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OBJECTIVES: We investigated salivary biomarkers of stress, more specifically, cortisol and alpha-amylase, to evaluate effects of individualized music listening (IML) in people with dementia. METHOD: Participants were N = 64 nursing home residents with dementia (meanage = 83.53 ± 7.71 years, 68.8% female). Participants were randomly assigned to either listening to their favorite music every other day for a period of six weeks (intervention), or standard care (control). Using the Saliva Children`s Swab (SCS), saliva was collected before, after, and 20 min after IML sessions at the beginning and end of the intervention period for the analysis of salivary alpha-amylase and cortisol. RESULTS: Using the SCS was feasible in people with dementia. Nevertheless, there was no effect of IML on salivary stress markers. DISCUSSION: Although using SCS was feasible, active patient engagement is required. Future studies need to corroborate findings in larger samples. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015641, ISRCTN registry: ISRCTN59052178.

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Non-pharmacological interventions include physical activity, biofield energy therapy, reiki, Tai chi, and therapeutic touch. However, no reports analyzed the effectiveness of biofield therapy on cognition and motor function performance in adult subjects. The study aimed to investigate the impact of remote biofield energy healing therapy on cognition and motor functioning in adults with self-perceived neuropsychological impairments. This was a randomized double-blind clinical trial that involved 114 participants with self-perceived neuropsychological impairments. The participants were divided into three groups (control, sham control, and biofield intervention). Cognitive and motor function scores were assessed using the NIH Toolbox at baseline (day 0), day 90, and day 180. The biofield treatment group showed significant improvements in language function (p < 0.0001), working memory (p < 0.0001), and episodic memory (p < 0.0001) scores. Other cognitive functions also improved, although not statistically significant. The biofield intervention group also demonstrated significant enhancements (p < 0.05 to p < 0.0001) in locomotion, standing balance, dexterity, grip strength, and muscle endurance. No adverse effects were reported. The results suggest that remote biofield energy therapy is a safe, noninvasive intervention that improves cognitive and motor functions in adults. Further research is needed to understand its clinical benefits.

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Introduction Preoperative anxiety refers to the feelings of unease, fear, or nervousness experienced by individuals before undergoing a surgical procedure. This anxiety can stem from various sources, including fear of the unknown, concerns about the surgical outcome, worries about pain or complications, and separation from loved ones during the procedure. Healthcare professionals can help minimize preoperative anxiety by employing various strategies and promoting better surgical experiences and outcomes. Hence, this study was designed to compare the effect of conventional preoperative verbal counseling versus preoperative verbal counseling using an anesthesia information sheet (AIS) on pre­operative anxiety of patients.  Methods A total of 80 patients were randomly placed into two groups of 40 each - preoperative verbal counseling (PC) and verbal counseling using an AIS. The Hamilton Anxiety Scale (HAM-A) was used to assess preoperative anxiety in both the group's pre- and post-counseling. Data was collected and compiled. Data was analyzed using SSPS software. Pearson correlation coefficient was used for the correlation of age, gender, education status, and ASA grading with pre- and post-counseling anxiety scores. Results A significant difference was seen in anxiety score pre- and post-counseling between group PC and AIS (p-value <0.05). The anxiety score after counseling in group PC was 16.27±4.57, which was significantly higher compared to group AIS (14.25±2.42; p-value=0.016). Conclusion As we continue to explore innovative ways to improve patient experiences and outcomes, integrating AISs into counseling practices stands as a promising strategy that can lead to more confident and well-informed patients, ultimately enhancing the quality of healthcare delivery.

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Alzheimer's disease (AD) is a neurodegenerative disorder that dramatically affects cognitive abilities and represents the most common cause of dementia. Currently, pharmacological interventions represent the main treatment to deal with the symptoms of AD; however, alternative approaches are readily sought. Transcranial pulse stimulation (TPS) is an emerging non-invasive neuromodulation technique that uses short, repetitive shockwaves with the potential to provide a wide range of vascular, metabolic, and neurotrophic changes and that has recently been shown to improve cognitive abilities in AD. This exploratory study aims to gain insight into the neurophysiological effect of one session of TPS in AD as reflected in electroencephalographic measures, e.g., spectral power, coherence, Tsallis entropy (TE), and cross-frequency coupling (cfc). We document changes in power (frontal and occipital), coherence (frontal, occipital and temporal), and TE (temporal and frontal) as well as changes in cfc (parietal-frontal, parietal-temporal, frontal-temporal). Our results emphasize the role of electroencephalographic measures as prospective markers for the neurophysiological effect of TPS.

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Physical inactivity contributes to over 800,000 deaths annually. Numerous non-pharmacological interventions provide a route to address this behavioural risk factor linked to the growth of non-communicable diseases. Here, we consider a nature-based intervention, specifically group outdoor health walks (GOHW), as a non-pharmacological intervention to increase physical activity and contribute to health and quality of life amongst older adults. We used the theoretically grounded Capability, Opportunity, Motivation, and Behaviour (COM-B) model as a lens to examine interviews with participants in a GOHW with an activity tracker and signposted by health clinics in Scotland, UK. Analysis identified capabilities, opportunities, and motivations, their impact on behaviour, and perceived physical and mental health. The application of the COM-B model to intervention evaluation allowed us to examine two separate behaviours, that of (i) engaging with the intervention itself, and (ii) incorporating the behaviour into one's life that the intervention targets. Analysis identified emerging capabilities, opportunities, and motivations that supported additional health-promoting behaviours, including increased time outdoors in nature and leadership to self-organise continued group walks. We offer insight into the design of nature-based interventions to effectively engage older adults with chronic health conditions and foster personal behaviour change for health and well-being.

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OBJECTIVE: To systematically investigate the efficacy of aromatherapy in patients with acute coronary syndrome (ACS). METHODS: We conducted a comprehensive search for papers published until November 2023 using the following databases: PubMed, Embase, and Cochrane Library. This study was conducted following the PRISMA and Cochrane Guidelines. The inclusion criteria were randomized controlled trials (RCTs) performed to assess the comparative effectiveness of inhalation aromatherapy versus controls in individuals diagnosed with ACS. The Jadad rating method was used to assess the quality of the included studies, and a meta-analysis was performed using the RevMan 5.4 software. Heterogeneity was quantified using the Higgins I2 (%) test. RESULTS: A total of 12 RCTs with 476 patients with ACS were included. Aromatherapy has been shown to reduce anxiety scores significantly (standard mean difference [SMD]: -1.18, 95 % confidence interval [CI]: -1.33 to -1.03; P < 0.00001) along with reduction in systolic blood pressure (MD = -8.78, 95 % CI [-13.92, -3.65], P = 0.008); diastolic blood pressure (MD = -7.76, 95 % CI [-11.39, -4.12], P < 0.001); mean artery pressure MD = -9.68, 95 % CI [-13.93.-5.44]; P < 0.0001). However, no significant effects were reported on the heart rate (MD = -6.98, 95 % CI [-15.46, 1.50], P = 0.11) and respiratory rate (MD = -0.67, 95 % CI [-2.52, 1.19], P = 0.48). A greater frequency of aromatherapy was associated greater anxiety -1.80 incidence, with 95 % CI [-2.04, -1.56]. Citrus essential oils exhibited the strongest effect (SMD = -1.97, 95 % CI [-3.34, -0.60], P = 0.005) in reducing anxiety levels. CONCLUSION: Aromatherapy appears to be an effective non-pharmacological intervention for reducing blood pressure and anxiety in individuals with ACS. This suggests that aromatherapy more than twice a day is effective in reducing anxiety levels. However, aromatherapy had no statistically significant impact on the heart or respiratory rates. Moreover, additional high-quality RCTs should be conducted to verify these results and explore the efficacy and mechanism of aromatherapy in patients with ACS.

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Objective: To retrieve, evaluate, and summarise the clinical evidence for non-pharmacological interventions in adult postoperative delirium (POD), encompassing the preoperative, intraoperative, and postoperative phases. Methods: The methods included conducting searches on UpToDate Clinical Consultants, the Scottish Intercollegiate Guidelines Network, the National Institute for Health and Care Excellence, the Registered Nurses' Association of Ontario, BMJ Best Practice, the Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, VIP, and the Chinese Biomedical Literature Service System. Clinical practice guidelines, clinical decision-making, evidence summaries, evidence synthesis, expert consensus, systematic reviews, and meta-analyses on non-pharmacological interventions for adult POD were examined, and the search period spanned between the establishment of each database and 30 October 2023. Results: A total of 17 documents were included, comprising three guidelines, one expert consensus, one clinical decision-making article, four evidence summaries, three systematic reviews, and five meta-analyses. These documents primarily focused on the following three aspects: preoperative, intraoperative, and postoperative care. In total, 30 "best evidence" instances were compiled. Conclusion: Considering the complexity and potential harm of adult POD, an accurate and timely evaluation of high-risk factors, alongside effective medical nursing strategies, is vital in its prevention and treatment. Non-pharmacological interventions remain the preferred choice for preventing and treating POD. Medical institutions should establish standardised processes for non-pharmacological intervention in adult POD, based on evidence-based medicine, to enhance the level of clinical care in this field.

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The human vestibular system is adversely affected by the aging process. Recent evidence indicates that vestibular information and cognitive functions are related, suggesting that age-related vestibular loss may contribute to cognitive impairment. In this study, we aimed to investigate the effects of repetitive, home-based galvanic vestibular stimulation (GVS) on cognitive functions in healthy older adults. Twenty-one participants (age = 64.66 ± 2.97 years, 12 females) were randomly allocated to either a home-based GVS or an active control group. The GVS intervention lasted 20 min per session, five times a week, for two weeks (10 sessions). Cognitive functions were assessed before and after the intervention using the Stroop Test, Trail Making Test A&B, and Dual-Task (digit recall and paper-pencil tracking test). Our findings revealed a significant group-by-time interaction effect for the tracking accuracy (F(1,18) = 7.713, p = 0.012, η p2 = 0.30), with only the home-based GVS group showing significant improvement (t = -2.544, p = 0.029). The proposed home-based GVS protocol offers a promising non-pharmacological avenue for enhancing visuospatial ability in healthy older adults. Further research is needed to investigate the effects of different GVS protocols on various cognitive functions, particularly in older individuals with different health conditions.

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Objectives: The complex effects of multiple co-occurring symptoms are a major cause of reduced quality of life; thus, it is necessary to identify symptom clusters experienced by patients and explore interventions. This study aimed to provide an overview of non-pharmacological interventions based on symptom clusters in adults to identify effective intervention strategies and methods. Methods. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. For the search databases, PubMed, Embase, Cochrane Library, CINAHL, RISS, KISS, and KISTI were used. It includes English and Korean experimental studies published up to May 2023. The literature quality was evaluated using the Joanna Briggs Institute Quality Assessment Tool. Results. Of the 18 studies selected, 15 were randomized controlled trials and three were quasi-experimental studies, all of which were conducted on patients with cancer. The symptom clusters-based interventions in the literature are classified as movement-based, relaxation-based, integrated, and miscellaneous interventions. Integrated interventions, which were effective in all studies, might prove to be very effective for managing symptom clusters. Movement-based intervention studies, which include dance, Qigong, and Tai Chi, might be very effective in improving health-related quality of life (HRQoL). Conclusions. This review demonstrates that non-pharmacological interventions reduce the occurrence and severity of symptom clusters, thereby improving HRQoL. Further studies are required to evaluate the effects of these interventions in patients with various chronic conditions other than cancer.

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BACKGROUND: Nearly two-thirds of family caregivers of persons living with Alzheimer's disease or related dementias (AD/ADRD) provide complex care, including medical care. Family caregivers typically receive little to no training on how to provide this care. Furthermore, family caregivers simultaneously grapple with the presence of behavioral and psychological symptoms of dementia (BPSD), diminished communication abilities, and comorbidities such as diabetes. We developed Learning Skills Together (LST), a 6-week digitally delivered psychoeducational program, to facilitate family caregiver abilities to administer complex care tasks. The goal of the present study is to test the efficacy of LST and to reduce adverse outcomes associated with caregiving, such as depressive symptomology and negative appraisal of BPSD. METHODS: To test the efficacy of LST, we will conduct a two-arm single-site randomized controlled trial (RCT) with N = 200 family caregivers of persons living with AD/ADRD. Eligible family caregivers will be randomly assigned to participate in either the LST intervention or a structurally equivalent control condition focused on healthy living. All family caregivers will complete four surveys, including a baseline survey administered prior to randomization, a post-intervention survey, and a 3- and 6-month follow-up survey to assess change in study outcomes. Between-group comparisons of each outcome will be evaluated using generalized estimating equation models. Mediation analyses will assess family caregiver self-efficacy as the intervention's mechanism of change in depressive symptomology and BPSD. We will also examine caregiver race, ethnicity, and gender as effect modifiers of the intervention. DISCUSSION: LST findings will inform the field of AD/ADRD and caregiving regarding optimally supporting family caregivers in managing complex care tasks. If efficacious, the LST intervention will support family caregivers in preserving their own mental health while providing complex care. TRIAL REGISTRATION: Clinical Trials.gov NCT05846984 . This study was registered on May 6, 2023.

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Background: Nearly two-thirds of family caregivers of persons living with Alzheimer's disease or related dementias (AD/ADRD) provide complex care, including medical care. Family caregivers typically receive little to no training on how to provide this care. Furthermore, family caregivers simultaneously grapple with the presence of behavioral and psychological symptoms of dementia (BPSD), diminished communication abilities, and comorbidities such as diabetes. We developed Learning Skills Together (LST), a six-week digitally delivered psychoeducational program, to facilitate family caregiver abilities to administer complex care tasks. The goal of the present study is to test the efficacy of LST and to reduce adverse outcomes associated with caregiving, such as depressive symptomology and negative appraisal of BPSD. Methods: To test the efficacy of LST, we will conduct a two-arm single-site randomised controlled trial (RCT) with N = 200 family caregivers of persons living with AD/ADRD. Eligible family caregivers will be randomly assigned to participate in either the LST intervention or a structurally equivalent control condition focused on healthy living. All family caregivers will complete four surveys, including a baseline survey administered prior to randomisation, a post-intervention survey, and a three- and six-month follow-up survey to assess change in study outcomes. Between-group comparisons of each outcome will be evaluated using generalized estimating equation models. Mediation analyses will assess family caregiver self-efficacy as the intervention's mechanism of change in depressive symptomology and BPSD. We will also examine caregiver race, ethnicity, and gender as effect modifiers of the intervention. Discussion: LST findings will inform the field of AD/ADRD and caregiving regarding optimally supporting family caregivers in managing complex care tasks. If efficacious, the LST intervention will support family caregivers in preserving their own mental health while providing complex care.

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Rolando Toro's Biodanza (SRT) is a therapeutic strategy that uses movement, music, and emotions to induce integrative living experiences. The present study aims to explore the efficacy of a three-month SRT intervention on motor, cognitive, and behavioral symptoms in patients with Parkinson's disease (PD). This study employed a randomized between-group design. Twenty-eight non-demented PD patients were enrolled in this study. Out of these, fourteen patients were assigned to the active treatment group using the Biodanza SRT system and fourteen to the untreated control group. The study group attended 2 h SRT classes once a week, completing twelve lessons in twelve weeks. All patients underwent: (i) a neurological examination to measure the severity of motor symptoms, balance, mobility, and risk of falls, and (ii) a neuropsychological battery to assess cognitive status, apathy, depressive symptomatology, and perceived quality of life (QoL), at study entry (T0) and at twelve weeks (T1, end of dance training). At T1, we observed a significant improvement in motor (i.e., severity of motor symptoms and balance) and cognitive parameters (i.e., working memory and delayed verbal memory) in all treated patients compared with the controls. Furthermore, a significant improvement in the social support dimension was found in all treated patients compared to the controls. A trend toward increased apathy was found in untreated patients at T1. The three-month Biodanza intervention significantly ameliorated the motor parameters of PD patients, with a parallel improvement in cognitive and QoL status. Hence, Biodanza intervention can, in the short term, represent a useful personalized medical intervention for the management of Parkinson's disease.

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BACKGROUND: For older adults with care needs, evidence for the effectiveness of psychotherapy on depression is scarce. METHODS: In PSY-CARE, a pragmatic randomized controlled trial, N = 197 home-living older adults with depression and care needs were randomized into outpatient psychotherapy or an active control condition. Residential psychotherapists offered age-sensitive cognitive-behavioral psychotherapy (at-home if needed). Control group participants received telephone counseling and a self-help guide. Outcomes were assessed at baseline (T1), after (T2), 3 months after (T3), and 12 months after the intervention (T4). RESULTS: There was a significant decrease in depressive symptoms across both arms with Cohen's d T4-T1 = .52 in the psychotherapy and .55 in the control group. Mixed models revealed no statistically significant difference in primary and secondary outcomes between interventions. Posthoc, we found control group participants with greater ADL limitations experienced significantly increased depressive symptoms compared to those reporting lower limitations. CONCLUSIONS: Interventions were successful in reducing depressive symptoms, even though treatment fidelity was decreased due to the COVID-19 pandemic. We could not demonstrate superior effectiveness of psychotherapy for older adults with care needs. CLINICAL IMPLICATIONS: Findings suggest that psychotherapy may be an important and superior treatment to circumvent aggravation of depression in older patients with high functional limitations. TRIAL REGISTRATION: The trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN55646265, February 15, 2019).

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BACKGROUND: The existing literature has limited detail on theory-driven interventions, particularly in pain studies. We adapted Bandura's self-efficacy framework toward a theory-driven, non-pharmacological intervention using auricular point acupressure (APA) and evaluated participants' perceptions of this intervention on their pain self-management. APA is a non-invasive modality based on auricular acupuncture principles. METHODS: We mapped our study intervention components according to Bandura's key sources of self-efficacy (performance accomplishments, vicarious experience, verbal persuasion, and emotional arousal) to facilitate the self-management of pain. Through a qualitative study design, we conducted virtual interviews at one and three months after a 4-week APA intervention among 23 participants using purposive sampling to describe their experiences in managing their pain based on our theory-driven APA intervention. RESULTS: Using thematic analyses, we found four themes: the enhanced self-management of pain, improved pain outcomes, the feasibility of technology, and the sustainability of APA. CONCLUSIONS: Describing how interventions are mapped according to the elements of theoretical frameworks can help to guide intervention development, advance science and knowledge development, and promote the implementation of interventions. As such, using Bandura's self-efficacy theory as a foundation for the APA intervention, APA was found to be feasible and sustainable, improving self-management, pain intensity, and pain-related outcomes. Participants provided recommendations for the further improvement of this theory-driven intervention.

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Objective: As a spectrum of neurodegenerative conditions, dementia presents a significant challenge to worldwide health. Mild cognitive impairment (MCI) is recognized as the intermediate stage between normal cognitive functioning and dementia. Studies highlight the significant impact of dietary patterns on the management of MCI and dementia. Currently, comprehensive research on dietary patterns specific to MCI and dementia is limited, but bibliometric analysis offers a method to pinpoint essential research directions. Methods: On November 18, 2023, a search was conducted in the Web of Science Core Collection (WoSCC) for publications on diet and MCI/dementia. Tools such as Rstudio, CiteSpace, and VOSviewer were employed to create a knowledge atlas. This atlas analyzed collaborations, reference co-citations, keyword patterns, and emerging trends. Results: The search yielded 1,493 publications on diet and MCI/dementia, indicating a growing interest despite fluctuations. Contributions came from 70 countries/regions and 410 organizations across 456 journals. The USA and China led in publication numbers, with significant contributions from Columbia University and Harvard Medical School. Top authors include Scarmeas Nikolaos, Morris Martha Clare, and Samieri Cecilia. The Ketogenic, Mediterranean, and MIND diets emerged as key dietary patterns for cognitive decline prevention, highlighting the role of genetic factors, especially ApoE polymorphisms, in cognitive deterioration. Conclusion: This study provides core countries, institutions, and authors in the field, and points out the development directions in the field. Future research directions in dietary for MCI and dementia will focus on: (1) the potential effects of the KD in alleviating oxidative stress and modulating gut microbiota in neurodegenerative diseases; (2) how diet influences cognitive health through patterns of ApoE and protein expression; (3) investigating the interactions between gut microbiota and brain function, known as the "gut-brain axis."

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BACKGROUND: Postintensive care syndrome (PICS) is common in critically ill adults who were treated in the intensive care unit (ICU). Although comparative analyses between types of non-pharmacological measures and usual care to prevent PICS have been performed, it remains unclear which of these potential treatments is the most effective for prevention. METHODS: To obtain the best evidence for non-pharmaceutical interventions in preventing PICS, a systematic review and Bayesian network meta-analyses (NMAs) will be conducted by searching nine electronic databases for randomized controlled trials (RCTs). Two reviewers will carefully screen the titles, abstracts, and full-text papers to identify and extract relevant data. Furthermore, the research team will meticulously check the bibliographic references of the selected studies and related reviews to discover any articles pertinent to this research. The primary focus of the study is to examine the prevalence and severity of PICS among critically ill patients admitted to the ICU. The additional outcomes encompass patient satisfaction and adverse effects related to the preventive intervention. The Cochrane Collaboration's risk-of-bias assessment tool will be utilized to evaluate the risk of bias in the included RCTs. To assess the efficacy of various preventative measures, traditional pairwise meta-analysis and Bayesian NMA will be used. To gauge the confidence in the evidence supporting the results, we will utilize the Confidence in NMA tool. DISCUSSION: There are multiple non-pharmacological interventions available for preventing the occurrence and development of PICS. However, most approaches have only been directly compared to standard care, lacking comprehensive evidence and clinical balance. Although the most effective care methods are still unknown, our research will provide valuable evidence for further non-pharmacological interventions and clinical practices aimed at preventing PICS. The research is expected to offer useful data to help healthcare workers and those creating guidelines decide on the most effective path of action for preventing PICS in adult ICU patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023439343.

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BACKGROUND: New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies aimed at these factors may provide a valuable tool for reducing the incidence of dementia. This study focused on the development of a mathematical model to predict the number of individuals with neurodegenerative diseases, specifically Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. Scenarios for non-pharmacological intervention therapies based on risk factor reduction were also assessed. The estimated total costs and potential cost savings from societal were included. METHODS: Based on demographic and financial data from the EU, a mathematical model was developed to predict the prevalence and resulting care costs of neurodegenerative diseases in the population. Each disease (Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis) used parameters that included prevalence, incidence, and death risk ratio, and the simulation is related to the age of the cohort and the disease stage. RESULTS: A replicable simulation for predicting the prevalence and resulting cost of care for neurodegenerative diseases in the population exhibited an increase in treatment costs from 267 billion EUR in 2021 to 528 billion EUR by 2050 in the EU alone. Scenarios related to the reduction of the prevalence of dementia by up to 20% per decade led to total discounted treatment cost savings of up to 558 billion EUR. CONCLUSION: The model indicates the magnitude of the financial burden placed on EU healthcare systems due to the growth in the population prevalence of neurodegenerative diseases in the coming decades. Lifestyle interventions based on reducing the most common risk factors could serve as a prevention strategy to reduce the incidence of dementia with substantial cost-savings potential. These findings could support the implementation of public health approaches throughout life to ultimately prevent premature mortality and promote a healthier and more active lifestyle in older individuals.

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This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention (NI), respiratory intervention (RI), psychological intervention (PSI), and integrated physical intervention (IPI), on functional status, quality of life, muscle strength, pulmonary function, and safety in patients with amyotrophic lateral sclerosis (ALS). We searched nine databases, PubMed, Cochrane, Embase, Scopus, Web of Science, CNKI, CBM, WFPD, and CSTJ, for randomized controlled trials of ALS patients. The primary outcome was the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were the McGill Quality of Life Questionnaire (McGill-QoL), Medical Research Council (MRC)-sum score, Forced Vital Capacity (FVC), and Fatigue Severity Scale (FSS) score. This NMA was conducted using random-effect models to calculate the standard mean difference (SMD) and 95% confidence interval (CI). All types of supplemental interventions had some benefit for patients with ALS. EI had a beneficial effect on the ALSFRS-R score (SMD: 1.01; 95% CI 0.50-1.51), FVC (SMD: 0.78; 95% CI 0.02-1.55), McGill-QoL (SMD: 0.71 95% CI 0.33-1.08), and MRC (SMD: 1.11; 95% CI 0.08-2.14). RI had a beneficial effect on the ALSFRS-R score (SMD: 0.83 95% CI 0.12-1.55). IPI had a beneficial effect on the ALSFRS-R score (SMD: 0.65 95% CI 0.06-1.24). NI had a beneficial effect on the McGill-QoL (SMD: 0.63 95% CI 0.02-1.23). The current study findings support a multimodal intervention strategy with an emphasis on EI for slowing disease progression in patients with ALS.

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Several biomarkers have been proposed to identify frailty, a multisystemic age-related syndrome. However, the complex pathophysiology and the absence of a consensus on a comprehensive and universal definition make it challenging to pinpoint a singular biomarker or set of biomarkers that conclusively characterize frailty. This review delves into the main laboratory biomarkers, placing special emphasis on those associated with various pathways closely tied to the frailty condition, such as inflammation, oxidative stress, mitochondrial dysfunction, metabolic and endocrine alterations and microRNA. Additionally, we provide a summary of different clinical biomarkers encompassing different tools that have been proposed to assess frailty. We further address various imaging biomarkers such as Dual Energy X-ray Absorptiometry, Bioelectrical Impedance analysis, Computed Tomography and Magnetic Resonance Imaging, Ultrasound and D3 Creatine dilution. Intervention to treat frailty, including non-pharmacological ones, especially those involving physical exercise and nutrition, and pharmacological interventions, that include those targeting specific mechanisms such as myostatin inhibitors, insulin sensitizer metformin and with special relevance for hormonal treatments are mentioned. We further address the levels of different biomarkers in monitoring the potential positive effects of some of these interventions. Despite the availability of numerous biomarkers, their performance and usefulness in the clinical arena are far from being satisfactory. Considering the multicausality of frailty, there is an increasing need to assess the role of sets of biomarkers and the combination between laboratory, clinical and image biomarkers, in terms of sensitivity, specificity and predictive values for the diagnosis and prognosis of the different outcomes of frailty to improve detection and monitoring of older people with frailty or at risk of developing it, being this a need in the everyday clinical practice.

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