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Background and Objectives With the emergence of healthy aging as a key societal issue in recent decades, technology has often been proposed as a solution to the challenges faced by aging societies. From a public health perspective, however, aging-related technologies have been inconsistently conceptualized and ill-defined. By examining how relevant concepts in “technology for aging” have been developed to date, we hope to identify gaps and begin clarifying the topic. Research Design and Methods We conducted a scoping review according to PRISMA-ScR, drawing on PubMed and Embase. We selected articles that directly reported concepts of technology for aging, or from which such concepts could be inferred. Results We identified 43 articles, most of which were narrative reviews (n = 31). Concepts of technology for aging were presented in diverse ways with some overlap. Most studies provided some terminology (n = 36), but with little conceptual uniformity. Conceptual discourse was often focused on the aging agenda; while technological aspects were poorly defined. A conceptual framework from a public health perspective was derived from 8 articles—it showed that technology strategies do not take a population approach. Discussion and Implications While the potential of “technology for aging” is vast, its real capacity to deliver a desirable life for older people remains underdeveloped. Clearer concepts and realistic goals at population level are lacking. Efficient investment must be made throughout the social system, and technology needs to be integrated via macro-level practices.

Dementia has been recognised as a key challenge in many ageing societies across the world. Several population-based studies have been developed to investigate dementia and cognitive ageing from perspectives of biology, health, psychology and social sciences. However, there is a need to provide a better understanding of ‘contexts’, the circumstance where these ageing populations existed, and heterogeneity within and across the populations in different time and places. In this article, we summarise some examples of earlier population-based studies undertaken by our research groups in England and Wales and their contribution to the epidemiology of dementia, neuropathology, cognitive and mental health in older age. We also describe how these studies illustrated variation among ageing populations and changes in their health conditions across time and place. These findings highlight the contribution that population-based studies can make, along with the vital to incorporate contexts in ageing research. A lifecourse approach within social context is needed to integrate life experiences, social circumstances, and multiple dimensions of cognition, functioning, physical health and wellbeing over the ageing process. We also discuss how evidence from population-based studies can support various international initiatives on dementia, healthy ageing and Sustainable Development Goals and facilitate tailored approaches for diverse populations across global societies.

BACKGROUND AND PURPOSE: The roles of blood low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides in the development of post-stroke dementia remain uncertain. This study was to investigate their potential associations. METHODS: A retrospective cohort study was conducted using the Clinical Practice Research Datalink. Patients with first-ever stroke but no prior dementia were followed up for 10 years. Cox regression was used to examine the association of baseline LDL-C, HDL-C and triglycerides with post-stroke dementia. RESULTS: Amongst 63,959 stroke patients, 15,879 had complete baseline data and were included in our main analysis. 10.8% developed dementia during a median of 4.6 years of follow-up. The adjusted hazard ratio of dementia for LDL-C (per log mmol/l increase) was 1.29 (95% confidence interval [CI] 1.14-1.47), with a linear increasing trend (p trend

Background:\ud Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited.\ud \ud Objective:\ud To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs.\ud \ud Methods:\ud We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders.\ud \ud Results:\ud Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer’s disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18–0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11–19.24) and 3.30 (1.02–10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders.\ud \ud Conclusions:\ud We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer’s disease; however, we cannot rule out effects owing to small numbers.

BACKGROUND: Previous research has examined the improvements in healthy years if different health conditions are eliminated, but often with cross-sectional data, or for a limited number of conditions. We used longitudinal data to estimate disability-free life expectancy (DFLE) trends for older people with a broad number of health conditions, identify the conditions that would result in the greatest improvement in DFLE, and describe the contribution of the underlying transitions. METHODS AND FINDINGS: The Cognitive Function and Ageing Studies (CFAS I and II) are both large population-based studies of those aged 65 years or over in England with identical sampling strategies (CFAS I response 81.7%, N = 7,635; CFAS II response 54.7%, N = 7,762). CFAS I baseline interviews were conducted in 1991 to 1993 and CFAS II baseline interviews in 2008 to 2011, both with 2 years of follow-up. Disability was measured using the modified Townsend activities of daily living scale. Long-term conditions (LTCs-arthritis, cognitive impairment, coronary heart disease (CHD), diabetes, hearing difficulties, peripheral vascular disease (PVD), respiratory difficulties, stroke, and vision impairment) were self-reported. Multistate models estimated life expectancy (LE) and DFLE, stratified by sex and study and adjusted for age. DFLE was estimated from the transitions between disability-free and disability states at the baseline and 2-year follow-up interviews, and LE was estimated from mortality transitions up to 4.5 years after baseline. In CFAS I, 60.8% were women and average age was 75.6 years; in CFAS II, 56.1% were women and average age was 76.4 years. Cognitive impairment was the only LTC whose prevalence decreased over time (odds ratio: 0.6, 95% confidence interval (CI): 0.5 to 0.6, p < 0.001), and where the percentage of remaining years at age 65 years spent disability-free decreased for men (difference CFAS II-CFAS I: -3.6%, 95% CI: -8.2 to 1.0, p = 0.12) and women (difference CFAS II-CFAS I: -3.9%, 95% CI: -7.6 to 0.0, p = 0.04) with the LTC. For men and women with any other LTC, DFLE improved or remained similar. For women with CHD, years with disability decreased (-0.8 years, 95% CI: -3.1 to 1.6, p = 0.50) and DFLE increased (2.7 years, 95% CI: 0.7 to 4.7, p = 0.008), stemming from a reduction in the risk of incident disability (relative risk ratio: 0.6, 95% CI: 0.4 to 0.8, p = 0.004). The main limitations of the study were the self-report of health conditions and the response rate. However, inverse probability weights for baseline nonresponse and longitudinal attrition were used to ensure population representativeness. CONCLUSIONS: In this study, we observed improvements to DFLE between 1991 and 2011 despite the presence of most health conditions we considered. Attention needs to be paid to support and care for people with cognitive impairment who had different outcomes to those with physical health conditions.

Despite many reported associations, the direct cause of neurodegeneration responsible for cognitive loss in Alzheimer's disease and some other common dementias is not known. The normal human plasma protein, serum amyloid P component, a constituent of all human fibrillar amyloid deposits and present on most neurofibrillary tangles, is cytotoxic for cerebral neurones in vitro and in experimental animals in vivo. The neocortical content of serum amyloid P component was immunoassayed in 157 subjects aged 65 or more with known dementia status at death, in the large scale, population-representative, brain donor cohort of the Cognitive Function and Ageing Study, which avoids the biases inherent in studies of predefined clinico-pathological groups. The serum amyloid P component values were significantly higher in individuals with dementia, independent of serum albumin content measured as a control for plasma in the cortex samples. The odds ratio for dementia at death in the high serum amyloid P component tertile was 5.24 (95% confidence interval 1.79-15.29) and was independent of Braak tangle stages and Thal amyloid-β phases of neuropathological severity. The strong and specific association of higher brain content of serum amyloid P component with dementia, independent of neuropathology, is consistent with a pathogenetic role in dementia.

Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study investigated the association between statin use and post-stroke dementia using data from the Clinical Practice Research Datalink. Patients without prior dementia who had an incident stroke but received no statins in the preceding year were followed for up to 10 years. We used inverse probability weighted marginal structural models to estimate observational analogues of intention-to-treat (ITT, statin initiation versus no initiation) and per-protocol (PP, sustained statin use versus no use) effects on the risk of dementia. To explore potential impact of unmeasured confounding, we examined the risks of coronary heart disease (CHD, positive control outcome), fracture and peptic ulcer (negative control outcomes). In 18,577 statin initiators and 14,613 non-initiators (mean follow-up of 4.2 years), the adjusted hazard ratio (aHR) for dementia was 0.70 (95% confidence interval [CI] 0.64-0.75) in ITT analysis and 0.55 (95%CI 0.50-0.62) in PP analysis. The corresponding aHRITT and aHRPP were 0.87 (95%CI 0.79-0.95) and 0.70 (95%CI 0.620.80) for CHD, 1.03 (95%CI 0.82-1.29) and 1.09 (95%CI 0.77-1.54) for peptic ulcer, and 0.88 (95%CI 0.80-0.96) and 0.86 (95%CI 0.75-0.98) for fracture. Statin initiation after stroke was associated with lower risk of dementia, with a potentially greater benefit in patients who persisted with statins over time. The observed association of statin use with post-stroke dementia may in part be overestimated due to unmeasured confounding shared with the association between statin use and fracture., NIHR

Patients and families need hope, not false hope

Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom’s Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4–20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.

Context The risk for dementia among subjects who are obese with normal metabolic profiles, or called metabolically healthy obese (MHO), remains uninvestigated. Objective To determine the association between late-life metabolic health and obesity status and risk of incident dementia. Design Retrospective cohort study. Setting The National Health Insurance System, Republic of Korea. Patients A total of 12,296,863 adults >50 years old who underwent health examinations from 2009 to 2012 without baseline history of dementia. Main outcome measure Incident overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Results Among subjects ≥60 years old, 363,932 (6.4%) developed dementia during a median follow-up of 65 months (interquartile range 51 to 74 months). The MHO group showed the lowest incidence of overall dementia [hazard ratio (HR) 0.85; 95% CI, 0.84 to 0.86] and AD (HR 0.87; 95% CI, 0.86 to 0.88), but not VaD, compared with the metabolically healthy nonobese group. All components of metabolic syndrome except obesity significantly elevated the risk of dementia, and these associations were more pronounced in VaD. In particular, being underweight dramatically increased the risk of dementia. Conclusions The MHO phenotype in late life demonstrated lower risk of overall dementia and AD but not VaD. Additional studies in other populations are warranted to elucidate current results and may predict individuals most at risk for developing dementia.

Dementia is a public health and socioeconomic concern that is widely predicted to worsen as the proportion of older adults making up our global population increases.1 By 2050, 152 million people worldwide are expected to experience dementia, along with its associated impact. In an ambitious act to galvanise a global response, the 2013 G8 Dementia Summit was convened with a primary aim to identify a cure or disease-modifying therapy for dementia by 2025.2 New evidence has since deepened our understanding of the potential for disease-modifying therapies, making this target even more unrealistic. In parallel, rapidly accumulating evidence has emphasised the importance of broader societal policies for dementia prevention across the lifecourse.3 Here, we review the goals, progress, and challenges of the Summit activities, and propose potential ways forward to align policy with the public health evidence for dementia prevention.

OBJECTIVES High levels of life course intellectually-stimulating activity are hypothesised to produce a cognitive reserve that mitigates against overt cognitive impairment in the face of neuropathology. Leisure-time musical instrument playing could be a viable source of that stimulation, but to date no systematic review has been undertaken to investigate the effect of musical instrument playing on the incidence of cognitive impairment and dementia. METHODS A systematic review and meta-analysis including any study with musical instrument playing as the exposure, and cognitive impairment and/or dementia as the outcome. RESULTS 1211 unduplicated articles were identified from literature searching, of which three articles were included: two cohort studies and one twin study. All studies were of good methodological quality, and reported large protective effects of musical instrument playing. The twin study reported that musicians were 64% less likely to develop mild cognitive impairment or dementia, after additionally adjusting for sex, education and physical activity. A meta-analysis of the cohort studies found a 59% reduction in the risk of developing dementia within the study follow up. The evidence base is limited by size, small sample sizes and the risk of reverse causality. CONCLUSION The three identified studies that investigated the specific relationship of musical instrument playing and subsequent incidence of cognitive impairment and dementia all reported a large protective association. The results are encouraging but should be interpreted with caution. Larger, more focussed studies are required to further explore this association, with a particular need to consider the cumulative lifetime quantity of music playing.

Background Universal health coverage (UHC), which is embedded within the United Nations Sustainable Development Goals, is defined by the World Health Organization as all individuals having access to required health services, of sufficient quality, without suffering financial hardship. Effective strategies for financing healthcare are critical in achieving this goal yet remain a challenge in Sub-Saharan Africa (SSA). This systematic review aims to determine reported health financing mechanisms in SSA within the published literature and summarize potential learnings. Methods A systematic review was conducted aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. On 19 to 30 July 2019, MEDLINE, EMBASE, Web of Science, Global Health Database, the Cochrane Library, Scopus and JSTOR were searched for literature published from 2005. Studies describing health financing approaches for UHC in SSA were included. Evidence was synthesised in form of a table and thematic analysis. Results Of all records, 39 papers were selected for inclusion. Among the included studies, most studies were conducted in Kenya (n=7), followed by SSA as a whole (n=6) and Nigeria (n=5). More than two thirds of the selected studies reported the importance of equitable national health insurance schemes for UHC. The results indicate that a majority of health care revenue in SSA is from direct out-of-pocket payments. Another common financing mechanism was donor funding, which was reported by most of the studies. The average quality score of all studies was 81.6%, indicating a high appraisal score. The interrater reliability Cohen’s kappa score, κ=0.43 (p=0.002), showed a moderate level of agreement. Conclusions Appropriate health financing strategies that safeguard financial risk protection underpin sustainable health services and the attainment of UHC. It is evident from the review that innovative health financing strategies in SSA are needed. Some limitations of this review include potentially skewed interpretations due to publication bias and a higher frequency of publications included from two countries in SSA. Establishing evidence-based and multi-sectoral strategies tailored to country contexts remains imperative.

Background: Children with special education needs (SEN), such as autistic children, benefit from being included in education along with typical peers. However, development and implementation of inclusive education (IE) is considered difficult. This paper identifies conditions that facilitate IE development for autistic children in the European Union and benchmarks to track IE policy development. Methods: Education policy data from thirty legislative regions in the European Union were analyzed through a qualitative comparative analysis using eight conditions: a definition of SEN, the right to education for children with SEN, support for teaching staff, support services for children with SEN, individualized learning outcomes, parental involvement, and mixed mainstream classes.Results: The right to education for children with SEN is implemented in all regions under study. Seven of the examined conditions were associated with an environment of IE in the European Union from an autism perspective: an established definition of SEN, support for teaching staff, general availability of support services for children with SEN, individualized learning outcomes, parental involvement, IE policies, and mixed mainstream classrooms. Mixed classrooms and support services for children with SEN were identified as necessary for IE. IE policies and support for teaching staff were present in all scenarios that facilitated IE. Even though the analysis was initially focused on autism, the policies consisted predominantly of general SEN policies. As such, the results can be interpreted in a wider context, beyond autism.Conclusion: Mixed mainstream classrooms and support services for children with special needs were found essential for consistent IE development. Support for teaching staff and IE policies facilitate IE and should be further explored and implemented.

Background: Exploring the domains of cognitive function which are most strongly associated with future dementia may help with understanding risk factors for, and the natural history of dementia. Objective: To examine the association of performance on a range of cognitive tests (both global and domain specific) with subsequent diagnosis of dementia through health services in a population of relatively healthy men and women and risk of future dementia. Methods: We examined the association between performance on different cognitive tests as well as a global score and future dementia risk ascertained through health record linkage in a cohort of 8,581 individuals (aged 48–92 years) between 2004–2019 with almost 15 years follow-up (average of 10 years) before and after adjustment for socio-demographic, lifestyle, and health characteristics. Results: Those with poor performance for global cognition (bottom 10%) were almost four times as likely to receive a dementia diagnosis from health services over the next 15 years than those who performed well HR = 3.51 (95% CI 2.61, 4.71 p

Purpose of review The paper applies recent conceptualisations of predictive processing to the understanding of inequalities in mental health. Recent findings Social neuroscience has developed important ideas about the way the brain models the external world, and how the interface between cognitive and cultural processes interacts. These resonate with earlier concepts from cybernetics and sociology. These approaches could be applied to understanding some of the dynamics leading to the patterning of mental health problems in populations. Summary The implications for practice are the way such thinking might help illuminate how we think and act, and how these are anchored in the social world.

Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100000272, Background: Poor performance in the 5‐chair stand test (5‐CST) indicates reduced lower limb muscle strength. The 5‐CST has been recommended for use in the initial assessment of sarcopenia, the accelerated loss of muscle strength and mass. In order to facilitate the use of the 5‐CST in sarcopenia assessment, our aims were to (i) describe the prevalence and factors associated with poor performance in the 5‐CST, (ii) examine the relationship between the 5‐CST and gait speed, and (iii) propose a protocol for using the 5‐CST. Methods: The population‐based study Cognitive Function and Ageing Study II recruited people aged 65 years and over from defined geographical localities in Cambridgeshire, Newcastle, and Nottingham. The study collected data for assessment of functional ability during home visits, including the 5‐CST and gait speed. We used multinomial logistic regression to assess the associations between factors including the SARC‐F questionnaire and the category of 5‐CST performance: fast (15 s), or unable, with slow/unable classed as poor performance. We reviewed previous studies on the protocol used to carry out the 5‐CST. Results: A total of 7190 participants aged 65+ from the three diverse localities of Cognitive Function and Ageing Study II were included (54.1% female). The proportion of those with poor performance in the 5‐CST increased with age, from 34.3% at age 65–69 to 89.7% at age 90+. Factors independently associated with poor performance included positive responses to the SARC‐F questionnaire, physical inactivity, depression, impaired cognition, and multimorbidity (all P < 0.005). Most people with poor performance also had slow gait speed (57.8%) or were unable to complete the gait speed test (18.4%). We found variation in the 5‐CST protocol used, for example, timing until a participant stood up for the fifth time or until they sat down afterwards. Conclusions: Poor performance in the 5‐CST is increasingly common with age and is associated with a cluster of other factors that characterize risk for poor ageing such as physical inactivity, impaired cognition, and multimorbidity. We recommend a low threshold for performing the 5‐CST in clinical settings and provide a protocol for its use.

In the last two decades, there has been in-depth investigation into understanding the pathogenesis, epidemiological profiling, and clinical characterization of dementia. However, these investigations have not led to successful interventions to prevent, delay, or reverse the pathological processes underlying dementia. Recent findings of a decrease in dementia risk in high-income countries such as the UK, USA and the Netherlands highlight that dementia, at least in some cases, is preventable. This article includes a synthesis of current knowledge on dementia epidemiology, biological underpinnings, risk factors, and current prevention programs, with the aim to set the path for research, funding, and policy initiatives to address the global public health challenge of how to prevent dementia or reduce risk within the framework of population-based studies. We advocate for development of novel approaches for intelligent data synthesis that go well beyond single approaches to enable powerful risk stratification analyses. An integrated approach is needed where researchers, funders, policymakers, and stakeholders contribute to and work together to formulate effective strategies for the global monitoring and development of population-based risk reduction, treatment, and prevention programs for dementia.

Diabetes mellitus is a risk factor for dementia, and nonenzymatic glycosylation of macromolecules results in formation of advanced glycation end-products (AGEs). We determined the variation in AGE formation in brains from the Cognitive Function and Ageing Study population-representative neuropathology cohort. AGEs were measured on temporal neocortex by enzyme-linked immunosorbent assay (ELISA) and cell-type specific expression on neurons, astrocytes and endothelium was detected by immunohistochemistry and assessed semiquantitatively. Fifteen percent of the cohort had self-reported diabetes, which was not significantly associated with dementia status at death or neuropathology measures. AGEs were expressed on neurons, astrocytes and endothelium and overall expression showed a positively skewed distribution in the population. AGE measures were not significantly associated with dementia. AGE measured by ELISA increased with Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neurofibrillary tangle score (p = 0.03) and Thal Aβ phase (p = 0.04), while AGE expression on neurons (and astrocytes), detected immunohistochemically, increased with increasing Braak tangle stage (p

Background: Prior atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease (CHD) and peripheral artery disease (PAD), are common among patients with stroke, a known risk factor for dementia. However, whether these conditions further increase the risk of post-stroke dementia remains uncertain. Objective: To examine whether prior ASCVD is associated with increased risk of dementia among stroke patients. Methods: A retrospective cohort study was conducted using the Clinical Practice Research Datalink with linkage to hospital data. Patients with first-ever stroke between 2006 and 2017 were followed up to 10 years. We used multi-variable Cox regression models to examine the associations of prior ASCVD with dementia and the impact of prior ASCVD onset and duration. Results: Among 63,959 patients, 7,265 cases (11.4%) developed post-stroke dementia during a median of 3.6-year follow-up. The hazard ratio (HR) of dementia adjusted for demographics and lifestyle was 1.18 (95% CI: 1.12–1.25) for ASCVD, 1.16 (1.10–1.23) for CHD, and 1.25 (1.13–1.37) for PAD. The HRs additionally adjusted for multimorbidity and medications were 1.07 (1.00–1.13), 1.04 (0.98–1.11), and 1.11 (1.00–1.22), respectively. Based on the fully adjusted estimates, there was no linear relationship between the age of ASCVD onset and post-stroke dementia (all p-trend >0.05). The adjusted risk of dementia was not increased with the duration of pre-stroke ASCVD (all p-trend >0.05). Conclusion: Stroke patients with prior ASCVD are more likely to develop subsequent dementia. After full adjustment for confounding, however, the risk of post-stroke dementia is attenuated, with only a slight increase with prior ASCVD.

BackgroundNeurotrauma is an important global health problem. The largest cause of neurotrauma worldwide is road traffic collisions (RTCs), particularly in low- and middle-income countries (LMICs). Neurotrauma and RTCs are preventable, and many preventative interventions have been implemented over the last decades, especially in high-income countries (HICs). However, it is uncertain if these strategies are applicable globally due to variations in environment, resources, population, culture and infrastructure. Given this issue, this scoping review aims to identify, quantify and describe the evidence on approaches in neurotrauma and RTCs prevention, and ascertain contextual factors that influence their implementation in LMICs and HICs.MethodsA systematic search was conducted using five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health on EBSCO host, Cochrane Database of Systematic Reviews), grey literature databases, government and non-government websites, as well as bibliographic and citation searching of selected articles. The extracted data were presented using figures, tables, and accompanying narrative summaries. The results of this review were reported using the PRISMA Extension for Scoping Reviews (PRISMA-ScR).ResultsA total of 411 publications met the inclusion criteria, including 349 primary studies and 62 reviews. More than 80% of the primary studies were from HICs and described all levels of neurotrauma prevention. Only 65 papers came from LMICs, which mostly described primary prevention, focussing on road safety. For the reviews, 41 papers (66.1%) reviewed primary, 18 tertiary (29.1%), and three secondary preventative approaches. Most of the primary papers in the reviews came from HICs (67.7%) with 5 reviews on only LMIC papers. Fifteen reviews (24.1%) included papers from both HICs and LMICs. Intervention settings ranged from nationwide to community-based but were not reported in 44 papers (10.8%), most of which were reviews. Contextual factors were described in 62 papers and varied depending on the interventions.ConclusionsThere is a large quantity of global evidence on strategies and interventions for neurotrauma and RTCs prevention. However, fewer papers were from LMICs, especially on secondary and tertiary prevention. More primary research needs to be done in these countries to determine what strategies and interventions exist and the applicability of HIC interventions in LMICs.

Background: The current evidence for higher physical activity and better cognitive function and lower risk of dementia is strong but not conclusive. More robust evidence is needed to inform public health policy. We provide further insight to discrepancies observed across studies, reporting on habitual inactivity including that during work. Methods: We examined cross-sectional and prospective relationships of physical inactivity during leisure and occupation time, with cognitive performance using a validated physical activity index in a cohort of 8585 men and women aged 40-79 years at baseline (1993-1997) for different domains using a range of cognitive measures. Cognitive testing was conducted between 2006-2011 (including pilot phase 2004-2006). Associations were examined using multinomial logistic regression adjusting for socio-demographic and health variables as well total habitual physical activity. Results: Inactivity during work was inversely associated with poor cognitive performance (bottom tenth percentile of a composite cognition score); Odds Ratio (OR) = 0·68 (95% Confidence Interval (CI) 0.54, 0·86) P=0·001. Results were similar cross-sectionally; OR = 0·65 (95% CI 0·45, 0·93) P=0·02. Manual workers had increased risk of poor performance compared to those with an occupation classified as inactive. Inactivity during leisure time was associated with increased risk of poor performance in the cross-sectional analyses only. Conclusions: The relationship between inactivity and cognition is strongly confounded by education, social class and occupation. Physical activity during leisure may be protective for cognition, but work related physical activity is not protective. A greater understanding of the mechanisms and confounding underlying these paradoxical findings is needed., This work was supported by the Medical Research Council, UK (MRC) http://www.mrc.ac.uk/ (Ref: MR/N003284/1, MC-UU_12015/1 to N.W.); Cancer Research UK, http://www.cancerresearchuk.org/ (CRUK, Ref: C864/A8257) and NIHR, https://www.nihr.ac.uk (Ref: NF-SI-0616–10090 to C.B.). The clinic for EPIC- orfolk 3HC was funded by Research into Ageing, now known as Age UK, http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/A2883)

BACKGROUND: This study aims to determine whether older adults reporting back pain (BP) are at increased risk of premature mortality, specifically, to examine the association with disabling/non-disabling pain separately. METHODS: Participants aged ≥75 years were recruited to the Cambridge City over-75s Cohort (CC75C) study. Participants answered interviewer-administered questions on BP and were followed up until death. The relationship between BP and mortality was examined using Cox regression, adjusted for potential confounding factors. Separate models were computed for men and women. RESULTS: From 1174 individuals with BP data, the date of death was known for 1158 (99%). A significant association was found between disabling BP and mortality (hazard ratio: 1.4; 95% confidence interval: 1.1-1.8) and this remained, albeit of borderline significance, following adjustment for socio-demographic variables and potential disease markers (1.3; 0.99-1.7). Further, this association was found to vary with sex: women experienced a 40% increase in the risk of mortality associated with disabling BP (1.4; 1.1-1.9), whereas no such increase was observed for men (1.0; 0.5-1.9). Participants with non-disabling BP were not at increased risk of mortality. CONCLUSIONS: This study confirmed previous findings regarding the relationship between pain and excess mortality. Further, we have shown that, among older adults, this association is specific to disabling pain and to women. Clinicians should be aware not only of the short-term implications of disabling BP but also the longer-term effects. Future research should attempt to understand the mechanisms underpinning this relationship to avoid excess mortality and should aim to determine why the relationship differs in men and women.

BACKGROUND: Previous imaging studies have suggested links between brain pathologies and factors that are associated with falls such as gait, balance and daily function. Possible neuropathological correlates of older people's falls have been suggested based on brain imaging studies, but to date none have been examined in brain tissue. METHODS: Falls data collected from repeated surveys of a population-based cohort of individuals aged at least 75 years old at baseline were related to neuropathological data collected from post-mortem examination of the study's associated brain donor collection (n=212). RESULTS: Amongst people without dementia, most cerebrovascular neuropathological features examined, particularly white matter pallor, microinfarcts and microscopic atherosclerosis, were increasingly common across the subgroups categorised by no reports of falling, only one or at least two reports of falling. The overall burden of pathology was greater in those with dementia, but only microinfarcts showed a similar increase with respect to reported falling status. CONCLUSIONS: Subclinical pathologies sharing a common vascular origin are associated with increased falling amongst people with no dementia, as are microinfarcts in those with dementia. Although further research is needed to address the mechanisms of falls and their neuropathological correlates, the findings from the current study would suggest that if cerebrovascular disease prevention reduces vascular neuropathology changes this may have direct benefits in reducing falls amongst older people with or without dementia.

Astrocytes play a major role in the pathogenesis of a range of neurodegenerative diseases, including Alzheimer’s disease (AD), undergoing dramatic morphological and molecular changes that can cause potentially both beneficial and detrimental effects. They comprise a heterogeneous population, requiring a panel of specific phenotype markers to identify astrocyte subtypes, changes in function and their relation to pathology. This study aimed to characterise expression of the astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, investigate the relationship between NDRG2 and a panel of astrocyte markers, and relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell body and radiating processes of astrocytes in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of NDRG2 did not correlate with other astrocyte markers, including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). NDRG2 showed a relationship to AT8+ neurofibrillary tangles (p = 0.001) and CD68+ microglia (p = 0.047), but not β-amyloid plaques or astrocyte nuclear γH2AX immunoreactivity, a marker of DNA damage response. These findings provide new insight into the astrocyte response to pathology in the ageing brain, and suggest NDRG2 may be a potential target to modulate this response.

Pathologies associated with the Tar-DNA binding protein 43 KDa (TDP-43) are associated with neurodegenerative diseases and aging. Phosphorylation of cellular proteins is a well-accepted mechanism of biological control and can be associated with disease pathways. Phosphorylation state associated with TDP-43 associated pathology has not been investigated with respect to dementia status in a population representative sample. TDP-43 immunohistochemistry directed toward phosphorylated (TDP-43P) and unphosphorylated (TDP-43U) was assessed in sections of hippocampus and temporal cortex from 222 brains donated to the population representative Cambridge City over-75s Cohort. Relationships between dementia status and age at death for TDP-43 immunoreactive pathologies by phosphorylation state were investigated. TDP-43 pathologies are common in the oldest old in the population and often do not conform to MacKenzie classification. Increasing age is associated with glial (TDP-43P) and neuronal inclusions (TDP-43P and TDP-43U), neurites, and granulovacuolar degeneration (GVD). Dementia status is associated with GVD and glial (TDP-43 P) and neural inclusions (TDP-43 P and U). Dementia severity was associated with glial (TDP-43P) and neuronal inclusions (TDP-43U and TDP-43P), GVD, and neurites. The associations between dementia severity and both glial cytoplasmic inclusions and GVD were independent from other pathologies and TDP-43 neuronal cytoplasmic inclusions. TDP-43 pathology contributes to dementia status and progression in a variety of ways in different phosphorylation states involving both neurons and glia, independently from age and from classic Alzheimer-related pathologies. TDP-43 pathologies as cytoplasmic inclusions in neurons or glia or as GVD contribute independently to dementia.

Background A previous Cochrane systematic review concluded there is insufficient evidence to support the routine use of 18F-FDG PET in clinical practice in people with mild cognitive impairment (MCI). Objectives To update the evidence and reassess the accuracy of 18F-FDG-PET for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease (AD) dementia at follow-up. Methods A systematic review including comprehensive search of electronic databases from January 2013 to July 2017, to update original searches (1999 to 2013). All key review steps, including quality assessment using QUADAS 2, were performed independently and blindly by two review authors. Meta-analysis could not be conducted due to heterogeneity across studies. Results When all included studies were examined across all semi-quantitative and quantitative metrics, exploratory analysis for conversion of MCI to AD dementia (n = 24) showed highly variable accuracy; half the studies failed to meet four or more of the seven sets of QUADAS 2 criteria. Variable accuracy for all metrics was also found across eleven newly included studies published in the last 5 years (range: sensitivity 56-100%, specificity 24-100%). The most consistently high sensitivity and specificity values (approximately ≥80%) were reported for the sc-SPM (single case statistical parametric mapping) metric in 6 out of 8 studies. Conclusion Systematic and comprehensive assessment of studies of 18FDG-PET for prediction of conversion from MCI to AD dementia reveals many studies have methodological limitations according to Cochrane diagnostic test accuracy gold standards, and shows accuracy remains highly variable, including in the most recent studies. There is some evidence, however, of higher and more consistent accuracy in studies using computer aided metrics, such as sc-SPM, in specialized clinical settings. Robust, methodologically sound prospective longitudinal cohort studies with long (≥5 years) follow-up, larger consecutive samples, and defined baseline threshold(s) are needed to test these promising results. Further evidence of the clinical validity and utility of 18F-FDG PET in people with MCI is needed.

International audience; Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.

Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.

Background For a decade, experts have suggested integrating mental health care into primary care to help bridge mental health Treatment Gap. General Practitioners (GPs) are the first port-of-call for many patients with mental ill-health. In Indonesia, the WHO mhGAP is being systematically introduced to its network of 10,000 primary care clinics as an add-on mental health training for pairs of GPs and Nurses, since the end of 2015. In one of 34 provinces, there exists an integrated care model: the co-location of clinical psychologists in primary care clinics. This trial evaluates patient outcomes among those provided mental health care by GPs with those treated by clinical psychologists in primary care. Methods In this partially-randomised, pragmatic, two-arm cluster non-inferiority trial, 14 primary care clinics were assigned to receive the WHO mhGAP training and 14 clinics with the co-location framework were assigned to the Specialist arm. Participants (patients) were blinded to the existence of the other pathway, and outcome assessors were blinded to group assignment. All adult primary care patients who screened positive for psychiatric morbidity were eligible. GPs offered psychosocial and/or pharmacological interventions and Clinical Psychologists offered psychosocial interventions. The primary outcome was health and social functioning as measured by the HoNOS and secondary outcomes include disability measured by WHODAS 2.0, health-related quality of life measured by EQ‐5D-3L, and resource use and costs evaluated from a health services perspective, at six months. Results 153 patients completed the outcome assessment following GP care alongside 141 patients following Clinical Psychologists care. Outcomes of GP care were proven to be statistically not inferior to Clinical Psychologists in reducing symptoms of social and physical impairment, reducing disability, and improving health-related quality of life at six months. Economic analyses indicate lower costs and better outcomes in the Specialist arm and suggest a 50% probability of WHO mhGAP framework being cost-effective at the Indonesian willingness to pay threshold per QALY. Conclusion General Practitioners supported by nurses in primary care clinics could effectively manage mild to moderate mental health issues commonly found among primary care patients. They provide non-stigmatising mental health care within community context, helping to reduce the mental health Treatment Gap. Trial registration ClinicalTrials.gov NCT02700490

ObjectiveStudies have shown area-level deprivation can increase the risk for mental disorders over and above individual-level circumstances, such as education and social class. The objective of this study is to determine whether area deprivation is associated with major depressive disorder (MDD) in British women and men separately while adjusting for individual-level factors.DesignLarge, population study.SettingUK population-based cohort.Participants30 445 people from the general population aged 40 years and older and living in England consented to participate at study baseline, and of these, over 20 000 participants completed a structured Health and Life Experiences Questionnaire used to capture MDD. Area deprivation was measured in 1991 using Census data, and current MDD was assessed in 1996–2000. 8236 men and 10 335 women had complete data on all covariates.Primary outcome measureMDD identified according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).ResultsIn this study, 3.3% (339/10 335) of women and 2.1% (177/8236) of men had MDD. Men living in the most deprived areas were 51% more likely to have depression than those living in areas that were not deprived (OR=1.51, 95% CI 1.01 to 2.24; p=0.043), but the association between deprivation and MDD was not statistically significant in women (OR=1.24, 95% CI 0.93 to 1.65; p=0.143).ConclusionThis study shows that the residential environment differentially affects men and women, and this needs to be taken into account by mental health policy-makers. Knowing that men living in deprived conditions are at high risk for having depression helps inform targeted prevention and intervention programmes.

Neurotrauma is an important global health problem. The largest cause of neurotrauma worldwide is road traffic collisions (RTCs), particularly in low- and middle-income countries (LMICs). Neurotrauma and RTCs are preventable, and many preventative interventions have been implemented over the last decades, especially in high-income countries (HICs). However, it is uncertain if these strategies are applicable globally due to variations in environment, resources, population, culture and infrastructure. Given this issue, this scoping review aims to identify, quantify and describe the evidence on approaches in neurotrauma and RTCs prevention, and ascertain contextual factors that influence their implementation in LMICs and HICs. A systematic search was conducted using five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health on EBSCO host, Cochrane Database of Systematic Reviews), grey literature databases, government and non-government websites, as well as bibliographic and citation searching of selected articles. The extracted data were presented using figures, tables, and accompanying narrative summaries. The results of this review were reported using the PRISMA Extension for Scoping Reviews (PRISMA-ScR). A total of 411 publications met the inclusion criteria, including 349 primary studies and 62 reviews. More than 80% of the primary studies were from HICs and described all levels of neurotrauma prevention. Only 65 papers came from LMICs, which mostly described primary prevention, focussing on road safety. For the reviews, 41 papers (66.1%) reviewed primary, 18 tertiary (29.1%), and three secondary preventative approaches. Most of the primary papers in the reviews came from HICs (67.7%) with 5 reviews on only LMIC papers. Fifteen reviews (24.1%) included papers from both HICs and LMICs. Intervention settings ranged from nationwide to community-based but were not reported in 44 papers (10.8%), most of which were reviews. Contextual factors were described in 62 papers and varied depending on the interventions. There is a large quantity of global evidence on strategies and interventions for neurotrauma and RTCs prevention. However, fewer papers were from LMICs, especially on secondary and tertiary prevention. More primary research needs to be done in these countries to determine what strategies and interventions exist and the applicability of HIC interventions in LMICs.

BACKGROUND: Studies from North America and Western Europe suggest stable or declining trends in impaired cognition across birth cohorts. OBJECTIVE: We aimed to examine changes in the age-specific prevalence of cognitive impairment in the Czech Republic. METHODS: The study used two samples from the population-based Czech Survey on Health, Ageing and Retirement in Europe. Age-specific prevalence of cognitive impairment (defined based on scores in verbal fluency, immediate recall, delayed recall, and temporal orientation) was compared between participants in wave 2 (2006/2007; n = 1,107) and wave 6 (2015; n = 3,104). Logistic regression was used to estimate the association between the wave and cognitive impairment, step-wise adjusting for sociodemographic and clinical characteristics. Multiple sensitivity analyses, focusing on alternative operationalizations of relative cognitive impairment, impact of missing cognitive data, and survival bias, were carried out. RESULTS: The most conservative estimate suggested that the age-specific prevalence of cognitive impairment declined by one fifth, from 11% in 2006/2007 to 9% in 2015. Decline was observed in all sensitivity analyses. The change was associated with differences in physical inactivity, management of high blood cholesterol, and increases in length education. CONCLUSION: Older adults in the Czech Republic, a country situated in the Central and Eastern European region, have achieved positive developments in cognitive aging. Longer education, better management of cardiovascular factors, and reduced physical inactivity seem to be of key importance.

Introduction: The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods: A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and Discussion: The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion: All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems, while emphasising the need to include as many children in the mainstream system as possible.

Background There is some evidence to suggest that social isolation may be associated with poor cognitive function in later life. However, findings are inconsistent and there is wide variation in the measures used to assess social isolation. Objective We conducted a systematic review and meta-analysis to investigate the association between social isolation and cognitive function in later life. Methods A search for longitudinal studies assessing the relationship between aspects of social isolation (including social activity and social networks) and cognitive function (including global measures of cognition, memory, and executive function) was conducted in PsycInfo, CINAHL, PubMed, and AgeLine. A random effects meta-analysis was conducted to assess the overall association between measures of social isolation and cognitive function. Sub-analyses investigated the association between different aspects of social isolation and each of the measures of cognitive function. Results Sixty-five articles were identified by the systematic review and 51 articles were included in the meta-analysis. Low levels of social isolation characterized by high engagement in social activity and large social networks were associated with better late-life cognitive function (r = 0.054, 95% CI: 0.043, 0.065). Sub-analyses suggested that the association between social isolation and measures of global cognitive function, memory, and executive function were similar and there was no difference according to gender or number of years follow-up. Conclusions Aspects of social isolation are associated with cognitive function in later life. There is wide variation in approaches to measuring social activity and social networks across studies which may contribute to inconsistencies in reported findings.

OBJECTIVES: To determine the prevalence of disabling and non-disabling back pain across age in older adults, and identify risk factors for back pain onset in this age group. METHODS: Participants aged ≥ 75 years answered interviewer-administered questions on back pain as part of a prospective cohort study [Cambridge City over-75s Cohort Study (CC75C)]. Descriptive analyses of data from two surveys, 1988-89 and 1992-93, estimated prevalence and new onset of back pain. Relative risks (RRs) and 95% CIs were estimated using Poisson regression, adjusted for age and gender. RESULTS: Prevalence of disabling and non-disabling back pain was 6 and 23%, respectively. While prevalence of non-disabling back pain did not vary significantly across age (χ²trend : 0.90; P = 0.34), the prevalence of disabling back pain increased with age (χ²trend : 4.02; P = 0.04). New-onset disabling and non-disabling back pain at follow-up was 15 and 5%, respectively. Risk factors found to predict back pain onset at follow-up were: poor self-rated health (RR 3.8; 95% CI 1.8, 8.0); depressive symptoms (RR 2.2; 95% CI 1.3, 3.7); use of health or social services (RR 1.7; 95% CI 1.1, 2.7); and previous back pain (RR 2.1; 95% CI 1.2-3.5). From these, poor self-rated health, previous back pain and depressive symptoms were found to be independent predictors of pain onset. Markers of social networks were not associated with the reporting of back pain onset. Conclusion. The risk of disabling back pain rises in older age. Older adults with poor self-rated health, depressive symptoms, increased use of health and social services and a previous episode of back pain are at greater risk of reporting future back pain onset.

BACKGROUND: Despite fast-growing 'older old' populations, 'place of care' trajectories for very old people approaching death with or without dementia are poorly described and understood. AIM: To explore end-of-life transitions of 'older old' people across the cognitive spectrum. DESIGN: Population-based prospective cohort (United Kingdom) followed to death. SETTING/PARTICIPANTS: Mortality records linked to 283 Cambridge City over-75s Cohort participants' cognitive assessments

© 2018, © 2018 Fundacion Infancia y Aprendizaje. As the number of older adults increases worldwide, it is becoming increasingly important to find effective ways of fostering better ageing trajectories. The models used to shape this process inform research, policy and practice and impact older adults themselves. Two important ageing models are successful ageing (SA) and resilience (RES). Aligning the conceptual framework in research contexts with those of older adults’ perspectives is an integral component of driving forward the research agenda in a manner that has the greatest potential to benefit older adults. Studies conducted with laypersons indicate that psychosocial components are important components of successful ageing models; therefore, it is imperative that these non-biomedical components are incorporated. There are many similarities between SA and RES models, but an important distinguishing feature is the incorporation of adversity into conceptualizations of resilience. SA models suggest high levels of functioning as a requirement for ageing successfully, regardless of the circumstances the individual experiences; resilience models take into account the level of adversity being experienced by the individual. Individuals can demonstrate RES by having a more positive outcome than would be expected given their level of adversity. The incorporation of psychosocial constructs into SA models and the integration of SA and RES paradigms has important implications for research and for older adults themselves. Through the promotion of models of ageing that include psychosocial components and elements of adversity, greater generalizability to a broader population is possible with enhanced potential for research derived from these efforts to more positively influence individuals’ trajectories of ageing.

OBJECTIVES: To characterize people of advanced old age in their last year of life and compare those dying in their late 80s with those dying aged 90 and older to inform policy and planning. DESIGN: Retrospective analysis of prospectively collected population-based data from the Cambridge City over-75s Cohort (CC75C) Study, United Kingdom. PARTICIPANTS: Men and women aged 85 and older at death who died less than 1 year after taking part in any CC75C survey (N=321). MEASUREMENTS: Physical health, functional disability, self-rated health, cognitive status. RESULTS: Functional and cognitive impairments were markedly higher for those who died aged 90 and older- predominantly women-than for those who died aged 85 to 89. At least half (49.4-93.6%) of subjects aged 90 and older needed maximum assistance in virtually every daily activity; those aged 85 to 89 needed this only for shopping and laundry. Disability in basic and instrumental activities rose from 59.1% before to 85.4% after the age of 90 and cognitive impairment (Mini-Mental State Examination score < or =21) from 41.7% to 69.4%. Despite this and proximity to death, 60.5% and 67.0%, respectively, rated their health positively. Only one in five reported needing more help. CONCLUSION: This study provides new data identifying high levels of physical and cognitive disability in very old people in the year before death. As the very old population rises, so will support needs for people dying in extreme old age. The mismatch between health perceptions and functional limitations suggests that these vulnerable older adults may not seek help from which they could benefit. These findings have major policy and planning implications for end-of-life care for the oldest old.

Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age.

BACKGROUND: Living alone may be associated with greater risk for social isolation and loneliness. Living alone, social isolation, loneliness, and limited engagement in social activity have all been associated with poorer cognitive function in later life. Hence, if individuals who live alone are also at greater risk of isolation and loneliness, this may exacerbate poor cognitive function. OBJECTIVE: To determine whether people living alone are more at risk of social isolation, feelings of loneliness, and limited social activity, and to examine the associations between living alone and cognitive function in later life. METHOD: Baseline (N = 2197) and two-year follow-up (N = 1498) data from community-dwelling participants, age ≥65 years, without cognitive impairment or depression at baseline from CFAS-Wales were used. Linear regression analyses were conducted to assess the association between living arrangement and cognitive function at baseline and two-year follow-up. RESULTS: People living alone were more isolated from family and experienced more emotional loneliness than those living with others, but were not more isolated from friends, did not experience more social loneliness, and were more likely to engage in regular social activity. Living alone was not associated with poorer cognitive function at baseline or two-year follow-up. DISCUSSION: These findings have positive implications and suggest that people who live alone in later life are not at greater risk of poor cognitive function at baseline or two-year follow-up. Social isolation may be more associated with poor cognitive function.

NICE recently published updated recommendations for diagnosing dementia and how people with this clinical syndrome navigate the care system. In this update, major changes from the previous version include the use of emerging diagnostic methods in research. NICE recommendations regarding the use of CSF biomarkers and FDG PET imaging for diagnosing dementia subtypes in specialist clinical setting are based on results from diagnostic test accuracy (DTA) studies identified and included in a systematic review conducted according to Cochrane DTA Handbook guidelines (http://methods.cochrane.org/sdt/handbook-dta-reviews). We have concerns about the way in which the evidence has been translated into practice recommendations., During the development of this work, JP was an employee of NICE, which is commissioned and funded by the Department of Health to develop clinical guidelines. No authors received specific funding to write this summary.

Background Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. Methods The study included a three-step process: (1) screening; (2) clinical assessment of ‘screen positives’ plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6–10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage. Results In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20–89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10–38). Conclusions Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture. Electronic supplementary material The online version of this article (10.1186/s13229-018-0246-0) contains supplementary material, which is available to authorized users.

The amyloid cascade hypothesis has dominated research to understand the role of Aβ in AD but has never been fully accepted by the whole AD research community. Two alternative hypotheses, the presenilin hypothesis and the APP matrix approach, have been less intensively investigated. Relationships between AD-associated neuropathologies, ageing and dementia are complex in the older human population. Uncertainties and confounds in AD research suggest the theoretical frameworks that direct research require improvement. Here we present key concepts for the APP matrix approach including: i) dynamic balance between competing cleavages; ii) multiple disease associated drivers and pathways; iii) a systematic approach to describing and understanding all proteolytic fragments derived from APP and iv) full consideration of fundamental biochemical concepts such as dose-response relationships, competitive inhibition, competitive binding etc. for each proteolytic fragment. The APP matrix approach aims to: i) create a descriptive molecular map of all the proteolytic fragments generated by the APP proteolytic system; ii) characterise this map with reference to dynamic regulatory feedback loops and fundamental biochemical concepts; iii) describe and model differences in the behaviour of this system in different cell types and species and iv) generate a dynamic functional model to characterise how specific molecular and neuropathological features relating to the APP proteolytic system are associated with dementia.

Background: This report maps autism and special education needs (SEN) policies, alongside teacher responsibilities in the education of children with SEN in Austria, Hungary, Czech Republic, and Slovakia.Methods and Procedure: A policy path analysis using a scoping review as an underlying methodological framework was performed.Outcomes and Results: The end of communism and accession to the European Union were critical for the countries under study. They passed crucial policies after international policies and adopted a three-stream approach towards providing education: (1) special schools; (2) special classes in mainstream schools; or (3) mainstream classes. Special schools remain for children that cannot participate in mainstream schools. Teachers are given high levels of responsibility.Conclusion and Implications: Changes in international guidance greatly impacted Austria, Hungary, Slovakia and the Czech Republic. The education systems aim for inclusion, though segregation remains for children that cannot thrive in mainstream schools. Teachers are pivotal in the education of children with SEN, more so than with typical children.

Background Trial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients. Methods MEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs). Results Of 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10–1.58, n = 15 studies, I2 = 0%) and 1.23 (95%CI 0.99–1.54, n = 14, I2 = 26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47–8.76, n = 2, I2 = 0%) and cognitive impairment (OR 2.70, 95%CI 1.09–6.69, n = 1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83–8.62, n = 3, I2 = 77.9%) and 3.34 (95%CI 0.79–14.1, n = 4, I2 = 96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65–1.21, n = 1) and 0.56 (95%CI 0.46-0.69, n = 3, I2 = 0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence. Conclusion Atherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required.

Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer’s disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and –II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging population-representative neuropathology cohort, and examined H2O2-modulation of MT transcription by human astrocytes. MT-I/II is primarily expressed by astrocytes in the aging brain, but is also associated with pyramidal neurons in a small proportion of cases. Astrocyte expression of MT-I/II does not correlate with Alzheimer-type pathology (Aβ plaques and neurofibrillary tangles) but does relate to astrocyte oxidative DNA damage (rs= 0.312, p= 0.006) and the astrocyte response to oxidative DNA damage in vivo (rs= 0.238, p= 0.04), and MT gene expression is significantly induced in human astrocytes response to oxidative stress in vitro (p=0.01). In contrast, neuronal MT-I/II does not relate to oxidative DNA damage or the neuronal DNA damage response, but is significantly higher in cases with high levels of local tangle pathology (p=0.007). As MT-I/II is neuroprotective against oxidative stress, modulation of MT-I/II expression is a potential therapeutic target to treat the onset and progression of cognitive impairment.

BACKGROUND AND OBJECTIVES: This paper describes the development of an item pool for a needs-based self-report outcome measure of the impact of caring for a relative, friend or neighbour with dementia on carer quality of life. The aims are to give a detailed account of the steps involved and describe the resulting item pool. METHODS: Seven steps were followed: generation of an initial item set drawing on 42 needs-led interviews with carers; a content and face validity check; assessment of psychometric potential; testing of response formats; pre-testing through cognitive interviews with 22 carers; administration rehearsal with two carers; and final review. RESULTS: An initial set of 99 items was refined to a pool of 70 to be answered using a binary response format. Items were excluded due to overlap with others, ceiling effects, ambiguity, dependency on function of the person with dementia or two-part phrasing. Items retained covered a breadth of areas of impact of caring and were understandable and acceptable to respondents. CONCLUSIONS: The resulting dementia carer-specific item pool reflects the accounts of a diverse sample of those who provide care for a person with dementia, allowing them to define the nature of the impact on their lives and resulting in a valid, acceptable set of items.