Prevalence, incidence, and mortality of Myasthenia Gravis and myasthenic syndromes: a systematic review.

INTRODUCTION: No systematic reviews were published in the last years investigating epidemiological data, involving Myasthenia Gravis (MG) and related myasthenic syndromes. The aim of this systematic review was to estimate the prevalence, incidence, and mortality of all MG types and myasthenic syndromes worldwide. METHODS: All literature published up to February 2024 was retrieved by searching the databases "Medline", "Embase", "ISI Web of Science" and "CINAHL" using the following search terms: (epidemiolog* OR frequency OR prevalence OR incidence OR mortality) AND (myasth* OR "anti-acetylcholine receptor antibody" OR "AChR" OR "MuSK" OR "anti-muscle specific kinase antibody" OR "LRP4" OR "seronegative MG"). RESULTS: A total of 94 studies, performed between 1952 and 2022, were included. Prevalence of MG ranged from 20 to 475 cases per million, with a mean prevalence of 173.3 (95% CI: 129.7-215.5) cases per million and a median prevalence of 129.6 cases per million. Incidence rates ranged from 2.3 to 61.3 cases per million person-years, with a mean incidence of 15.7 (95% CI: 11.5-19.9) and a median of 13.3 cases. Mortality rates showed a mean of 1.4 (95% CI: 0.8-2.1) cases per million person-years. AChR-MG was the clinical subtype more frequent in terms of prevalence and incidence. DISCUSSION: The prevalence and incidence of MG have significantly increased over the last years worldwide, probably due to the improvement of epidemiological methodologies and current advances in diagnosis. However, we observed a significant variation in frequencies of MG between and within countries because of methodological biases and complex heterogeneity of the disease characterized by several phenotypes and different clinical responses.

A multicomponent personalized prevention program in the primary care setting: a randomized clinical trial in older people with noncommunicable chronic diseases (Primacare_P3 study).

BACKGROUND: Multicomponent interventions based on a comprehensive geriatric assessment (CGA) could promote active aging and improve health status in older people with Noncommunicable Chronic Diseases (NCDs), but conflicting evidences are available. AIM: To evaluate the efficacy of a CGA-based multicomponent personalized preventive program (PPP) in reducing unplanned hospitalization rates during 12-month follow-up in community-dwelling older people with NCDs. MATERIALS AND METHODS: In this randomized clinical trial (RCT), 1216 older adults recruited by 33 general practitioners (GPs) will be randomly allocated to intervention group (IG) or usual care control group (CG). The IG will receive a multicomponent PPP developed on the findings of the CGA-based Multidimensional Prognostic Index short-form (Brief-MPI), including structured interventions to improve functional, physical, cognitive, and nutritional status, to monitor NCDs and vaccinations, and to prevent social isolation. Participants in the CG will receive usual care. Brief-MPI, resilience, and health-related quality of life will be assessed after 6 and 12 months. Moreover, saliva samples will be collected at baseline in IG to measure biomarkers of oxidative stress, inflammatory cytokines, and oral microbiome. EXPECTED RESULTS: The CGA-based PPP might reduce unplanned hospitalization rates and potentially institutionalization rates, emergency department (ED) and unplanned GP visits, and mortality. Further outcomes explored in the IG will be the adherence to PPP, resilience, health-related quality of life, and multidimensional frailty as assessed by the Brief-MPI. CONCLUSIONS: Results will suggest whether the CGA-based multicomponent PPP is able to improve specific outcomes in a primary care setting. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT06224556 ; Registered January 25, 2024.

The Italian guideline on comprehensive geriatric assessment (CGA) for the older persons: a collaborative work of 25 Italian Scientific Societies and the National Institute of Health.

BACKGROUND: The guideline was promoted by the Italian General Practitioners-Primary Care and Geriatrics Hospital-Community Societies and was carried out involving the National Institute of Health and an Expert Panel including representatives from 25 Scientific and Health-Professional Organizations. The aim of the Guideline was to develop evidence-based recommendations on the efficacy of CGA in older people across different clinical settings and the accuracy and utility of CGA-based tools to assess prognosis. METHODS: According to the methodological handbook of the Italian National System of Guidelines and NICE criteria (National Institute for Health and Care Excellence in England), the Guideline was produced based on the Grading of Recommendations Assessment, Development and Evaluation. Over 20,000 records gathered through databases searches were initially selected. Sixteen recommendations on CGA efficacy were defined based on 117 studies that met the inclusion criteria and were performed in general practices and primary care (26 studies included), medical and surgical clinics (16 studies), emergency departments (17 studies), hospital medical and surgical wards (53 studies), long-term care facilities and nursing homes (5 studies), hospices and palliative care networks (no studies). Nine recommendations on CGA-based prognostic tools were issues based on 42 included studies carried out in general practices and primary care (5 studies), medical and surgical clinics (4 studies), and hospital wards (33 studies). RESULTS: Using CGA can be useful to reduce hospitalization, mortality, institutionalization, the risk of delirium, and improve appropriateness in drug prescription and maintain functional activities in different settings. Further research on the efficacy of CGA in rehabilitative facilities, nursing homes, and hospice and palliative-care settings is recommended. CGA-based tools, particularly the Multidimensional Prognostic Index, should be used to predict some negative outcomes in different settings. CONCLUSIONS: This Guideline may be useful in clinical practice and as a tool to support research on the use of CGA in older people.

A Systematic Review on Drugs Acting as Nicotinic Acetylcholine Receptor Agonists in the Treatment of Dementia.

Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine receptor agonists using Clinicaltrial (CT) and EudraCT databases. Structured searches identified 39 trials, which used 15 different drugs designed to increase the function of the nAChRs. Most of the identified clinical trials were phase II trials, with some of them classified as ongoing for several years. The systematic screening of the literature led to the selection of 14 studies out of the 8261 bibliographic records retrieved. Six trials reported detailed data on adverse events associated with the intervention, while twelve trials reported data on efficacy measures, such as attention, behavior and cognition. Overall, smost of the physical side effects of cholinergic agonists were reported to be well tolerated. Some trials also reported improvements in attention. However, the efficacy of these drugs in other cognitive and behavioral outcomes remains highly controversial.

Advances in amyloid-targeting monoclonal antibodies for Alzheimer's disease: clinical and public health issues.

INTRODUCTION: Alzheimer's disease (AD) is a major global public health challenge. To date, no treatments have been shown to stop the underlying pathological processes. The cerebral accumulation of amyloid-beta (Ab) is still considered as the primum movens of AD and disease-modifying treatments targeting Ab are reaching - or have already reached - clinical practice. AREAS COVERED: The authors explore the main advancements from Aß-targeting monoclonal antibodies (mAbs) for the treatment of AD. From a public health perspective, they address ethically relevant issues such as the benevolence and non-maleficence principles. They report on the potential biological and clinical benefits of these drugs, discussing minimal clinically important differences (MCID) and other relevant outcomes. They examine the short- and long-term effects of amyloid-related imaging abnormalities (ARIA), and explore the differences between eligibility criteria in clinical trials, appropriate use recommendations, and prescribing information content. In doing so, they contextualize the discussion on the disagreements among different regulatory authorities. EXPERT OPINION: Although anti-ß-amyloid monoclonal antibodies may be effective in selected scenarios, non-negligible knowledge gaps and implementation limits persist. Overcoming these gaps can no longer be postponed if we are to ensure the principles of Quality of Care for patients with cognitive impairment who would be eligible for this class of drugs.

Frequency and characterization of cognitive impairments in patients diagnosed with paediatric central nervous system tumours: a systematic review.

Background: This systematic review has been conducted with the aim of characterizing cognitive deficits and analyzing their frequency in survivors of paediatric Central Nervous System tumours. Materials and methods: All literature published up to January 2023 was retrieved searching the databases "PubMed", "Cochrane", "APA PsycInfo" and "CINAHL". The following set of pre-defined inclusion criteria were then individually applied to the selected articles in their full-text version: i) Retrospective/prospective longitudinal observational studies including only patients diagnosed with primary cerebral tumours at ≤ 21 years (range 0-21); ii) Studies including patients evaluated for neuro-cognitive and neuro-psychological deficits from their diagnosis and/or from anti-tumoral therapies; iii) Studies reporting standardized tests evaluating patients' neuro-cognitive and neuro-psychological performances; iv) Patients with follow-ups ≥ 2 years from the end of their anti-tumoral therapies; v) Studies reporting frequencies of cognitive deficits. Results: 39 studies were included in the analysis. Of these, 35 assessed intellectual functioning, 30 examined memory domains, 24 assessed executive functions, 22 assessed attention, 16 examined visuo-spatial skills, and 15 explored language. A total of 34 studies assessed more than one cognitive function, only 5 studies limited their analysis on a single cognitive domain. Attention impairments were the most recurrent in this population, with a mean frequency of 52.3% after a median period post-treatment of 11.5 years. The other cognitive functions investigated in the studies showed a similar frequency of impairments, with executive functions, language, visuospatial skills and memory deficits occurring in about 40% of survivors after a similar post-treatment period. Longitudinal studies included in the systematic review showed a frequent decline over time of intellectual functioning. Conclusions: Survivors of paediatric Central Nervous System tumours experience cognitive sequelae characterized by significant impairments in the attention domain (52.3%), but also in the other cognitive functions. Future studies in this research field need to implement more cognitive interventions and effective, but less neurotoxic, tumour therapies to preserve or improve neurocognitive functioning and quality of life of this population.

An updated overview of recent and ongoing deep brain stimulation (DBS) trials in patients with dementia: a systematic review.

BACKGROUND: Dementia affects more than 55 million people worldwide. Several technologies have been developed to slow cognitive decline: deep brain stimulation (DBS) of network targets in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have been recently investigated. OBJECTIVE: This study aimed to review the characteristics of the populations, protocols, and outcomes of patients with dementia enrolled in clinical trials investigating the feasibility and efficacy of DBS. MATERIALS AND METHODS: A systematic search of all registered RCTs was performed on Clinicaltrials.gov and EudraCT, while a systematic literature review was conducted on PubMed, Scopus, Cochrane, and APA PsycInfo to identify published trials. RESULTS: The literature search yielded 2122 records, and the clinical trial search 15 records. Overall, 17 studies were included. Two of 17 studies were open-label studies reporting no NCT/EUCT code and were analysed separately. Of 12 studies investigating the role of DBS in AD, we included 5 published RCTs, 2 unregistered open-label (OL) studies, 3 recruiting studies, and 2 unpublished trials with no evidence of completion. The overall risk of bias was assessed as moderate-high. Our review showed significant heterogeneity in the recruited populations regarding age, disease severity, informed consent availability, inclusion, and exclusion criteria. Notably, the standard mean of overall severe adverse events was moderately high (SAEs: 9.10 ± 7.10%). CONCLUSION: The population investigated is small and heterogeneous, published results from clinical trials are under-represented, severe adverse events not negligible, and cognitive outcomes uncertain. Overall, the validity of these studies requires confirmation based on forthcoming higher-quality clinical trials.

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer's Disease and Mild Cognitive Impairment from Healthy Controls.

The most frequently used biomarkers to support the diagnosis of Alzheimer's Disease (AD) are Aß42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.

The National Italian Guidelines on the diagnosis and treatment of children with pediatric ataxias.

Background: Ataxia is a rare neurological condition causing a deficit in the coordination of motor activities, preventing the fluidity of movements. Children with ataxia may show several different ataxic signs, along with difficulties in walking autonomously and ataxic gait often associated with trunk instability. Ataxic signs can be either acute or chronic, and in either case, the diagnosis can be extremely complex. Symptoms and their etiology are often widely heterogeneous, even within the same condition. Methods: The guideline was developed based on the methodology defined by the Methodological Handbook of the Italian National Guideline System (SNLG) and was reported following the AGREE-II checklist. The SNLG methodology required the adoption of the GRADE approach for the whole development process. To facilitate the implementation of the contents and recommendations from the guideline, two care pathways were developed based on the NICE and the European Pathway Association (EPA) models. Results: The guideline included 28 clinical questions, 4 on the identification and management of acute ataxias, and 24 on the diagnosis and management of chronic ataxias. The document included 44 recommendations, 37 clinical recommendations, and 7 recommendations for research. Conclusion: The working group, despite the lack and methodological limitations of the evidence, deemed as essential to provide indications and recommendations, in particular in some clinically relevant areas. The care pathway was produced as a tool to facilitate the implementation of the contents and recommendations. The interactive version of the pathway is available on the SNLG website along with a leaflet dedicated to families and caregivers.

The Italian fund for Alzheimer's and other dementias: strategies and objectives to face the dementia challenge.

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper.

Computer-Based Cognitive Training in Children with Primary Brain Tumours: A Systematic Review.

Background: Late neurocognitive sequelae are common among long-term brain tumour survivors, resulting in significantly worse quality of life. Cognitive rehabilitation through specific APP/software for PC/tablets represents an innovative intervention spreading in recent years. In this study, we aim to review the current evidence and trends regarding these innovative approaches. Methods: A systematic literature review was performed. Inclusion criteria were: (i) Studies recruiting patients diagnosed with any brain tumour before 21 years of age; (ii) studies assessing the role of digital interventions on cognitive outcomes. Case reports, case series, reviews, letters, conference proceedings, abstracts, and editorials were excluded. Results: Overall, nine studies were included; 152 patients (67.8% males) with brain tumours underwent a digital intervention. The mean age at diagnosis and the intervention enrolment ranged from 4.9 to 9.4 years and 11.1 to 13.3 years, respectively. The computer-based software interventions employed were: Cogmed, Captain's Log, Fast ForWord, and Nintendo Wii. Most of these studies assessed the effects of cognitive training on working memory, attention, and performance in daily living activities. Conclusions: The studies suggest that this type of intervention improves cognitive functions, such as working memory, attention, and processing speed. However, some studies revealed only transient positive effects with a significant number of dropouts during follow-up. Trials with greater sample sizes are warranted. Motivating families and children to complete cognitive interventions could significantly improve cognitive outcomes and quality of life.

Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials.

BACKGROUND: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD). OBJECTIVE: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes. METHODS: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library. RESULTS: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15). CONCLUSION: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.

Artificial intelligence-enhanced intraoperative neurosurgical workflow: current knowledge and future perspectives.

INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) augment decision-making processes and productivity by supporting surgeons over a range of clinical activities: from diagnosis and preoperative planning to intraoperative surgical assistance. We reviewed the literature to identify current AI platforms applied to neurosurgical perioperative and intraoperative settings and describe their role in multiple subspecialties. EVIDENCE ACQUISITION: A systematic review of the literature was conducted following the PRISMA guidelines. PubMed, EMBASE, and Scopus databases were searched from inception to December 31st, 2020. Original articles were included if they: presented AI platforms implemented in perioperative, intraoperative settings and reported ML models' performance metrics. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed appropriate. The risk of bias and applicability of predicted outcomes were assessed using the PROBAST tool. EVIDENCE SYNTHESIS: Forty-one articles were included. All studies evaluated a supervised learning algorithm. A total of 10 ML models were described; the most frequent were neural networks (N.=15) and tree-based models (N.=13). Overall, the risk of bias was medium-high, but applicability was considered positive for all studies. Articles were grouped into four categories according to the subspecialty of interest: neuro-oncology, spine, functional and other. For each category, different prediction tasks were identified. CONCLUSIONS: In this review, we summarize the state-of-art applications of AI for the intraoperative augmentation of neurosurgical workflows across multiple subspecialties. ML models may boost surgical team performances by reducing human errors and providing patient-tailored surgical plans, but further and higher-quality studies need to be conducted.

Prevalence of amyotrophic lateral sclerosis in Latium region, Italy.

OBJECTIVE: Prevalence estimate of amyotrophic lateral sclerosis (ALS) ranged between 1.1/100,000 and 11.2/100,000 inhabitants with different design of the study (prospective or retrospective) and sample size. The aim of this study is to conduct for the first time an estimate of the ALS prevalence in the Latium region. MATERIALS AND METHODS: The study was performed in Latium, a region located in the center of Italy, with a population, as of January 1, 2016, of 5888.472 inhabitants. In this region, a network of 15 clinical centers (of which 4 referral ALS centers are located in Rome) and 10 local health authorities involved in the diagnosis and treatment of ALS patients has been identified. Each patient was classified according to the El Escorial revised criteria. RESULTS: The prevalence study in 2016 identified 353 ALS cases (200 males). By considering population aged >=20 years, the total crude prevalence rate resulted 7.33 (CI95% 6.59-8.14) × 100,000 and 8.75 and 6.05 in males and females, respectively. Age-specific prevalence rates did not differ among males and females in the population aged less than 49 years. The difference emerged in population aged > 50 years. This type of diagnosis was recorded for 343 patients (11 missing). 68% of these patients have a definite diagnosis, 14% likely, 11% possible, and 12% defined as suspect. CONCLUSIONS: The estimate of prevalence rates observed in this study is probably in line with the values reported in the literature for prospective prevalence studies.

Reasons for SARS-CoV-2 infection in children and their role in the transmission of infection according to age: a case-control study.

BACKGROUND: The locations where children get exposed to SARS-CoV-2 infection and their contribution in spreading the infection are still not fully understood. Aim of the article is to verify the most frequent reasons for SARS-CoV-2 infection in children and their role in the secondary transmission of the infection. METHODS: A case-control study was performed in all SARS-CoV-2 positive children (n = 81) and an equal number of age- and sex- matched controls who were referred to the S. Camillo-Forlanini Pediatric Walk-in Center of Rome. The results of all SARS-CoV-2 nasopharyngeal swabs performed in children aged < 18 years from October 16 to December 19, 2020 were analyzed. RESULTS: School contacts were more frequent in controls than in cases (OR 0.49; 95% CI: 0.3-0.9), while household contacts were higher in cases (OR 5.09; 95% CI: 2.2-12.0). In both cases and controls, school contacts were significantly less frequent, while on the contrary household contacts seemed to be more frequent in nursery school children compared to primary school or middle/high school children. A multivariate logistic regression showed that the probability of being positive to SARS-CoV-2 was significantly lower in children who had school contacts or who had flu symptoms compared to children who had household contacts. Results showed a 30.6% secondary attack rate for household contacts. CONCLUSION: In our study population, the two most frequent reasons for SARS-CoV-2 infection were school and home contacts. The risk of being positive was 5 times lower in children who had school contacts than in children who had household contacts.

A National Survey of Centers for Cognitive Disorders and Dementias in Italy.

BACKGROUND: Italy has one of the oldest populations in the World and more than one million dementia cases can be estimated at the national level. OBJECTIVE: The objectives of this national survey include: 1) to report the administrative features and the professional competencies of Centers for Cognitive Disorders and Dementias (CCDDs); 2) to document possible discrepancies by geographic macro-area; and 3) to identify the features of CCDDs that are associated with a better quality in the provision of care. METHODS: A survey of Italian CCDDs was conducted between February 2014 and December 2015. A list of CCDDs was obtained through direct interactions with designed delegates from each Italian region. A questionnaire was defined on five sections concerning: 1) location of the CCDD; 2) access to the CCDD; 3) organization of the CCDD; 4) services and treatments provided; and 5) quantitative data on the activities of the CCDD. RESULTS: Overall, 577 out of the 597 eligible CCDDs returned the completed survey questionnaire (response rate: 96.6%): 260 (45.1%) from Northern Italy, 103 (17.8%) from Central Italy, and 214 (37.1%) from Southern-Islands Italy. More than a third of CCDDs were open only once or twice weekly. A median of 450 (IQR: 200-800) patients regularly attended these services. Most patients (70%) were affected by dementia or mild cognitive impairment (19%). CONCLUSION: We have provided a snapshot of the organization and activities of CCDDs in Italy and documented existing inequalities in the provision of care.

Anticancer drugs repurposed for Alzheimer's disease: a systematic review.

BACKGROUND: The relationship between cancer and dementia is triggering growing research interest. Several preclinical studies have provided the biological rationale for the repurposing of specific anticancer agents in Alzheimer's disease (AD), and a growing number of research protocols are testing their efficacy and safety/tolerability in patients with AD. METHODS: The aim of the present systematic review was to provide an overview on the repurposing of approved anticancer drugs in clinical trials for AD by considering both ongoing and completed research protocols in all phases. In parallel, a systematic literature review was conducted on PubMed, ISI Web, and the Cochrane Library to identify published clinical studies on repurposed anticancer agents in AD. RESULTS: Based on a structured search on the ClinicalTrials.gov and the EudraCT databases, we identified 13 clinical trials testing 11 different approved anticancer agents (five tyrosine kinase inhibitors, two retinoid X receptor agonists, two immunomodulatory agents, one histone deacetylase inhibitor, and one monoclonal antibody) in the AD continuum. The systematic literature search led to the identification of five published studies (one phase I, three phase II, and one phase IIb/III) reporting the effects of antitumoral treatments in patients with mild cognitive impairment or AD dementia. The clinical findings and the methodological characteristics of these studies are described and discussed. CONCLUSION: Anticancer agents are triggering growing interest in the context of repurposed therapies in AD. Several clinical trials are underway, and data are expected to be available in the near future. To date, data emerging from published clinical studies are controversial. The promising results emerging from preclinical studies and identified research protocols should be confirmed and extended by larger, adequately designed, and high-quality clinical trials.

Exploring the association of early life physical activity and risk of dementia: a systematic review.

INTRODUCTION: Physical activity has been included in the list of twelve modifiable risk factors for dementia, despite conflicting results from observational and controlled studies. In particular it is not clear whether physical inactivity near the time of dementia diagnosis is a consequence or cause of dementia. We review all available studies reporting the possible association between having engaged in PA before 60 years of age and the risk of dementia. EVIDENCE ACQUISITION: We performed a systematic review based on the methodology reported in the Cochrane handbook for systematic reviews and following the PRISMA statement. Bibliographic searches were carried out on the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Further references were retrieved from published systematic reviews on the same topic. Included studies were assessed using the Newcastle Ottawa scale. EVIDENCE SYNTHESIS: The bibliographic search yielded 1381 records. A total of 11 studies were included. Three of the included studies were case control studies, while the remaining 8 were cohort studies The overall quality of included studies was high. However, clinical criteria for the diagnosis of dementia, criteria to define and measure and PA and time-reference of exposure were heterogeneous, with some studies considering specific age range of exposure, and other reports dealing with more generic "adult age." CONCLUSIONS: This review suggests that there is insufficient evidence to conclude whether PA in early life may affect the incidence of dementia in later life. Studies in this field are very complicated and recognizing the impact of PA in early life given all the confounding factors is very difficult. Further studies are warranted. In these studies, it will be crucial to define the type, quantity and intensity of PA as well as to stratify analysis by sex, cultures and social classes.

Decreasing trend in the incidence and prevalence of dementia: a systematic review.

INTRODUCTION: The progressive ageing of the population is one of the main socio-demographic phenomena, taking place at a global level. Several recent population-based studies conducted worldwide suggest that the age-specific risk of dementia may be changing in some countries and areas. EVIDENCE ACQUISITION: This systematic review was performed using the methodology proposed by the Cochrane handbook for systematic reviews and reported following the PRISMA statement. A structured bibliographic search was performed on the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. All included studies were qualitatively assessed using the Methodological Evaluation of Observational REsearch (MORE). EVIDENCE SYNTHESIS: The bibliographic search yielded 2394 records. Three more articles were retrieved from other sources. A total of ten studies were included, five reported data on a possible reduction in the prevalence of dementia, and five reported data on a possible reduction in its incidence. CONCLUSIONS: The present systematic review focused on the recent observations of a possible decrease in the frequency of dementia and cognitive impairment in some Western countries (USA, UK, Sweden, the Netherlands, France, Iceland) between 1977 and 2014. The included studies have a high heterogeneity in terms of the clinical criteria used to diagnose dementia, and of the criteria used to define the clinical condition preceding dementia, such as isolated cognitive impairment. Moreover, the methodological quality with which they were conducted was also heterogeneous, with scores ranging from 1 to 7 using the MORE tool.