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Objectives This paper models cognitive aging, across mid and late life, and estimates birth cohort and sex differences in both initial levels and aging trajectories over time in a sample with multiple cohorts and a wide span of ages. Methods The data used in this study came from the first 9 waves of the English Longitudinal Study of Ageing, spanning 2002–2019. There were n = 76,014 observations (proportion male 45%). Dependent measures were verbal fluency, immediate recall, delayed recall, and orientation. Data were modeled using a Bayesian logistic growth curve model. Results Cognitive aging was substantial in 3 of the 4 variables examined. For verbal fluency and immediate recall, males and females could expect to lose about 30% of their initial ability between the ages of 52 and 89. Delayed recall showed a steeper decline, with males losing 40% and females losing 50% of their delayed recall ability between ages 52 and 89 (although females had a higher initial level of delayed recall). Orientation alone was not particularly affected by aging, with less than a 10% change for either males or females. Furthermore, we found cohort effects for initial ability level, with particularly steep increases for cohorts born between approximately 1930 and 1950. Discussion These cohort effects generally favored later-born cohorts. Implications and future directions are discussed. [ABSTRACT FROM AUTHOR]

Background Aging is associated with an increasing risk of decline in cognitive abilities. The decline is, however, not a homogeneous process. There are substantial differences across individuals although previous investigations have identified individuals with distinct cognitive trajectories. Evidence is accumulating that lifestyle contributes significantly to the classification of individuals into various clusters. How and whether genetically related individuals, like twins, change in a more similar manner is yet not fully understood. Methods In this study, we fitted growth mixture models to Mini Mental State Exam (MMSE) scores from participants of the Swedish OCTO twin study of oldest-old monozygotic and same-sex dizygotic twins with the purpose of investigating whether twin pairs can be assigned to the same class of cognitive change. Results We identified four distinct groups (latent classes) whose MMSE trajectories followed different patterns of change over time: two classes of high performing individuals who remained stable and declined slowly, respectively, a group of mildly impaired individuals with a fast decline and a small group of impaired individuals who declined more rapidly. Notably, our analyses show no association between zygosity and class assignment. Conclusions Our study provides evidence for a more substantial impact of environmental, rather than genetic, influences on cognitive change trajectories in later life. [ABSTRACT FROM AUTHOR]

Background: Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods: We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results: A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95–0.99]), high education (OR = 1.64 [1.23–2.17]), male sex (OR = 1.56 [1.19–2.04]), and positive family history of dementia (OR = 1.66 [1.19–2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02–1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81–4.94]). These results were similar across prescreen settings. Conclusions: Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD. [ABSTRACT FROM AUTHOR]

Objective: Ageing is associated with changes in cognition in some, but not all domains. In young-old adults, defined as persons aged 65-84 years, baseline cognitive function has been shown to impact on cognitive trajectories. Whether similar patterns occur in the very-old, defined as persons aged 85 years and over, is not known.Methods: Longitudinal changes (5 years' follow-up) in global and domain specific cognitive function including memory, attention and speed were investigated in participants from the Newcastle 85+ Study (n = 845). At baseline, participants were grouped using Mini-Mental State Examination cut-off scores and dementia status into the following: not impaired, mildly impaired or severely impaired/dementia groups.Results: Only a limited number of cognitive measures showed significant decline in performance over time. Where observed, change generally occurred only in the severely impaired group. In the severely impaired group, small differences in baseline age were associated with poorer performance over time on most measures. Education was not protective against cognitive decline in any group.Conclusions: There are individuals who maintain a high level of cognitive function or only show mild impairments even into their ninth decade of life. This group of successful cognitive agers may provide insight for identifying predictors of cognitive integrity in later life. In individuals with severe impairment, cognitive performance shows significant decline over time, especially in measures of attention and speed. Further work to identify those individuals at highest risk of cognitive decline is necessary to implement early support and intervention strategies in this rapidly expanding age group. © 2017 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To model trajectories of visuospatial reasoning measured using Kohs Block Design test under realistic missing data assumptions and evaluate their association with hazard of death. Methods: A joint longitudinal-survival model was used to estimate trajectories of visuospatial reasoning under a missing not at random assumption of participants from the Origins of Variance in the Old–Old: Octogenarian Twins study. Sensitivity analyses to missing data assumptions were conducted. Results: Visuospatial reasoning declined at constant rate. Baseline age, dementia status, education, and history of stroke were associated with visuospatial reasoning performance, but only dementia was associated with its rate of decline. Importantly, our results demonstrated an association between poorer visuospatial reasoning and increased hazard of death. Baseline age and sex were associated with risk of death. Discussion: We confirmed an association between visuospatial reasoning and death under plausible missing data assumptions. [ABSTRACT FROM AUTHOR]

Objective To investigate the reciprocity of social support and cognitive function in late life. Method Analyses were based on three parallel repeat measures of social support and cognition from the Whitehall II cohort, providing 10-year follow-up of 6,863 participants (mean age 55.8 years, SD 6.0 at baseline). Alternative hypotheses were evaluated via four bivariate dual change score models: Full coupling model estimated mutual influences of social support and cognition on subsequent changes in each other; social causation model assumed a unidirectional influence from social support onto changes in cognition, while the opposite assumption was tested by health selection model; last, no coupling model suggested independent growth of these two sets of variables. Results A better cognition at the preceding stage was related to less positive changes in confiding support and less negative changes in practical support. In contrast, influences from social support on subsequent changes in cognition were not detected. Discussion This empirical study provides some evidence for the health selection mechanism, such that cognition modified changes in social support. The hypothesized neuroprotective effect of social support was not detectable. [ABSTRACT FROM AUTHOR]

Background It is currently unclear whether (and when) physical function exhibits a terminal decline phase, that is, a substantial acceleration of decline in the very last years before death. Methods 702 deceased adults aged 70 years and older from the Yale PEP Study provided 4 133 measurements of physical function (Short Physical Performance Battery, SPPB) up to 20 years before death. In addition, continuous gait and chair rise subtest scores (in seconds) were assessed. Generalized mixed regression models with random change points were used to estimate the onset and the steepness of terminal decline in physical function. Results Decline accelerated in the last years of life in all 3 measures of physical function. The onset of terminal decline occurred 1 year before death for the SPPB, and at 2.5 and 2.6 years before death for chair rise and gait speed test scores, respectively. Terminal declines in physical function were 6–8 times steeper than pre-terminal declines. Relative to those whose condition leading to death was frailty, participants who died from dementia and cancer had an up to 6 months earlier and 3 months later onset of terminal decline in SPPB, respectively. Conclusions Terminal decline in physical function among older adults is comparable to the more established terminal decline phenomenon in cognition. Our results provide additional evidence of late-life rapid decline in physical function due to impending death. [ABSTRACT FROM AUTHOR]

Many medical (and ecological) processes involve the change of shape, whereby one trajectory changes into another trajectory at a specific time point. There has been little investigation into the study design needed to investigate these models. We consider the class of fixed effect change-point models with an underlying shape comprised two joined linear segments, also known as broken-stick models. We extend this model to include two sub-groups with different trajectories at the change-point, a change and no change class, and also include a missingness model to account for individuals with incomplete follow-up. Through a simulation study, we consider the relationship of sample size to the estimates of the underlying shape, the existence of a change-point, and the classification-error of sub-group labels. We use a Bayesian framework to account for the missing labels, and the analysis of each simulation is performed using standard Markov chain Monte Carlo techniques. Our simulation study is inspired by cognitive decline as measured by the Mini-Mental State Examination, where our extended model is appropriate due to the commonly observed mixture of individuals within studies who do or do not exhibit accelerated decline. We find that even for studies of modest size ( n = 500, with 50 individuals observed past the change-point) in the fixed effect setting, a change-point can be detected and reliably estimated across a range of observation-errors. [ABSTRACT FROM AUTHOR]

We examined the individual and synergistic effects of type 2 diabetes and elevated depressive symptoms on memory and executive function trajectories over 10 and eight years of follow-up, respectively. Our sample comprised 10,524 community-dwellers aged ≥50 years in 2002–03 from the English Longitudinal Study of Ageing. With respect to memory (word recall), participants with either diabetes or elevated depressive symptoms recalled significantly fewer words compared with those free of these conditions (reference category), but more words compared with those with both conditions. There was a significant acceleration in the rate of memory decline in participants aged 50–64 years with both conditions (-0.27, 95% CI, -0.45 to -0.08, per study wave), which was not observed in those with either condition or aged ≥65 years. With respect to executive function (animal naming), participants aged ≥65 years with diabetes or those with elevated depressive symptoms named significantly fewer animals compared with the reference category, while those with both conditions named fewer animals compared with any other category. The rate of executive function decline was significantly greater in participants with both conditions (-0.54, 95% CI, -0.99 to -0.10; and –0.71, 95% CI, -1.16 to -0.27, per study wave, for those aged 50–64 and ≥65 years, respectively), but not in participants with either condition. Diabetes and elevated depressive symptoms are inversely associated with memory and executive function, but, individually, do not accelerate cognitive decline. The co-occurrence of diabetes and elevated depressive symptoms significantly accelerates cognitive decline over time, especially among those aged 50–64 years. [ABSTRACT FROM AUTHOR]

No single study has collected data over individuals' entire lifespans. To understand changes over the entire life course, it is necessary to combine data from various studies that cover the whole life course. Such combination may be methodologically challenging due to potential differences in study protocols, information available and instruments used to measure the outcome of interest. Motivated by our interest in modelling blood pressure changes over the life course, we propose the use of Bayesian adaptive splines within a hierarchical setting to combine data from several UK-based longitudinal studies where blood pressure measures were taken in different stages of life. Our method allowed us to obtain a realistic estimate of the mean life course trajectory, quantify the variability both within and between studies, and examine overall and study specific effects of relevant risk factors on life course blood pressure changes. [ABSTRACT FROM AUTHOR]

An important assumption in many linear mixed models is that the conditional distribution of the response variable is normal. This assumption is violated when the models are fitted to an outcome variable that counts the number of correctly answered questions in a questionnaire. Examples include investigations of cognitive decline where models are fitted to Mini Mental State Examination scores, the most widely used test to measure global cognition. Mini Mental State Examination scores take integer values in the 0-30 range, and its distribution has strong ceiling and floor effects. This article explores alternative distributions for the outcome variable in mixed models fitted to mini mental state examination scores from a longitudinal study of ageing. Model fit improved when a beta-binomial distribution was chosen as the distribution for the response variable. [ABSTRACT FROM AUTHOR]

The terminal decline hypothesis states that in the proximity of death, an individual's decline in cognitive abilities accelerates. We aimed at estimating the onset of faster rate of decline in global cognition using Mini Mental State Examination (MMSE) scores from participants of the Cambridge City over 75 Cohort Study (CC75C), a U.K. population-based longitudinal study of aging where almost all participants have died. The random change point model fitted to MMSE scores structured as a function of distance to death allowed us to identify a potentially different Onset of change in rate of decline before death for each individual in the sample. Differences in rate of change before and after the onset of change in rate of decline by sociodemographic variables were investigated. On average, the onset of a faster rate of change occurred about 7.7 years before death and varied across individuals. Our results show that most individuals experience a period of slight decline followed by a much sharper decline. Education, age at death, and cognitive impairment at study entry were identified as modifiers of rate of change before and after change in rate of decline. Gender differences were found in rate of decline in the final stages of life. Our study suggests that terminal decline is a heterogeneous process, with its Onset varying between individuals. [ABSTRACT FROM AUTHOR]

Objectives. We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline. Method. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point. Results. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time. Conclusion. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. [ABSTRACT FROM PUBLISHER]

Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged ≥85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1–35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5–6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4–5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11–1.89) than those with no history of delirium. In individuals with dementia and no history of delirium (n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia (n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1–3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2–6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein ϵ status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia. [ABSTRACT FROM AUTHOR]

Objectives: Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia.Methods: In this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.3 [0.8] years; wave 3) of the Lothian Birth Cohort 1936 (LBC1936) into non-MCR or MCR groups. We examined their baseline (age 69.5 [0.8] years; wave 1) risk factors for MCR at waves 3, 4, and 5 (6, 9, and 12 years later respectively).Results: MCR prevalence rate ranged from 5.3% to 5.7% across the three waves. The presence of MCR was associated with older baseline age (6 and 9 years later), lower occupational socioeconomic status (6 years later), and worse scores in a range of tests of executive function (6, 9 and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment, and almost everyone in the MCR group had either Prefrailty or Frailty.Conclusions: The prevalence of MCR in this Scottish cohort is lower than the pooled global average, possibly reflecting the general good health of the LBC cohort. However, it is higher than the prevalence in two neighbouring countries' cohorts, which may reflect the younger average ages of those cohorts. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether it is possible to detect decline in global scores of cognitive function in the proximity of death whilst simultaneously investigating potential risk profiles. Methods: Using the Mini Mental State Examination in a population study of the oldest old in which 99% of participants have died, a linear and quadratic time-to-death repeated measures random effects models were used to detect decline and potential factors which might indicate individual variation. Results: Decline and acceleration of this decline were detectable in the period before death. Some between person variation was detected in this pattern, which included differences in cognitive performance by age at death (-0.2 (SE=0.02)), sex (-1.2 (SE=0.2)), initial cognitive impairment (-7.5 (SE=0.2)) and mobility (-0.6 (SE=0.2)), in rate of decline by age at death (-0.04 (SE=0.005)), sex (-0.1 (SE=0.06)), initial cognitive impairment (-0.3 (SE=0.07)) and mobility (-0.1 (SE=0.05)) and differences in change in rate of decline by sex (-0.008 (SE=0.004)), initial cognitive impairment (-0.02 (SE=0.04)) and mobility (-0.01 (SE=0.003)). Conclusion: Using an extension of existing methods for exploring terminal decline, the phenomenon of decline in global cognition measures in the proximity of death was clearly detected as well as potential variables which could influence that pattern. Further work is required to explore whether similar methods can be used to detect the onset of the acceleration of this decline in each individual together with the potential to identify individual level factors that can allow clinicians to distinguish between the normal and preterminal phases of change in extreme old age. [ABSTRACT FROM AUTHOR]

The article discusses a new smooth polynomial change point model. The authors used data from a population-based longitudinal study of ageing, the Cambridge City over 75 Cohort Study. The study also aimed to identify how individuals many years before death experience a change in the rate of decline in their cognitive ability. They illustrated how the new model together with the Bacon-Watts model can be used as a mixed effects model.

Objectives Investigate the impact of the changes in eligibility within England and Wales (E&W) for prescription within the UK National Health Service for treatment of Alzheimer's disease (AD). Methods A population-based study in England and Wales with 13 004 individuals measured with MMSE at baseline was used to examine the distributions of individuals within eligibility criteria. Information obtained from informants enabled classification of the study defined dementia cases to ICD10 diagnosis of subtype (AD, dementia with vascular risk, both or other). Results Fifty six per cent of dementia patients (representing 323 000 individuals in E&W) fall into the new MMSE criteria band. A further 120 000, 20% of dementia patients, are estimated to have disease that is considered too mild for treatment. Further examination of type of dementia showed that those with mixed AD and vascular dementia had similar proportions of dementia cases within the treatable MMSE group as the subgroup with AD alone, though with mixed disease individuals more often score below the lower threshold. There is substantial instability in the eligibility groupings over a short time period. Conclusions The population impact of new NICE criteria of excluding high MMSE scores is to exclude one in five individuals with AD and a further one in ten of those with a mixed disease. Changing the guidance has almost balanced the loss of treatment for the high MMSE group (13%) with the introduction of treatment for those scoring 10/11 (11%). Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: the investigation of cognitive decline in the older population has been hampered by analytical considerations. Most studies of older people over prolonged periods suffer from loss to follow-up, yet this has seldom been investigated fully to date. Such considerations limit our understanding of how basic variables such as education can affect cognitive trajectories. Methods: we examined cognitive trajectories in a population-based cohort study in Cambridge, UK, of people aged 75 and over in whom multiple interviews were conducted over time. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Socio-demographic variables were measured, including educational level and social class. An age-based quadratic latent growth model was fitted to cognitive scores. The effect of socio-demographic variables was examined on all latent variables and the probability of death and dropout. Results: at baseline, age, education, social class and mobility were associated with cognitive performance. Education and social class were not related to decline or its rate of change. In contrast, poor mobility was associated with lower cognitive performance, increased cognitive decline and increased rate of change of cognitive decline. Gender, age, mobility and cognitive ability predicted death and dropout Conclusions: contrary to much of the current literature, education was not related to rate of cognitive decline or change in this rate as measured by MMSE. Higher levels of education do not appear to protect against cognitive decline, though if the MMSE is used in the diagnostic process, individuals with less education may be diagnosed as having dementia somewhat earlier. [ABSTRACT FROM AUTHOR]

Executive functions (EF), either conceptualized as skills involved in regulation of cognition and emotion in service of goal‐oriented behavior, or reductively as working memory, flexibility and inhibitory control, are commonly invoked constructs in developmental science. Two main traditions on EFs measurement prevail, one consisting of ratings obtained through questionnaires that inquire on behavior in common situations, the other based on performance in laboratory tasks. Whether both types of assessment actually refer to the same constructs is not consensual. Further, the role of school context in the degree of correspondence between both types of measures remains largely unexplored. Here, we show in a sample of over 220 children (age M = 5.6, SD = 0.4 years), by means of multilevel models, that whether EF tasks can predict BRIEF‐P ratings and vice‐versa, depends on the process considered and on the school SES. Inhibitory control, planning, and global executive functioning are associated with BRIEF‐P ratings in all schools. In contrast, we found no association among measures of flexibility independently of school SES. For working memory, we found that questionnaire rating predicts span only in high SES schools, but span predicts behaviors across schools. Our findings contribute to a growing body of literature that proposes constructs assessed by questionnaires and tasks only partially overlap and suggests that school SES may be a relevant factor to consider when questionnaires are answered by teachers. [ABSTRACT FROM AUTHOR]

Research suggests that frailty is associated with higher inflammation levels. We investigated the longitudinal association between chronic inflammation and frailty progression. Participants of the Lothian Birth Cohort 1936, aged 70 at baseline were tested four times over 12 years (wave 1: n = 1091, wave 4: n = 550). Frailty was assessed by; the Frailty Index at waves 1–4 and Fried phenotype at waves 1, 3 and 4. Two blood-based inflammatory biomarkers were measured at wave 1: Fibrinogen and C-reactive protein (CRP). Fully-adjusted, linear mixed effects models showed higher Fibrinogen was significantly associated with higher wave 1 Frailty Index score (β = 0.011, 95% CI[0.002,0.020], p <.05). Over 12 year follow-up, higher wave 1 CRP (β = 0.001, 95% CI[0.000,0.002], p <.05) and Fibrinogen (β = 0.004, 95% CI[0.001,0.007], p <.05) were significantly associated with increased Frailty Index change. For the Fried phenotype, wave 1 Pre-frail and Frail participants had higher CRP and Fibrinogen than Non-frail participants (p <.001). Logistic regression models calculated risk of worsening frailty over follow-up and we observed no significant association of CRP or Fibrinogen in minimally-adjusted nor fully-adjusted models. Findings showed a longitudinal association of higher wave 1 CRP and Fibrinogen on worsening frailty in the Frailty Index, but not Fried Phenotype. A possible explanation for this disparity may lie in the conceptual differences between frailty measures (a biopsychosocial vs physical approach). Future research, which further explores different domains of frailty, as well the associations between improving frailty and inflammation levels, may elucidate the pathway through which inflammation influences frailty progression. This may improve earlier identification of those at high frailty risk. • Research exploring inflammation and frailty change over time is lacking. • Inflammation is associated with frailty over time when measured by a Frailty Index. • Understanding this association may help improve frailty interventions. • Results differ according to the tool used to measure frailty. • Future research should continue to compare different ways of measuring frailty. [ABSTRACT FROM AUTHOR]

Background and purpose: The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin. Methods: This study used data from the PREVENT dementia programme. Three MedDiet scores were created (the Pyramid, Mediterranean Diet Adherence Screener [MEDAS] and MEDAS continuous) from a self‐reported food frequency questionnaire. Primary outcomes were hippocampal volume and cube‐transformed white matter hyperintensity volume. Secondary outcomes included cornu ammonis 1 and subiculum hippocampal subfield volumes, cortical thickness and measures of cognition. Sex‐stratified analyses were run to explore differential associations between diet and brain health by sex. An exploratory path analysis was conducted to study if any associations between diet and brain health were mediated by cardiovascular risk factors for dementia. Results: In all, 504 participants were included in this analysis, with a mean Pyramid score of 8.10 (SD 1.56). There were no significant associations between any MedDiet scoring method and any of the primary or secondary outcomes. There were no differences by sex in any analyses and no significant mediation between the Pyramid score and global cognition by cardiovascular risk factors. Conclusions: Overall, this study did not find evidence for an association between the MedDiet and either neuroimaging or cognition in a midlife population study. Future work should investigate associations between the MedDiet and Alzheimer's disease and related dementias biomarkers as well as functional neuroimaging in a midlife population. [ABSTRACT FROM AUTHOR]

Objectives: To assess the heterogeneity of transitions toward dependency in older adults and to explore the robustness of results to different operationalizations of dependency. Method: Using data from people aged 60 years and older from a national representative study in Uruguay (Encuesta Longitudinal de Protección Social, N = 5071), we fitted multinomial regressions adjusted by sociodemographic and health characteristics to model transitions into dependency and death. We used a harder operationalization with basic activities of daily living (Katz-dependency) and Comprehensive-dependency with basic, instrumental, and advanced activities. Results: Increasing age (RRR = 1.08, CI = [1.05; 1.12], p <.001) and having comorbidities (RRR = 2.16, CI = [1.31; 3.57], p =.003) increased the risk of transition from nondependent to dependent using Katz-dependency. Women with at least two chronic conditions have increased risk of Comprehensive-dependency (RRR = 1.79, CI = [1.15; 2.80], p =.010). Discussion: Inconsistencies in findings emerged when evaluating transitions into dependency with the different measures, which may have social care implications. [ABSTRACT FROM AUTHOR]

Background: The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. Methods: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer's disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. Results: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG β: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG β: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic β: -0.24, 95% CI: -0.45, -0.03; diastolic β: -0.16, 95% CI: -0.29, -0.03; BMI β: -0.09, 95% CI: -0.16, -0.01). Conclusions: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies. [ABSTRACT FROM AUTHOR]

Background Most previous studies of frailty trajectories in older adults focus on the average trajectory and ignore death. Longitudinal quantile analysis of frailty trajectories permits the definition of reference curves, and the application of mortal cohort inference provides more realistic estimates than models that ignore death. Methods Using data from individuals aged 65 or older (n  = 25 446) from the Survey of Health, Ageing, and Retirement in Europe (SHARE) from 2004 to 2020, we derived repeated values of the Frailty Index (FI) based on the accumulation of health deficits. We applied weighted Generalized Estimating Equations to estimate the quantiles of the FI trajectory, adjusting for sample attrition due to death, sex, education, and cohort. Results The FI quantiles increased with age and progressed faster for those with the highest level of frailty (⁠ β ^ a 0.9 = 0.0229, p  < .001; β ^ a 0.5 = 0.0067, p  < .001; H0: β a 0.5 = β a 0.9 ⁠ , p  < .001). Education was consistently associated with a slower progression of the FI in all quantiles (⁠ β ^ a e 0.1 = −0.0001, p  < .001; β ^ a e 0.5 =−0.0004, p  < .001; β ^ a e 0.9 = −0.0003, p  < .001) but sex differences varied across the quantiles. Women with the highest level of frailty showed a slower progression of the FI than men when considering death. Finally, no cohort effects were observed for the FI progression. Conclusions Quantile FI trajectories varied by age, sex, education, and cohort. These differences could inform the practice of interventions aimed at older adults with the highest level of frailty. [ABSTRACT FROM AUTHOR]

This study examined how socioeconomic status (SES) influences on decision‐making processing. The roles of anticipatory/outcome‐related cardiac activity and awareness of task contingencies were also assessed. One hundred twelve children (Mage = 5.83, SDage = 0.32; 52.7% female, 51.8% low‐SES; data collected October–December 2018 and April–December 2019) performed the Children's Gambling Task, while heart rate activity was recorded. Awareness of gain/loss contingencies was assessed after completing the task. Distinct decision‐making strategies emerged among low and middle/high‐SES children. Despite similar awareness levels between SES groups, future‐oriented decision‐making was linked solely to the middle/high‐SES group. Somatic markers did not manifest unequivocally. However, contrasting cardiac patterns were evident concerning feedback processing and the association between anticipatory activity and awareness (low: acceleration vs. middle/high: deceleration). Results are interpreted from an evolutionary‐developmental perspective. [ABSTRACT FROM AUTHOR]

Background Life course epidemiology examines associations between repeated measures of risk and health outcomes across different phases of life. Empirical research, however, is often based on discrete-time models that assume that sporadic measurement occasions fully capture underlying long-term continuous processes of risk. Methods We propose (i) the functional relevant life course model (fRLM), which treats repeated, discrete measures of risk as unobserved continuous processes, and (ii) a testing procedure to assign probabilities that the data correspond to conceptual models of life course epidemiology (critical period, sensitive period and accumulation models). The performance of the fRLM is evaluated with simulations, and the approach is illustrated with empirical applications relating body mass index (BMI) to mRNA-seq signatures of chronic kidney disease, inflammation and breast cancer. Results Simulations reveal that fRLM identifies the correct life course model with three to five repeated assessments of risk and 400 subjects. The empirical examples reveal that chronic kidney disease reflects a critical period process and inflammation and breast cancer likely reflect sensitive period mechanisms. Conclusions The proposed fRLM treats repeated measures of risk as continuous processes and, under realistic data scenarios, the method provides accurate probabilities that the data correspond to commonly studied models of life course epidemiology. fRLM is implemented with publicly-available software. [ABSTRACT FROM AUTHOR]

Summary: Multimorbidity—the coexistence of at least two chronic health conditions within the same individual—is an important global health challenge. In high‐income countries (HICs), multimorbidity is dominated by non‐communicable diseases (NCDs); whereas, the situation may be different in low‐ and middle‐income countries (LMICs), where chronic communicable diseases remain prominent. The aim of this systematic review was to identify determinants (including risk and protective factors) and potential mechanisms underlying multimorbidity from published longitudinal studies across diverse population‐based or community‐dwelling populations in LMICs. We systematically searched three electronic databases (Medline, Embase, and Global Health) using pre‐defined search terms and selection criteria, complemented by hand‐searching. All titles, abstracts, and full texts were independently screened by two reviewers from a pool of four researchers. Data extraction and reporting were according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Methodological quality and risk of bias assessment was performed using the Newcastle‐Ottawa Scale for cohort studies. Data were summarized using narrative synthesis. The search yielded 1782 records. Of the 52 full‐text articles included for review, 8 longitudinal population‐based studies were included for final data synthesis. Almost all studies were conducted in Asia, with only one from South America and none from Africa. All studies were published in the last decade, with half published in the year 2021. The definitions used for multimorbidity were heterogeneous, including 3–16 chronic conditions per study. The leading chronic conditions were heart disease, stroke, and diabetes, and there was a lack of consideration of mental health conditions (MHCs), infectious diseases, and undernutrition. Prospectively evaluated determinants included socio‐economic status, markers of social inequities, childhood adversity, lifestyle behaviors, obesity, dyslipidemia, and disability. This review revealed a paucity of evidence from LMICs and a geographical bias in the distribution of multimorbidity research. Longitudinal research into epidemiological aspects of multimorbidity is warranted to build up scientific evidence in regions beyond Asia. Such evidence can provide a detailed picture of disease development, with important implications for community, clinical, and interventions in LMICs. The heterogeneity in study designs, exposures, outcomes, and statistical methods observed in the present review calls for greater methodological standardisation while conducting epidemiological studies on multimorbidity. The limited evidence for MHCs, infectious diseases, and undernutrition as components of multimorbidity calls for a more comprehensive definition of multimorbidity globally. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) describes a borderland between healthy cognition and dementia. Progression to and reversion from MCI is relatively common but more research is required to understand the factors affecting this fluidity and improve clinical care interventions.Objective: We explore these transitions in MCI status and their predictive factors over a six-year period in a highly-phenotyped longitudinal study, the Lothian Birth Cohort 1936.Methods: MCI status was derived in the LBC1936 at ages 76 (n = 567) and 82 years (n = 341) using NIA-AA diagnostic guidelines. Progressions and reversions between healthy cognition and MCI over the follow-up period were assessed. Multinomial logistic regression assessed the effect of various predictors on the likelihood of progressing, reverting, or maintaining cognitive status.Results: Of the 292 participants who completed both time points, 41 (14%) participants had MCI at T1 and 56 (19%) at T2. Over the follow-up period, 74%remained cognitively healthy, 12%transitioned to MCI, 7%reverted to healthy cognition, and 7%maintained their baseline MCI status. Findings indicated that membership of these transition groups was affected by age, cardiovascular disease, and number of depressive symptoms.Conclusion: Findings that higher baseline depressive symptoms increase the likelihood of reverting from MCI to healthy cognition indicate that there may be an important role for the treatment of depression for those with MCI. However, further research is required to identify prevention strategies for those at high risk of MCI and inform effective interventions that increase the likelihood of reversion to, and maintenance of healthy cognition. [ABSTRACT FROM AUTHOR]

An active lifestyle has been associated with better cognitive performance in many studies. However, most studies have focused on leisure activities or paid work, with less consideration of the kind of prosocial activities, many people engage in, including volunteering, grandparenting, and family care. In the present study, based on four waves of the German Ageing Survey (N = 6,915, aged 40–85 at baseline), we used parallel growth curves to investigate the longitudinal association of level and change in volunteering, grandparenting, and family care with level and change in processing speed. Given the gendered nature of engagement in these activities over the life span, we tested for gender differences in the associations. Only volunteering was reliably associated with higher speed of processing at baseline, no consistent longitudinal associations were found. Our results show that although prosocial activities are of great societal importance, expectations of large rewards in terms of cognitive health may be exaggerated. Public Significance Statement: Men and women differ in their rate of volunteering, grandparenting, and family care, as well as their cognitive aging when operationalized as processing speed. Those who volunteer in midlife show better cognitive performance, but the direction of effects is not clear. [ABSTRACT FROM AUTHOR]

The Mediterranean diet (MedDiet) has been associated with better brain health and reduced incidence of dementia. Few studies have compared the effects of the MedDiet in early Alzheimer's disease or compared the effects of the diet within and outside of the Mediterranean region. The Mediterranean diet adherence screener (MEDAS) and MEDAS continuous scores were calculated at the baseline visit of the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (n = 1625). The scores were included in linear regression models to test for associations with hippocampal volume, log-transformed white matter lesion volume, cerebrospinal fluid pTau 18 , and Aβ 42. Higher MEDAS scores were associated with lower log-transformed white matter lesion volume (β: −0.07, standard error [SE]: 0.02, p < 0.001). This association was only seen in the Mediterranean region (β: −0.12, SE: 0.03, p < 0.001). In the non-Mediterranean region, higher MEDAS continuous scores were associated with lower cerebrospinal fluid Aβ 42 (β: −68.30, SE: 14.32, p < 0.001). More research is needed to understand the differences in the associations seen with the MedDiet and Alzheimer's disease biomarkers in different European regions. • Mediterranean diet (MedDiet) has been associated with lower incidence of dementia. • Higher MedDiet scores were associated with lower white matter lesion volume. • This finding was only significant in the Mediterranean region. • In the non-Mediterranean, higher MedDiet scores were associated with lower Aβ 42. • There are different effects of MedDiet on brain health by biogeographical region. [ABSTRACT FROM AUTHOR]

Background: Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer's Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition. Methods: We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task. Results: The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions. Conclusions: Our findings indicate that APOEe4 and MAPTA alleles modulate brain functional connectivity in the brain regions within the DMN in cognitively intact young adults. APOEe4 carriers also showed a link between connectivity and cognition. [ABSTRACT FROM AUTHOR]

Cerebral hemodynamic alterations have been observed in apolipoprotein ε4 (APOE4) carriers at midlife, however the physiological underpinnings of this observation are poorly understood. Our goal was to investigate cerebral blood flow (CBF) and its spatial coefficient of variation (CoV) in relation to APOE4 and a measure of erythrocyte anisocytosis (red blood cell distribution width – RDW) in a middle-aged cohort. Data from 563 participants in the PREVENT-Dementia study scanned with 3 T MRI cross-sectionally were analysed. Voxel-wise and region-of-interest analyses within nine vascular regions were run to detect areas of altered perfusion. Within the vascular regions, interaction terms between APOE4 and RDW in predicting CBF were examined. Areas of hyperperfusion in APOE4 carriers were detected mainly in frontotemporal regions. The APOE4 allele differentially moderated the association between RDW and CBF, an association which was more prominent in the distal vascular territories (p – [0.01, 0.05]). The CoV was not different between the considered groups. We provide novel evidence that in midlife, RDW and CBF are differentially associated in APOE4 carriers and non-carriers. This association is consistent with a differential hemodynamic response to hematological alterations in APOE4 carriers. [ABSTRACT FROM AUTHOR]

The potential for future prevention of Alzheimer's disease and related dementias (ADRD) through healthy lifestyle change is spurring a positive brain health movement. However, most ADRD research continues to focus on mid- and later life. We lack evidence regarding risk exposure and protective factors in young adulthood, i.e., 18–39 years. Brain capital is an emerging framework that represents the combination of education, knowledge, skills, and optimal brain health that people accumulate over their lives. Building on this framework, we present a new model that focuses on optimizing brain health in young adulthood; namely, young adult brain capital. Increasing focus on younger populations is critical for developing citizens who are emotionally intelligent, resilient and can anticipate and cope with rapid changes in the world. By understanding the values that are key drivers and motivators for young adults, we can empower the next generation to become active agents in optimizing their brain health and reducing their risk for future ADRD. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively healthy middle‐aged and older individuals. Methods: In the UK Biobank participants with linked health‐care records (n = 163,043, aged 40–71 at baseline), of whom about 17 000 had MRI data available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas and fractional anisotropy and median diffusivity of 25 white‐matter tracts. Results: Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (7/9 FDR‐adjusted significant associations, standardised betas (β) range: −0.039, −0.003). When using the anticholinergic scale exhibiting the strongest association with cognitive functions, anticholinergic burden due to only some classes of drugs exhibited negative associations with cognitive function, with β‐lactam antibiotics (β = −0.035, PFDR < 0.001) and opioids (β = −0.026, PFDR < 0.001) exhibiting the strongest effects. Anticholinergic burden was not associated with any measure of brain macrostructure or microstructure (PFDR > 0.08). Conclusions: Anticholinergic burden is weakly associated with poorer cognition, but there is little evidence for associations with brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability. [ABSTRACT FROM AUTHOR]

Background The existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear. Methods Drawing data from the Rush Memory and Aging Project (N  = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0–16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies. Results Higher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82–0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86–0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02–1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states. Conclusions Findings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration. [ABSTRACT FROM AUTHOR]

Objectives: Assessing for recovery in delirium is essential in guiding ongoing investigation and treatment. Yet, there is little scrutiny and no research or clinical consensus on how recovery should be measured. We reviewed studies which used tests of neuropsychological domains and functional ability to track recovery of delirium longitudinally in acute hospital settings. Methods/Design: We systematically searched databases (MEDLINE, PsycInfo, CINAHL, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials), from inception to October 14th, 2022. Inclusion criteria were: adult acute hospital patients (≥18 years) diagnosed with delirium by a validated tool; 1+ repeat assessment using an assessment tool measuring domains of delirium/functional recovery ≤7 days from baseline. Two reviewers independently screened articles, performed data extraction, and assessed risk of bias. A narrative data synthesis was completed. Results: From 6533 screened citations, we included 39 papers (reporting 32 studies), with 2370 participants with delirium. Studies reported 21 tools with an average of four repeat assessments including baseline (range 2–10 assessments within ≤7 days), measuring 15 specific domains. General cognition, functional ability, arousal, attention and psychotic features were most commonly assessed for longitudinal change. Risk of bias was moderate to high for most studies. Conclusions: There was no standard approach for tracking change in specific domains of delirium. The methodological heterogeneity of studies was too high to draw firm conclusions on the effectiveness of assessment tools to measure delirium recovery. This highlights the need for standardised methods for assessing recovery from delirium. Key points: Assessing for recovery is an essential part of delirium care, to guide clinicians' ongoing investigation and treatment and to provide accurate information to patients and carers.It is unclear what assessment tools are used to measure delirium recovery on a longitudinal basis, specifically which neuropsychological and functional domains should be assessed.A total of 21 assessment tools measuring 15 different symptom domains of delirium were used in the included studies, however, there was no standard approach for tracking change in these domains over time.The symptom domains most frequently assessed for longitudinal change in the included studies were general cognition, functional ability, arousal, attention and psychotic features. [ABSTRACT FROM AUTHOR]

Background: Motoric cognitive risk (MCR) is a syndrome characterised by measured slow gait speed and self‐reported cognitive complaints. MCR is a high‐risk state for adverse health outcomes in older adults, particularly cognitive impairment and dementia. Previous studies have identified risk factors for MCR, but the effect of socioeconomic status has, to date, been insufficiently examined. This study explored the association between MCR and socioeconomic status, as determined by occupational social class and years of education. Methods: Some 692 community‐based adults of the Lothian Birth Cohort 1936 (LBC1936), aged 70 years at baseline, were followed up after 6 years and classified into non‐MCR and MCR groups. We applied logistic regression analyses adjusting for demographic, lifestyle, and health covariates to investigate the association between MCR and years of education and occupational social class, categorised into manual versus non‐manual occupations. Results: MCR prevalence at age 76 years was 5.6% (95% CI 4.0–7.6). After multivariate adjustment, participants of lower socioeconomic status (manual occupation) had a greater than three‐fold increased likelihood of MCR (adjusted odds ratio 3.55, 95% CI 1.46–8.74; p = 0.005) compared with those of higher socioeconomic status (non‐manual occupation). Conclusions: Working in a manual job earlier in life triples the risk of MCR later in life, regardless of education. Unravelling this association will likely reveal important pathophysiological mechanisms underlying MCR and may unearth modifiable risk factors which could be targeted to reduce the incidence of MCR and, ultimately, dementia. Policy and healthcare practice addressing dementia risks such as MCR in their social context and early in the lifecourse could be effective strategies for reducing health inequalities in older age. [ABSTRACT FROM AUTHOR]

Background: vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. Objective: to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Risk of 2-year incident dementia in individuals with disease and cognitive impairment was also tested. Methods: participants were from the Cognitive Function and Ageing Study. At baseline, 13,004 individuals aged ≥65 years were enrolled into the study. Individuals were grouped by baseline disorder status (present, absent) for each condition. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). Dementia was assessed at 2 years. Results: in the cross-sectional analysis, hypertension, PVD and CHD were not associated with cognitive impairment. Stroke was associated with impaired global (MMSE) and CAMCOG sub-scale (including memory and non-memory) scores. Diabetes was associated with impairments in global cognitive function (MMSE) and abstract thinking. In the longitudinal analysis, cognitive impairments were associated with incident dementia in all groups. Conclusion: the neuropsychological profile in individuals with vascular disorders depends on the specific condition investigated. In all conditions cognitive impairment is a risk factor for dementia. A better understanding of which cognitive domains are affected in different disease groups could help improve operationalisation of the neuropsychological criteria for VCI-ND and could also aid with the development of dementia risk prediction models in persons with vascular disease. [ABSTRACT FROM AUTHOR]

The Flynn effect refers to increases over time in measured (particularly fluid) intelligence of approximately 3 IQ points per decade. We define the Flynn effect at the family level, using longitudinal data and two new family-level cohort definitions. Multilevel growth curve analyses of the National Longitudinal Survey of Youth 1979 data showed that children in families with later-born mothers had higher average PIAT math scores, and lower average reading comprehension scores and growth, in young and middle childhood. Children in families where the first child was born later had higher average PIAT math, reading recognition, and reading comprehension scores, as well as larger developmental growth. The latter family-level Flynn effects were of higher magnitudes than the usual individual-level Flynn effect found in previous studies. Our results, showing family level-intercept and slope Flynn effects for both maternal birthyear and first child birthyear, have implications for research aiming to explain the Flynn effect. [ABSTRACT FROM AUTHOR]

Research suggests that personality traits are associated with mild cognitive impairment (MCI), dementia, and mortality risk, but the timing of when traits are most important in the progression to dementia and the extent to which they are associated with years of cognitive health span are unclear. This project applied secondary data analysis to the Rush Memory and Aging Project (N = 1954; baseline Mage = 80 years; 74% female) over up to 23 annual assessments. Multistate survival modeling examined the extent to which conscientiousness, neuroticism, and extraversion, assessed using the NEO Five Factor Inventory, were associated with transitions between cognitive status categories and death. Additionally, multinomial regression models estimated cognitive health span and total survival based on standard deviation units of personality traits. Adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4, personality traits were most important in the transition from no cognitive impairment (NCI) to MCI. For instance, higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI, hazard ratio (HR) = 0.78, 95% CI [0.72, 0.85] and higher neuroticism was associated with an increased risk of transitioning from NCI to MCI, HR = 1.12, 95% CI [1.04, 1.21]. Additional significant and nonsignificant results are discussed in the context of the existing literature. While personality traits were not associated with total longevity, individuals higher in conscientiousness and extraversion, and lower in neuroticism, had more years of cognitive health span, particularly female participants. These findings provide novel understanding of the simultaneous associations between personality traits and transitions between cognitive status categories and death, as well as cognitive health span and total longevity. [ABSTRACT FROM AUTHOR]

Background: It is now acknowledged that Alzheimer's disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. Objective: We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals who are cognitively healthy, but at risk for late life AD. Participants (40–59 years) completed cognitive and clinical assessments at baseline (N = 206) and two years follow-up (N = 174). Methods: Mid-life activities were measured with the Lifetime of Experiences Questionnaire. We assessed the impact of lifestyle activities, known risk factors for sporadic late-onset AD (Apolipoprotein E ɛ4 allele status, family history of dementia, and the Cardiovascular Risk Factors Aging and Dementia score), and their interactions on cognition. Results: More frequent engagement in physically, socially, and intellectually stimulating activities was associated with better cognition (verbal, spatial, and relational memory), at baseline and follow-up. Critically, more frequent engagement in these activities was associated with stronger cognition (verbal and visuospatial functions, and conjunctive short-term memory binding) in individuals with family history of dementia. Impaired visuospatial function is one of the earliest cognitive deficits in AD and has previously associated with increased AD risk in this cohort. Additionally, conjunctive memory functions have been found impaired in the pre-symptomatic stages of AD. Conclusion: These findings suggest that modifiable lifestyle activities offset cognitive decrements due to AD risk in mid-life and support the targeting of modifiable lifestyle activities for the prevention of AD. [ABSTRACT FROM AUTHOR]

Background: It is now acknowledged that Alzheimer's disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. Objective: We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals who are cognitively healthy, but at risk for late life AD. Participants (40–59 years) completed cognitive and clinical assessments at baseline (N = 206) and two years follow-up (N = 174). Methods: Mid-life activities were measured with the Lifetime of Experiences Questionnaire. We assessed the impact of lifestyle activities, known risk factors for sporadic late-onset AD (Apolipoprotein E ɛ4 allele status, family history of dementia, and the Cardiovascular Risk Factors Aging and Dementia score), and their interactions on cognition. Results: More frequent engagement in physically, socially, and intellectually stimulating activities was associated with better cognition (verbal, spatial, and relational memory), at baseline and follow-up. Critically, more frequent engagement in these activities was associated with stronger cognition (verbal and visuospatial functions, and conjunctive short-term memory binding) in individuals with family history of dementia. Impaired visuospatial function is one of the earliest cognitive deficits in AD and has previously associated with increased AD risk in this cohort. Additionally, conjunctive memory functions have been found impaired in the pre-symptomatic stages of AD. Conclusion: These findings suggest that modifiable lifestyle activities offset cognitive decrements due to AD risk in mid-life and support the targeting of modifiable lifestyle activities for the prevention of AD. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a robust predictor of cognitive impairment. Impairment in allocentric processing may help identify those at increased risk for Alzheimer's disease dementia. The objective of this study was to investigate the performance of participants with and without diabetes on a task of allocentric spatial processing. This was a cross‐sectional secondary data analysis study using baseline data from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS). Participants were aged 50 years and above and were free of dementia at baseline. Participants with no missing data on the variables of interest were included in this study. Our exposure variable was diabetes reported in the medical history. Our primary outcome was the Four Mountains Test (4MT), a novel task of allocentric processing. Covariates included demographics (age, sex, family history of dementia and years of education), APOEε4 carrier status, cognitive status (Clinical Dementia Rating scale), cerebrospinal fluid phosphorylated tau and amyloid‐beta 1–42. Of 1324 participants (mean age = 65.95 (±7.45)), 90 had diabetes. Participants with diabetes scored 8.32 (±2.32) on the 4MT compared with 9.24 (±2.60) for participants without diabetes. In a univariate model, diabetes was significantly associated with worse 4MT total scores (β = −.92, p =.001), remaining significant in a fully adjusted model (β = −.64, p =.01). Cerebrospinal fluid phosphorylated tau was significantly higher in participants with diabetes compared with those without. Novel cognitive tests, such as the 4MT, may be appropriate to identify early cognitive changes in this high‐risk group. Identifying those at greatest risk for future neurodegeneration is key to prevention efforts. [ABSTRACT FROM AUTHOR]

Introduction: Recent research suggests that the experience of frailty progression may be heterogeneous, with latent subpopulations of older adults following distinct trajectories of frailty. We aimed to investigate this notion and determine whether certain factors are associated with the membership of these subpopulations. Methods: Data from 5 data waves collected over 12 years in participants of the Lothian Birth Cohort 1936, aged 70 at baseline, were used to derive the frailty index (FI) (NW1 = 1,091, NW5 = 431). These were used in latent class mixed modelling to estimate subpopulations of frailty trajectories. Results: A quadratic latent class mixed model found 3 distinct groupings, which followed a low (61%, n = 632), medium (36%, n = 368), or high (3%, n = 28) FI trajectory. Each grouping had different intercepts and slopes, with the high grouping following the steepest trajectory indicating a rapid increase in frailty. Findings showed that in general, those in the low grouping were younger, had higher education, higher age 11 cognitive ability, and were from a higher social class than those in the medium and high groupings. Discussion/Conclusion: Our findings demonstrate heterogeneity in frailty trajectories over 12 years in individuals aged 70 years at baseline. Membership of higher frailty trajectory groupings was associated with lower social class, less education, and lower childhood cognitive ability, indicating the potential for future interventions to target individuals who are at the greatest risk of belonging to the high frailty trajectory. Future research is required to continue this line of inquiry by exploring other risk and protective factors, and importantly, to assess whether it is possible to realign an individual's membership to a less detrimental grouping of frailty trajectory. [ABSTRACT FROM AUTHOR]

Neighborhood features have been postulated to be key predictors of frailty. However, evidence is mainly limited to cross-sectional studies without indication of long-term impact. We explored how neighborhood social deprivation (NSD) across the life course is associated with frailty and frailty progression among older Scottish adults. Participants (n  = 323) were persons selected from the Lothian Birth Cohort 1936 with historical measures of NSD in childhood (1936–1955), young adulthood (1956–1975), and mid- to late adulthood (1976–2014). Frailty was measured 5 times between the ages of 70 and 82 years using the Frailty Index. Confounder-adjusted life-course models were assessed using a structured modeling approach; associations were estimated for frailty at baseline using linear regression and for frailty progression using linear mixed-effects models. Accumulation was the most appropriate life-course model for males; greater accumulated NSD was associated with higher frailty at baseline (b  = 0.017, 95% confidence interval: 0.005, 0.029). Among females, the mid- to late adulthood sensitive period was the best-fitting life-course model, and higher NSD in this period was associated with widening frailty trajectories (b = 0.005, 95% confidence interval: 0.0004, 0.009). To our knowledge, this is the first investigation of the life-course impact of NSD on frailty in a cohort of older adults. Policies designed to address deprivation and inequalities across the full life course may support healthy aging. [ABSTRACT FROM AUTHOR]

A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a surrogate endpoint in clinical trials. The current systematic review evaluates the association between cerebrospinal fluid protein markers of synapse loss and neuronal injury and cognition. We performed a systematic search which revealed 67 studies reporting an association between cerebrospinal fluid markers of interest and neuropsychological performance. Despite the substantial heterogeneity between studies, we found some evidence for an association between neurofilament‐light and worse cognition in Alzheimer's diseases, frontotemporal dementia and typical cognitive ageing. Moreover, there was an association between cerebrospinal fluid neurogranin and cognition in those with an Alzheimer's‐like cerebrospinal fluid biomarker profile. Some evidence was found for cerebrospinal fluid neuronal pentraxin‐2 as a correlate of cognition across dementia syndromes. Due to the substantial heterogeneity of the field, no firm conclusions can be drawn from this review. Future research should focus on improving standardization and reporting as well as establishing the importance of novel markers such as neuronal pentraxin‐2 and whether such markers can predict longitudinal cognitive decline. [ABSTRACT FROM AUTHOR]

The article discusses the mapping of machine learning (ML) approaches for description, prediction, and causal inference in the social and health sciences. It provides a comprehensive, systematic meta-mapping of research questions in the social and health sciences to appropriate ML approaches by incorporating the necessary requirements to statistical analysis in these disciplines.