Dementia incidence trend in England and Wales, 2002–19, and projection for dementia burden to 2040: analysis of data from the English Longitudinal Study of Ageing

Background: Dementia incidence declined in many high-income countries in the 2000s, but evidence on the post-2010 trend is scarce. We aimed to analyse the temporal trend in England and Wales between 2002 and 2019, considering bias and non-linearity. // Methods: Population-based panel data representing adults aged 50 years and older from the English Longitudinal Study of Ageing were linked to the mortality register across wave 1 (2002–03) to wave 9 (2018–19) (90 073 person observations). Standard criteria based on cognitive and functional impairment were used to ascertain incident dementia. Crude incidence rates were determined in seven overlapping initially dementia-free subcohorts each followed up for 4 years (ie, 2002–06, 2004–08, 2006–10, 2008–12, 2010–14, 2012–16, and 2014–18). We examined the temporal trend of dementia incidence according to age, sex, and educational attainment. We estimated the trend of dementia incidence adjusted by age and sex with Cox proportional hazards and multistate models. Restricted cubic splines allowed for potential non-linearity in the time trend. A Markov model was used to project future dementia burden considering the estimated incidence trend. // Findings: Incidence rate standardised by age and sex declined from 2002 to 2010 (from 10·7 to 8·6 per 1000 person-years), then increased from 2010 to 2019 (from 8·6 to 11·3 per 1000 person-years). Adjusting for age and sex, and accounting for missing dementia cases due to death, estimated dementia incidence declined by 28·8% from 2002 to 2008 (incidence rate ratio 0·71, 95% CI 0·58–0·88), and increased by 25·2% from 2008 to 2016 (1·25, 1·03–1·54). The group with lower educational attainment had a smaller decline in dementia incidence from 2002 to 2008 and a greater increase after 2008. If the upward incidence trend continued, there would be 1·7 million (1·62–1·75) dementia cases in England and Wales by 2040, 70% more than previously forecast. // Interpretation: Dementia incidence might no longer be declining in England and Wales. If the upward trend since 2008 continues, along with population ageing, the burden on health and social care will be large. // Funding: UK Economic and Social Research Council

Impact of hypertension prevalence trend on mortality and burdens of dementia and disability in England and Wales to 2060: a simulation modelling study

BACKGROUND: Previous estimates of the impact of public health interventions targeting hypertension usually focus on one health outcome. This study aims to consider the effects of change in future hypertension prevalence on mortality, dementia, and disability simultaneously. METHODS: We modelled three plausible scenarios based on observed trends of hypertension prevalence from 2003 to 2017 in England: observed trends continue (baseline scenario); 2017 prevalence remains unchanged; and 2017 prevalence decreases by 50% by 2060. We used a probabilistic Markov model to integrate calendar trends in incidence of cardiovascular disease, dementia, disability, and mortality to forecast their future occurrence in the population of England and Wales. Assuming the hypertension prevalence trend modifies health transition probabilities, we compared mortality outcomes and the burden of dementia and disability to 2060 for the scenarios. FINDINGS: If the decline in hypertension prevalence stops, there would be a slight increase in the number of additional deaths to 2060 (22·9 [95% uncertainty interval 19·0-26·6] more deaths per 100 000 population), although the burdens of disability and dementia in absolute terms would change little. Alternatively, if the downward hypertension prevalence trend accelerates (with prevalence falling by 50% between 2017 and 2060), there would be a modest additional reduction in deaths (57·0 [50·4-63·5] fewer deaths per 100 000 population), a small increase in dementia burden (9·0 [5·1-13·2] more cases per 100 000 population), no significant effect on disability burden, and an 8% gain in healthy life expectancy at age 65 years from 2020 to 2060 (5·3 years vs 4·9 years) compared with the baseline scenario. INTERPRETATION: The major future impact of alternative hypertension prevention strategies appears to be on future life expectancy. The salutary effect of lower population blood pressure distribution on incidence of dementia and disability might not offset expansion of the susceptible population due to reduced mortality. FUNDING: British Heart Foundation and UK Economic and Social Research Council

Growing old in China in socioeconomic and epidemiological context: systematic review of social care policy for older people

BACKGROUND: From 2020 to 2050, China's population aged ≥65 years old is estimated to more than double from 172 million (12·0%) to 366 million (26·0%). Some 10 million have Alzheimer's disease and related dementias, to approach 40 million by 2050. Critically, the population is ageing fast while China is still a middle-income country. METHODS: Using official and population-level statistics, we summarise China's demographic and epidemiological trends relevant to ageing and health from 1970 to present, before examining key determinants of China's improving population health in a socioecological framework. We then explore how China is responding to the care needs of its older population by carrying out a systematic review to answer the question: 'what are the key policy challenges to China achieving an equitable nationwide long-term care system for older people?'. Databases were screened for records published between 1st June 2020 and 1st June 2022 in Mandarin Chinese or English, reflecting our focus on evidence published since introduction of China's second long-term care insurance pilot phase in 2020. RESULTS: Rapid economic development and improved access to education has led to widescale internal migration. Changing fertility policies and household structures also pose considerable challenges to the traditional family care model. To deal with increasing need, China has piloted 49 alternative long-term care insurance systems. Our findings from 42 studies (n = 16 in Mandarin) highlight significant challenges in the provision of quality and quantity of care which suits the preference of users, varying eligibility for long-term care insurance and an inequitable distribution of cost burden. Key recommendations include increasing salaries to attract and retain staff, introduction of mandatory financial contributions from employees and a unified standard of disability with regular assessment. Strengthening support for family caregivers and improving smart old age care capacity can also support preferences to age at home. CONCLUSIONS: China has yet to establish a sustainable funding mechanism, standardised eligibility criteria and a high-quality service delivery system. Its long-term care insurance pilot studies provide useful lessons for other middle-income countries facing similar challenges in terms of meeting the long-term care needs of their rapidly growing older populations

Is there a common latent cognitive construct for dementia estimation across two Chinese cohorts?

INTRODUCTION: It is valuable to identify common latent cognitive constructs for dementia prevalence estimation across Chinese aging cohorts. METHODS: Based on cognitive measures of 12015 Chinese Longitudinal Healthy Longevity Survey (CLHLS; 13 items) and 6623 China Health and Retirement Longitudinal Study (CHARLS; 9 items) participants aged 65 to 99 in 2018, confirmatory factor analysis was applied to identify latent cognitive constructs, and to estimate dementia prevalence compared to Mini-Mental State Examination (MMSE) and nationwide estimates of the literature. RESULTS: A common three-factor cognitive construct of orientation, memory, and executive function and language was found for both cohorts with adequate model fits. Crude dementia prevalence estimated by factor scores was similar to MMSE in CLHLS, and was more reliable in CHARLS. Age-standardized dementia estimates of CLHLS were lower than CHARLS among those aged 70+, which were close to the nationwide prevalence reported by the COAST study and Global Burden of Disease. DISCUSSION: We verified common three-factor cognitive constructs for both cohorts, providing an approach to estimate dementia prevalence at the national level. HIGHLIGHTS: Common three-factor cognitive constructs were identified in Chinese Longitudinal Healthy Longevity Survey (CLHLS) and China Health and Retirement Longitudinal Study (CHARLS). Crude dementia estimates using factor scores were reliable in both cohorts. Estimates of CHARLS were close to current evidence, but higher than that of CLHLS

The impact of school-based screening on service use in adolescents at risk for mental health problems and risk-behaviour.

Early detection and intervention can counteract mental disorders and risk behaviours among adolescents. However, help-seeking rates are low. School-based screenings are a promising tool to detect adolescents at risk for mental problems and to improve help-seeking behaviour. We assessed associations between the intervention "Screening by Professionals" (ProfScreen) and the use of mental health services and at-risk state at 12 month follow-up compared to a control group. School students (aged 15 ± 0.9 years) from 11 European countries participating in the "Saving and Empowering Young Lives in Europe" (SEYLE) study completed a self-report questionnaire on mental health problems and risk behaviours. ProfScreen students considered "at-risk" for mental illness or risk behaviour based on the screening were invited for a clinical interview with a mental health professional and, if necessary, referred for subsequent treatment. At follow-up, students completed another self-report, additionally reporting on service use. Of the total sample (N = 4,172), 61.9% were considered at-risk. 40.7% of the ProfScreen at-risk participants invited for the clinical interview attended the interview, and 10.1% of subsequently referred ProfScreen participants engaged in professional treatment. There were no differences between the ProfScreen and control group regarding follow-up service use and at-risk state. Attending the ProfScreen interview was positively associated with follow-up service use (OR = 1.783, 95% CI = 1.038-3.064), but had no effect on follow-up at-risk state. Service use rates of professional care as well as of the ProfScreen intervention itself were low. Future school-based interventions targeting help-seeking need to address barriers to intervention adherence.Clinical Trials Registration: The trial is registered at the US National Institute of Health (NIH) clinical trial registry (NCT00906620, registered on 21 May, 2009), and the German Clinical Trials Register (DRKS00000214, registered on 27 October, 2009)

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

The Apache Point Observatory Galactic Evolution Experiment (APOGEE)

The Apache Point Observatory Galactic Evolution Experiment (APOGEE), one of the programs in the Sloan Digital Sky Survey III (SDSS-III), has now completed its systematic, homogeneous spectroscopic survey sampling all major populations of the Milky Way. After a three-year observing campaign on the Sloan 2.5 m Telescope, APOGEE has collected a half million high-resolution (R ~ 22,500), high signal-to-noise ratio (>100), infrared (1.51–1.70 μm) spectra for 146,000 stars, with time series information via repeat visits to most of these stars. This paper describes the motivations for the survey and its overall design—hardware, field placement, target selection, operations—and gives an overview of these aspects as well as the data reduction, analysis, and products. An index is also given to the complement of technical papers that describe various critical survey components in detail. Finally, we discuss the achieved survey performance and illustrate the variety of potential uses of the data products by way of a number of science demonstrations, which span from time series analysis of stellar spectral variations and radial velocity variations from stellar companions, to spatial maps of kinematics, metallicity, and abundance patterns across the Galaxy and as a function of age, to new views of the interstellar medium, the chemistry of star clusters, and the discovery of rare stellar species. As part of SDSS-III Data Release 12 and later releases, all of the APOGEE data products are publicly available

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962