds to that body of literature that we continue to see grow."

"Having a better understanding of what those differences are and how they are contributing to the disease is important," Snyder told Medscape Medical News, "because ultimately when we have a therapy or when we have a diagnostic tool we need to understand how that is going to work in men and women."

Snyder noted that in 2015, the Alzheimer's Association launched the Sex and Gender in Alzheimer's funding initiative, which at that time invested over $2 million.  "We continue to make investments in this area of research and to date we have over 12 projects around $3 million dollars, really looking to answer some of these questions."

This research was supported by a grant from Eli Lilly & Co. Mielke has served as a consultant to Lysosomal Therapeutics Inc and Eli Lilly Co and receives unrestricted research grants from Biogen, Lundbeck, and Roche. A complete list of author disclosures is included in the original article. Snyder has disclosed no relevant financial relationships.

Alz Dement. Published online June 12, 2018. Abstract

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