Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia: a collaborative international guideline

Cognition; Dementia; ExerciseCognició; Demència; ExerciciCognición; Demencia; EjercicioBackground Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. Objectives To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. Methods Guideline content was developed with input from several scientific and lay representatives’ societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. Recommendations Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind–body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. Conclusions Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health.Open access funding provided by Università degli Studi di Palermo within the CRUI-CARE Agreement

Mitochondrial genetic haplogroups and cardiovascular diseases: Data from the Osteoarthritis Initiative

Background: Some case-control studies reported that mitochondrial haplogroups could be associated with the onset of cardiovascular diseases (CVD), but the literature regarding this topic is limited. We aimed to investigate whether any mitochondrial haplogroup carried a higher or lower risk of CVD in a large cohort of North American people affected by knee osteoarthritis or at high risk for this condition. Materials and methods: A longitudinal cohort study including individuals from the Osteoarthritis Initiative was done. Haplogroups were assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups have been named following this nomenclature: HV, JT, UK, IWX, and superHV/others. The strength of the association between mitochondrial haplogroups and incident CVD was evaluated through a Cox’s regression analysis, adjusted for potential confounders, and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). Results: Overall, 3,288 Caucasian participants (56.8% women) with a mean age of 61.3±9.2 years without CVD at baseline were included. During a median follow-up of 8 years, 322 individuals (= 9.8% of baseline population) developed a CVD. After adjusting for 11 potential confounders at baseline and taking those with the HV haplotype as reference (the most frequent), those with JT carried a significant lower risk of CVD (HR = 0.75; 95%CI: 0.54–0.96; p = 0.03). Participants with the J haplogroup had the lowest risk of CVD (HR = 0.71; 95%CI: 0.46–0.95; p = 0.02). Conclusions: The presence of JT haplogroups (particularly J) may be associated with a reduced risk of CVD. However, this result was not based on a high level of statistical significance. Thus, future research with larger sample size is needed to assess whether our results can be corroborated

Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: a Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials

There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes, compared with a placebo. Several databases were searched investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or conditions at high risk of diabetes. Data were reported as standardized mean differences (SMDs) with their 95% confidence intervals (CIs) using follow-up data of glucose and insulin-sensitivity parameters. Compared with placebo, Mg supplementation reduced fasting plasma glucose in people with diabetes. In people at high risk of diabetes, Mg supplementation significantly improved plasma glucose per se, and after a 2 h oral glucose tolerance test. Furthermore, Mg supplementation demonstrated an improvement in insulin sensitivity markers. In conclusion, Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes. Moreover, our work indicates that Mg supplementation may improve insulin-sensitivity parameters in those at high risk of diabetes

Mitochondrial genetic haplogroups and depressive symptoms: A large study among people in North America

Background: A possible relationship between mitochondrial haplogroups and psychiatric diseases (e.g. schizophrenia and bipolar disorder) has been postulated, but data regarding depression is still limited. We investigated whether any mitochondrial haplogroup carried a significant higher risk of depressive symptoms in a large prospective cohort of North American people included in the Osteoarthritis Initiative. Methods: Cross sectional data was derived from the Osteoarthritis Initiative. The haplogroup was assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups were named following this nomenclature: H, U, K, J, T, V, SuperHV, I, W, X or Others. Depression was ascertained through the 20-item Center for Epidemiologic Studies- Depression (CES-D), with >16 indicating depressive symptoms. Results: Overall, 3,601 Caucasian participants (55.9% women), mean age of 61.7±9.3 years were included. No difference was observed in mitochondrial haplogroups frequency among those with depressive symptoms (n=285, =7.9% of the baseline population) compared to participants with no depressive symptoms (N=3,316) (chi-square test=0.53). Using a logistic regression analysis, adjusted for eight potential confounders, with those having the haplogroup H as the reference group (the most common haplogroup), no significant mitochondrial haplogroup was associated with prevalent depressive symptoms. The same results were evident in secondary analysis in which we matched depressed and non-depressed participants for age and sex. Limitations: cross-sectional design; only CES-D for evaluating mood; participants not totally representative of general population. Conclusions: We found no evidence of any relationship between specific mitochondrial haplogroups and depressive symptoms. Future longitudinal research is required to confirm/ refute these findings

Risk and protective factors for cannabis, cocaine, and opioid use disorders: An umbrella review of meta-analyses of observational studies

Several meta-analyses of observational studies have addressed the association between risk and protective factors and cannabis/cocaine/opioid use disorders, but results are conflicting. No umbrella review has ever graded the credibility of this evidence (not significant/weak/suggestive/highly suggestive/convincing). We searched Pubmed-MEDLINE/PsycInfo, last search September 21, 2020. We assessed the quality of meta-analyses with the AMSTAR-2 tool. Out of 3,072 initial references, five were included, providing 19 associations between 12 putative risk/protective factors and cannabis/cocaine/opioid use disorders (cases: 4539; N=1,118,872,721). While 84% of the associations were statistically significant, none was convincing. One risk factor (smoking) had highly suggestive evidence for association with nonmedical use of prescription opioid medicines (OR=3.07, 95%CI:2.27 to 4.14). Convincing evidence emerged in sensitivity analyses on antisocial behavior and cannabis use disoder (OR 3.34, 95%CI 2.53-4.41). Remaining associations had weak evidence. The quality of meta-analyses was rated as moderate in two (40%), low in one (20%), and critically low in two (40%). Future research is needed to better profile risk/protective factors for cannabis/cocaine/opioid use disorders disorders informing preventive approaches

Glucosamine sulphate: an umbrella review of health outcomes

BACKGROUND & AIMS: Glucosamine sulphate (GS) can be used as background therapy in people affected by knee osteoarthritis (OA). The knowledge regarding the efficacy and safety of GS is of importance since its use worldwide is increasing. Therefore, the present study aimed to map and grade the diverse health outcomes associated with GS using an umbrella review approach. METHODS: Medline, Cinhal and Embase databases were searched until 01st April 2020. An umbrella review of systematic reviews and meta-analyses of randomized controlled trials (RCTs) was carried out. The evidence from RCTs was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool. RESULTS: From 140 articles returned, 11 systematic reviews, for a total of 21 outcomes (37 RCTs; 3,949 participants; almost all using 1,500 mg/day), were included. No systematic reviews/meta-analyses of observational studies were included. Regarding the findings of the meta-analyses, 9/17 outcomes were statistically significant, indicating that GS is more effective than placebo. A high certainty of evidence, as assessed by the GRADE, supported the use of GS (vs. placebo), in improving the Lequesne index, joint space width change, joint space width change after 3 years of follow-up, joint space narrowing and OA progression. No difference in terms of adverse effects was found between GS and placebo. In systematic reviews, GS was associated with a better glucose profile and a better physical function performance than placebo. CONCLUSIONS: GS, when used as prescription drug (i.e. crystalline glucosamine sulfate) at 1,500mg daily dosage, can positively affect the cartilage structure, reduce pain, improve function and glucose metabolism in people with knee OA, without having a greater incidence of adverse effects than placebo

Physical activity and exercise in dementia : an umbrella review of intervention and observational studies

Background: Dementia is a common condition in older people. Among the potential risk factors, increasing attention has been focused on sedentary behaviour. However, synthesizing literature exploring whether physical activity/exercise can affect health outcomes in people with dementia or with mild cognitive impairment (MCI) is still limited. Therefore, the aim of this umbrella review, promoted by the European Geriatric Medicine Society (EuGMS), is to understand the importance of physical activity/exercise for improving cognitive and non-cognitive outcomes in people with dementia/MCI. Methods: Umbrella review of systematic reviews (SR) (with or without meta-analyses) of randomized controlled trials (RCTs) and observational (prospective and case-control in people with MCI) studies based on a systematic literature search in several databases. The certainty of evidence of statistically significant outcomes attributable to physical activity/exercise interventions was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Among 1,160 articles initially evaluated, 27 systematic reviews (4 without meta-analysis) for a total of 28,205 participants with dementia/MCI were included. No observational study on physical activity/exercise in MCI for preventing dementia was included. In SRs with MAs, physical activity/exercise was effective in improving global cognition in Alzheimer’s disease and in all types of dementia (very low/low certainty of evidence). Moreover, physical activity/ exercise significantly improved global cognition, attention, executive function, and memory in MCI, with a certainty of evidence varying from low to moderate. Finally, physical activity/exercise improved non-cognitive outcomes in people with dementia including falls and neuropsychiatric symptoms. SRs, without meta-analysis, corroborated these results. Conclusions: Supported by very low to moderate certainty of evidence, physical activity/exercise has a positive effect on several cognitive and non-cognitive outcomes in people with dementia and MCI, but RCTs, with low risk of bias/confounding, are still needed to confirm these findings

Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature

The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition

Risk stratification in heart failure decompensation in the community: HEFESTOS score

Aims: Because evidence regarding risk stratification predicting prognosis of patients with heart failure (HF) decompensation attended in primary care is lacking, we developed and externally validated a model to forecast death/hospitalization during the first 30 days after an episode of decompensation. The predictive model is based on variables easily obtained in primary care settings. Methods and results: HEFESTOS is a multinational study consisting of a derivation cohort of HF patients recruited in 14 primary healthcare centres in Barcelona and a validation cohort from primary healthcare in 9 other European countries. The derivation and validation cohorts included 561 and 250 patients, respectively. Percentages of women in the derivation and validation cohorts were 56.3% and 47.6% (P = 0.026), respectively. Mean age was 82.2 years (SD 8.03) in the derivation cohort, and 79.3 years (SD 10.3) in the validation one (P = 0.001). HF with preserved ejection fraction represented 72.1% in the derivation cohort and 58.8% in the validation one (P = 0.004). Mortality/hospitalization during the first 30 days after a decompensation episode was 30.5% and 26% (P = 0.225) for the derivation and validation cohorts, respectively. Multivariable logistic regression models were performed to develop a score of risk. The identified predictors were worsening of dyspnoea [odds ratio (OR): 2.5; P = 0.001], orthopnoea (OR: 2.16; P = 0.01), paroxysmal nocturnal dyspnoea (OR: 2.25; P = 0.01), crackles (OR: 2.35; P = 0.01), New York Heart Association functional class III/IV (OR: 2.11; P = 0.001), oxygen saturation ≤ 90% (OR: 4.98; P 100 b.p.m. (OR: 2.72; P = 0.002), and previous hospitalization due to HF (OR: 2.45; P 20%. Outcome incidence was 2.7% for the low-risk group, 12.8% for medium risk, and 46.2% for high risk in the derivation cohort, and 9.1%, 12.9%, and 39.6% in the validation one. Conclusions: The HEFESTOS score, based on variables easily accessible in a community setting and validated in an external European cohort, properly predicted the risk of death/hospitalization during the first 30 days after an HF decompensation episode

Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

Background. Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic. Methods. We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALTpatients as the primary outcome. The secondary outcome was the hazard ratio (HR), adjusted for the maximum number of covariates available, using ALT- patients as reference. Results. Eight articles comprising a total of 551 patients with sarcomas (226 ALT+ and 325 ALT-) were selected. The ALT+ group showed a higher mitotic count and a higher tumor grade compared with the ALT- group (p<0.01). Furthermore, we demonstrate a strong impact of ALT on survival. In fact, ALT+ patients showed a statistically significant higher risk of death than ALTpatients, when also considering data from multivariate analyses (RR = 1.50; 95% CI: 1.15–1.96; p =0.003; HR = 2.02; 95% CI: 1.22–3.38; p = 0.007). Conclusions. Our results indicate that ALT is associated with an increased risk of death in patients with sarcoma. In these neoplasms, ALT should be taken into account for a precise prognostic stratification and design of potential therapeutic strategies