The Alzheimer’s Association created the Women's Alzheimer’s Research Initiative (WARI) to help unlock the mysteries of Alzheimer’s disease in women. A woman’s estimated lifetime risk of developing Alzheimer’s at age 65 is 1 in 6 (for men it is 1 in 11), and nearly two-thirds of the more than 5 million Americans already living with the disease are women. This disparity cannot be fully explained by women’s greater longevity and lower death rates relative to men.

With generous support from The Judy Fund and others, the Alzheimer’s Association made nine $250,000 awards in 2016 to scientists for investigations into how sex and gender contribute to dementia. These studies included:

• Whether there are sex differences in the mechanisms that underlie stress and Alzheimer’s disease
• Whether APOE4, a gene associated with the greatest increased risk of developing Alzheimer’s at age 65 or older, impacts the effects of estrogen on brain function
• Whether there are sex differences in the way risk factors interact to influence the development of Alzheimer’s

To enable more research in this promising area of dementia science, The Judy Fund has committed more than $1 million since 2017 to sponsor seven additional grants to investigators studying sex and gender in Alzheimer’s:

• Dr. Cindy Barha is studying how exercise affects the brains of men and women differently.
• Dr. Rachel Buckley is looking at the higher rates of tau protein accumulation in women and its impact on cognitive performance.
• Dr. Paola Gilsanz is studying how social and biological factors influence risk of cognitive decline and dementia in males and females.
• Dr. Karienn Montgomery’s investigation could provide new information on how nerve cell communication is disrupted in Alzheimer’s disease and how these mechanisms may differ between males and females.
• Dr. Aleph Prieto is investigating whether there could be sex-specific differences in how biological processes modulate nerve cell communication signals in the brain in Alzheimer’s.
• Dr. Adriana Strutt is exploring whether a new tool she developed called SASEI (Strutt Adult Sexual Expression Inventory) can help identify and measure changes in sexual behavior in people with Alzheimer’s and other dementias.
• Dr. Kristen Zuloaga is exploring the interplay between menopause and metabolic diseases and how it could impact the development of Alzheimer's.

All of these studies will make important contributions to inform early detection, treatment and prevention strategies for women and men alike.

This Alzheimer’s Association award to Dr. Edward Koo was the first award sponsored by The Judy Fund.

Amyloid precursor protein (APP) is the parent molecule of beta-amyloid, the protein that accumulates as “plaques” in the brain of someone living with Alzheimer’s. Plaques are one of the two hallmarks of the disease. Dr. Koo investigated how APP and its metabolic products can affect how some genes work. His results showed that APP metabolism can stimulate a gene that is involved in abnormally modifying the tau protein to form “tangles” in the brain — the other hallmark of Alzheimer’s.

“Dr. Koo’s study set the groundwork for identifying specific therapeutic targets for the treatment of Alzheimer’s,” says Heather Snyder, Ph.D., Alzheimer’s Association senior director of Medical and Scientific Relations. “His work provided support for the growing evidence to advance possible therapies, such as those that reduce inflammation.”

In 2004 The Judy Fund sponsored a five-year study by Dr. Philip D. Sloane focusing on the quality of care in assisted living facilities. With the findings from this investigation Dr. Sloane obtained a $2.5 million grant from the National Institutes of Health to develop “Alzheimer’s Medical Advisor: A Caregiver’s Guide,” which was published in July 2017.

Dr. Sloane’s work also helped shape the new Alzheimer’s Association Dementia Care Practice Recommendations, which were published in February 2018. The recommendations, targeted to professional care providers who work with people living with dementia and their families, use person-centered best practices to define quality care across all care settings and throughout the disease course.

“The number of people living with Alzheimer’s disease is growing, so there’s also a growing need for people who can care for them with skill and sensitivity,” says Joanne Pike, Dr.P.H., Alzheimer’s Association chief program officer. “Widespread adoption of these recommendations has the potential to improve quality of life for countless people living with dementia.”

In 2009 The Judy Fund sponsored a Zenith Fellows Award to Dr. Bradley Hyman for his investigation of how different forms of abnormal tau (neurofibrillary tangles or soluble tau) affect nerve cell damage and death in mouse models and human brain tissue. There are different hypotheses in the field as to the toxic form of tau, and identifying the damaging form is essential to devising an effective treatment.

Dr. Hyman’s studies have provided new insight into the role of tau in Alzheimer’s and suggest that soluble forms of tau called “oligomers” (multiple units of tau clumping together) are the toxic form and may be an important therapeutic target. Numerous efforts are underway today to target the toxic forms of tau, mainly by blocking their formation or removing them from the brain.

Mounting evidence suggests that the Alzheimer’s disease process may begin 10-20 years before clinical symptoms appear. Detecting the disease via the measure of biological changes, or “biomarkers,” is critical for developing and testing interventions that could have a major impact on the course of the disease, especially when there are no symptoms.

To help advance early detection and diagnosis of Alzheimer’s disease The Judy Fund sponsored a Zenith Fellows Award to Dr. Randall Bateman in 2011. He is using novel methods to create a simple blood-based test to measure the levels and rates of clearance of beta-amyloid to help reliably detect and understand how this protein relates to the early stages of Alzheimer’s disease.

In 2017 Dr. Bateman presented promising findings suggesting that measuring beta-amyloid in blood has potential to identify those at most risk with 89 percent accuracy. Today his work continues, and he is joined by many other scientists in this area. They are optimistic that a blood test for Alzheimer’s will be on the market in the coming years.

Recognizing the importance of the research being enabled by the Women’s Alzheimer’s Research Initiative (WARI), The Judy Fund has invested in other Association-funded projects exploring the role of sex and gender in Alzheimer’s.

Research suggests that exercise can help improve brain health and decrease the risk of dementia, but there is variation in the benefit of different exercise interventions.

Dr. Cindy Barha and colleagues are studying whether male and female brains respond in different ways to aerobic training and resistance strength training. Their findings may provide new information on how exercise affects the brains of men and women differently. A better understanding of these mechanisms could help scientists develop sex-specific, personalized exercise interventions that more effectively slow or prevent memory decline in people with mild cognitive impairment (MCI).

In 2018 the Alzheimer’s Association launched the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a two-year clinical trial led and funded by the Association that is evaluating whether a multicomponent, nonpharmalogical lifestyle intervention, including more exercise, can slow cognitive decline in older people who are at increased risk for dementia.