Digging into the intrinsic capacity concept: Can it be applied to Alzheimer's disease?

Historically, aging research has largely centered on disease pathology rather than promoting healthy aging. The World Health Organization's (WHO) policy framework (2015-2030) underscores the significance of fostering the contributions of older individuals to their families, communities, and economies. The WHO has introduced the concept of intrinsic capacity (IC) as a key metric for healthy aging, encompassing five primary domains: locomotion, vitality, sensory, cognitive, and psychological. Past AD research, constrained by methodological limitations, has focused on single outcome measures, sidelining the complexity of the disease. Our current scientific milieu, however, is primed to adopt the IC concept. This is due to three critical considerations: (I) the decline in IC is linked to neurocognitive disorders, including AD, (II) cognition, a key component of IC, is deeply affected in AD, and (III) the cognitive decline associated with AD involves multiple factors and pathophysiological pathways. Our study explores the application of the IC concept to AD patients, offering a comprehensive model that could revolutionize the disease's diagnosis and prognosis. There is a dearth of information on the biological characteristics of IC, which are a result of complex interactions within biological systems. Employing a systems biology approach, integrating omics technologies, could aid in unraveling these interactions and understanding IC from a holistic viewpoint. This comprehensive analysis of IC could be leveraged in clinical settings, equipping healthcare providers to assess AD patients' health status more effectively and devise personalized therapeutic interventions in accordance with the precision medicine paradigm. We aimed to determine whether the IC concept could be extended from older individuals to patients with AD, thereby presenting a model that could significantly enhance the diagnosis and prognosis of this disease.

Winners do what they fear: exercise and peripheral arterial disease-an umbrella review.

AIMS: This systematic review aims to evaluate and summarize findings from published meta-analyses on the effects of regular exercise in patients with peripheral arterial disease (PAD). The review will assess the impact of exercise on functional parameters, health-related quality of life, haemodynamic parameters, physical activity levels, adverse events, and mortality. METHODS AND RESULTS: A systematic search was performed in PubMed, Web of Science, Scopus, and Cochrane Library databases (up to May 2023) to identify meta-analyses including randomized controlled trials that examined the effects of regular exercise in patients with PAD. Sixteen studies, with a total of 198 meta-analyses, were identified. Results revealed with strong evidence that patients with PAD who exercised improved functional and health-related quality of life parameters. Specifically, supervised aerobic exercise (i.e. walking to moderate-maximum claudication pain) improves maximum walking distance [mean difference (MD): 177.94 m, 95% confidence interval (CI) 142.29-213.60; P < 0.00001; I2: 65%], pain-free walking distance (fixed MD: 68.78 m, 95% CI 54.35-83.21; P < 0.00001; I2: 67%), self-reported walking ability [i.e. distance score (MD: 9.22 points, 95% CI 5.74-12.70; P < 0.00001; I2: 0%), speed score (MD: 8.71 points, 95% CI 5.64-11.77; P < 0.00001, I2: 0%), stair-climbing score (MD: 8.02 points, 95% CI 4.84-11.21; P < 0.00001, I2: 0%), and combined score (MD: 8.76 points, 95% CI 2.78-14.74; P < 0.0001, I2: 0%)], aerobic capacity (fixed MD: 0.62 mL/kg/min, 95% CI 0.47-0.77, P < 0.00001, I2: 64%), and pain score (MD: 7.65, 95% CI 3.15-12.15; P = 0.0009; I2: 0%), while resistance exercise improves lower limb strength (standardized mean difference: 0.71, 95% CI 0.29-1.13, P = 0.0009; I2: 0%]. Regarding other outcomes, such as haemodynamic parameters, no significant evidence was found, while physical activity levels, adverse events, and mortality require further investigation. CONCLUSION: Synthesis of the currently available meta-analyses suggests that regular exercise may be beneficial for a broad range of functional tasks improving health-related quality of life in patients with PAD. Supervised aerobic exercise is the best type of exercise to improve walking-related outcomes and pain, while resistance exercise is more effective to improve lower limb strength.

Regular exercise is beneficial for a wide range of functional capacity-related outcomes that seem to improve health-related quality of life in patients with peripheral arterial disease (PAD). Supervised aerobic exercise (i.e. walking to moderate­maximum claudication pain) is the best type of exercise to improve walking-related outcomes and pain. Resistance exercise improves lower limb strength.

Validation and Determination of Physical Activity Intensity GT3X+ Cut-Points in Children and Adolescents with Physical Disabilities: Preliminary Results in a Cerebral Palsy Population.

BACKGROUND: Children and adolescents with disabilities engage in low levels of moderate-to-vigorous intensity physical activity (MVPA), which may create the onset of a sedentary lifestyle. In light of this, MVPA levels must be quantified with a valid tool such as accelerometry. This study aimed to: (i) analyze the accuracy of Evenson cut-points by estimating MVPA and sedentary behavior (SB) in children and adolescents with disabilities; (ii) define new equations to estimate energy expenditure (EE) with the GT3X+ accelerometer in this population and particularly in those with cerebral palsy (CP); (iii) define specific GT3X+ cut-points to estimate MVPA in those with CP. METHODS: A total of 23 children and adolescents with disabilities (10 ± 3 years; 44%females) participated in the study. GT3X+-counts and oxygen uptake (VO2) were measured in four laboratory walking conditions. RESULTS: (i) Evenson cut-points were accurate; (ii) new equations were defined to effectively predict EE; (iii) specific GT3X+ cut-points (VM ≥ 702 counts·min-1; Y-Axis ≥ 360 counts·min-1) were defined for estimating MVPA levels in children and adolescents with CP. CONCLUSIONS: The use of specific cut-points for ActiGraph GT3X+ seems to be accurate to estimate MVPA levels in children and adolescents with disabilities and, particularly, in those with CP, at least in laboratory conditions.

Physical Exercise and the Hallmarks of Breast Cancer: A Narrative Review.

Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden.

Acute effects of electrostimulation and blood flow restriction on muscle thickness and fatigue in the lower body.

Neuromuscular electrical stimulation (NMES) in combination with blood flow restriction (BFR) enhances muscle hypertrophy and force-generating capacity. The present study aimed to investigate the acute effects of BFR and NMES, both in isolation and in combination, on muscle thickness (MT) and fatigue in the lower body of 20 young healthy subjects. Different stimuli were applied for 25 min, defined by the combination of BFR with high- and low-frequency NMES, and also isolated BFR or NMES. Changes in MT were then evaluated by ultrasound of the rectus femoris (RF) and vastus lateralis (VL) muscles at the end of the session (POST) and 15 min later (POST 15'). Lower limb fatigue was evaluated indirectly by strength performance. Results showed that RF MT was higher under the combined protocol (BFR + NMES) or isolated BFR than under NMES - regardless of the frequency - both at POST (p ≤ 0.018) and POST 15' (p ≤ 0.016). No significant changes in MT were observed under isolated NMES or BFR at POST 15' when compared with basal values (p ≥ 0.067). No significant differences were observed for VL MT between conditions (p = 0.322) or for fatigue between conditions (p ≥ 0.258). Our results indicate that a combination of BFR and NMES acutely increases MT in sedentary subjects. Also, although not significantly, BFR conditions had a greater tendency to induce fatigue than isolated NMES.HighlightsThe combination of blood flow restriction (BFR) and neuromuscular electrical stimulation (NMES) produces higher acute cell swelling than the isolated application of either NMES or BFR.BFR in isolation appears to produce greater cell swelling than NMES, regardless of the frequency used.BFR conditions had a greater tendency to induce fatigue than isolated NMES.

Exercise and the hallmarks of peripheral arterial disease.

Peripheral arterial disease (PAD) is a prevalent cardiovascular disease. The main hallmarks of this condition are atherosclerosis and myopathy in the lower limbs, with progressive deterioration of the functional capacity and quality of life of affected individuals. There is evidence supporting physical exercise as an effective alternative for the treatment of PAD. In this context, unraveling the biological mechanisms by which exercise intervention might improve the clinical manifestation of PAD can help gain insight into the pathophysiology of this condition, as well as explore new treatment and preventive approaches. In this review, we thus describe the different mechanisms by which exercise could impact the different hallmarks of PAD. Physical exercise positively modulates pathways related to inflammation and the atherosclerotic process and can attenuate the progression of lower-limb myopathy, with subsequent improvements in patients' functional capacity and health-related quality of life. At the whole-body level, these improvements translate into a better functional status and wellbeing.

Defining and assessing intrinsic capacity in older people: A systematic review and a proposed scoring system.

INTRODUCTION: The World Health Organization has introduced the term 'intrinsic capacity' (IC) as a marker of healthy ageing. However, controversy exists on the definition and assessment of IC. We aimed to review the definitions and methods used for the assessment of IC in older adults. In addition, we proposed a new IC scoring method. METHODS: A systematic search was performed in PubMed, Web of Science, Cochrane Library, Scopus and SPORTDiscus (up to February 10th, 2022) for studies assesing IC in older adults (>60 years). RESULTS: Thirty-three studies were included. There is overall consensus on the definition of IC as well as on its different dimensions, that is: locomotion, vitality, sensory, cognition and psychological. However, the methods for assessing each of these five dimensions differ substantially across studies and there is no consensus on the best method to compute an eventual global compound score to evaluate IC taking into account all its different dimensions. CONCLUSIONS: The IC represents a highly relevant clinical concept that has been unfortunately underutilized. We propose a standardization for the assessment of each dimension of IC, with a global 0 (worst) to 10 (highest) score.

Moderate Intensity Functional Training as Adjuvant Treatment in Patients With Peripheral Arterial Disease: A Case Report.

BACKGROUND: Traditional aerobic training and muscle resistance ("strength") training have been shown to be effective for improving functional and health-related quality of life (HRQoL) outcomes in peripheral arterial disease (PAD). However, the transfer of the current resistance exercise modes proposed to other activities of daily living (ADLs) is questionable. Moderate intensity functional training (MIFT) has emerged with the aim of achieving cardiovascular and neuromuscular adaptations simultaneously with functional exercises typical of ADLs. The effect of MIFT in patients with PAD is not yet known. Our purpose is to verify the influence of the combination of intermittent treadmill walking exercise with MIFT on functional capacity and HRQoL in patients with PAD. METHODS: Three patients with PAD participated in a novel supervised exercise therapy program of 6 weeks duration based on intermittent treadmill walking exercise and MIFT. RESULTS: After the training period, the 3 patients showed high adherence to the program (95%) and they improved total distance (TD) (25%, 9%, and 21%), claudication onset distance (COD) (56%, 19%, and 151%), total number of repetitions (33%, 24%, and 33%) and total work capacity (80%, 79%, and 72%). Also, physical component in Short Form-36 Health Survey (SF-36) and Vascular Quality of Life Questionnaire-6 (VascuQol-6) showed increases in the patients. CONCLUSIONS: The 6-week intervention in patients with PAD, based on intermittent treadmill walking exercise and MIFT, seems to improve their functional status and total work capacity in functional exercises as well as their HRQoL.