Physical Activity and Frontotemporal Dementia: A Narrative Review of Mechanisms and Clinical Evidence.

BACKGROUND: Frontotemporal Dementia (FTD) is a progressive neurodegenerative disorder marked by early-onset behavioral and cognitive impairments with no current disease-specific treatment. As traditional pharmacologic interventions provide only symptomatic relief and carry significant limitations, nonpharmacologic strategies such as physical activity (PA) are gaining attention as potential disease-modifying approaches. SUMMARY: This narrative review synthesizes emerging evidence on the neuroprotective effects of PA in FTD, including its possible relationship to neurotrophic signaling, neuroinflammation, mitochondrial function, and axonal integrity. Relevant literature was identified through a review of preclinical and clinical studies of PA and FTD. KEY MESSAGES: Preclinical and clinical studies suggest that PA may be associated with slower symptom progression and mild behavioral and cognitive improvements in patients with FTD. Although limited by small sample sizes, observational studies, and variability in study design, preliminary data suggest that further studies on PA and FTD are warranted, including mechanistic investigations. Randomized controlled trials are needed to establish guidelines for exercise prescriptions that can be tailored to FTD patients. Until then, supervised PA in FTD care may be considered a potential adjunct pending further validation due to its accessibility, low risk, and potential for broad therapeutic benefit.