First-Borns Carry a Higher Metabolic Risk in Early Adulthood: Evidence from a Prospective Cohort Study

Background: Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.Methodology and Principal Findings: Body composition and metabolic risk were assessed in 2,249 men, aged 17-19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score (Delta = -0.25, 95%CI -0.35, -0.15, p<0.001) but showed greater weight gain during infancy (change in weight z-score from birth to 20 months: Delta = 0.39, 95%CI 0.28-0.50, P<0.0001) and had greater mean height (Delta = 1.2 cm, 95%CI: 0.7-1.6, p<0.0001) and weight (Delta = 0.34 kg, 95%CI: 0.13-0.55, p<0.002) at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.Conclusions/Significance: First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors

Behavioural and psychological symptoms in the older population without dementia - Relationship with socio-demographics, health and cognition

Abstract Background Behavioural and psychological symptoms are associated with dementia, but are also present in a significant number of the older population without dementia. Here we explore the distribution of behavioural and psychological symptoms in the population without dementia, and their relationship with domains and severity of health and cognitive impairment. Methods The Medical Research Council Cognitive Function and Ageing Study is a two-phase longitudinal study of ageing representative of the population aged 65 and over of England and Wales. A subsample of 1781 participants without a study diagnosis of dementia was included in this study. Information on symptoms including depression, apathy, anxiety, feelings of persecution, hallucination, agitated behaviour, elation, irritability, sleep problems, wandering, confabulation and misidentification, cognitive function, health related factors and socio-demographic information was extracted from interviews with participants and knowledgeable informants. Participants were classified according to the Mini-Mental State Examination and by criteria for subtypes of mild cognitive impairment (MCI). The prevalence of behavioural and psychological symptoms and associations with cognitive function, health and socio-demographics was examined. Co-occurrence of symptoms was tested using factor analysis. Results Most symptoms were reported more frequently in those with more severe cognitive impairment. Subjective memory complaints were the strongest independent predictor of reported symptoms, and most were reported more often in those classified as having MCI than in those with cognitive impairments that did not meet the MCI criteria. The pattern of co-occurrence of symptoms is similar to that seen in dementia. Conclusions Our results highlight that behavioural and psychological symptoms are prevalent in the cognitively impaired older population, and partly explain the variation observed in previous cohorts of individuals with MCI. Behavioural and psychological symptoms offer a target for intervention and so are an important consideration in the assessment of cognitively impaired older people.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Does education explain the terminal decline in the oldest-old? Evidence from two longitudinal studies of ageing

AbstractBackground Cognitive performance substantially deteriorates close to death, as postulated by the terminal decline hypothesis. However, the association between education and terminal decline remains controversial. This study investigated the role of education in terminal decline in two European longitudinal studies of oldest-old. Methods Participants were from the Newcastle 85+, UK (n=702), and Octogenarian Twins (OCTO-Twin), Sweden (n= 845). They were assessed biannually over three and five consecutive waves, respectively. In a coordinated analysis, multilevel models were used to examine the association between education and terminal decline on mini-mental state examination (MMSE), controlling for age at baseline, dementia incidence, sex, and time to death from the study entry within each cohort. Cognitive decline was modelled as a linear function of time to death in both cohorts and as a quadratic function in the OCTO-Twin study (because of longer follow-up). Education was a continuous measure (ranging from 6 to 20 years in Newcastle 85+ and 0 to 23 years in OCTO-Twin). Findings A typical British man, aged 85 at baseline, with 10 years’ education, entered the terminal phase at around 2·5 years before death, and the mean rate of decline was −1·04 MMSE points with each year closer to the time of death (SEM 0·25, p&lt;0·0001). By contrast, a Swedish man, aged 83 years, with an average of 7 years’ education, entered the terminal phase at around 8 years from death, after which the rate of cognitive decline steepened by −1·70 points per year closer to the time of death (SEM 0·20, p&lt;0·0001) and accelerated by −0·11 (SEM 0·01, p&lt;0·0001). Education was positively associated with the estimated mean MMSE scores before death only in OCTO-Twin (0·43, SEM 0·15; p=0·003) and did not attenuate the rate of terminal decline in either cohort. Interpretation Decline and acceleration of this decline were detectable in both studies before death, with steeper rates of decline observed in the Swedish cohort. However, this process was not lessened by education itself. This work contributes to a better understanding of the transition from the subtle cognitive changes associated with age to those of neurological substance, and the role of education in this decline. Funding The funding sources of this work were the Alzheimer's Society (grant number 144) and the Medical Research Council (unit programme number MC_UU_12019/1)

Risk Prediction Models for Post-Stroke Dementia

A strong association exists between stroke and dementia with both diseases linked to ageing. Survival rates from stroke are improving which would equate to an ever-expanding population of patients at risk of future dementia. Early or timelier identification of dementia has become a priority in many countries, including the UK. Although screening for dementia is not advocated, targeting at risk populations could be used to reduce an individual’s risk via intervention (i.e., personalised medicine), where available. One approach to improving identification of high-risk dementia individuals is using risk prediction models. Such models could be applied to stroke survivors. Dementia risk prediction models specific to stroke survivors have recently been developed and will be discussed her

Predicting dementia from primary care records: a systematic review and meta-analysis

Introduction Possible dementia is usually identified in primary care by general practitioners (GPs) who refer to specialists for diagnosis. Only two-thirds of dementia cases are currently recorded in primary care, so increasing the proportion of cases diagnosed is a strategic priority for the UK and internationally. Clinical entities in the primary care record may indicate risk of developing dementia, and could be combined in a predictive model to help find patients who are missing a diagnosis. We conducted a meta-analysis to identify clinical entities with potential for use in such a predictive model for dementia in primary care. Methods and Findings We conducted a systematic search in PubMed, Web of Science and primary care database bibliographies. We included cohort or case-control studies which used routinely collected primary care data, to measure the association between any clinical entity and dementia. Meta-analyses were performed to pool odds ratios. A sensitivity analysis assessed the impact of non-independence of cases between studies. From a sift of 3836 papers, 20 studies, all European, were eligible for inclusion, comprising >1 million patients. 75 clinical entities were assessed as risk factors for all cause dementia, Alzheimer’s (AD) and Vascular dementia (VaD). Data included were unexpectedly heterogeneous, and assumptions were made about definitions of clinical entities and timing as these were not all well described. Meta-analysis showed that neuropsychiatric symptoms including depression, anxiety, and seizures, cognitive symptoms, and history of stroke, were positively associated with dementia. Cardiovascular risk factors such as hypertension, heart disease, dyslipidaemia and diabetes were positively associated with VaD and negatively with AD. Sensitivity analyses showed similar results. Conclusions These findings are of potential value in guiding feature selection for a risk prediction tool for dementia in primary care. Limitations include findings being UK-focussed. Further predictive entities ascertainable from primary care data, such as changes in consulting patterns, were absent from the literature and should be explored in future studies

What would a population-level approach to dementia risk reduction look like, and how would it work?

Dementia is a leading global public health challenge. Prevention approaches have traditionally focused on individual-level strategies. However, such approaches have limited potential, particularly for resource-constrained populations in which exposure to risk factors is greatest, and exposure to protective factors is lowest. A population-level approach to dementia risk reduction is therefore essential to meet the scale of the challenge and to tackle global inequalities in risk and incidence of disease. Such approaches can be highly cost effective. In this viewpoint article, we describe what such an approach should look like, barriers and facilitators to success, and how we should go about achieving it. We include 10 strategic goals to achieve population-level dementia risk reduction and protection enhancement, targeted at researchers, professionals, funders, science communicators, governments, businesses, and policy makers. If we are to significantly reduce the prevalence of dementia there must be increased emphasis on population-level approaches. Highlights: Dementia risk reduction is a global public health priority Population-level approaches change societal conditions to make them less conducive to dementia's modifiable risk factors, and increase exposure to protective factors. Urgent development of population-level approaches is required to reduce the prevalence of, and inequalities in, dementia Action is required from researchers, governments and business, funders, public health professionals, and science communicators

Metabolic biomarkers of appetite control in Parkinson\u27s disease patients with and without cognitive impairment

\ua9 2024 The Author(s)Background: Appetite dysregulation in Parkinson\u27s Disease (PD) appears to be linked to physical and cognitive deterioration. PD patients with and without cognitive impairment (CI) were compared to an age-matched control group to explore predictors of appetite control in fasting and post-prandial conditions. Methods: Fifty-five patients were recruited and divided into three groups: twenty controls (age: 74 y, BMI: 25.8 kg/m2), nineteen PD patients without CI (72.5 y, 25.1 kg/m2) and sixteen PD patients with CI (74.3 y, 24.0 kg/m2). Self-reported appetite perception and circulating blood metabolic biomarkers were measured in fasting and over a 3-h post-prandial period. Biomarkers included glucose, insulin, tumour necrosis factor alpha (TNF-α), leptin, acyl-ghrelin, total ghrelin, peptide YY (PYY), glucagon like peptide 1 (GLP-1), insulin growth factor 1 (IGF-1), growth factor (GF) and triglycerides. Patients were then provided with a mixed meal to eat ad libitum with the aim to evaluate links between metabolic biomarkers and control of energy intake. Results: PD patients with CI had a significant lower protein intake (7.4 \ub1 2.5 g, p = 0.01) compared to controls (21.9 \ub1 3.1 g) and PD patients without CI (14.3 \ub1 3.0 g). Post-prandial plasma GLP-1 concentrations were associated with decreased hunger perception (B\ub1SE, −5.3 \ub1 2.4 mm\ub7h−1, p = 0.04). PYY concentrations were significantly associated with GLP-1 in fasting (r = 0.40, p = 0.005) and post-prandial (r = 0.46, p &lt; 0.001) conditions. In a multivariate model, post-prandial PYY concentrations were a significant predictor of ad libitum energy intake in all subjects (B\ub1SE, −87.5 \ub1 34.9 kcal, p = 0.01) and in patients with PD (B\ub1SE, −106.8 \ub1 44.9 kcal, p = 0.04). Conclusions: PYY and GLP-1 appeared to influence appetite control in PD patients and their roles merit further investigation

Qualitative study exploring knowledge and attitudes towards dementia risk prediction, barriers to dementia services and service improvement recommendations with diverse populations in England

\ua9 Author(s) (or their employer(s)) 2025.Objectives This study explored knowledge of dementia, attitudes towards dementia risk prediction and barriers and facilitators to accessing dementia services for diverse populations in England. Design Qualitative study using task group methodology, interrogated through framework analysis. Setting Task groups were held primarily in-person at local community venues (n=12) with one task group conducted online. Participants 147 individuals (mean age=63 years old, 62% female) were recruited, representing low-income and ethnically diverse groups from two sites (Nottingham and Newcastle, UK). Participants were from diverse ethnic backgrounds with 37% Black or Black British, 24% Asian or Asian British, 20% white, 9% not provided, 7% Arab and 1% other ethnicities. Results Participants possessed some knowledge about dementia but highlighted a need for better access to information about dementia. Participants were knowledgeable about dementia risk factors, but knowledge of risk prediction was low. Attitudes towards dementia risk prediction were cautiously optimistic, and the use of risk prediction tools was viewed as empowering. However, participants stressed the need to consider the psychological impact of a high-risk result. Barriers to accessing dementia services included stigma, denial, language, cultural and religious views about dementia. Recommendations for service improvement included engaging with communities in their spaces, workforce training around dementia awareness, cultural competency and communicating with diverse groups, improving the provision of information in different languages and access to translators. Conclusions As international policy on dementia shifts focus to prevention, there is a growing interest in identifying those at high risk and intervening early. This study illustrates current levels of dementia knowledge and attitudes towards risk prediction among socioeconomically and ethnically diverse groups in the UK. Barriers to health services for diverse populations and service improvement recommendations offer a starting point for providers to develop culturally aware and inclusive dementia services

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study

Background: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. Methods: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. Results: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (−1.8 Mini-Mental State Examination points [95% CI –3.5 to –0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9–41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. Conclusions: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementi