Anna Pedrinolla

High-intensity treadmill training improves gait ability, VO2peak and cost of walking in stroke survivors: preliminary results of a pilot randomized controlled trial.

BACKGROUND Stroke is a major cause of death and long-term disability across the globe. Previous studies have demonstrated the trainability of stroke survivors and documented beneficial effects of aerobic exercises on cardiovascular fitness and gait ability. AIM The main aim of this study was to compare the effects of a high-intensity treadmill training (HITT) against low-intensity treadmill training (LITT) on gait ability, quality of life, cardiorespiratory fitness and cost of walking in chronic stroke subjects. DESIGN Randomized, controlled pilot study. SETTING Patients were recruited among Neurorehabilitation Unit outpatient. POPULATION The sample was composed of 16 subjects suffering from chronic stroke. METHODS Subjects were enrolled and randomly allocated either in the HITT (N.=8) or in the LITT (N.=8). Both groups performed 3-month training, 3 times per week. Subjects were evaluated before starting the training and after the end of the training by mean of clinical scales (Six-Minute Walk Test, Ten-Meter Walk Test, Health Survey Questionnaire SF-36, Stroke Impact Scale) and instrumental tests (gait analysis, VO2peak and walking energy cost). RESULTS Fifteen subjects completed the study and no dropouts were observed. One patient in the LITT refused to initiate the training. The HITT group produced greater improvements than LITT group on the Six-Minute Walk Test (HITT: 64.25 meters, LITT: 6 meters; p=0.005) and Ten-Meter Walk Test performances (HITT: -1.7 s, LITT: 0.6 s; P=0.007), stride length (HITT: 3.3 cm, LITT: 0.4 cm, P=0.003), step length non-paretic side (HITT: 0.5 cm, LITT: 2.4 cm, P=0.008), step length paretic side (HITT: 1.8 cm, LITT: 0.7 cm, P=0.004), cadence (HITT: 1.6 step/min, LITT: 0.6 step/min, P=0.021) and symmetry ratio (HITT: 0.04 cm, LITT: 0.01 cm, P=0.004), VO2peak (HITT: 4.6 mL/kg/min, LITT: 0.87 mL/kg/min; P=0.015) and walking energy cost at 100% of self-selected speed (HITT: -30.8 mL/kg∙km, LITT: -20 5 mL/kg∙km; P=0.021). Significant changes were found on Six-Minute Walk Test (P=0.012) and Ten-Meter Walk Test (P=0.042) performances, spatio-temporal gait parameters (stride length P=0.011, step length paretic side P=0.012, cadence P=0.037 and symmetry ratio P=0.012), VO2peak (P=0.025) and cost of walking at 100% of self-selected speed (P=0.018) in the HITT group. In the LITT no significant results were observed. CONCLUSIONS HITT could be considered a feasible training and led to improvement in gait ability and enhanced VO2peak and reduction in cost of walking compared to LITT. CLINICAL REHABILITATION IMPACT Chronic stroke survivors should be encouraged to engage regular aerobic treadmill training at medium/high intensity. HITT is safe and feasible and has positive effects on gait ability, cardiovascular fitness and cost of walking in subjects with stroke in chronic phase.

Age-Associated ALU Element Instability in White Blood Cells Is Linked to Lower Survival in Elderly Adults: A Preliminary Cohort Study.

Background ALU element instability could contribute to gene function variance in aging, and may partly explain variation in human lifespan. Objective To assess the role of ALU element instability in human aging and the potential efficacy of ALU element content as a marker of biological aging and survival. Design Preliminary cohort study. Methods We measured two high frequency ALU element subfamilies, ALU-J and ALU-Sx, by a single qPCR assay and compared ALU-J/Sx content in white blood cell (WBCs) and skeletal muscle cell (SMCs) biopsies from twenty-three elderly adults with sixteen healthy sex-balanced young adults; all-cause survival rates of elderly adults predicted by ALU-J/Sx content in both tissues; and cardiovascular disease (CVD)- and cancer-specific survival rates of elderly adults predicted by ALU-J/Sx content in both tissues, as planned subgroup analyses. Results We found greater ALU-J/Sx content variance in WBCs from elderly adults than young adults (P < 0.001) with no difference in SMCs (P = 0.94). Elderly adults with low WBC ALU-J/Sx content had worse four-year all-cause and CVD-associated survival than those with high ALU-J/Sx content (both P = 0.03 and hazard ratios (HR) ≥ 3.40), while WBC ALU-J/Sx content had no influence on cancer-associated survival (P = 0.42 and HR = 0.74). SMC ALU-J/Sx content had no influence on all-cause, CVD- or cancer -associated survival (all P ≥ 0.26; HR ≤ 2.07). Conclusions These initial findings demonstrate that ALU element instability occurs with advanced age in WBCs, but not SMCs, and imparts greater risk of all-cause mortality that is likely driven by an increased risk for CVD and not cancer.

Exercise training on locomotion in patients with Alzheimer's disease. A feasibility Study

BACKGROUND Although current literature has shown that patients with Alzheimers disease (AD) have worse locomotion compared with healthy counterparts, no studies have focused on the efficacy of exercise training in improving gait abnormalities including biomechanics and metabolic aspects, in this population. OBJECTIVE To verify the effectiveness of exercise training (ET) on gait parameters (i.e., speed, step and stride length, single and double support, and energy cost of walking (Cw)) in patients with AD with respect to a standard cognitive treatment (CT). METHODS In this study, we included a small portion of data belonging to a larger study (ClinicalTrials.gov number, NCT03034746). Patients with AD (Mini-Mental State Examination 22±5) were included in the study. Gait parameters and Cw were assessed at baseline and after 6 months (72 treatment sessions) of treatment. ET included 90 min of aerobic and strength training. CT included 90 min of cognitive stimuli. RESULTS The 16 patients assigned to ET exhibited significant improvement of Cw (-0.9±0.1 J/kg·m-1), while differences in gait parameters were negligible. The effect on gait parameters were undetectable in the 18 patients assigned to CT (-0.2±0.5 J/kg·m-1). CONCLUSIONS Data from this study showed that ET program seems effective in improving Cw in patients with AD. Interestingly, the positive effect of ET on Cw was not coupled with ameliorations of patients gait parameters, suggesting that the gain of metabolic aspects of locomotion were the main factors responsible for this positive result.

Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral Circulatory Impairments During Aging and Alzheimer's Disease

Advanced aging, vascular dysfunction, and nitric oxide (NO) bioavailability are recognized risk factors for Alzheimers disease (AD). However, the contribution of AD, per se, to this putative pathophysiological mechanism is still unclear. To better answer this point, we quantified cortical perfusion with arterial spin labeling (PVC-CBF), measured ultrasound internal carotid (ICA), and femoral (FA) artery blood flow in a group of patients with similar age (~78 years) but different cognitive impairment (i.e., mild cognitive impairment MCI, mild AD-AD1, moderate AD-AD2, and severe AD-AD3) and compared them to young and healthy old (aged-matched) controls. NO-metabolites and passive leg-movement (PLM) induced hyperemia were used to assess systemic vascular function. Ninety-eight individuals were recruited for this study. PVC-CBF, ICA, and FA blood flow were markedly (range of 9–17%) and significantly (all p < 0.05) reduced across the spectrum from YG to OLD, MCI, AD1, AD2, AD3 subjects. Similarly, plasma level of nitrates and the values of PLM were significantly reduced (range of 8–26%; p < 0.05) among the six groups. Significant correlations were retrieved between plasma nitrates, PLM and PVC-CBF, CA, and FA blood flow. This integrative and comprehensive approach to vascular changes in aging and AD showed progressive changes in NO bioavailability and cortical, extracranial, and peripheral circulation in patients with AD and suggested that they are directly associated with AD and not to aging. Moreover, these results suggest that AD-related impairments of circulation are progressive and not confined to the brain. The link between cardiovascular and the central nervous systems degenerative processes in patients at different severity of AD is likely related to the depletion of NO.

A Comparison of Lysosomal Enzymes Expression Levels in Peripheral Blood of Mild- and Severe-Alzheimer’s Disease and MCI Patients: Implications for Regenerative Medicine Approaches

The association of lysosomal dysfunction and neurodegeneration has been documented in several neurodegenerative diseases, including Alzheimer’s Disease (AD). Herein, we investigate the association of lysosomal enzymes with AD at different stages of progression of the disease (mild and severe) or with mild cognitive impairment (MCI). We conducted a screening of two classes of lysosomal enzymes: glycohydrolases (β-Hexosaminidase, β-Galctosidase, β-Galactosylcerebrosidase, β-Glucuronidase) and proteases (Cathepsins S, D, B, L) in peripheral blood samples (blood plasma and PBMCs) from mild AD, severe AD, MCI and healthy control subjects. We confirmed the lysosomal dysfunction in severe AD patients and added new findings enhancing the association of abnormal levels of specific lysosomal enzymes with the mild AD or severe AD, and highlighting the difference of AD from MCI. Herein, we showed for the first time the specific alteration of β-Galctosidase (Gal), β-Galactosylcerebrosidase (GALC) in MCI patients. It is notable that in above peripheral biological samples the lysosomes are more sensitive to AD cellular metabolic alteration when compared to levels of Aβ-peptide or Tau proteins, similar in both AD groups analyzed. Collectively, our findings support the role of lysosomal enzymes as potential peripheral molecules that vary with the progression of AD, and make them useful for monitoring regenerative medicine approaches for AD.

Exercise-induced adaptations in patients with Alzheimer’s disease: the role of circadian scheduling

PurposePhysical exercise is recognized to induce several benefits to patients with AD; therefore, it is crucial to maximize its effect. Even though these patients show circadian rhythm dysregulations, no comprehensive recommendations for physical exercise circadian scheduling exist. Thus, the aim of this review was to investigate the most favorable times of the day to administer exercise to patients with AD.MethodsA comprehensive PubMed research was led to identify studies related to the time of exercise intervention and exercise circadian scheduling in people with AD. The following terms were applied: Alzheimer’s disease, exercise, physical exercise intervention time, and circadian rhythm dysregulation.ResultsTen studies were included. Seven records regarded AD and physical exercise, two circadian physical exercise, and one gait/balance control impairment.ConclusionsMost of the authors included in this review indicate morning as the best time of the day to administer physical exercise to patients with AD. Furthermore, some authors considered show benefits to these patients from post-meridian exercise intervention as well as others hypothesize efficacy from exercise circadian programs. Nevertheless, the paucity of studies in this field limits the conclusion of this review. For these reasons, we think that research should invest more to better focus on the circadian approach to physical exercise scheduling for patients with AD.

Muscle cramps: A comparison of the two-leading hypothesis

Exercise-Associated Muscle Cramps (EAMC) are a common painful condition of muscle spasms. Despite scientists tried to understand the physiological mechanism that underlies these common phenomena, the etiology is still unclear. From 1900 to nowadays, the scientific world retracted several times the original hypothesis of heat cramps. However, recent literature seems to focus on two potential mechanisms: the dehydration or electrolyte depletion mechanism, and the neuromuscular mechanism. The aim of this review is to examine the recent literature, in terms of physiological mechanisms of EAMC. A comprehensive search was conducted on PubMed and Google Scholar. The following terminology was applied: muscle cramps, neuromuscular hypothesis (or thesis), dehydration hypothesis, Exercise-Associated muscle cramps, nocturnal cramps, muscle spasm, muscle fatigue. From the initial literature of 424 manuscripts, sixty-nine manuscripts were included, analyzed, compared and summarized. Literature analysis indicates that neuromuscular hypothesis may prevails over the initial hypothesis of the dehydration as the trigger event of muscle cramps. New evidence suggests that the action potentials during a muscle cramp are generated in the motoneuron soma, likely accompanied by an imbalance between the rising excitatory drive from the muscle spindles (Ia) and the decreasing inhibitory drive from the Golgi tendon organs. In conclusion, from the latest investigations there seem to be a spinal involvement rather than a peripheral excitation of the motoneurons.

Role of Exercise in Vascular Function and Inflammatory Profile in Age-Related Obesity

In western countries, aging is often accompanied by obesity and age-related obesity is characterized by vascular dysfunction and a low-grade inflammatory profile. Exercise is a nonpharmacological strategy able to decrease the development and incidence of risk factors for several health-threatening diseases. Nonetheless, its long-term effect on vascular function and inflammation in age-related obesity is still unclear. The aim of this study was to investigate the effect of regular, supervised exercise on inflammatory profile and vascular function in age-related obesity. We also hypothesized that vascular function and inflammatory profile would have been correlated in overweight and obese individuals. Thirty normal weight (NW; 70 ± 5 years, 23.9 ± 2.6 BMI) and forty overweight and obese elderly (OW&OB; 69 ± 5 years, 30.1 ± 2.3 BMI) regularly taking part in a structured, supervised exercise program were enrolled in the study and evaluated for vascular function (flow-mediated dilation; FMD) and inflammatory profile (plasma CRP, IL-1β, IL-1ra, IL-6, IL-8, IL-10, TNF-α, and MCP-1). Although no differences between groups were found concerning performance and the weekly amount of physical activity, the OW&OB group compared with the NW group demonstrated higher systolic and diastolic blood pressure (+10%, p = 0.001; +9%, p = 0.005, respectively); lower FMD% (−36%, p < 0.001) and FMD/shear rate (−40%, p = 0.001); and higher levels of CRP (+33%, p = 0.005), IL-6 (+36%, p = 0.048), MCP-1 (+17%, p = 0.004), and TNF-α (+16%, p = 0.031). No correlations between vascular function and inflammation were found in OW&OB or NW. Although exercising regularly, overweight and obese elderly exhibited poorer vascular function and higher proinflammatory markers compared with the leaner group. These results support the idea that exercise alone cannot counteract the negative effect of adiposity on vascular function and inflammatory profile in elderly individuals and these two processes are not necessarily related.

Inflammatory Response to Exercise in a Pancreatic-cancer Patient: a CaseReport

Background: Pancreatic-adenocarcinoma is relatively uncommon, but has been proven to be an unyielding adversity. Although it is known the importance of exercise in improving quality of life in cancer patients, currently there are no available data identifying the inflammatory-response during exercise in pancreatic-cancer patients undergoing chemotherapy. Methods: A control-supported case study was performed on a 67 yr old man diagnosed with stage IV pancreaticcancer. Two 24-hour non-stop ultra-endurance walking races (24 hr Walk) completed by the patient prior to cancerdiagnosis (No Chemo, 6 months prior to the diagnosis) and after cancer-diagnosis during chemotherapy (Chemo) were compared. Comparison to control-participants without cancer (n=2, Ctrl 1 and Ctrl 2) was also conducted. Throughout 24 hr Walk blood-samples were collected every 6 hours and analyzed for intereukin-1β (IL-1β), interleukin-1ra (IL-1ra), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), monochemoattractant protein-1 (MCP-1), C-reactive protein (CRP), alanine aminotransferase (ALT), pancreatic amylase (AmylP), and albumin. All training performed since the cancer-diagnosis was monitored. Results: No adverse events occurred neither during 24 hr walks nor during the training. The number of walk per week, distance, and speed diminished following the diagnosis of pancreatic-cancer. Changes in IL-1β, IL-6, IL-8, IL-10, TNF-α, MCP-1, ALT, AmylP, and albumin did not differ between No Chemo and Chemo. IL-1ra decreased in No Chemo, but increased in Chemo. CRP increased in both No Chemo and Chemo, and in the controls as well. Changes in ALT and AmylP in Ctrl 1 and Ctrl 2 differed to both No Chemo and Chemo. Conclusions: Understanding the inflammatory-response to exercise in cancer-patients may be useful to design and delivery adapted exercise-programs in this growing population. The inflammatory-response, hepatic, and pancreatic functionality during prolonged-exercise were not exacerbated by concurrent chemotherapy in a pancreatic-cancer patient.