Table 2.

Effects of PA on circulating BDNF levels. In the first six rows, single studies have been reported, while the last two rows refer to reviews/meta-analyses. In the “Conclusion” column the main results of the analyses, as well as a few comments on them, are given.

Protocol/Aims [Ref]	Subjects/Studies Included	Methods of Analysis	Conclusions
The aim of the study was to test the effects of two high-intensity exercise protocols, already known to improve cardiovascular health, to also affect BDNF levels [103]	Experiment 1: 8 men (average age: 28 years) Experiment 2: 21 men (average age: 27 years) Both experiments included: -high-intensity interval-training (HIT), at 90% of maximal work rate for 1 min, alternating with 1 min of rest; -continuous exercise (CON), at 70% of maximal work rate. Both protocols lasted 20 min.	Experiment 1: serum [BDNF] was measured at 30 min before starting the exercise, at 0, 6, 10, 14, and 18 min during the exercise, and at the end of the exercise (20 min). Experiment2: Serum BDNF was measured only at the beginning (0 min) and at the end (20 min) of the experiment. BDNF was evaluated by an enzyme-linked immunoassay (ELISA).	-Similar BDNF kinetics were observed in both protocols, with maximal BDNF level reached toward the end of training; -Both protocols (CON and HIT) significantly increased BDNF, with HIT more effective Shorter bouts of high-intensity exercise are slightly more effective than continuous high-intensity exercise for elevating serum BDNF. Moreover, 73% of the participants preferred the HIT protocol Thus, the authors suggest that the HIT is an effective and preferred intervention for elevating BDNF and potentially promoting brain health.
The aim of this analysis was to study the possible relationship between exercise intensity, memory, and BDNF [104]	16 young subjects (average age: 23 years): 9 men and 7 women	3 exercise sessions at different intensities relative to ventilator threshold (Vt) (VO2max, Vt − 20%, Vt + 20%). Each session lasted approximately 30 min. Following exercise, the Rey Auditory Verbal Learning Test (RAVLT) was performed to assess short-term memory, learning, and long-term memory recall. 24 h later, the participants completed the RAVLT recognition trial, to evaluate another measure of long-term memory. Blood was drawn before exercise, immediately post-exercise, and after the 30-min recall test. Serum BDNF was evaluated by ELISA.	Long-term memory as assessed after the 24-h delay differed as a function of exercise intensity: the largest benefits were observed with the maximal intensity exercise. BDNF significantly increased in response to exercise. However, no difference was noticed in relation to exercise intensity. Similarly, no significant association was found with memory. The authors suggest that “future research is warranted so that we can better understand how to use exercise to benefit cognitive performance”.
The aim of the study was to compare basal- and post-exercise- levels of circulating BDNF, in comparison with cognitive training and mindfulness practice [105]	19 healthy subjects (age: 65–85 years)	Exercises: (1) physical aerobic exercise at a moderate level, using a Swedish version of the EA Sports Active 2™ program on a Microsoft Xbox360™ game console connected to a Microsoft Kinect™ accessory and an ordinary TV set; (2) cognitive training through a computerized working memory training program; (3) mindfulness practice through the use of the Mindfulness App (http://www.mindapps.se/themindfulnessapp/). Each program lasted 35 min. All the participants went through all the three training programs, in a random sequence. Serum BDNF was evaluated by ELISA.	Exercise caused a significant increase in BDNF levels. Moreover, in the same subject, a single bout of exercise had a significantly higher impact on serum BDNF levels than cognitive training and mindfulness practice. However, considerable variability of BDNF responses was found when comparing different subjects.
The aim of the study was to compare the effect of ‘open-skill’ with ‘closed-skill’ exercise (as defined in terms of predictability of context situations) on BDNF production [102]	20 adult males: all subjects participated in both closed (running) and open (badminton) skill exercise sessions, in counterbalanced order on separate days. Exclusion criteria: - cardiovascular disease, diabetes, history of neurological problems, pre-existing injuries, smoking or intake of recreational drugs; hearing or vision problems.	Exercise sessions: −5 min of warm-up exercises, −30 min of running or badminton. Exercise intensity: 60% of the heart rate reserve level (HRR) During each session, venous blood samples were obtained immediately before and after exercise. Serum BDNF was evaluated by ELISA. Cognitive performance was also evaluated by a modified form of the task-switching paradigm, and controlled via the Neuroscan Stim software.	Badminton exercise resulted in significantly higher serum BDNF levels relative to running. This study provides interesting evidence in support of the benefits of open-skills exercise on BDNF production and executive function.
The aim of the study was to analyse the effect of aquarobic exercise on serum irisin and BDNF levels [106]	26 elderly women: Control group: 12 subjects Exercise group: 14	Exercise sessions: 16-week aquarobic exercise program, including two sessions a week. Each session lasted for 60 min: −10 min of warm-up, −40 min of exercise, −10 min of cool. Serum irisin and BDNF levels were evaluated (three times in the exercise group and two times in the control group) by ELISA.	Aquarobic exercises improve the serum irisin and BDNF levels.
The aim of this study was to evaluate the effect of long-term exercise on memory and biomarkers related to cognition and oxidative stress, in healthy middle-aged subjects [107]	68 healthy men: Group 1: 21 young sedentary subjects (age: 17–25 years); Group 2: 16 young trained subjects (age: 18–25 years), Group 3: 25 middle-aged sedentary subjects (age: 47–67 years) Group 4: 24 middle-aged trained subjects (age: 46–68 years). Exclusion criteria: -history of severe disease, pain, cognitive deficiencies, head trauma. -use of neuroactive or psychoactive drugs or antioxidants.	Comparison of the BDNF levels in the four groups was performed by a two-way ANOVA. The effect of PA on cognitive abilities was evaluated by a combination of neuropsychological tests, among which: the Trail Making Test, Part A and Part B, the Wechsler Adult Intelligence Scale IV Digit Span Subtest32, the Stroop Interference Test31, the Computerized tests from Cambridge Neuropsychological Test Automated Battery (CANTAB software, Cambridge Cognition, UK), and the Free and Cued Selective Reminding Test (FCSRT)33 Serum BDNF levels were measured by ELISA.	The Free and Cued Immediate Recall tests showed significant improvements in memory in the middle-aged trained individuals when compared to the sedentary ones. A significantly lower resting level of serum BDNF (and plasma Cathepsin B) was observed in both trained groups. In particular, BDNF and CTSB levels were inversely correlated with weekly hours of exercise.
The aim of the analysis was to find out any exercise-dependent correlation between BDNF concentration and aerobic metabolism in healthy subjects [100]	Studies were included when they reported BDNF analysis before and after at least one session of exercise. Total studied included: 20	Analysis based on papers collected from PubMed, Scopus, and Medline databases.	PA-induced BDNF increase is related to the amount of aerobic energy required in the exercise, in a dose-dependent manner.
Protocols: -Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) -Cochrane Handbook of Systematic Reviews of Interventions [108]	Inclusion criteria: studied conducted on adolescents trained with different exercise protocols, and including evaluations of pre- and post-intervention BDNF levels.	Data derived from PubMed, EMBASE, Scopus, ScienceDirect, Web of Science, SPORTDiscus, the Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL.	The results show that BDNF levels increase after interventions, regardless of whether the aerobic exercises were acute or chronic.