Role of exercise in modulating prefrontal cortical activation for improved gait and cognition in Parkinson's disease patients.

PURPOSE: This narrative review evaluated the impact of exercise on gait and cognitive functions in patients with Parkinson's disease (PD), focusing on prefrontal cortical (PFC) activation assessed using near-infrared spectroscopy (NIRS). METHODS: A literature search was conducted in the PubMed and Web of Science databases using keywords such as "Parkinson's disease," "gait," "cognitive functions," "exercise," and "NIRS," focusing on publications from the last decade. Studies measuring PFC activity using NIRS during gait tasks in patients with PD were selected. RESULTS: The review indicated that patients with PD demonstrate increased PFC activity during gait tasks compared to healthy controls, suggesting a greater cognitive demand for movement control. Exercise has been shown to enhance neural efficiency, thus improving gait and cognitive functions. CONCLUSION: Exercise is crucial for improving gait and cognitive functions in patients with PD through increased PFC activation. This emphasizes the importance of incorporating exercise into PD management plans and highlights the need for further studies on its long-term effects and the neurobiological mechanisms underlying its benefits, with the aim of optimizing therapeutic strategies and improving patients' quality of life.

Mild exercise improves executive function with increasing neural efficiency in the prefrontal cortex of older adults.

This study examined whether a 3-month mild-exercise intervention could improve executive function in healthy middle-aged and older adults in a randomized control trial. Ultimately, a total of 81 middle-aged and older adults were randomly assigned to either an exercise group or a control group. The exercise group received 3 months of mild cycle exercise intervention (3 sessions/week, 30-50 min/session). The control group was asked to behave as usual for the intervention period. Before and after the intervention, participants did color-word matching Stroop tasks (CWST), and Stroop interference (SI)-related reaction time (RT) was assessed as an indicator of executive function. During the CWST, prefrontal activation was monitored using functional near-infrared spectroscopy (fNIRS). SI-related oxy-Hb changes and SI-related neural efficiency (NE) scores were assessed to examine the underlying neural mechanism of the exercise intervention. Although the mild-exercise intervention significantly decreased SI-related RT, there were no significant effects of exercise intervention on SI-related oxy-Hb changes or SI-related NE scores in prefrontal subregions. Lastly, changes in the effects of mild exercise on NE with advancing age were examined. The 81 participants were divided into two subgroups (younger-aged subgroup [YA], older-aged subgroup [OA], based on median age [68 years.]). Interestingly, SI-related RT significantly decreased, and SI-related NE scores in all ROIs of the prefrontal cortex significantly increased only in the OA subgroup. These results reveal that a long-term intervention of very light-intensity exercise has a positive effect on executive function especially in older adults, possibly by increasing neural efficiency in the prefrontal cortex.

Effects of physical exercise interventions on cognitive function in Parkinson's disease: An updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether physical exercise interventions can improve cognitive function, including overall performance and specific domains, in patients with Parkinson's disease (PD) and to provide potential evidence on how cognitive benefits can be optimized by exercise prescriptions. METHODS: Using PubMed, Web of Science, and Cochrane Library (from inception to August 2022), four independent reviewers screened the search results and extracted data from randomized controlled trials of physical exercise interventions in patients with PD with an outcome measure of cognitive function. Random-effects meta-analysis models were used to report standardized mean differences (SMDs) with 95 % confidence intervals (CIs). RESULTS: Twenty-one randomized controlled trials including 761 patients with PD were eligible for inclusion. Physical exercise interventions led to significant improvements in global cognitive function (SMD = 0.69; 95 % CI = 0.31 to 1.06; P < 0.001). With respect to cognitive domains, the significant effect of exercise was found on executive function (SMD = 0.94; 95 % CI = 0.05 to 1.83; P = 0.039), but not on attention/working memory, language, memory, and visuospatial function. In moderator variable analyses, the effect on global cognition was observed in combined exercise programs (SMD = 0.79; 95 % CI = 0.46 to 1.12; P < 0.001), whereas there were no significant positive effects in aerobic exercise programs, strength exercise programs, and flexibility exercise programs. In addition, exercise interventions of light-to-moderate intensity with at least 60 min in duration, and of any frequency or period, were beneficial to the global cognitive function. CONCLUSION: This updated systematic review and meta-analysis suggests that physical exercise interventions are effective in improving global cognitive function and, to a lesser extent, executive function in patients with PD. At least 60 min a day of combined exercise programs on as many days of the week as feasible may be recommended as the non-pharmacological therapeutic option to improve cognitive function.

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up.

OBJECTIVE: Although orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DESIGN: An 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. SETTING AND PARTICIPANTS: A total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. METHODS: The patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. RESULTS: The prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (ß = -0.11, 95% CI -0.20 to -0.02, t = -2.44, P = .015) and Semantic Fluency Test (SFT) (ß = -0.44, 95% CI -0.81 to -0.08, t = -2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (ß = -0.08, 95% CI -0.14 to -0.01, t = -2.20, P = .028) and SFT (ß = -0.36, 95% CI -0.63 to -0.08, t = -2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. CONCLUSIONS AND IMPLICATIONS: Both OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.

Effects of high-intensity interval training and moderate-intensity continuous training on sarcopenia-related parameters in participants with Parkinson's disease: A 24-week randomized pilot trial substudy.

OBJECTIVE: To evaluate the potential efficacy of two different supervised exercise regimens, namely high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on sarcopenia-related parameters in participants with Parkinson's disease (PD). METHODS: We analyzed data from a randomized controlled pilot trial (CRIS identifier: KCT0007130). An aerobic exercise intervention using a cycle ergometer (40-60 min) in combination with calisthenics (5 min) was performed in three sessions/week for 24 weeks for HIIT (60% maximum aerobic power for 30-50 s with 1-min rest intervals) and MICT (50% peak oxygen consumption) groups. Changes in sarcopenia-related parameters, including appendicular skeletal muscle mass (ASM), ASM index (ASM/height2), handgrip strength, 6-min walking distance, and 30-s chair-stand test (30CST) score, were compared among the HIIT (n = 9), MICT (n = 10), and usual care (n = 11) groups. RESULTS: The HIIT group showed greater increases in leg lean mass (p = 0.011), ASM (p = 0.035), and ASM index (p = 0.025), and greater improvements in 6-min walking distance (p = 0.024) and 30CST scores (p = 0.026) compared with the usual care group. However, among these parameters, only the 30CST score significantly improved in the MICT group compared to the usual care group (p = 0.002). Three of the four (75%) sarcopenic patients who underwent HIIT showed improved sarcopenia after the 24-week exercise intervention, whereas it did not improve in the sarcopenic patients included in the MICT (n = 2) and usual care (n = 2) groups. CONCLUSION: This study suggests that HIIT may be superior to MICT in improving sarcopenia in patients with PD. Further large-scale investigations are required to confirm our findings.

Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson's disease: an 8-year follow-up study.

BACKGROUND: To explore whether peripheral blood neutrophils and lymphocytes are associated with longitudinal motor and cognitive decline in patients with early Parkinson's disease (PD) and, to uncover the disease-specific mechanisms underlying these associations. METHODS: Data were obtained from the Parkinson's Progression Markers Initiative cohort. We included 376 patients with recently diagnosed, drug-naïve PD and 178 matched healthy controls. The patients underwent annual assessments, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 test to measure motor function and the Montreal Cognitive Assessment (MoCA) to measure cognitive function, for up to 8 years of follow-up. Dopamine transporter (DAT) imaging was performed at baseline and the 1-year, 2-year and 4-year follow-up visits. RESULTS: At baseline, patients with PD showed higher neutrophil and lower lymphocyte counts, resulting in a higher neutrophil-to-lymphocyte ratio (NLR) than that in healthy controls. Higher neutrophil counts were associated with a greater increase in MDS-UPDRS part 3 scores in patients with PD (estimate: 0.25, 95% CI: 0.12 to 0.37, p<0.001). Correspondingly, higher neutrophil levels were related to a greater reduction in DAT activity in the caudate (estimate: -0.007, 95% CI: -0.014 to -0.001, p=0.046) and putamen (estimate: -0.0039, 95% CI: -0.0077 to -0.0002, p=0.042). However, there were no significant effects of lymphocyte count and NLR on changes in the MDS-UPDRS part 3 and MoCA scores and striatal DAT uptake over time. CONCLUSION: Among the blood biomarkers, only a higher neutrophil count was associated with faster motor progression along with accelerated nigrostriatal dopaminergic degeneration in patients with PD. The impact of neutrophils and lymphocytes on longitudinal cognitive changes remains unclear. TRIAL REGISTRATION NUMBER: NCT01141023.

Reliability and validity of the 21-m shuttle-run test and its application to youth soccer players during the preseason training.

PURPOSE: This study has two purposes: first to assess the reliability and validity of the 21-m shuttle-run test (21-m SRT) and, second, to evaluate the practicality of the 21-m SRT for youth soccer players during preseason training. METHODS: Twenty-seven youth soccer players (15.9 ± 0.7 yrs., males) participated in the present study. To assess the reliability of the test, each player performed the 21-m SRT twice, on separate days. Criterion validity of the 21-m SRT was determined by examining the relationship between directly measured V3 O2max and 21-m SRT performance. To test the practicality of the 21-m SRT, three 21-m SRTs and two graded exercise tests on a treadmill were performed by each youth soccer player during preseason training. RESULTS: Results revealed that the 21-m SRT has high correlation coefficients (r = 0.87) between test and retest and has moderate correlation coefficients (r = 0.465) between V3 O2max and SRT performance. As V3 O2max significantly increased after the training period, SRT performance (distance and heart rate immediately after the 67th shuttle run) also positively changed during the preseason training period. CONCLUSION: The 21-m SRT has high reliability with moderate validity, and it is an effective tool for coaches to examine aerobic capacity and the efficacy of a training program for youth soccer players during the preseason training period.

Association of Early Weight Change With Cognitive Decline in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVE: To examine whether early weight change is associated with subsequent deterioration in cognitive function, including overall performance and specific domains, in Parkinson disease (PD). METHODS: This observational study used data from the Parkinson Progression Markers Initiative cohort. The patients underwent annual nonmotor assessments covering neuropsychiatric, sleep-related, and autonomic symptoms for up to 8 years of follow-up. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and detailed neuropsychological testing. Linear mixed-effects models were applied to investigate the association of early weight change with longitudinal evolution of cognitive and other nonmotor symptoms. RESULTS: A total of 358 patients with early PD were classified into weight loss (decrease of >3% body weight during the first year; n = 98), weight maintenance (within ±3%; n = 201), and weight gain (increase of >3%; n = 59) groups. The weight loss group showed a significantly faster decline in MoCA scores than the weight maintenance group (ß = -0.19, 95% CI -0.28 to -0.10). With respect to specific cognitive domains, the weight loss group showed a steeper decline in sematic fluency test scores (ß = -0.37, 95% CI -0.66 to -0.08) and MoCA phonemic fluency scores (ß = -0.18, 95% CI -0.31 to -0.05) and, to a lesser extent, Letter-Number Sequencing scores (ß = -0.07, 95% CI -0.14 to 0.01) compared with the weight maintenance group. Conversely, the weight gain group showed a slower decline in the Symbol Digit Modalities Test scores (ß = 0.34, 95% CI 0.05 to 0.63), although no association was found with longitudinal changes in MoCA scores. We did not find any significant effects of weight change on the progression of other nonmotor symptoms. DISCUSSION: Early weight loss was associated with a faster progression of decline in global cognitive function and executive function in patients with PD, whereas early weight gain was associated with a slower progression of decline in processing speed and attention. The impact of early weight change on nonmotor symptoms seemed to be specific to cognition.

The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review.

Exercise is an effective intervention for both the prevention and the treatment of obesity and insulin resistance because skeletal muscle secretes many bioactive proteins that contribute to the beneficial effect of exercise. It has been revealed that irisin plays an important role in metabolic homeostasis and both acute and chronic exercises increase circulating irisin in experimental animal models and in humans. Although previous studies have reported that the irisin-related signaling mechanism may play a beneficial role in the treatment of metabolic diseases including obesity, metabolic syndrome, insulin resistance, and diabetes mellitus, studies on whether irisin plays a key role in vascular function and vascular complications are still insufficient. Therefore, the current review aims to summarize the accumulating evidence showing the potential role of irisin, especially in vascular reactivity and vascular abnormalities such as atherosclerosis.

Trends in exercise neuroscience: raising demand for brain fitness.

Physical exercise is increasingly recognized as an important component in the neuroscience related field. What is the targeting of exercise and what accounts for the exercise's benefits observed in neuroscience? Several types of exercise have been studied in various fields across physiological, psychological, and biochemical experiments of neuroscience. However, more clarity is needed to unveil optimal exercise conditions such as frequency, intensity, type, and time. In this review, we briefly highlight the positive effects of exercise on promoting brain function. Key areas relate to exercise neuroscience are as follow: structural level with synaptic plasticity and neurogenesis, functional level with behavioral development, and molecular level with possible mechanisms that involved in exercise-induced brain plasticity. Overall, we provide the importance of understanding the exercise neuroscience and highlight suggestions for future health research.

Acute Sprint Interval Exercise Increases Both Cognitive Functions and Peripheral Neurotrophic Factors in Humans: The Possible Involvement of Lactate.

There is increasing attention to sprint interval exercise (SIE) training as a time-efficient exercise regime. Recent studies, including our own (Kujach et al., 2018), have shown that acute high-intensity intermittent exercise can improve cognitive function; however, the neurobiological mechanisms underlying the effect still remain unknown. We thus examined the effects of acute SIE on cognitive function by monitoring the peripheral levels of growth and neurotrophic factors as well as blood lactate (LA) as potential mechanisms. Thirty-six young males participated in the current study and were divided into two groups: SIE (n = 20; mean age: 21.0 ± 0.9 years) and resting control (CTR) (n = 16; mean age: 21.7 ± 1.3 years). The SIE session consisted of 5 min of warm-up exercise and six sets of 30 s of all-out cycling exercise followed by 4.5 min of rest on a cycling-ergometer. Blood samples to evaluate the changes of serum concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and blood LA were obtained at three time points: before, immediately after, and 60 min after each session. A Stroop task (ST) and trail making test (TMT) parts A and B were used to assess cognitive functions. Acute SIE shortened response times for both the ST and TMT A and B. Meanwhile, the peripheral levels of BDNF, IGF-1, and VEGF were significantly increased after an acute bout of SIE compared to those in CTR. In response to acute SIE, blood LA levels significantly increased and correlated with increased levels of BDNF, IGF-1, and VEGF. Furthermore, cognitive function and BDNF are found to be correlated. The current results suggest that SIE could have beneficial effects on cognitive functions with increased neuroprotective factors along with peripheral LA concentration in humans.

Rapid stimulation of human dentate gyrus function with acute mild exercise.

Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.

Hypoxia-induced lowered executive function depends on arterial oxygen desaturation.

Although it has been traditionally thought that decreasing SpO2 with ascent to high altitudes not only induces acute mountain sickness but also can decrease executive function, the relationship between decreased SpO2 levels and hypoxia-induced lowered executive function is still unclear. Here we aimed to clarify whether hypoxia-induced lowered executive function was associated with arterial oxygen desaturation, using 21 participants performing the color-word Stroop task under normoxic and three hypoxic conditions (FIO2 = 0.165, 0.135, 0.105; corresponding to altitudes of 2000, 3500, and 5000 m, respectively). Stroop interference significantly increased under severe hypoxic condition (FIO2 = 0.105) compared with the other conditions. Moreover, there was a negative correlation between Stroop interference and SpO2. In conclusion, acute exposure to severe hypoxic condition decreased executive function and this negative effect was associated with decreased SpO2. We initially implicated an arterial oxygen desaturation as a potential physiological factor resulting in hypoxia-induced lowered executive function.

Neural basis for reduced executive performance with hypoxic exercise.

While accumulating evidence suggests positive effects of exercise on executive function, such effects vary with environment. In particular, exercise in a hypoxic environment (hypobaric or normobaric hypoxia), leading to decreased oxygen supply, may dampen or cancel such effects. Thus, we further explore the relation between the effects of hypoxic exercise on executive function and their underlying neural mechanisms by monitoring changes of cortical activation patterns using functional near-infrared spectroscopy (fNIRS). Fifteen healthy participants performed color-word Stroop tasks (CWST) before and after a 10 min bout of moderate-intensity exercise (50%V̇O2peak) under normoxic and hypoxic conditions (fraction of inspired oxygen (FIO2) = 0.135). During the CWST, we monitored prefrontal activation using fNIRS. CWST performance under hypoxic conditions decreased compared with normoxic conditions. In addition, CWST-related activation in the left dorsolateral prefrontal cortex (DLPFC) was reduced after a bout of hypoxic exercise. There was statistically significant association between decreased CWST performance and activation in the left DLPFC. These results suggest that moderate exercise under normobaric hypoxic conditions has negative effects on executive function by reducing task-related activations in the DLPFC.

A transferable high-intensity intermittent exercise improves executive performance in association with dorsolateral prefrontal activation in young adults.

Although growing attention has been drawn to attainable, high-intensity intermittent exercise (HIE)-based intervention, which can improve cardiovascular and metabolic health, for sedentary individuals, there is limited information on the impact and potential benefit of an easily attainable HIE intervention for cognitive health. We aimed to reveal how acute HIE affects executive function focusing on underlying neural substrates. To address this issue, we examined the effects of acute HIE on executive function using the color-word matching Stroop task (CWST), which produces a cognitive conflict in the decision-making process, and its neural substrate using functional near infrared spectroscopy (fNIRS). Twenty-five sedentary young adults (mean age: 21.0 ± 1.6 years; 9 females) participated in two counter-balanced sessions: HIE and resting control. The HIE session consisted of two minutes of warm-up exercise (50 W load at 60 rpm) and eight sets of 30 s of cycling exercise at 60% of maximal aerobic power (mean: 127 W ± 29.5 load at 100 rpm) followed by 30 s of rest on a recumbent-ergometer. Participants performed a CWST before and after the 10-minute exercise session, during both of which cortical hemodynamic changes in the prefrontal cortex were monitored using fNIRS. Acute HIE led to improved Stroop performance reflected by a shortening of the response time related to Stroop interference. It also evoked cortical activation related to Stroop interference on the left-dorsal-lateral prefrontal cortex (DLPFC), which corresponded significantly with improved executive performance. These results provide the first empirical evidence using a neuroimaging method, to our knowledge, that acute HIE improves executive function, probably mediated by increased activation of the task-related area of the prefrontal cortex including the left-DLPFC.

Aerobic fitness associates with mnemonic discrimination as a mediator of physical activity effects: evidence for memory flexibility in young adults.

A physically active lifestyle has beneficial effects on hippocampal memory function. A potential mechanism for this effect is exercise-enhanced hippocampal plasticity, particularly in the dentate gyrus (DG). Within hippocampal memory formation, the DG plays a crucial role in pattern separation, which is the ability to discriminate among similar experiences. Computational models propose a theoretical hypothesis that enhanced DG-mediated pattern separation leads to "memory flexibility"-a selective improvement in the ability to overcome moderate levels of mnemonic interference. Thus, in the current cross-sectional study of healthy young adults, we tested the working hypothesis that aerobic fitness, as a physiological indicator of endurance capacity associated with physical activity, is strongly associated with mnemonic discrimination at moderate interference levels. When divided the sample (n = 75) based on a median split of aerobic fitness, the higher fitness group had better discrimination performance for moderate interference levels compared to the lower fitness group, namely, exhibited memory flexibility. Moreover, aerobic fitness levels were positively associated with discrimination performance for moderate interference levels, as a mediator of physical activity effects. This evidence suggests that aerobic fitness levels are associated with hippocampal DG-related memory, which is consistent with literature showing positive effect of physical exercise on hippocampal memory.

Acute moderate exercise improves mnemonic discrimination in young adults.

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O2peak ) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc.

The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization.

Previous studies have shown that higher aerobic fitness is related to higher cognitive function and higher task-related prefrontal activation in older adults. However, a holistic picture of these factors has yet to be presented. As a typical age-related change of brain activation, less lateralized activity in the prefrontal cortex during cognitive tasks has been observed in various neuroimaging studies. Thus, this study aimed to reveal the relationship between aerobic fitness, cognitive function, and frontal lateralization. Sixty male older adults each performed a submaximal incremental exercise test to determine their oxygen intake (V·O2) at ventilatory threshold (VT) in order to index their aerobic fitness. They performed a color-word Stroop task while prefrontal activation was monitored using functional near infrared spectroscopy. As an index of cognitive function, Stroop interference time was analyzed. Partial correlation analyses revealed significant correlations among higher VT, shorter Stroop interference time and greater left-lateralized dorsolateral prefrontal cortex (DLPFC) activation when adjusting for education. Moreover, mediation analyses showed that left-lateralized DLPFC activation significantly mediated the association between VT and Stroop interference time. These results suggest that higher aerobic fitness is associated with cognitive function via lateralized frontal activation in older adults.