Dopamine Pharmacodynamics: New Insights.

Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.

The role of the Sunfrail tool in the screening of frailty and in integrated community-hospital care pathways: a retrospective observational study.

BACKGROUND: One of the most problematic expression of ageing is frailty, and an approach based on its early identification is mandatory. The Sunfrail-tool (ST), a 9-item questionnaire, is a promising instrument for screening frailty. AIMS: To assess the diagnostic accuracy and the construct validity between the ST and a Comprehensive Geriatric Assessment (CGA), composed by six tests representative of the bio-psycho-social model of frailty; To verify the discriminating power of five key-questions of the ST; To investigate the role of the ST in a clinical-pathway of falls' prevention. METHODS: In this retrospective study, we enrolled 235 patients from the Frailty-Multimorbidity Lab of the University-Hospital of Parma. The STs' answers were obtained from the patient's clinical information. A patient was considered frail if at least one of the CGAs' tests resulted positive. RESULTS: The ST was associated with the CGA's judgement with an Area Under the Curve of 0.691 (CI 95%: 0.591-0.791). Each CGA's test was associated with the ST total score. The five key-question showed a potential discriminating power in the CGA's tests of the corresponding domains. The fall-related question of the ST was significantly associated with the Short Physical Performance Battery total score (OR: 0.839, CI 95%: 0.766-0.918), a proxy of the risk of falling. DISCUSSION: The results suggest that the ST can capture the complexity of frailty. The ST showed a good discriminating power, and it can guide a second-level assessment to key frailty domains and/or clinical pathways. CONCLUSIONS: The ST is a valid and easy-to-use instrument for the screening of frailty.

Gait characteristics in community-dwelling older persons with low skeletal muscle mass and low physical performance.

BACKGROUND: Demographic changes in the western world entail new clinical approaches and challenges in older persons. Low skeletal muscle mass and low physical performance in older persons are both predisposing conditions for disability and obtaining knowledge in this cohort is essential. AIM: The primary aim of the study was to analyze a broader spectrum of gait characteristics within this specific population and differentiate them across different test conditions. METHODS: Two centers participating at the SPRINTT project with hi-tech gait analysis available conducted a cross-sectional descriptive study on N = 115 community-dwelling older persons with low muscle mass and physical performance. Reference values of 13 gait parameters were collected across different conditions: usual gait speed, fast gait speed, and usual gait speed while simultaneously naming animals. RESULTS AND DISCUSSION: This study shows the first spatio-temporal reference values in a community-dwelling older population composed of individuals with low skeletal muscle mass and low physical performance. In comparison to the normative spatio-temporal gait parameters in older persons reported in the literature, this population showed some differences. The mean gait speed was lower than 1 m/s, considered as a cutoff for vulnerable community-dwelling individuals, which corresponds to a greater risk of falls, hospitalization, and mortality. The stride length variability was higher, exposing to a greater risk of falling, and was also associated with a higher risk of developing cognitive decline. CONCLUSION: This study represents the first step in the development of quantitative reference values in community-dwelling older persons with low physical performance and low skeletal muscle mass.

Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria.

BACKGROUND: Although the prevalence of sarcopenic obesity is increasing, nowadays a universally accepted definition still does not exist. Because, this clinical entity is defined as the combination of obesity and sarcopenia, the diagnosis appears to be strictly linked to criteria used for sarcopenia and the available prevalence data are not uniform. To investigate the prevalence of sarcopenic obesity in older persons according to EWGSOP2 and FNIH criteria. Second, to evaluate the prevalence of diabetes in patients with sarcopenia diagnosed by the two definitions. METHODS: Observational multicenter study performed in 2014 on older patients admitted to 12 Italian hospitals (GLISTEN Study). Data were collected through standardized questionnaires, which assessed: socio-demographic data, cognitive status, functional abilities, pharmacological therapy, comorbidities, and blood tests. Moreover, muscle mass and strength and physical performance were evaluated. RESULTS: Six hundred and ten were included in the analyses. Among sarcopenic patients, the prevalence of sarcopenic obesity was 30.8% with FNIH and 0% with EWGSOP2 criteria. According to EWGSOP2 criteria, 23.7% of sarcopenic and 30.8% of non-sarcopenic patients were affected by diabetes (p = 0.101); otherwise, using FNIH criteria, 36.3% of sarcopenic and 26.9% of non-sarcopenic patients were diabetic (p = 0.030). After adjustment for potential confounders, diabetic patients had a 73% higher probability of being sarcopenic according to FNIH criteria (OR 1.73; 95% CI 1.13-2.64). CONCLUSIONS: The EWGSOP2 and FNIH sarcopenia criteria are differently related to the prevalence of obesity and diabetes. The EWGSOP2 criteria seem to be not suitable to identify people with sarcopenic obesity.

Gut microbiota and motoric-cognitive frailty in hospitalized older persons.

PURPOSE OF REVIEW: In older people, many systems spontaneously change without diseases. Because of the ageing process, the gut microbiota undergoes a reduced species richness, altered balance between species, with an increased interindividual variability. The result is the reduced resilience in the presence of diseases and medications. These changes are more evident in older persons with neurodegenerative diseases and cognitive-motoric frailty. RECENT FINDINGS: A relationship between liver alteration, gut microbiota and the presence of viruses and gram-bacteria is conceivable. They determine the acceleration of neurodegenerative diseases with cognitive and motoric frailty. Hospitalization represents one of the stressors for the gut microbiota, producing dysbiosis and increasing the representation of pathobionts. The gut microbiota alterations during hospitalization may be associated with negative clinical outcomes. This phenomenon together with liver dysfunction could produce an acceleration of the trajectory of cognitive-motoric frailty towards disability and mortality. The observation that predisability is associated of both losses of cognition and motoric performance, has allowed introducing a new syndrome, the motoric-cognitive risk syndrome, which is a condition of increased risk of dementia and mobility-disability. SUMMARY: The interaction between liver and gut microbiota may accelerate the neurodegenerative diseases and represents a promising marker of prognostic trajectories in older patients.

Design and methodology of the chronic kidney disease as a dysmetabolic determinant of disability among older people (CKD-3D) study: a multicenter cohort observational study.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in older people and represents a global health issue since it increases the risk of associated comorbidities and all-cause mortality. Furthermore, older people with reduced renal function might be at higher risk for developing functional limitation and disability. Moreover, the current creatinine-based measures of renal function are influenced by several factors in older population. The aims of the CKD-3D project are to perform an observational study to expand the knowledge about CKD-disability relationship and to investigate the use of novel biomarkers of kidney function. METHODS: An observational, multicenter, prospective cohort study will be conducted in 75 + old patients consecutively admitted to acute care wards of geriatric medicine at participating hospitals. The study planned to enroll 440 patients undergoing clinical and laboratory evaluations at baseline and after 12 months. Face-to-face follow-up at 6 months and telephone follow-up at 3 and 9 months will be carried out. Comprehensive Geriatric Assessment (CGA) and the measurement of Cystatin C, Beta-Trace Protein and Beta2-Microglobulin levels will be included. DISCUSSION: This study will provide useful information to prevent CKD-related disability by collecting real-life data over 1-year period. The combined approach of CGA and the investigation of innovative existing biomarkers will make it possible to develop new recommendations and guidelines for a patient-centered approach. It is believed that such a study may lead to an improvement of knowledge on CKD in elderly patients and may also have implications in daily clinical practice and in decision-making process.

Bionic for Training: Smart Framework Design for Multisensor Mechatronic Platform Validation.

Home monitoring supports the continuous improvement of the therapy by sharing data with healthcare professionals. It is required when life-threatening events can still occur after hospital discharge such as neonatal apnea. However, multiple sources of external noise could affect data quality and/or increase the misdetection rate. In this study, we developed a mechatronic platform for sensor characterizations and a framework to manage data in the context of neonatal apnea. The platform can simulate the movement of the abdomen in different plausible newborn positions by merging data acquired simultaneously from three-axis accelerometers and infrared sensors. We simulated nine apnea conditions combining three different linear displacements and body postures in the presence of self-generated external noise, showing how it is possible to reduce errors near to zero in phenomena detection. Finally, the development of a smart 8Ws-based software and a customizable mobile application were proposed to facilitate data management and interpretation, classifying the alerts to guarantee the correct information sharing without specialized skills.

Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI.

BACKGROUND: The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons. METHODS: We studied the in vivo correlation between the amyloid deposition at Positron Emission Tomography (amyloid-PET) and the presence of memory loss, reduced executive function, neuropsychiatric symptoms and physical performance in older persons with MCI. Amyloid-PET was performed with 18F-flutemetamol and quantitatively analyzed. RESULTS: We evaluated 48 subjects, 21 men and 27 women. We performed in each patient a comprehensive geriatric assessment (CGA) including Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Activity Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Neuropsychiatric inventory (NPI) questionnaire, 15 Geriatric Depression Scale (GDS), Short Physical Performance Battery (SPPB) and Hand Grip strength. Then, each patient underwent amyloid-PET. Mean age of the enrolled subjects was 74.6 ± 7.8 years. All of these subjects showed preserved cognitive function at MMSE > 24, while 29 of 48 subjects (61.0%) had altered CDT. Mean NPI score was 6.9 ± 5.9. The mean value of SPPB score was 9.0 ± 2.6, while the average muscle strength of the upper extremities measured by hand grip was 25.6 ± 7.7 Kg. CT/MRI images showed cortical atrophic changes in 26 of the 48 examined subjects (54.0%), while cerebrovascular modifications were present in 31 subjects (64.5%). Pathological burden of amyloid deposits was detected in 25 of 48 (52.0%) patients with a mean value of global z-score of 2.8 (subjects defined as MCI due to AD). After stratifying subjects in subclasses of clinical alterations, more probability of pathological amyloid deposition was found in subjects with impaired CDT and higher NPI score (O.R. = 3.45 [1.01-11.2], p = 0.04), with both impaired CDT and low physical performance (O.R. = 5.80 [1.04-32.2], p = 0.04), with altered CDT and high NPI score (O.R. = 7.98 [1.38-46.0], p = 0.02), and finally in those subjects with altered CDT, high NPI and low physical performance (O.R. = 5.80 [1.05-32.2], p = 0.04). CONCLUSION: Our findings support the recent hypothesis that amyloid deposition could be associated with multiple cerebral dysfunction, mainly affecting executive, behavioral and motor abilities.

Delirium in COVID-19: epidemiology and clinical correlations in a large group of patients admitted to an academic hospital.

BACKGROUND: Delirium incidence and clinical correlates in coronavirus disease-19 (COVID-19) pneumonia are still poorly investigated. AIM: To describe the epidemiology of delirium in patients hospitalized for suspect COVID-19 pneumonia during the pandemic peak in an academic hospital of Northern Italy, identify its clinical correlations and evaluate the association with mortality. METHODS: The clinical records of 852 patients admitted for suspect COVID-19 pneumonia, defined as respiratory symptoms or fever or certain history of contact with COVID-19 patients, plus chest CT imaging compatible with alveolar-interstitial pneumonia, were retrospectively analyzed. Delirium was defined after careful revision of daily clinical reports in accordance with the Confusion Assessment Method criteria. Data on age, clinical presentation, comorbidities, drugs, baseline lab tests and outcome were collected. The factors associated with delirium, and the association of delirium with mortality, were evaluated through binary logistic regression models. RESULTS: Ninety-four patients (11%) developed delirium during stay. They were older (median age 82, interquartile range, IQR 78-89, vs 75, IQR 63-84, p < 0.001), had more neuropsychiatric comorbidities and worse respiratory exchanges at baseline. At multivariate models, delirium was independently and positively associated with age [odds ratio (OR) 1.093, 95% confidence interval (CI) 1.046-1.143, p < 0.001], use of antipsychotic drugs (OR 4.529, 95% CI 1.204-17.027, p = 0.025), serum urea and lactate-dehydrogenase at admission. Despite a higher mortality in patients with delirium (57% vs 30%), this association was not independent of age and respiratory parameters. CONCLUSIONS: Delirium represents a common complication of COVID-19 and a marker of severe disease course, especially in older patients with neuropsychiatric comorbidity.

Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.

AIMS: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. METHODS: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. RESULTS AND DISCUSSION: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. CONCLUSION: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.

Treatment of Delirium in Older Persons: What We Should Not Do!

The presentation of common acute diseases in older age is often referred to as "atypical". Frequently, the symptoms are neither single nor tissue related. In most cases, the onset of symptoms and diseases is the expression of a diminished reserve with a failure of the body system and imbalance of brain function. Delirium is one of the main devastating and prevalent atypical symptoms and could be considered as a geriatric syndrome. It encompasses an array of neuropsychiatric symptoms and represents a disarrangement of the cerebral function in response to one or more stressors. The most recent definition, reported in the DSM-V, depicts delirium as a clear disturbance in attention and awareness. The deficit is to be developed in a relatively short time period (usually hours or days). The attention disorder must be associated with another cognitive impairment in memory, orientation, language, visual-spatial or perception abilities. For the treatment, it is imperative to remove the potential causes of delirium before prescribing drugs. Even a non-pharmacological approach to reducing the precipitating causes should be identified and planned. When we are forced to approach the pharmacological treatment of hyperactive delirium in older persons, we should select highly cost-effective drugs. High attention should be devoted to the correct balance between improvement of psychiatric symptoms and occurrence of side effects. Clinicians should be guided in the correct choice of drugs following cluster symptoms presentation, excluding drugs that could potentially produce complications rather than advantages. In this brief point-of-view, we propose a novel pharmacological flow-chart of treatment in relation to the basic clusters of diseases of an older patient acutely admitted to the hospital and, in particular, we emphasize "What We Should Not Do!", with the intention of avoiding possible side effects of drugs used.

The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing.

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

BACKGROUND AND AIMS: Increased uric acid levels correlate with cardiovascular disease and cardiovascular/overall mortality. To identify a uric acid threshold above which cardiovascular mortality rises, we studied the relationship between uric acid concentration and overall/cardiovascular mortality. METHODS AND RESULTS: We analyzed data from the InCHIANTI study, a cohort study of Italian community-dwelling people with 9 years of follow-up. We selected a sample of 947 individuals over 64 years of age, free from cardio-cerebrovascular disease and with available uric acid measurement at baseline. The sample was divided according to plasma uric acid tertiles. The Hazard ratio (HR) for mortality was calculated by multivariate Cox proportional hazard model. Mean age of participants was 75.3 ± 7.3 years; the mean value of uric acid was 5.1 ± 1.4 mg/dl. Over 9-years of follow-up, 342 (36.1%) participants died, 143 deaths (15.1%) were due to cardiovascular disease. Subjects with higher uric acid concentrations presented a higher cardiovascular mortality [II (4.6-5.5 mg/dl) vs I (1.8-4.5 mg/dl) tertile HR: 1.98, 95%C.I. 1.22-3.23; III (≥5.6 mg/dl) vs I tertile HR: 1.87, 95%C.I. 1.13-3.09]. We found a non-linear association between uric acid concentrations and cardiovascular mortality with the lowest mortality for values of about 4.1 mg/dl and a significant risk increment for values above 4.3 mg/dl. CONCLUSION: In community-dwelling older individuals free from cardio-cerebrovascular events, the lowest 9-year cardiovascular mortality was observed for uric acid values far below current target values. If confirmed, these data might represent the background for investigating the efficacy of uric acid levels reduction in similar populations.

Physical performance across the thyroid function values within the normal range in adult and older persons.

BACKGROUND: Thyroid hormone variation may be correlated with adverse health outcomes, even within the normal reference range in euthyroid individuals. AIMS: To determine the association between plasma thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and physical performance score in middle age and older adults who had levels of all three hormones in the normal range. METHODS: In this community-based, cross-sectional study, euthyroid participants of the Invecchiare in Chianti study, aged 23-102 years (N = 1060), were considered. Physical performance was evaluated by the Summary Physical Performance Battery (SPPB) score. Plasma TSH, FT3, and FT4 levels were predictors, and SPPB score was the outcome. RESULTS: At the univariate analyses, TSH, FT4, and FT3 were not significantly associated with SPPB score in young individuals, whereas, in older participants, SBBP score was positively (P < 0.001) associated with FT3, and negatively associated with both TSH (P < 0.02) and FT4 (P < 0.001). After adjusting for multiple confounders, FT3 remained significantly associated with SPPB (beta ± SE, 0.35 ± 0.17, P = 0.04), but FT4 and TSH were not. Results did not change when all the three hormones FT3, FT4, and TSH were simultaneously considered in the fully adjusted model (beta ± SE for FT3, 0.37 ± 0.18, P = 0.04). DISCUSSION: The results of this study demonstrate that SPPB score is positively associated with circulating FT3 but not with FT4 or with TSH, in older euthyroid individuals. CONCLUSIONS: In euthyroid older adults, circulating FT3 may play an important role in the thyroid effects on physical function.

Short-Physical Performance Battery (SPPB) score is associated with falls in older outpatients.

BACKGROUND: The capacity of Short-Physical Performance Battery (SPPB) test to discriminate between fallers and non-fallers is controversial, and has never been compared with fall risk assessment-specific tools, such as Performance-Oriented Mobility Assessment (POMA). AIM: To verify the association of SPPB and POMA scores with falls in older outpatients. METHODS: 451 older subjects (150 males, mean age 82.1 ± 6.8) evaluated in a geriatric outpatient clinic for suspected frailty were enrolled in this cross-sectional study. Self-reported history of falls and medication history were carefully assessed. Each participant underwent comprehensive geriatric assessment, including SPPB, POMA, Geriatric Depression Scale (GDS), mini-mental state examination (MMSE) and mini-nutritional assessment-short form (MNA-SF). Multivariate logistic regression and receiver-operating characteristic (ROC) analyses were performed to determine the factors associated with the status of faller. RESULTS: 245 (54.3%) subjects were identified as fallers. They were older and had lower SPPB and POMA test scores than non-fallers. At ROC analysis, SPPB (AUC 0.676, 95% CI 0.627-0.728, p < 0.001) and POMA (AUC 0.677, 95% CI 0.627-0.726, p < 0.001) scores were both associated with falls. At multivariate logistic regression models, SPPB total score (OR 0.83, 95% CI 0.76-0.92, p < 0.001), POMA total score (OR 0.94, 95% CI 0.91-0.98, p = 0.002) and SPPB balance score alteration (OR 2.88, 95% CI 1.42-5.85, p = 0.004), but not POMA balance subscale score alteration, were independently associated with recorded falls, as also GDS, MMSE and MNA-SF scores. CONCLUSIONS: SPPB total score was independently associated with reported falls in older outpatients, resulting non-inferior to POMA scale. The use of SPPB for fall risk assessment should be implemented.

Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study.

BACKGROUND: A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. AIM: To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. METHODS: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4-9) and a body mass index of 20-30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. RESULTS: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. CONCLUSIONS: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.

Polypharmacy and sarcopenia in hospitalized older patients: results of the GLISTEN study.

BACKGROUND: Recently the Berlin Aging Study II (BASE-II) showed that polypharmacy is associated with clinically relevant sarcopenia among community-dwelling older persons. Here we report findings from the GLISTEN study about the association of polypharmacy with sarcopenia among older medical in-patients. METHODS: The GLISTEN study investigated prevalence and clinical correlates of sarcopenia in older patients admitted to geriatric and internal medicine acute care wards of 12 Italian hospitals. RESULTS: In this sample of older medical in-patients with high prevalence of sarcopenia (34.7%) and polypharmacy (70.2%) we did not observe a significant association of polypharmacy with sarcopenia. CONCLUSIONS: Present findings demonstrate that the association of polypharmacy with sarcopenia, observed in the BASE-II study, is not evident in the GLISTEN sample, being our patients significantly older, more multi-morbid, with high prevalence of sarcopenia and polypharmacy, suggesting that this association might vary according to the heterogeneous health, functional, and nutritional characteristics of older people.

Assessing sarcopenia with vastus lateralis muscle ultrasound: an operative protocol.

BACKGROUND: Muscle ultrasound (MUS) has so far not been implemented for sarcopenia assessment in clinical geriatric practice due to allegedly low reproducibility of results in the absence of standardization of procedures. However, rigorous and standardized application of this technique yields highly reproducible results. Its application, especially if integrated with clinical evaluation and comprehensive geriatric assessment, proofs very useful for rapidly obtaining information on muscle mass and architecture. OBJECTIVE: Here, we present a standardized protocol for performing right vastus lateralis (RVL) MUS and measuring parameters of muscle size and architecture. METHODS: RVL muscle thickness (MT), fascicle length (FL), pennation angle (PA), echo-intensity (EI) and cross-sectional area (CSA) can be assessed with this protocol. A portable instrument equipped with a 5-cm long 3-11 mHz linear probe should be used with both B-mode real-time and extended-field-of-view (EFOV) techniques. Longitudinal B-mode and transverse EFOV images should be acquired during each exam, and analyzed with NIH-ImageJ software. CONCLUSIONS: This operative protocol represents a good compromise between the feasibility of MUS in clinical settings and the need of obtaining precise measurements of muscle parameters. Future studies should verify the reproducibility of the proposed technique, and its correlation with appendicular lean mass and parameters of muscle function.

Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.

Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.