(Re)constructing identity following acquired brain injury: The complex journey of recovery after stroke.

INTRODUCTION: People with poststroke acquired brain injury (ABI) face a complex and often troubled identity reconstruction journey. The literature is rich with studies related to the psychological and neuropsychological components involved in rehabilitation, but it is lacking with respect to the investigation of the existential dimensions and the challenges associated with finding new senses and meanings for one's identity and future perspectives, body and interpersonal relationships. METHODS: The aim of this study is to investigate the narrative processes of identity reconstruction after brain damage. Through a qualitative approach, 30 autobiographical narratives about self, body and the relationships with others were collected and analyzed. Semistructured interviews were used for the data collection. Narrative and positioning analysis were applied. RESULTS: Four main positionings emerged: sanctioning a radical break with one's previous life; assuming a sense of salvation and compulsory as well as irreversible adaptation to the limitations associated with one's condition; feeling different and disabled; and considering new possibilities and active constructions of self-being in relationship with others. These results underline the narrative processes of construction of the injury and the identity and delineate possible resources and instruments to improve the clinical practice for health practitioners. They are also valuable for other professionals who deal with neurological services and rehabilitation, such as psychological counselling and support for persons who have experienced ABI and their families. PATIENT OR PUBLIC CONTRIBUTION: This work resulted from a close collaboration between two universities and a hospital neurological rehabilitation department in the Veneto Region (Northern Italy). Three associations of people with stroke and their families living in the same area contributed to designing the research on the basis of the needs expressed by their members with the aim to identify strategies and devices to be implemented in the public service to improve the care pathway. They also participated in the interpretation of the data.

Rehabilitation of somatic sensation and related deficit of motor control by Mirror Box Therapy: a case report.

Somatosensory disorders are often present after cerebral stroke. These deficits are associated with patients' disability. Therefore, their rehabilitation takes an importance in recovery program. However, the treatment of sensation remains poorly considered during neurorehabilitation and evidence for active sensory training is limited. Mirror Box Therapy is a simple training used to treat upper extremity motor deficits and pain also in patients with stroke. However, the effects of Mirror Box Therapy on somatosensory impairments in post-stroke patients are not deeply investigated and often exclusively motor exercises are provided during therapy.The aim of the present study was to investigate the effects of Mirror Box Therapy sensory training on somatosensory deficits in a stroke patient presenting upper limb impairment.The patient underwent to four weeks of training, five days a week. Before, during and after the Mirror Box Therapy treatment, the patient was assessed by Rivermead Assessment of Somatosensory Performance. Before and after training also upper limb motor function and performance in activities of daily living were assessed.After training patient showed an improvement in somatosensory performance. The gain was maintained at follow-up.This case report shows the effects of Mirror Box Therapy sensory training on the upper extremity for the improvement of sensation and movement in a patient with a thalamo-capsular hemorrhagic stroke during the subacute phase.

Exercise training improves vascular function in patients with Alzheimer's disease.

PURPOSE: Vascular dysfunction has been demonstrated in patients with Alzheimer's disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD. METHODS: Thirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate-high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session. RESULTS: EX group has increased FMD% (+ 3.725%, p < 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p < 0.05; SR + 134%, p < 0.05), but not during CTRL treatment. CONCLUSION: Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population.

Effects of Neck Taping in the Treatment of Hemispatial Neglect in Chronic Stroke Patients: A Pilot, Single Blind, Randomized Controlled Trial.

Background and objectives: Hemispatial neglect is a common consequence of stroke, with an estimated incidence of 23%. Interventions for treating hemispatial neglect may be categorized as either top-down or bottom-up processing. The aim of top-down approaches is to train the person to voluntarily compensate for their neglect. Such approaches require awareness of the disorder and a high level of active participation by the patient. Differently, bottom-up approaches are based on manipulation of a patient's sensory environment and so require less awareness of behavioral bias. In line with the latter, it is conceivable that elastic therapeutic taping applied to the left neck surface may provide bottom-up inputs that reduce hemispatial neglect symptoms. The aim of this study was to assess the effect of therapeutic neck taping on visuo-spatial abilities, neck motion, and kinesthetic sensibility in chronic stroke patients with hemispatial neglect. Materials and Methods: After randomization, 12 chronic stroke patients with hemispatial neglect received 30 consecutive days of real (treatment group) or sham (control group) neck taping. The outcomes were as follows: Stars Cancellation Test; neck active range of motion; Letter Cancellation Test; Comb and Razor Test; Cervical Joint Position Error Test evaluated before and after one month of taping. Results: Between-group comparison showed significant differences only for the Cervical Joint Position Error Test after treatment (p = 0.009). Conclusions: Our preliminary findings support the hypothesis that neck taping might improve cervicocephalic kinesthetic sensibility in chronic stroke patients with hemispatial neglect. Further studies are needed to strengthen our results and better investigate the effects of elastic therapeutic taping on visuo-spatial abilities in stroke patients with hemispatial neglect.

Effects of contralesional robot-assisted hand training in patients with unilateral spatial neglect following stroke: a case series study.

BACKGROUND: A reduction of hemispatial neglect due to stroke has been associated with activation of the contralesional hand in the contralesional hemispace. Robot-assisted upper limb training was found to effectively improve paretic arm function in stroke patients. To date no proof of concept of robot-assisted hemispatial neglect therapy has been reported in literature. This study aimed to determine whether robot-assisted left (contralesional) hand activation alone could lead to an improvement in hemispatial neglect following stroke. METHODS: Three stroke patients with right brain injury underwent a 2-week training program of robotic left hand activation with the Gloreha® hand rehabilitation glove, which provides repetitive, passive mobilization of the fingers. Outcomes were assessed using the Line Crossing test, the Bells test, the Sentence Reading test, the Saccadic Training, the Sustained Attention to Response Task, and the Purdue Pegboard test. RESULTS: Changes were observed after treatment as follows. Line Crossing test: all patients showed improved performance (6.7%, 89.5% and 80% increase in lines crossed) with two patients reaching normal performance levels. Bells test: one patient improved performance (50% increase), while one patient showed no change and one patient declined (-10.3% change); no patient reached normal performance levels. Sentence Reading test: all patients showed improved performance (800%, 57.1% and 42.9% increase in number of sentences read) with no patient reaching normal performance level. Saccadic Training: all patients showed improved performance (-62.8%, -15.5% and -9.7% change of the left hemifield reaction time). Sustained Attention to Response Task: all patients showed improved performance (-20.5%, -5.8% and -10% change of the reaction time) with two patients reducing incorrect responses (-42.9% and -73.3%) and one patient increasing them (9.1%). Purdue Pegboard test: all patients showed improved performance (100%, 27.3% and 75% change in the left + right + both hands sub-item score). CONCLUSIONS: Some caution is warranted when interpreting our results, as the responses to the intervention were variable and might have been due to a placebo effect or fluctuating clinical conditions. However, robot-assisted hemispatial neglect therapy might be useful in stroke patients. Larger-scale investigations are needed to confirm our preliminary findings.

Effects of upper limb vibratory stimulation training on motor symptoms in Parkinson's disease: an observational study.

OBJECTIVES: Parkinson's disease is characterized by motor and non-motor symptoms. Tremor is one of the motor symptoms that can affect manual skills and have an impact on daily activities. The aim of the current study is to investigate the effect of upper limb training provided by a specific vibratory device (Armshake®, Move It GmbH - Bochum, Germany) on tremor and motor functionality in patients with Parkinson's disease. Furthermore, the training effect on global cognitive functioning is assessed. DESIGN: An uncontrolled before-after clinical trial. PATIENTS: Individuals with diagnosis of Parkinson's disease, motor upper limbs deficits, and absence of dementia. METHODS: Participants underwent a 3-week programme (3 times a week) and was evaluated before, after, and at 1 month follow-up by motor (Fahn Tolosa Marin Tremor Rating Scale, Unified Parkinson's Disease Rating Scale - part III, Purdue Pegboard Test, Disability of the Arm, Shoulder and Hand Questionnaire) and cognitive (Montreal Cognitive Assessment) scales. RESULTS: Twenty subjects are included. After treatment a statistically significant improvement in tremor, manual dexterity and activities of daily living was found. The data indicated no effects on global cognitive functioning. CONCLUSION: These findings suggest positive effects of vibratory stimulation training on upper limb motor symptoms in Parkinson's disease.

Effect of Upper Limb Motor Rehabilitation on Cognition in Parkinson's Disease: An Observational Study.

Parkinson's disease is characterized by motor and cognitive deficits that usually have an impact on quality of life and independence. To reduce impairment, various rehabilitation programs have been proposed, but their effects on both cognitive and motor aspects have not been systematically investigated. Furthermore, most intervention is focused on lower limb treatment rather than upper limbs. In the present study, we investigated the effect of 3-week upper limb vibratory stimulation training on cognitive functioning in 20 individuals with Parkinson's disease. We analyzed cognitive (Montreal Cognitive Assessment, Trial Making Test, Digit Symbol, Digit Span Forward and Backward and Alertness) and motor performance (Unified Parkinson's Disease Rating Scale-part III; Disability of the Arm, Shoulder and Hand Questionnaire) before treatment, at the end of treatment and one month post treatment. After rehabilitation, a statistically significant improvement was observed in terms of global cognitive status, attention, global motor functioning and disability. The results suggest an impact of upper limb motor rehabilitation on cognition in Parkinson's disease. Future studies on neuromotor interventions should investigate their effects on cognitive functioning to improve understanding of cognitive motor interaction in Parkinson's disease.

Combined transcranial Direct Current Stimulation and robot-assisted arm training in patients with stroke: a systematic review.

BACKGROUND: Upper limb motor deficits in patients with severe stroke often remain unresolved over time. Combining transcranial Direct Current Stimulation with robotic therapy is an innovative neurorehabilitation approach that holds promise to improve upper limb impairment after stroke. OBJECTIVE: To investigate the effects of robotic training in combination with transcranial Direct Current Stimulation for treating poststroke upper limb impairment. METHODS: PubMed, MEDLINE, Cochrane Library, and EMBASE electronic databases were searched using keywords, MeSH terms, and strings: "Stroke"[MeSH] AND ("Upper Extremity"[MeSH] OR "upper limb") AND ("Transcranial Direct Current Stimulation" [MeSH] OR "tDCS") AND ("robotics" OR "robotic therapy"). Full-text articles published in English up to October 2020 were included. Each was rated for quality according to the Physiotherapy Database (PEDro) score: eight out of eleven scored more than 8 points; their results were considered reliable for this review. RESULTS: Of the total of 171 publications retrieved, 11 met the inclusion criteria. The results of studies that examined the same outcome measures were pooled to draw conclusions on the effectiveness of transcranial Direct Current Stimulation and robot-assisted training in corticomotor excitability, upper limb kinematics, muscle strength and tone, function, disability, and quality of life after stroke. CONCLUSIONS: To date, there is insufficient evidence to support the hypothesis that transcranial Direct Current Stimulation enhances the effects of robot-assisted arm training in poststroke patients. Further studies with more accurate, comparable and standardized methodology are needed in order to better define the effects of robotic training in combination with transcranial Direct Current Stimulation on poststroke upper limb impairment. Therefore, given the scarce resources available to rehabilitation researches, other, more promising approaches should be given attention.

Physiotherapy versus Consecutive Physiotherapy and Cognitive Treatment in People with Parkinson's Disease: A Pilot Randomized Cross-Over Study.

BACKGROUND: Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions that can usually be treated by physiotherapy or cognitive training, respectively. The effects of consecutive physiotherapy and cognitive rehabilitation programs on PD deficits are less investigated. OBJECTIVE: We investigated the effects of 3 months of physiotherapy (physiotherapy treatment group) or consecutive physiotherapy and cognitive (physiotherapy and cognitive treatment group) rehabilitation programs on cognitive, motor, and psychological aspects in 20 PD patients. METHODS: The two groups switched programs and continued rehabilitation for another 3 months. The outcomes were score improvement on cognitive (Montreal Cognitive Assessment, Frontal Assessment Battery, Trail Making Test, Verbal Phonemic Fluency, Digit Span, and Rey Auditory Verbal Learning), motor (Unified Parkinson's Disease Rating Scale-III, Berg Balance Scale, Two-Minute Walking Test, and Time Up and Go), and psychological (Beck Depression Inventory and State-Trait Anxiety Inventory) scales. RESULTS: Between-group comparison revealed a significant difference in functional mobility between the two rehabilitation programs. Improvements in walking abilities were noted after both interventions, but only the patients treated with consecutive training showed better performance on functional mobility and memory tasks. CONCLUSION: Our findings support the hypothesis that consecutive physiotherapy plus cognitive rehabilitation may have a greater benefit than physiotherapy alone in patients with PD.

Effects of robot-assisted gait training on postural instability in Parkinson's disease: a systematic review.

INTRODUCTION: Postural instability is a cardinal feature of Parkinson's disease, together with rest tremor, rigidity and bradykinesia. It is a highly disabling symptom that becomes increasingly common with disease progression and represents a major source of reduced quality of life in patients with Parkinson's disease. Rehabilitation aims to enable patients with Parkinson's disease to maintain their maximum level of mobility, activity and independence. To date, a wide range of rehabilitation approaches has been employed to treat postural instability in Parkinson's disease, including robotic training. Our main aim was to conduct a systematic review of current literature about the effects of robot-assisted gait training on postural instability in patients with Parkinson's disease. EVIDENCE ACQUISITION: A systematic search using the following MeSH terms "Parkinson disease," "postural balance," "robotics," "rehabilitation" AND string "robotics [mh]" OR "robot-assisted" OR "electromechanical" AND "rehabilitation [mh]" OR "training" AND "postural balance [mh]" was conducted on PubMed, Cochrane Library and Pedro electronic databases. Full text articles in English published up to December 2020 were included. Data about patient characteristics, robotic devices, treatment procedures and outcome measures were considered. Every included article got checked for quality. Level of evidence was defined for all studies. EVIDENCE SYNTHESIS: Three authors independently extracted and verified data. In total, 18 articles (2 systematic reviews, 9 randomized controlled trials, 4 uncontrolled studies and 3 case series/case reports) were included. Both end-effector and exoskeleton devices were investigated as to robot-assisted gait training modalities. No clear relationship between treatment parameters and clinical conditions was observed. We found a high level of evidence about the effects of robot-assisted gait training on balance and freezing of gait in patients with Parkinson's disease. CONCLUSIONS: This systematic review provides to the reader a complete overview of current literature and levels of evidence about the effects of robot-assisted gait training on postural instability issues (static and dynamic balance, freezing of gait, falls, confidence in activities of daily living and gait parameters related to balance skills) in patients with Parkinson's disease.

Effects of robot-assisted gait training combined with virtual reality on motor and cognitive functions in patients with multiple sclerosis: A pilot, single-blind, randomized controlled trial.

BACKGROUND: Studies on robot-assisted gait training rehabilitation in multiple sclerosis have reported positive effects on mobility and quality of life. However, their effects on cognitive functions are difficult to determine because not all trials have included cognition assessments. Virtual reality-based training provides enhanced opportunity for stimulating cognitive abilities by repetitive practice, feedback information, and motivation for endurance practice. OBJECTIVE: To compare the effects of innovative robot-assisted gait training combined with virtual reality versus standard robot-assisted gait training on information processing speed, sustained attention, working memory, and walking endurance in patients with multiple sclerosis. METHODS: Seventeen outpatients were randomly assigned to receive robot-assisted gait training either with or without virtual reality. The robot assisted gait training + virtual reality group underwent end-effector system training engendered by virtual reality. The standard training group underwent end-effector system training. A blinded rater evaluated patients before and after treatment and at one month follow-up. The outcome measures were the Paced Auditory Serial Addition Test, Phonemic Fluency Test, Novel Task, Digit Symbol, Multiple Sclerosis Quality of Life-54, 2-Minutes Walk Test, 10-Meter Walking Test, Berg Balance Scale, gait analysis, and stabilometric assessment. RESULTS: Between-group comparisons showed a significant change on the 2-Minutes Walk Test (p = 0.023) after treatment in the robot-assisted gait training + virtual reality group. Significant improvement were obtained also in executive functions (p = 0.012). Both gains were maintained at the 1-month follow-up evaluation (p = 0.012, p = 0.012) in the robot-assisted gait training + virtual reality group. Both group improved quality of life after treatment (Multiple Sclerosis Quality of Life-54: Mental Health p = 0.018, Physical Health p = 0.017). CONCLUSIONS: Both training lead to positive influenced on executive functions. However larger positive effects on gait ability were noted after robot-assisted gait training engendered by virtual reality with multiple sclerosis. Robot-assisted gait training provides a therapeutic alternative and motivational of traditional motor rehabilitation.

Rehabilitation and Biomarkers of Stroke Recovery: Study Protocol for a Randomized Controlled Trial.

Background: Stroke is a leading cause of disability. Nonetheless, the care pathway for stroke rehabilitation takes partially into account the needs of chronic patients. This is due in part to the lack of evidence about the mechanisms of recovery after stroke, together with the poor knowledge of related and influencing factors. Here we report on the study protocol "Rehabilitation and Biomarkers of Stroke Recovery," which consists of 7 work-packages and mainly aim to investigate the effects of long-term neurorehabilitation on stroke patients and to define a related profile of (clinical-biological, imaging, neurophysiological, and genetic-molecular) biomarkers of long-term recovery after stroke. The work-package 1 will represent the main part of this protocol and aims to compare the long-term effects of intensive self-rehabilitation vs. usual (rehabilitation) care for stroke. Methods: We planned to include a total of 134 adult subacute stroke patients (no more than 3 months since onset) suffering from multidomain disability as a consequence of first-ever unilateral ischemic stroke. Eligible participants will be randomly assigned to one of the following groups: intensive self-rehabilitation (based on the principles of "Guided Self-Rehabilitation Contract") vs. usual care (routine practice). Treatment will last 1 year, and patients will be evaluated every 3 months according to their clinical presentation. The following outcomes will be considered in the main work-package: Fugl-Meyer assessment, Cognitive Oxford Screen Barthel Index, structural and functional neuroimaging, cortical excitability, and motor and somatosensory evoked potentials. Discussion: This trial will deal with the effects of an intensive self-management rehabilitation protocol and a related set of biomarkers. It will also investigate the role of training intensity on long-term recovery after stroke. In addition, it will define a set of biomarkers related to post-stroke recovery and neurorehabilitation outcome in order to detect patients with greater potential and define long-term individualized rehabilitation programs. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04323501.

An Indoor Therapeutic Garden for Behavioral Symptoms in Alzheimer's Disease: A Randomized Controlled Trial.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) affect 60-90% of patients with Alzheimer's disease (AD). OBJECTIVE: To determine if environmental therapy is an effective strategy to reduce BPSD, we tested 163 patients with AD with Neuropsychiatric Inventory (NPI) before and after 6 months of an indoor therapeutic garden (TG) or standard environment. METHODS: A single-blind randomized controlled trial on AD patients with BPSD. Participants were randomized to an indoor TG (N = 82), or standard environment (control, N = 81) for 6 months. PRIMARY OUTCOME: change in the NPI score from baseline (T0) to end of treatment (T1). SECONDARY OUTCOMES: change in use of quetiapine, cognition, activities of daily living, salivary cortisol, blood pressure from T0 to T1. RESULTS: NPI score significantly ameliorated (TG versus control: -31.8 points), quetiapine dosage (-150 mg), blood pressure (-2.6 mm Hg), and salivary cortisol (-6.4 to -2.1 Nmol/l) were significantly reduced, the Mini-Mental State Examination significantly improved (1.8 points) in the TG versus control arm at T1 (p < 0.001). No adverse events were reported. CONCLUSION: The indoor TG seems safe and may reduce BPSD, medication intake, and cortisol levels in AD.

Visually evoked responses from the blind field of hemianopic patients.

Hemianopia is a visual field defect characterized by decreased vision or blindness in the contralesional visual field of both eyes. The presence of well documented above-chance unconscious behavioural responses to visual stimuli presented to the blind hemifield (blindsight) has stimulated a great deal of research on the neural basis of this important phenomenon. The present study is concerned with electrophysiological responses from the blind field. Since previous studies found that transient Visual Evoked Potentials (VEPs) are not entirely suitable for this purpose here we propose to use Steady-State VEPs (SSVEPs). A positive result would have important implications for the understanding of the neural bases of conscious vision. We carried out a passive SSVEP stimulation with healthy participants and hemianopic patients. Stimuli consisted of four black-and-white sinusoidal Gabor gratings presented one in each visual field quadrant and flickering one at a time at a 12Hz rate. To assess response reliability a Signal-to-Noise Ratio analysis was conducted together with further analyses in time and frequency domains to make comparisons between groups (healthy participants and patients), side of brain lesion (left and right) and visual fields (sighted and blind). The important overall result was that stimulus presentation to the blind hemifield yielded highly reliable responses with time and frequency features broadly similar to those found for cortical extrastriate areas in healthy controls. Moreover, in the intact hemifield of hemianopics and in healthy controls there was evidence of a role of prefrontal structures in perceptual awareness. Finally, the presence of different patterns of brain reorganization depended upon the side of lesion.

Comparison between physical and cognitive treatment in patients with MCI and Alzheimer's disease.

Cognitive and physical activity treatments (CT and PT) are two non-pharmacological approaches frequently used in patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). The aim of this study was to compare CT and PT in these diseases. Eighty-seven patients were randomly assigned to CT (n=30), PT (n=27) or control group (CTRL; n=30) for 6 months. The global cognitive function was measured by Mini Mental State Examination (MMSE). Specific neuropsychological tests explored attention, memory, executive functions, behavioral disorders. Cardiovascular risk factors (CVD) were collected. All measures were performed before (T0), after treatments (T1), and at three-months follow-up (T2). MMSE did not change from T0 to T1 and T2 in patients assigned to PT and CT, while CTRL patients showed a decline MCI: -11.8%, AD: -16.2%). Between group differences (MCI vs AD) were not found at T1 and T2. Significant worsening was found for CTRL in MCI (T0- T1: P=.039; T0-T2: P<.001) and AD (T0-T1: P<.001; T0-T2: P<.001), and amelioration was found for CT in AD (T0-T2: P<.001). Attention, executive functions and behavioral disorders were unaffected by either PT or CT. Memory was increased in patients with MCI assigned to PT (+6.9%) and CT (+8.5%).. CVD were ameliorated in the PT group. CTRL patients of both groups, revealed significant decline in all functions and no between groups differences were detected. PT appear to ameliorate CVD. Although between groups differences were not found, results suggest a major retention in MCI compared with AD, suggesting that the latter might benefit better of constant rather than periodic treatments. This study confirms the positive effects of CT and PT in mitigating the cognitive decline in MCI and AD patients, and it is the first to demonstrate their similar effectiveness on maintaining cognitive function.

Neuromuscular and Muscle Metabolic Functions in MELAS Before and After Resistance Training: A Case Study.

Mitochondrial encephalomyopathy, lactic acidosis, and recurrent stroke-like episodes syndrome (MELAS) is a rare degenerative disease. Recent studies have shown that resistant training (RT) can ameliorate muscular force in mitochondrial diseases. However, the effects of RT in MELAS are unknown. The aim of this case report was to investigate the effects of RT on skeletal muscle and mitochondrial function in a 21-years old patient with MELAS. RT included 12 weeks of RT at 85% of 1 repetition maximum. Body composition (DXA), in vivo mitochondrial respiration capacity (mVO2) utilizing Near-infrared spectroscopy on the right plantar-flexor muscles, maximal voluntary torque (MVC), electrically evoked resting twitch (EET) and maximal voluntary activation (VMA) of the right leg extensors (LE) muscles were measured with the interpolated twitch technique. The participant with MELAS exhibited a marked increase in body mass (1.4 kg) and thigh muscle mass (0.3 kg). After the training period MVC (+5.5 Nm), EET (+2.1 N⋅m) and VMA (+13.1%) were ameliorated. Data of mVO2 revealed negligible changes in the end-exercise mVO2 (0.02 mM min-1), Δ mVO2 (0.09 mM min-1), while there was a marked amelioration in the kinetics of mVO2 (τ mVO2; Δ70.2 s). This is the first report of RT-induced ameliorations on skeletal muscle and mitochondrial function in MELAS. This case study suggests a preserved plasticity in the skeletal muscle of a patient with MELAS. RT appears to be an effective method to increase skeletal muscle function, and this effect is mediated by both neuromuscular and mitochondrial adaptations.

Non-Aß-Dependent Factors Associated with Global Cognitive and Physical Function in Alzheimer's Disease: A Pilot Multivariate Analysis.

Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aß-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO2max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA). Baseline multifactorial information was submitted to two separate backward stepwise regression analyses to identify the variables associated with cognitive and physical decline in demented patients. A multivariate regression was then applied to verify the stepwise regression. The results indicated that the combination of 6MWT and VO2max was associated with both global cognitive and physical function (MMSE = 11.384 + (0.00599 × 6MWT) - (0.235 × VO2max)); (PPT = 1.848 + (0.0264 × 6MWT) + (19.693 × VO2max)). These results may offer important information that might help to identify specific targets for therapeutic strategies (NIH Clinical trial identification number NCT03034746).

Exercise Training on Locomotion in Patients with Alzheimer's Disease: A Feasibility Study.

BACKGROUND: Although current literature has shown that patients with Alzheimer's 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 patient's 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 Alzheimer's 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.

Changes in Plasma ß-NGF and Its Receptors Expression on Peripheral Blood Monocytes During Alzheimer's Disease Progression.

Alzheimer's disease (AD), the most common cause of dementia, is characterized by the deposition of extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles, and by neuroinflammation. During the pathogenesis of AD, monocyte-macrophage lineage cells become increasingly ineffective in clearing Aß deposits, less able to differentiate, and shift toward pro-inflammatory processes. Beta-nerve growth factor (ß-NGF) and its receptors, TrKA and p75NTR, produce several biological responses, including cell apoptosis and survival, and inflammation. In the central nervous system, the involvement of these receptors in several critical hallmarks of AD is well known, but their role in circulating monocytes during the progression of dementia is unclear. We investigated the relationship between plasma ß-NGF concentration and TrkA/p75NTR receptor expression in monocytes of patients with mild cognitive impairment (MCI), mild AD, and severe AD. We observed that plasma ß-NGF concentration was increased with a higher expression of TrKA, but not of p75NTR, in monocytes from patients with MCI and mild AD, whereas ß-NGF concentration and TrKA expression were decreased and p75NTR expression was increased, associated with caspase 3-mediated apoptosis, in patients with severe AD. In our study, we show evidence of variation in plasmatic ß-NGF and monocytic TrkA/p75NTR receptor expression during the progression of dementia. These novel findings add evidence to support the hypothesis for the involvement of ß-NGF and its receptors on monocytes during AD progression.