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Exercise and Brain Health Activities Are Associated with a Slower Rate of Frontotemporal Dementia

People with a genetic risk for frontotemporal dementia—many of whom are in the early stages of the disease—seem to benefit from exercise and engaging in activities associated with brain health: reading, games, and socializing.

Those who spent more time involved in these activities had fewer symptoms and a slower rate of progression, according to results of a longitudinal study published in January in Alzheimer's & Dementia.                                              

"It is pretty exciting to see an effect," said Kaitlin Casaletto, PhD, a neuropsychologist and assistant professor at the University of California, San Francisco Memory and Aging Center.

The findings are part of the so-called ARTFL/LEFFTES study, a multicenter study following 174 families with a history of FTD. There are 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers in the study.

The scientists collected information from genetic testing, clinical evaluations, family history, lifestyle questionnaires from patients, and interviews on functional changes in activities of daily living from caregivers. They also pulled brain scans and data on neurobehavioral testing at baseline and at different points in the study.

The investigators used the FTLD-modified global Clinical Dementia Rating Scale (FTLD-CDR) to track disease severity and administered tests to track changes in language and behavior, hallmarks of FTD.            

They measured activity with two scales: the Physical Activity Scale for the Elderly, an 11-item self-reported questionnaire that asks about all forms of exercise (recreational, household and work-related) over the past week, and the Cognitive Activity Scale.

Dr. Casaletto and her colleagues reported that greater physical and cognitive activities led to an estimated 55 percent slower clinical decline in those who carry a gene for FTD. Even leisure activities seemed to have a role in slowing cognitive decline. In fact, those who had tissue loss in their brain but reported the highest activity levels performed two-fold better on a range of cognitive tests conducted annually compared with those who spent less time on these activities.

"In other words, more active MC (mutation carriers) appeared to be defying tradition brain-behavior relationships and 'outperforming' what their brain volumes would otherwise predict," the study authors wrote.

Changes in brain volume itself did not appear to be related to this effect, although the scientists said that the number of patients in the study may have been too small.        

Dr. Casaletto cautioned that the results so far only report a correlation. "It is possible that some participants have less-active lifestyles because they have a more severe or aggressive form of FTD, which is already impacting their ability to be active," she said. "Clinical trials that manipulate cognitive and physical activity levels in people with FTD mutations are needed to prove that lifestyle changes can alter the course of the disease."                      

The findings suggest that the age-old theory of cognitive reserve may have a role in the progression of this disease—even with strong disease genes at play. It is still too early to know how long these activities will confer some protection against the biology of this disease. The scientists are now trying to understand how exercise and other lifestyle activities protect the diseased brain.                                                     

Scientists are just beginning to understand the genetic complexities of FTD. There are a range of symptoms and people with the genetic mutation in the same family will present at different times and with vastly different phenotypes.           About 50 percent of the mutation carriers were asymptomatic at the inception of the study.                                      

The scientists hope that the finding could help in developing primary prevention approaches to change the trajectory of the disease course. There have been other hints from ongoing studies following patients with autosomal AD diseases that people have better cognitive and functional outcomes if they exercise.

 "We are starting to understand that everyday behavior can affect our brains," said Dr. Casaletto. "If we can figure out the biology of these protective behaviors, it could have major implications for future interventions."                                           

Given that leisure activities were only captured by self-reporting in the current study, the UCSF team will counterbalance this limitation by adding fitness watch-like devices to objectively record activity levels in the next part of the study. The team has also started an intervention study (ACTAN) to measure the biological effects of exercise and other leisure activities in healthy older adults.

Dr. Casaletto receives research support from the NIH and Larry L. Hillblom Foundation.

Link Up to More Information

Casaletto KB, Staffaroni AM, Wolf A, et al. Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration. Alzheimers Dement 2020;16(1):91–105.