Influence of sleep on motor skill acquisition in children: a systematic review.

Effects of sleep on procedural (implicit) memory consolidation in children remain controversial. The aim of this systematic review was to synthesise the evidence on the influence of sleep on motor skills acquisition in children. Four electronic databases were searched: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medica Database (Embase), and Biblioteca Virtual em Saúde (BVS). Original studies, published until October 17, 2023, on motor skill acquisition in children aged ≤12 years, in which the intervention group slept after motor skill training, while the control group remained awake, were considered for inclusion. Risk of bias was evaluated using the Cochrane's Risk of Bias 2 tool. The review protocol was pre-registered at the International Prospective Register of Systematic Reviews (PROSPERO protocol number: CRD42022363868) and all reported items followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of the 7241 articles initially retrieved, nine met the primary criteria and were included in this review. Of these, six studies reported that daytime or night-time sleep intervention improved motor skill acquisition, as compared to wakefulness. All studies presented a high risk of bias. In conclusion, the evidence summarised suggests that sleep may enhance motor skills acquisition and could be important for motor development in childhood. However, due to the high risk of bias in the included studies, future randomised controlled trials with high methodological quality are necessary to better clarify this topic.

Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

BACKGROUND: The clinical picture of coronavirus disease 2019 (COVID-19)-associated sepsis is similar to that of sepsis of other aetiologies. The present study aims to analyse the role of syndecan-1 (SDC-1) as a potential predictor of septic shock in critically ill patients with COVID-19. METHODS: This is a prospective study of 86 critically ill patients due to COVID-19 infection. Patients were followed until day 28 of hospitalization. Vascular biomarkers, such as vascular cell adhesion protein-1, SDC-1, angiopoietin-1 and angiopoietin-2, were quantified upon admission and associated with the need for vasopressors in the first 7 d of hospitalization. RESULTS: A total of 86 patients with COVID-19 (mean age 60±16 y; 51 men [59%]) were evaluated. Thirty-six (42%) patients died during hospitalization and 50 (58%) survived. The group receiving vasopressors had higher levels of D-dimer (2.46 ng/ml [interquartile range {IQR} 0.6-6.1] vs 1.01 ng/ml [IQR 0.62-2.6], p=0.019) and lactate dehydrogenase (929±382 U/l vs 766±312 U/l, p=0.048). The frequency of deaths during hospitalization was higher in the group that received vasoactive amines in the first 24 h in the intensive care unit (70% vs 30%, p=0.002). SDC-1 levels were independently associated with the need for vasoactive amines, and admission values >269 ng/ml (95% CI 0.524 to 0.758, p=0.024) were able to predict the need for vasopressors during the 7 d following admission. CONCLUSIONS: Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

The double burden of malnutrition and environmental enteric dysfunction as potential factors affecting gut-derived melatonin in children under adverse environments.

Poor environmental conditions combined with continuous unhealthy and unsafe diets may substantially increase the risk of a vicious cycle of enteric infections (EED-environmental enteric dysfunction) and malnutrition (DBM-double burden of malnutrition) in children. Gut melatonin, mainly produced by the intestinal microbiota, can modulate the composition, variety, and dynamics of the microbiota itself and may affect and be affected by intestinal microbiota alterations due to DBM and EED.

Melatonin supplementation enhances pulmonary rehabilitation outcomes in COPD: a randomized, double-blind, placebo-controlled study.

Melatonin (MLT), the main product of the pineal gland, is involved in muscle tissue repair and regeneration, besides several other important physiologic functions. In COPD, MLT administration can improve lung oxidative stress and sleep quality, but its potential effects on the outcomes of pulmonary rehabilitation (PR) have not been previously investigated. A randomized controlled trial was undertaken to test the hypothesis that a combined approach of rehabilitative exercise training and MLT supplementation could maximize functional performance, health status and quality of life in patients with COPD. Thirty-nine individuals with COPD referred to a supervised PR program at the Federal University of Ceara, Brazil, were randomized to receive MLT (3 mg/day; n = 18) or placebo (n = 21). Exercise capacity (6-min walk test - 6MWT), health status (COPD assessment test), and quality of life (airways questionnaire 20) were investigated as primary outcomes. No differences were observed at baseline in demographic, anthropometric and clinical characteristics between MLT and placebo groups. At the end of PR, superiority of the MLT group was demonstrated in improvement in the distance covered in the 6MWT (71 ± 26 vs. 25 ± 36 m; p < 0.01), health status (-11 ± 6 vs. -3 ± 5; p < 0.01), and quality of life (-6.9 ± 3.0 vs. -1.9 ± 2.4; p < 0.01), compared to the placebo group. In conclusion, MLT supplementation during the course of 12 weeks of PR can improve functional capacity, health status and quality of life in patients with COPD. These findings may have significant implications for the management of this condition.

Morningness/eveningness in gestational diabetes mellitus: clinical characteristics and maternal-neonatal outcomes

ABSTRACT Objective: This study aims to evaluate the impact of morning-evening preference in pregnancy outcomes in gestational diabetes mellitus (GDM). Materials and methods: This is a prospective cohort study of 2nd-3rd trimester GDM outpatient care in Fortaleza, Brazil (2018-2020). Eveningness was defined by the Horne-Östberg Morningness-Eveningness-Questionnaire (MEQ ≤ 41). Furthermore, we obtained a 7-day actigraphic register. Subjective sleep quality, daytime somnolence, insomnia, fatigue and depressive symptoms were also evaluated. Associations with pregnancy outcomes were investigated. Results: Among 305 patients with GDM, evening preference was found in 21 (6.9%). Patients with evening preference had worse sleep quality (p < 0.01), greater severity of insomnia (p < 0.005), fatigue (p < 0.005) and depressive symptoms (<0.009). Evening chronotype was associated with preeclampsia [p = 0.01; OR = 0.27; CI 0.09-0.79] and a greater need for admission to a neonatal intensive care unit (NICU) [p = 0.02; OR = 0.23; CI .0.06-0.80]. A lower MEQ score confirmed an association with preeclampsia [p = 0.002; OR = 0.94; CI 0.90-0.97] and this was maintained after controlling for age, arterial hypertension, sleep quality, fatigue and depressive symptoms [p < 005; OR = 0.91; CI 0.87-0.95]. Conclusion: In GDM, patients with evening preference had worse sleep quality, more insomnia, fatigue, and depressive symptoms. Furthermore, eveningness was independently associated with preeclampsia. These results indicate the important role of eveningness in adverse pregnancy outcomes.

Morningness/eveningness in gestational diabetes mellitus: clinical characteristics and maternal-neonatal outcomes.

Objective: This study aims to evaluate the impact of morning-evening preference in pregnancy outcomes in gestational diabetes mellitus (GDM). Methods: This is a prospective cohort study of 2nd-3rd trimester GDM outpatient care in Fortaleza, Brazil (2018-2020). Eveningness was defined by the Horne-Östberg Morningness-Eveningness-Questionnaire (MEQ ≤ 41). Furthermore, we obtained a 7-day actigraphic register. Subjective sleep quality, daytime somnolence, insomnia, fatigue and depressive symptoms were also evaluated. Associations with pregnancy outcomes were investigated. Results: Among 305 patients with GDM, evening preference was found in 21 (6.9%). Patients with evening preference had worse sleep quality (p < 0.01), greater severity of insomnia (p < 0.005), fatigue (p < 0.005) and depressive symptoms (<0.009). Evening chronotype was associated with preeclampsia [p = 0.01; OR = 0.27; CI 0.09-0.79] and a greater need for admission to a neonatal intensive care unit (NICU) [p = 0.02; OR = 0.23; CI .0.06-0.80]. A lower MEQ score confirmed an association with preeclampsia [p = 0.002; OR = 0.94; CI 0.90-0.97] and this was maintained after controlling for age, arterial hypertension, sleep quality, fatigue and depressive symptoms [p < 005; OR = 0.91; CI 0.87-0.95]. Conclusion: In GDM, patients with evening preference had worse sleep quality, more insomnia, fatigue, and depressive symptoms. Furthermore, eveningness was independently associated with preeclampsia. These results indicate the important role of eveningness in adverse pregnancy outcomes.

Condylar Position in the Treatment of Obstructive Sleep Apnea with a Mandibular Advancement Device: A Pilot Study.

Objective To evaluate, through a tomographic analysis, the positional changes of the condyle when using a mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA), and to assess if the condylar positions influence OSA polysomnographic patterns. Materials and Methods Ten OSA patients underwent treatment with an MAD, and polysomnographic and tomographic examinations were performed before therapy (T0) and after MAD placement (T1). Results By comparing the T0 and T1 measurements, we observed advancement and extrusion of the condyles in all patients ( p < 0.001), as well as a decrease in the apnea-hypopnea index (AHI) ( p < 0.001), increases in the mean ( p = 0.001) and minimum ( p < 0.001) oxyhemoglobin saturation, and a significant correlation between the anterior displacement of the right ( p = 0.003) and left ( p = 0.015) condyles. Discussion Condylar advancement was directly correlated with OSA improvement: the greater the advancement, the better the AHI.

Exercise modifies lipid and glucose metabolism alterations induced by sleep deprivation in mice.

Insufficient sleep compromises lipid/glucose homeostasis. In opposition, exercise increases energy expenditure and has positive effects on glucose and fatty acid metabolism. Presently, it is hypothesized that exercise ameliorates metabolic dysfunction associated with sleep deprivation (SD). The effects of exercise (EX), SD and EX before SD. (EX+SD) on lipid and glucose metabolism were evaluated. Swiss mice were assigned to 4 groups (N=12, each) control, exercise (EX, 8 weeks, 1-hour of treadmill/9cm/s, 5x/week, from noon to 1:00 p.m.), SD (SD-72h, multiple platforms method), and exercise before SD (EX+SD). Exercise increased blood glucose, lactate and triglycerides (p<0.05). Both, SD and EX+SD reduced blood triglycerides (p<0.05). EX increased VLDL and reduced LDL; conversely, SD and EX+SD reduced VLDL and increased LDL. Hepatic triglycerides were markedly reduced by SD (p<0.05) and this was prevented by previous exercise (EX+SD). In summary, exercise improved essential cholesterol fractions and exercise before SD increased hepatic cholesterol and prevented hepatic triglycerides depletion.

Asthma control, social jetlag, and sleep impairment in high school adolescents.

INTRODUCTION: Social jetlag is associated with several negative health outcomes, but its impact on asthma control has not been previously investigated. Although impaired sleep is common in asthma, studies on the relationship between sleep quality, social jetlag and asthma control in adolescents are scarce. OBJECTIVE: To investigate the relationship between asthma control and sleep quality, sleep-wake pattern and excessive daytime sleepiness in adolescents. METHODS: This was a cross-sectional study of 1457 Brazilian high-school adolescents. Asthma was identified using the International Study of Asthma and Allergies in Childhood questionnaire, and disease control was measured by the Asthma Control Test. Sleep-wake pattern and social jetlag were assessed by the Munich Chrono-Type Questionnaire; sleep quality, by the Pittsburgh Sleep Quality Index; and daytime sleepiness, by the Epworth Sleepiness Scale. RESULTS: Asthma was present in 250 (17.2%) participants and was classified as uncontrolled in 120 (47.9%). Both uncontrolled and controlled asthma groups, compared with non-asthmatics, had worse sleep quality (81.7% vs 77.4% vs 56.5%; p < 0.001) and excessive daytime sleepiness (EDS: 56.2% vs 56.5% vs 39.2%; p < 0.001). On average, adolescents with uncontrolled asthma, compared to non-asthmatics, showed later sleep onset (mean ± SD: 23:54pm ± 1 h:45min vs 23:20pm ± 1 h:27min; p = 0.002) and shorter sleep duration (5.7 h ± 1.8 h vs 6.3 h ± 1.4 h; p = 0.002) on school days. No significant difference in social jetlag was found among the three groups. CONCLUSIONS: Asthma is associated with EDS and poor-quality sleep in adolescents. Social jetlag is common in these subjects and is not related to the presence and control of asthma.

A retrospective study of the influence of obesity on polysomnography and cephalometric parameters in males with obstructive sleep apnea.

OBJECTIVE: Evaluate the influence of obesity on the polysomnographic and cephalometric parameters in obstructive sleep apnea (OSA). METHODS: Fifty records of male patients with OSA, containing information on dental, medical, polysomnographic, and cephalometric exams were selected. The degree of obesity was based on Body Mass Index (BMI). Group I comprised normal or overweight individuals (BMI ≤ 29.9 kg/m2), whereas Group II consisted of obese individuals (BMI ≥ 29.9 kg/m2). RESULTS: BMI significantly correlated with apnea and hypopnea index (p < 0.0005), minimal oxyhemoglobin saturation (p < 0.0005), and two cephalometric variables (soft palate length, p = 0.01 and width, p = 0.01). Group II showed a significant correlation with the position of the hyoid bone (p = 0.02). Soft palate length and width significantly differed between groups (p = 0.014; 0.016). CONCLUSION: Obese males present wider and longer soft palate dimensions, and patients with a greater BMI present a more inferiorly positioned hyoid bone.

Hyperglycemia in pregnancy: sleep alterations, comorbidities and pharmacotherapy.

OBJECTIVE: To investigate sleep alterations and associated factors in pregnant diabetic women (n=141). METHODS: Sleep profile, sociodemographics and clinical information were collected. Poor sleep quality (Pittsburgh Sleep Quality Index >5) and excessive daytime sleepiness (Epworth Sleepiness Scale ≥10), sleep duration (h), sleep latency (min), frequent sleep interruption and short sleep (≤6 h) were assessed in type 1 diabetes mellitus (16.3%), type 2 diabetes mellitus (25.5%) and gestational diabetes mellitus (58.2%). RESULTS: Poor sleep quality was found in 58.8% of patients and daytime sleepiness in 25.7%, regardless of hyperglycemia etiology. No correlation existed between daytime sleepiness and poor sleep quality (Pearson correlation r=0.02, p=0.84). Short sleep duration occurred in 1/3 of patients (31.2%). Sleep interruptions due to frequent urination affected 72% of all and sleep interruptions due to any cause 71.2%. Metformin was used by 65.7% of type 2 diabetes mellitus and 28.7% of gestational diabetes mellitus. In gestational diabetes mellitus, parity number was independently associated with poor sleep quality (p=0.02; OR=1.90; 95%CI 1.07-3.36) and metformin use was also independently associated with poor sleep quality (p=0.03; OR=2.36; 95%CI 1.05-5.29). CONCLUSIONS: Our study originally shows that poor sleep quality and excessive daytime sleepiness are frequent in diabetic pregnancy due to different etiologies. Interestingly, only in gestational diabetes mellitus, metformin therapy and higher parity were associated with poor sleep quality.

Depressive symptoms are associated with impaired sleep, fatigue, and disease activity in women with rheumatoid arthritis.

OBJECTIVES: To investigate the associations between sleep quality, fatigue, disease activity and depressive symptoms in women with rheumatoid arthritis (RA). METHODS: Female patients with previous diagnosis of RA from a Rheumatology Outpatient Clinic at a tertiary referral centre, in Fortaleza, Brazil, were consecutively recruited into the study. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); fatigue by the Fatigue Severity Scale (FSS); daytime sleepiness by the Epworth Sleepiness Scale (ESS); and depressive symptoms by the Beck Depression Inventory II (BDI-II). RA activity was measured by the disease activity score (DAS28). RESULTS: One hundred ten women (mean age ± SD = 51.1 ± 13.0 y) were included in the study. On average, patients with depressive symptoms (BDI-II > 13), as compared to those without, showed poorer sleep quality (PSQI: 10.09 ± 4.1 vs 7.33 ± 3.55; p = 0.001 respectively), more fatigue (FSS: 4.69 ± 1.89 vs 3.34 ± 1.8; p = 0.001) and higher disease activity level (DAS28: 4.36 ± 1.53 vs 3.7 ± 1.39; p = 0,047). The logistic regression analysis showed that sleep quality is an independent predictor of depressive symptom severity. CONCLUSION: Depressive symptoms, impaired sleep and fatigue are common in women with RA. Poor sleep is associated with greater frequency and severity of depressive symptoms in these patients, suggesting that screening for sleep and mood problems may be relevant both in clinical research and routine patient care. Future studies investigating the impact of measures to promote healthy sleep on depressive symptom control in this patient population are warranted.

Hyperglycemia in pregnancy: sleep alterations, comorbidities and pharmacotherapy

SUMMARY OBJECTIVE: To investigate sleep alterations and associated factors in pregnant diabetic women (n=141). METHODS: Sleep profile, sociodemographics and clinical information were collected. Poor sleep quality (Pittsburgh Sleep Quality Index >5) and excessive daytime sleepiness (Epworth Sleepiness Scale ≥10), sleep duration (h), sleep latency (min), frequent sleep interruption and short sleep (≤6 h) were assessed in type 1 diabetes mellitus (16.3%), type 2 diabetes mellitus (25.5%) and gestational diabetes mellitus (58.2%). RESULTS: Poor sleep quality was found in 58.8% of patients and daytime sleepiness in 25.7%, regardless of hyperglycemia etiology. No correlation existed between daytime sleepiness and poor sleep quality (Pearson correlation r=0.02, p=0.84). Short sleep duration occurred in 1/3 of patients (31.2%). Sleep interruptions due to frequent urination affected 72% of all and sleep interruptions due to any cause 71.2%. Metformin was used by 65.7% of type 2 diabetes mellitus and 28.7% of gestational diabetes mellitus. In gestational diabetes mellitus, parity number was independently associated with poor sleep quality (p=0.02; OR=1.90; 95%CI 1.07-3.36) and metformin use was also independently associated with poor sleep quality (p=0.03; OR=2.36; 95%CI 1.05-5.29). CONCLUSIONS: Our study originally shows that poor sleep quality and excessive daytime sleepiness are frequent in diabetic pregnancy due to different etiologies. Interestingly, only in gestational diabetes mellitus, metformin therapy and higher parity were associated with poor sleep quality.

Depressive symptoms are associated with impaired sleep, fatigue, and disease activity in women with rheumatoid arthritis

Abstract Objectives: To investigate the associations between sleep quality, fatigue, disease activity and depressive symptoms in women with rheumatoid arthritis (RA). Methods: Female patients with previous diagnosis of RA from a Rheumatology Outpatient Clinic at a tertiary referral centre, in Fortaleza, Brazil, were consecutively recruited into the study. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); fatigue by the Fatigue Severity Scale (FSS); daytime sleepiness by the Epworth Sleepiness Scale (ESS); and depressive symptoms by the Beck Depression Inventory II (BDI-II). RA activity was measured by the disease activity score (DAS28). Results: One hundred ten women (mean age ± SD = 51.1 ± 13.0 y) were included in the study. On average, patients with depressive symptoms (BDI-II > 13), as compared to those without, showed poorer sleep quality (PSQI: 10.09 ± 4.1 vs 7.33 ± 3.55; p = 0.001 respectively), more fatigue (FSS: 4.69 ± 1.89 vs 3.34 ± 1.8; p = 0.001) and higher disease activity level (DAS28: 4.36 ± 1.53 vs 3.7 ± 1.39; p = 0,047). The logistic regression analysis showed that sleep quality is an independent predictor of depressive symptom severity. Conclusion: Depressive symptoms, impaired sleep and fatigue are common in women with RA. Poor sleep is associated with greater frequency and severity of depressive symptoms in these patients, suggesting that screening for sleep and mood problems may be relevant both in clinical research and routine patient care. Future studies investigating the impact of measures to promote healthy sleep on depressive symptom control in this patient population are warranted.(AU)

Adaptation of the night eating questionnaire for Brazilian adolescents.

INTRODUCTION: Night Eating Syndrome (NES) is characterized by a delay in the circadian rhythm of food intake and affects 1.5% of the general population, occurring more frequently in obese people. The Night Eating Questionnaire (NEQ) was originally developed for the American adult population. It is a self-administered instrument widely used in the identification and follow-up of individuals with NES. Although the NEQ has been translated and validated for Brazilian adults, there are no reports of its adaptation for use in Brazilian adolescents. The present study aimed to adapt and evaluate reliability and reproducibility of the NEQ for Brazilian adolescents. MATERIAL AND METHODS: Initially, a semantic adaptation of the Portuguese version of the NEQ was performed by 3 professionals with experience with adolescents. The suggested text was analyzed and consolidated item by item by the researchers and then presented to 21 adolescents from an intermediate school in Fortaleza. The questions with low level of understanding (<90%) were modified and the questionnaire was re-applied to 23 adolescents, obtaining satisfactory understanding. RESULTS: The version of the NEQ for Brazilian adolescents, compared to the adult version, contains changes in items 3, 5, 6, 7 and 13. The questionnaire was administered to 463 students aged 11 to 17 years (mean ± SD = 13.7 ± 1.2), from 3 schools. The internal consistency, measured by the Cronbach's alpha coefficient, was 0.73. The reproducibility that was measured after one week in 27 adolescents was 0.92 (95% CI 0.82-0.96). CONCLUSION: The new version of the NEQ for Brazilian adolescents presents excellent reproducibility and good internal consistency and is a simple and useful instrument to evaluate nocturnal eating symptoms in this age group.

Chronotype in bipolar disorder: an 18-month prospective study

Objective: Circadian dysregulation plays an important role in the etiology of mood disorders. Evening chronotype is frequent in these patients. However, prospective studies about the influence of chronotype on mood symptoms have reached unclear conclusions in patients with bipolar disorder (BD). The objective of this study was to investigate relationship between chronotype and prognostic factors for BD. Methods: At the baseline, 80 euthymic BD patients answered a demographic questionnaire and clinical scales to evaluate anxiety, functioning and chronotype. Circadian preference was measured using the Morningness-Eveningness Questionnaire, in which lower scores indicate eveningness. Mood episodes and hospitalizations were evaluated monthly for 18 months. Results: Among the BD patients, 14 (17.5%) were definitely morning type, 35 (43.8%), moderately morning, 27 (33.7%) intermediate (neither) and 4 (5%) moderately evening. Eveningness was associated with obesity or overweight (p = 0.03), greater anxiety (p = 0.002) and better functioning (p = 0.01), as well as with mood episodes (p = 0.04), but not with psychiatric hospitalizations (p = 0.82). This group tended toward depressive episodes (p = 0.06), but not (hypo)mania (p = 0.56). Conclusion: This study indicated that evening chronotype predicts a poor prognostic for BD. It reinforces the relevance of treating rhythm disruptions even during euthymia to improve patient quality of life and prevent mood episodes.

Sleep duration and daytime sleepiness in a large sample of Brazilian high school adolescents.

OBJECTIVE: To investigate the prevalence and main factors associated with short and long sleep duration and excessive daytime sleepiness in Brazilian adolescents. METHODS: This was a cross-sectional study of 11.525 students of both genders, aged 14-17 years, from the public high-school system. Sleep duration was assessed by self-report and <8 h of sleep per day was considered short sleep and >10 h, long sleep. Socio-demographic and behavioral factors were investigated through a purpose-built questionnaire and daytime somnolence was assessed by the Epworth sleepiness scale (ESS). RESULTS: The overall prevalence of short and long sleep was 54.7% and 3.3%, respectively. Frequency of short sleep was lowest in the afternoon shift (38.2%) and highest in the morning shift (62.9%) and full-day students (70.0%). Insufficient sleep was more frequent in working (63.0%) than non-working adolescents (53.1%; p = 0.001) and among those who used their cell phone before bedtime (56.3%) compared to non-users (49.7%, p = 0.001). On average, ESS score was higher in subjects with short and long sleep (respectively, 9.7 ± 4.4 and 10.0 ± 4.5) compared to those with normal sleep duration (8.9 ± 4.2; p = 0.001). CONCLUSION: Insufficient sleep and excessive daytime sleepiness are very common among urban high-school Brazilian adolescents. Full day and morning school shifts are associated with short sleep and daytime somnolence, suggesting later start times may have a role in reducing sleep loss in these subjects. Older age, work activity, and cell phone use before bedtime, are also risk factors for of short sleep in adolescents. Although less common, long sleep can also be associated with excessive daytime sleepiness.

Exercise effects on brain and behavior in healthy mice, Alzheimer's disease and Parkinson's disease model-A systematic review and meta-analysis.

This systematic review and meta-analysis examines how exercise modifies brain and behavior in healthy mice, dementia (D) and Parkinson disease (PD) models. A search was performed on the Medline and Scopus electronic databases (2008-2019). Search terms were "mice", "brain", "treadmill", "exercise", "physical exercise". In the total, 430 were found but only 103 were included. Animals n = 1,172; exercised 4-8 weeks (Range 24 h to 32 weeks), 60 min/day (Range 8-120 min per day), and 10/12 m/min (Range 0.2 m/min to 36 m/min). Hippocampus, cerebral cortex, striatum and whole brain were more frequently investigated. Exercise improved learning and memory. Meta-analysis showed that exercise increased: cerebral BDNF in health (n = 150; z = 5.8, CI 3.43-12.05; p < 0.001 I2 = 94.3 %), D (n = 124; z = 4.18, CI = 2.22-9.12; p < 0.001; I2 = 93.7 %) and PD (n = 16 z = 4.26, CI 5.03-48.73 p < 0.001 I2 = 94.8 %). TrkB improved in health (n = 84 z = 5.49, CI 3.8-17.73 p < 0.001, I2 = 0.000) and PD (n = 22; z = 3.1, CI = 2.58-67.3, p < 0.002 I2 = 93.8 %). Neurogenesis increased in health (n = 68; z = 7.08, CI 5.65-21.25 p < 0.001; I2 17.58) and D model (n = 116; z = 4.18, CI 2.22-9.12 p < 0.001 I2 93.7 %). Exercise augmented amyloid clearance (n = 166; z = 7.51 CI = 4.86-14.85, p < 0.001 I2 = 58.72) and reduced amyloid plaques in D models (n = 49; z = 4.65, CI = 3.94-15.3 p < 0.001 I2 = 0.000). In conclusion, exercise improved brain and behavior, neurogenesis in healthy and dementia models, reduced toxicity and cerebral amyloid. Evidence regarding inflammation, oxidative stress and energy metabolism were scarce. Studies examining acute vs chronic exercise, extreme training and the durability of exercise benefit were rare. Vascular or glucose metabolism changes were seldom reported.