The Power of an Active Lifestyle to Boost Cognitive Resilience – Even for Those at High Genetic Risk

May 03, 2020

Science Updates, News

As published in Dimensions Magazine - Spring 2020 

By Genevieve Wanucha

An active lifestyle in mid-life is one of the few known ways to reduce risk of Alzheimer’s disease and related dementias, according major consensus reports such as The Lancet Commission on Dementia. But what about people at risk of developing dementia at a younger age? Now, a new study adds a hopeful twist: A life full of light exercise and hobbies may slow disease progression, even for those who inherited gene mutations that cause frontotemporal dementia (FTD).

“In the scientific field of FTD, there's still a lot of skepticism about whether these types of lifestyle behaviors can really impact the brain,” says Kaitlin Casaletto, PhD, Assistant Professor of Neurology at the UCSF Memory and Aging Center and ADRC collaborator. Casaletto is the author of the new study in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. “To show that perhaps behaviors could be linked to better outcomes for people at such a high biological risk for dementia is really exciting.” 

FTD is a spectrum of neurodegenerative diseases that affect behavior, decision-making, language, or motor function, and typically begins between the ages of 45 and 65. It is the most common form of dementia in people under 65, accounting for 5 to 15 percent of dementia cases overall. Forty percent of cases are linked to several known genetic mutations. 

The results suggest that an active, healthy lifestyle can potentially enhance the capabilities of brain tissue, despite the physical change that has happened.

In this high-risk group, doctors see a wide variability in outcomes. Some people live symptom-free for longer than others, while others experience more severe disease – sometimes even members of the same family – suggesting a role of other biological or environmental factors. “We hypothesized that the activities people engage in each day of their lives may contribute to the very different trajectories we see in clinic, including when the disease develops and how it progresses,” says Casaletto. For folks who carry genetic mutations, this idea gives hope that the future isn’t set in stone.

The team studied how lifestyle differences impacted the progression of FTD in 105 people with dominant genetic mutations. These people were still asymptomatic or had experienced only mild, early-stage symptoms. The participants came from two large multisite studies, recently combined into the ALLFTD study, led by the UCSF Memory and Aging Center. The UW ADRC is one of the ALLFTD study sites and contributed participant data to this new research on resilience in FTD.

Researchers tracked the progression of participants’ disease over time, based on measures collected during annual visits. These include MRI scans to measure the amount of brain degeneration, tests of thinking and memory, and self-reports of daily cognitive and physical activity, for example, reading, jogging, taking classes, gardening, or cooking. At the same time, their family members completed assessments of how well their loved ones were doing with managing finances, medications, self-care, driving, and so on. 

Even after only two to three visits (one to two years into the ongoing study), Casaletto and her team saw significant differences in the speed of progression and severity of FTD symptoms between the most and least mentally and physically active individuals in the study, with active lifestyles showing similar effects across participants. From the family member reports, the researchers found that functional decline was 55 percent slower in the most active 25 percent of participants, compared to the least active 5 percent. 

Among participants with progressive brain atrophy detected in a follow-up MRI scan 1 year later, the most active participants continued to perform twice as well as the least active participants on cognitive tests. These results suggest that engaged lifestyles may help the brain to better withstand effects of FTD, a phenomenon called cognitive resilience.

“The results suggest that an active, healthy lifestyle can potentially enhance the capabilities of brain tissue, despite the physical change that has happened,” says Kimiko Domoto-Reilly, MD, Assistant Professor of Neurology at the UW MBWC and ADRC, and ALLFTD UW site Principal Investigator. “This is a good reminder that we can’t just look at a person’s brain scan and jump to conclusions about someone’s symptom progression.” 

As a caveat, this study reports correlation, not causation. It wasn’t designed to account for the possibility that some participants have less active lifestyles because early effects of disease are already impacting their ability or motivation to be active. “This nice paper from UCSF focusing on a small group of persons at high genetic risk for frontotemporal dementia didn’t address this concern, so there may be some doubt about whether they were finding a potentially modifiable factor or a consequence of a person’s developing early manifestations of FTD,” said Dr. Eric Larson, MD, Clinical Professor at the UW School of Public Health/Senior Investigator and Executive Director at Kaiser Permanente WA Health Research Institute. “However, the findings that a physically and mentally active lifestyle might confer resilience makes sense in the light of an abundance of existing evidence from other research.” Dr. Larson authored an influential 2006 study showing that exercise was associated with reduced risk for dementia in a community cohort of adults in the UW Adult Changes in Thought Study.

To better define the benefit of active lifestyles in FTD, the researchers plan to conduct clinical trials that manipulate cognitive and physical activity levels in people living with FTD, or at risk for developing FTD. These studies would involve taking actual measures of activity, with wearable technology, for example.

The results are welcome news to clinicians who ache to help high-risk patients interested in how to best protect their brain health. “This is a population that needs hope now – not later,” says Domoto-Reilly. “How do we jump in and help? It’s incredible to have found support for non-pharmacological interventions that are immediately implementable and customizable to what the individual already loves to do.” •



K.B Casaletto et al. Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration. Alzheimer's & Dementia, 2020.

Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Annals of Internal Medicine, 2006.

The ALLFTD Study: