Ageism has been shown to have a negative impact on older people's health and wellbeing. Though multiple scales are currently being used to measure this increasingly important issue, syntheses of the psychometric properties of these scales are unavailable. This means that existing estimates of ageism prevalence may not be accurate. We conducted a systematic review aimed at identifying available ageism scales and evaluating their scope and psychometric properties. A comprehensive search strategy was used across fourteen different databases, including PubMed and CINAHL. Independent reviewers extracted data and appraised risk of bias following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Of the 29,664 records identified, 106 studies, assessing 11 explicit scales of ageism, were eligible for inclusion. Only one scale, the 'Expectations Regarding Aging' met minimum requirements for psychometric validation (i.e., adequate content validity, structural validity and internal consistency). Still, this scale only assesses the 'stereotype' dimension of ageism, thus failing to evaluate the other two ageism dimensions (prejudice and discrimination). This paper highlights the need to develop and validate a scale that accounts for the multidimensional nature of ageism. Having a scale that can accurately measure ageism prevalence is key in a time of increasing and rapid population ageing, where the magnitude of this phenomenon may be increasing.

Emerging data show that the health and economic impacts of COVID-19 are being disproportionately borne by individuals who are not only biologically, but also socially vulnerable. Based on preliminary data from Sweden and other reports, in this paper we propose a conceptual framework whereby different factors related to bio-logical and social vulnerability may explain the specific COVID-19 burden among older people. There is already some evidence showing large social disparities in the prevention, treatment, prognosis and/or long-term consequences of COVID-19. The remaining question is to what extent these affect older adults specifically. We provide the rationale to address this question with scientific methods and proper study designs, where the interplay between individuals' biomedical status and their social environment is the focus. Only through interdisciplinary research integrating biological, clinical and social data will we be able to provide new insights into the SARS-CoV-2 pandemic and inform actions aimed at reducing older adults' vulnerability to COVID-19 or other similar pandemics in the future.

Aging is a natural process accompanied by a progressive accumulation of damage in all constituent macromolecules (nucleic acids, lipids and proteins). Accumulation of damage in proteins leads to failure of proteostasis (or vice versa) due to increased levels of unfolded, misfolded or aggregated proteins and, in turn, to aging and/or age-related diseases. The major cellular proteolytic machineries, namely the proteasome and the lysosome, have been shown to dysfunction during aging and age-related diseases. Regarding the proteasome, it is well established that it can be activated either through genetic manipulation or through treatment with natural or chemical compounds that eventually result to extension of lifespan or deceleration of the progression of age-related diseases. This review article focuses on proteasome activation studies in several species and cellular models and their effects on aging and longevity. Moreover, it summarizes findings regarding proteasome activation in the major age-related diseases as well as in progeroid syndromes.

Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly prevalent in the population. Besides being an important causative factor of cardiovascular diseases, FH has been considered an early risk factor for Alzheimer's disease. Cognitive and emotional behavioral impairments in LDL receptor knockout (LDLr-/-) mice are associated with neuroinflammation, blood-brain barrier dysfunction, impaired neurogenesis, brain oxidative stress, and mitochondrial dysfunction. Notably, today, LDLr-/- mice, a widely used animal model for studying cardiovascular diseases and atherosclerosis, are also considered an interesting tool for studying dementia. Here, we reviewed the main findings in LDLr-/- mice regarding the relationship between FH and brain dysfunctions and dementia development.

Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention. We searched journals in the top two quartiles of geriatrics and gerontology (from Clarivate Journal Citation Reports) for articles published between 01 January 2018 and 20 December 2022. Several recent developments were identified, including new biomarkers and biomarker panels for frailty screening and diagnosis, using artificial intelligence to identify frailty, and investigating the altered response to medications by older adults with frailty. Other areas with novel developments included exercise (including technology-based exercise), multidimensional interventions, person-centred and integrated care, assistive technologies, analysis of frailty transitions, risk-factors, clinical guidelines, COVID-19, and potential future treatments. This review identified a strong need for the implementation and evaluation of cost-effective, community-based interventions to manage and prevent frailty. Our findings highlight the need to better identify and support older adults with frailty and involve those with frailty in shared decision-making regarding their care.

Cognitive impairment is a central non-motor symptom of Parkinson’s disease (PD), and there are no established treatments. Computerized cognitive training (CCT) is a safe and efficacious strategy but its efficacy in PD is unclear. We aimed to investigate the efficacy of CCT on cognitive, psychosocial and daily function, and assess potential effect moderators in people with PD without dementia. Randomized controlled trials of CCT were included in multivariate meta-analyses and meta-regressions. Seventeen studies (16 trials) encompassing 679 participants were included. The pooled effect of CCT relative to control was small and statistically significant for overall cognitive function (g=0.16; 95% CI 0.02–0.29). There was robust evidence for benefit on clinical measures of global cognition across 10 trials (g=0.33; 95% CI 0.19–0.48), especially in PD with mild cognitive impairment (PD-MCI), as well as on individual cognitive domains. Greater CCT dose and PD-MCI population were associated with larger effect sizes, but no statistically significant differences were found between subgroups. There was no significant difference in the efficacy of home-based compared to supervised training. Our findings suggest that CCT is associated with cognitive benefits in PD, including when delivered remotely. Larger, well-powered trials are warranted to examine what specific CCT regimens are most likely to promote cognitive and everyday functioning in the long-term.

As the population ages, the number of people with dementia is expected to increase in the coming decades, with consequences at the societal and individual levels. In this narrative review, we provide a summary of the scientific evidence concerning dementia prevention, with a focus on the following three strategies: 1) Targeting the body to protect the brain, including prevention and treatment of cardiovascular morbidity; 2) Compensatory interventions to counteract brain ageing, including education and life-long engagement in cognitively and socially stimulating activities; and 3) Lifespan health promotion, such as a physically active lifestyle, smoking cessation, and a healthy and balanced diet. Next, we consider the biological mechanisms by which these strategies may act by taking into account the main pathways implicated in the development and progression of dementia: neurodegeneration, brain resilience, vascular damage, neuroinflammation, and oxidative stress. Based on the current evidence, and in line with the declining trends of dementia incidence in high-income countries, we conclude that timely multidomain preventive actions are promising strategies to reduce the dementia epidemic worldwide. There is still a considerable gap between the epidemiological evidence and its underlying biological mechanisms. Filling this gap will be crucial to move forward in dementia prevention worldwide.

In addition to the deposition of beta-amyloid plaques, neurofibrillary tangles composed of aggregated hyperphosphorylated tau are one of the pathological hallmarks of Alzheimer's disease and other neurodegenerative disorders. Until now, our understanding about the natural history and topography of tau deposition has only been based on post-mortem and cerebrospinal fluid studies, and evidence continues to implicate tau as a central driver of downstream neurodegenerative processes and cognitive decline. Recently, it has become possible to assess the regional distribution and severity of tau burden in vivo with the development of novel radiotracers for positron emission tomography (PET) imaging. In this article, we provide a comprehensive discussion of tau pathophysiology, its quantification with novel PET radiotracers, as well as a systematic review of tau PET imaging in normal aging and various dementia conditions: mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, and Lewy body dementia. We discuss the main findings in relation to group differences, clinical-cognitive correlations of tau PET, and multi-modal relationships among tau PET and other pathological markers. Collectively, the small but growing literature of tau PET has yielded consistent anatomical patterns of tau accumulation that recapitulate post-mortem distribution of neurofibrillary tangles which correlate with cognitive functions and other markers of pathology. In general, AD is characterised by increased tracer retention in the inferior temporal lobe, extending into the frontal and parietal regions in more severe cases. It is also noted that the spatial topography of tau accumulation is markedly distinct to that of amyloid burden in aging and AD. Tau PET imaging has also revealed characteristic spatial patterns among various non-AD tauopathies, supporting its potential role for differential diagnosis. Finally, we propose novel directions for future tau research, including (a) longitudinal imaging in preclinical dementia, (b) multi-modal mapping of tau pathology onto other pathological processes such as neuroinflammation, and (c) the need for more validation studies against post-mortem samples of the same subjects. (C) 2017 Elsevier B.V. All rights reserved.

Cancer and ageing can be regarded as two different manifestations of the same underlying process—accumulation of cellular damage—and therefore both are closely linked. Nowadays, the ageing of populations worldwide is leading to an unprecedented increase in cancer cases and fatalities, and therefore the understanding of links between cancer and ageing is more important than ever. Spalax is considered an excellent model for ageing and, additionally, for cancer research, due to not show clear age-related phenotypic changes and not develop spontaneous tumours, despite its relatively long lifespan (∼20 years in captivity). Thereby, the purpose of this review is to summarize the recent knowledge on Spalax, with a particular emphasis on the molecular mechanisms associated with their longevity and cancer resistance.Previous article in issue

Cognitive impairment is a central non-motor symptom of Parkinson's disease (PD), and there are no established treatments. Computerized cognitive training (CCT) is a safe and efficacious strategy but its efficacy in PD is unclear. We aimed to investigate the efficacy of CCT on cognitive, psychosocial and daily function, and assess potential effect moderators in people with PD without dementia. Randomized controlled trials of CCT were included in multivariate meta-analyses and meta-regressions. Seventeen studies (16 trials) encompassing 679 participants were included. The pooled effect of CCT relative to control was small and statistically significant for overall cognitive function (g=0.16; 95% CI 0.02–0.29). There was robust evidence for benefit on clinical measures of global cognition across 10 trials (g=0.33; 95% CI 0.19–0.48), especially in PD with mild cognitive impairment (PD-MCI), as well as on individual cognitive domains. Greater CCT dose and PD-MCI population were associated with larger effect sizes, but no statistically significant differences were found between subgroups. There was no significant difference in the efficacy of home-based compared to supervised training. Our findings suggest that CCT is associated with cognitive benefits in PD, including when delivered remotely. Larger, well-powered trials are warranted to examine what specific CCT regimens are most likely to promote cognitive and everyday functioning in the long-term.

Combining physical exercise with cognitive training is a popular intervention in dementia prevention trials and guidelines. However, it remains unclear what combination strategies are most beneficial for cognitive and physical outcomes. We aimed to compare the efficacy of the three main types of combination strategies (simultaneous, sequential or exergaming) to either intervention alone or control in older adults. Randomized controlled trials of combined cognitive and physical training were included in multivariate and network meta-analyses. In cognitively healthy older adults and mild cognitive impairment, the effect of any combined intervention relative to control was small and statistically significant for overall cognitive (k = 41, Hedges' g = 0.22, 95 % CI 0.14 to 0.30) and physical function (k = 32, g = 0.25, 95 % CI 0.13 to 0.37). Simultaneous training was the most efficacious approach for cognition, followed by sequential combinations and cognitive training alone, and significantly better than physical exercise. For physical outcomes, simultaneous and sequential training showed comparable efficacy as exercise alone and significantly exceeded all other control conditions. Exergaming ranked low for both outcomes. Our findings suggest that simultaneously and sequentially combined interventions are efficacious for promoting cognitive alongside physical health in older adults, and therefore should be preferred over implementation of single-domain training.

A literature search was carried out to summarize the existing scientific evidence concerning occurrence, causes, and consequences of multimorbidity (the coexistence of multiple chronic diseases) in the elderly as well as models and quality of care of persons with multimorbidity. According to pre-established inclusion criteria, and using different search strategies, 41 articles were included (four of these were methodological papers only). Prevalence of multimorbidity in older persons ranges from 55 to 98%. In cross-sectional studies, older age, female gender, and low socioeconomic status are factors associated with multimorbidity, confirmed by longitudinal studies as well. Major consequences of multimorbidity are disability and functional decline, poor quality of life, and high health care costs. Controversial results were found on multimorbidity and mortality risk. Methodological issues in evaluating multimorbidity are discussed as well as future research needs, especially concerning etiological factors, combinations and clustering of chronic diseases, and care models for persons affected by multiple disorders. New insights in this field can lead to the identification of preventive strategies and better treatment of multimorbid patients.

Background: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated.

Objectives: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop ‘Nutrition for the Ageing Brain: Functional Aspects and Mechanisms’ in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe).

Conclusion: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age.

Background: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated.

Objectives: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop 'Nutrition for the Ageing Brain: Functional Aspects and Mechanisms' in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe).

Conclusion: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age.

Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in ageing by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive ageing. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive ageing.

Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in aging by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive aging. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive aging.

Background: Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear.

Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/ or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and randomeffect models. Sensitivity analysis was performed based on age and the setting where the study was conducted.

Results: Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60-88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68-87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had higher levels of tumor necrosis factor alpha compared with their robust and non-sarcopenic counterparts.

Conclusions: A set of metabolic, hematologic, and inflammatory biomarkers was found to be shared by frailty and sarcopenia. These findings fill a knowledge gap in the quest of biomarkers for these conditions and provide a rationale for biomarker selection in studies on frailty and sarcopenia.

Background: Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer’s Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers.

Method: This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed.

Results: Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD.

Conclusion: Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.

Central theories of cognitive aging propose that education is an important protective factor for decline in cognitive performance in older age. We conducted a systematic review and meta-analysis of reported estimates of an association between educational attainment and change in performance in six cognitive domains (episodic memory, processing speed, verbal fluency, crystallized intelligence, fluid intelligence, and global ability) in the general population of older individuals. The systematic search (11th of October 2019) identified 92 eligible articles. The episodic memory domain had the highest number of estimates (37 estimates from 18 articles, n =109,281) included in the meta-analysis. The fewest estimates (6 estimates from 6 articles, n = 5263) were included for fluid intelligence. Pooled mean estimates from an inverse-variance weighted random effects analysis were not statistically significant and indicated that any association between education and change in cognitive performance is likely of a negligible magnitude. The estimates for education's role (one additional year) for change in cognitive performance ranged from -0.019 (95 % confidence interval, CI = -0.047, 0.010) to 0.004SD (CI = -0.003, 0.012) per decade. Even if the larger positive point estimates (i.e., protective effects) are selectively considered, the influence of education on change is still at least 12 times less important for the cognitive functioning of an older individual than the association between education and level of cognitive performance. Sensitivity analyses did not substantially alter these results. However, heterogeneity was substantial, and remained largely unexplained by mean age, mean educational attainment, Gini coefficient, GDP per capita, maximum follow-up period, and publication year. Overall, education is an important factor in aging due to its robust association with level of performance, but the current base of empirical evidence is not revealing a consistent and substantial association between educational attainment and changes in cognitive performance in the general population. Theories of cognitive aging must be updated to incorporate this pattern of findings.

Background: There have been few systematic reviews and no meta-analyses of the clinical benefits of nutritional support in patients with, or at risk of developing, pressure ulcers. Therefore, this systematic review and meta-analysis was undertaken to address the impact of enteral nutritional support on pressure ulcer incidence and healing and a range of other clinically relevant outcome measures in this group. Methods: Fifteen studies (including eight randomised controlled trials (RCTs)) of oral nutritional supplements (ONS) or enteral tube feeding (ETF), identified using electronic databases (including Pub Med and Cochrane) and bibliography searches, were included in the systematic review. Outcomes including pressure ulcer incidence, pressure ulcer healing, quality of life, complications, mortality, anthropometry and dietary intake were recorded, with the aim of comparing nutritional support versus routine care (e.g. usual diet and pressure ulcer care) and nutritional formulas of different composition. Of these 15 studies, 5 RCTs comparing ONS (4 RCTs) and ETF (1 RCT) with routine care could be included in a meta-analysis of pressure ulcer incidence. Results: Meta-analysis showed that ONS (250-500 kcal, 2-26 weeks) were associated with a significantly lower incidence of pressure ulcer development in at-risk patients compared to routine care (odds ratio 0.75, 95% CI 0.62-0.89, 4 RCTs, n = 1224, elderly, post-surgical, chronically hospitalised patients). Similar results were obtained when a combined meta-analysis of ONS (4 RCT) and ETF (1 RCT) trials was performed (OR 0.74, 95% CI 0.62-0.88, 5 RCTs, n = 1325). Individual studies showed a trend towards improved healing of existing pressure ulcers with disease-specific (including high protein) versus standard formulas, although robust RCTs are required to confirm this. Although some studies indicate that total nutritional intake is improved, data on other outcome measures (quality of life) are lacking. Conclusions: This systematic review shows enteral nutritional support, particularly high protein ONS, can significantly reduce the risk of developing pressure ulcers (by 25%). Although studies suggest ONS and ETF may improve healing of PU, further research to confirm this trend is required. © 2005 Elsevier Ireland Ltd. All rights reserved.

Background: Multimorbidity, the coexistence of multiple chronic diseases in an individual, is highly prevalent and challenging for healthcare systems. However, its risk factors remain poorly understood.Objective: To systematically review studies reporting multimorbidity risk factors.Methods: A PRISMA-compliant systematic review was conducted, searching electronic databases (MEDLINE, EMBASE, Web of Science, Scopus). Inclusion criteria were studies addressing multimorbidity transitions, trajectories, continuous disease counts, and specific patterns. Non-human studies and participants under 18 were excluded. Associations between risk factors and multimorbidity onset were reported.Results: Of 20,806 identified studies, 68 were included, with participants aged 18-105 from 23 countries. Nine risk factor categories were identified, including demographic, socioeconomic, and behavioral factors. Older age, low education, obesity, hypertension, depression, low pysical function were generally positively associated with multimorbidity. Results for factors like smoking, alcohol consumption, and dietary patterns were inconsistent. Study quality was moderate, with 16.2% having low risk of bias.Conclusions: Several risk factors seem to be consistently associated with an increased risk of accumulating chronic diseases over time. However, heterogeneity in settings, exposure and outcome, and baseline health of partici-pants hampers robust conclusions.

Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of this umbrella review is to synthesize and grade all preventative and therapeutic interventions for delirium. We searched five databases from database inception up to March 15th, 2023 and we included meta -analyses of randomized controlled trials (RCTs) to decrease the risk of/the severity of delirium. From 1959 records after deduplication, we included 59 systematic reviews with meta -analyses, providing 110 meta -analytic estimates across populations, interventions, outcomes, settings, and age groups (485 unique RCTs, 172,045 participants). In surgery setting, for preventing delirium, high GRADE evidence supported dexmedetomidine (RR =0.53; 95%CI: 0.46 -0.67, k =13, N =3988) and comprehensive geriatric assessment (OR =0.46; 95%CI =0.32 -0.67, k =3, N =496) in older adults, dexmedetomidine in adults (RR =0.33, 95%CI =0.24 -0.45, k =7, N =1974), A2-adrenergic agonists after induction of anesthesia (OR = 0.28, 95%CI = 0.19 -0.40, k =10, N =669) in children. High certainty evidence did not support melatonergic agents in older adults for delirium prevention. Moderate certainty supported the effect of dexmedetomidine in adults and children (k =4), various non -pharmacological interventions in adults and older people (k =4), second -generation antipsychotics in adults and mixed age groups (k =3), EEG -guided anesthesia in adults (k =2), mixed pharmacological interventions (k =1), five other specific pharmacological interventions in children (k =1 each). In conclusion, our work indicates that effective treatments to prevent delirium differ across populations, settings, and age groups. Results inform future guidelines to prevent or treat delirium, accounting for safety and costs of interventions. More research is needed in non -surgical settings.

Untangling the interdependency of infections, immunity and frailty may help to clarify their roles in the maintenance of health in aging individuals, and the recent COVID-19 pandemic has further highlighted such priority. In this scoping review we aimed to systematically collect the evidence on 1) the impact of common infections such as influenza, pneumonia and varicella zoster on frailty development, and 2) the role played by frailty in the response to immunization of older adults. Findings are discussed under a unifying framework to identify knowledge gaps and outline their clinical and public health implications to foster a healthier aging. Twenty-nine studies (113,863 participants) selected to answer the first question provided a moderately strong evidence of an association between infections and physical as well as cognitive decline – two essential dimensions of frailty. Thirteen studies (34,520 participants) investigating the second aim, showed that frailty was associated with an impaired immune response in older ages, likely due to immunosenescence. However, the paucity of studies, the absence of tools to predict vaccine efficacy, and the lack of studies investigating the efficacy of newer vaccines in presence of frailty, strongly limit the formulation of more personalized immunization strategies for older adults. The current evidence suggests that infections and frailty repeatedly cross each other pathophysiological paths and accelerate the aging process in a vicious circle. Such evidence opens to several considerations. First, the prevention of both conditions pass through a life course approach, which includes several individual and societal aspects. Second, the maintenance of a well-functioning immune system may be accomplished by preventing frailty, and vice versa. Third, increasing the adherence to immunization may delay the onset of frailty and maintain the immune system homeostasis, beyond preventing infections.

Alzheimer's disease is a neurodegenerative disease mainly characterized by cortico-neuronal atrophy, impaired memory and other cognitive declines. On the other hand, schizophrenia is a neuro-developmental disorder with an overtly active central nervous system pruning system resulting into abrupt connections with common symptoms including disorganised thoughts, hallucination and delusion. Nevertheless, the fronto-temporal anomaly presents itself as a common denominator for the two pathologies. There is even a strong presumption of increased risk of developing co-morbid dementia for schizophrenic individuals and psychosis for Alzheimer's disease patients, overall leading to a further deteriorated quality of life. However, convincing proofs of how these two disorders, although very distant from each other when considering their aetiology, develop coexisting symptoms is yet to be resolved. At the molecular level, the two primarily neuronal proteins β-amyloid precursor protein and neuregulin 1 have been considered in this relevant context, although the conclusions are for the moment only hypotheses. In order to propose a model for explaining the psychotic schizophrenia-like symptoms that sometimes accompany AD-associated dementia, this review projects out on the similar sensitivity shared by these two proteins regarding their metabolism by the β-site APP cleaving enzyme 1.

This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.

This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.