Long-Term Multimodal Exercise Intervention for Patients with Frontotemporal Lobar Degeneration: Feasibility and Preliminary Outcomes.

Introduction: After Alzheimer's disease, frontotemporal lobar degeneration (FTLD) is the second most common form of early-onset dementia. Despite the heavy burden of care for FTLD, pharmacological and non-pharmacological treatments with sufficient efficacy remain scarce. This study aimed to evaluate the feasibility of a multimodal exercise program for FTLD and to examine preliminary changes in the clinical outcomes of the program in FTLD. Methods: This single-arm preliminary study was conducted from July 2017 to July 2018 and recruited 4 male patients with FTLD aged 60-78 years. Patients exercised under the supervision of an exercise instructor once every 2 weeks for 48 weeks. The multimodal exercise program comprised cognitive training, moderate-intensity continuous training, strength training, balance training, and flexibility and relaxation training. Feasibility was measured using dropout and attendance rates. Cognitive, psychological, physical, and behavioral function tests were conducted before and after the intervention. Results: All patients completed the intervention (100%) and attended well (93.6%). Positive changes in scores in the Stroop Color-Word Test (cognitive; 5 out of 6 items), Mood Check List-short form 2 (psychological), movement subscales of the Stereotypy Rating Inventory (behavioral), and Timed Up and Go (TUG, physical) assessments demonstrated a medium-to-high effect size (open effect size: 0.52-0.97). While there were improvements in some domains, such as recovery self-efficacy and exercise efficacy, the MMSE-J scores showed an overall slight decline, especially in the semantic dementia case where a marked decrease was observed. Additionally, three physical function items showed no effect, except for a positive outcome in the TUG test. Functional near-infrared spectroscopy revealed increased activation in the frontal lobe, indicated by elevated oxygenated hemoglobin levels before and after the exercise intervention. This pattern of activation suggests that the intervention may have stimulated neural activity in the frontal lobe, potentially enhancing cognitive and behavioral functions, including executive function and attention. Conclusion: The long-term multimodal exercise intervention may be feasible and positively change the cognitive, psychological, physical, and behavioral functions in older adults with FTLD. Although the intervention led to improvements in certain areas, there were also declines observed in various functions, which may not necessarily be due to the intervention itself but rather reflect the natural progression of the disease.