Can the risk of developing FTD be changed by environmental exposures, lifestyle, diet, and other factors? Are the genetic risks fully understood? These questions are regularly asked by affected families and at-risk individuals. On January 22-24, 2025, the third annual AFTD Holloway Summit convened academic scientists, nonprofit partners, persons with lived experience, and AFTD staff and board members to discuss the state of risk factor research for FTD. Through the leadership of meeting co-chairs, Kaitlin Casaletto, PhD (UCSF) and Chiadi Onyike, MD, MHS (Johns Hopkins University), an agenda was developed that covered the current status of FTD risk factor research and what has been learnt from related fields such as Alzheimer’s or ALS that could apply to FTD.

AFTD Holloway Summits are made possible through the generous support of AFTD Board Member Kristin Holloway and the Holloway Family Fund.

“Navigating Lee’s FTD diagnosis was such a difficult and confusing time, and wondering about preceding risk factors only added to that uncertainty,” AFTD Board Member Kristin Holloway said. “While risk factor research in FTD is still early, I was proud to see researchers convened at this year’s Holloway Summit discussing the best ways to get better answers for these questions at the forefront of people’s minds impacted by FTD.”

Discussions at the Holloway Summit were based on the premise that many factors could, at least theoretically, contribute to risk of FTD. Examples include occupation, lifestyle, head trauma, exposure to pesticides or pollution, genetics, early childhood stress, and many more. A 2020 report of the Lancet Commission summarized 12 modifiable or lifestyle factors which influence likelihood of dementia later in life. These include less education in early life, in mid-life: hearing loss, traumatic brain injury, hypertension, high alcohol consumption, obesity, and in later life: smoking, depression, social isolation, physical inactivity, air pollution, and diabetes

The field of FTD has much to learn from related fields such as Alzheimer’s disease and ALS. Both have had far more research completed on this topic. Lessons learned from these related neurodegenerative diseases were woven throughout the Holloway Summit program as one mechanism to aid in the forward momentum of FTD risk factor research. Moreover, the disease mechanisms of FTD partially overlap with these diseases, raising the possibility that some conclusions from these diseases could apply to FTD.

Unfortunately, risk factor research is challenging to conduct for a disease like FTD. Large amounts of data are needed, and that data must be reliable and interpretable.  The theoretical risk factors, such as history of head trauma or environmental toxin exposure, are rarely documented reliably in sources like medical records. Even more concerning for FTD, diagnosis itself is often inaccurate. Some people are diagnosed incorrectly as having FTD while others have their FTD diagnosis missed or mislabeled as “all-cause dementia,” Alzheimer’s disease, or psychiatric disease. As a result, it is difficult to fully identify the factors directly linked to FTD onset and progression.

At the Holloway Summit, there were vibrant discussions around risk factor study design and increasing the ongoing efforts to identify risk factors for FTD. Panel discussion highlighted resources available for risk factor research and the ethical considerations for conducting and communicating risk factor research. These sessions were a few components in the program that sought to foster collaboration and accelerate risk factor research forward.

Importantly, the field of risk factor research in FTD is relatively new. While the Holloway Summit was foundational to support further research, there are no known definitive risk factors beyond genetics currently. Families touched by FTD, researchers, and clinicians, should take care when analyzing any risk factor studies, and understand that it would take repeated research, studying many people, and a significant period of time, to definitively identify a risk factor. As new scientific studies emerge, they should be interpreted with care. First, the results of any single study should be confirmed with other studies that use different or complementary methods. Such confirmation is central to the scientific approach. Even once confirmed, healthcare providers and families should not always act on the information. For example, if life-long fitness and exercise is associated with a lower risk of FTD (as it is for other types of dementia), it may not follow that a diagnosed person will have a slower rate of decline if they start exercising after diagnosis. The safety and overall benefit of action should always be central to any decision-making.

AFTD is committed to keeping the community informed about risk factor research and guiding researchers to continue these studies. A consensus article will be written by Holloway Summit attendees which will then be shared with the FTD community.

For more information about current and past Holloway Summit meetings, check out the Holloway Summit page on our website.