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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]

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]

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: 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]

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]

Background: Given increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories.Method: Applying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9-81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs.Results: Controlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association.Conclusions: These results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA. [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]

Background: Cognitive dispersion, variation in performance across cognitive domains, is posited as a non-invasive and cost-effective marker of early neurodegeneration. Little work has explored associations between cognitive dispersion and Alzheimer's disease (AD) biomarkers in healthy older adults. Even less is known about the influence or interaction of biomarkers reflecting brain pathophysiology or other risk factors on cognitive dispersion scores.Objective: The main aim of this study was to examine whether higher cognitive dispersion was associated with cerebrospinal fluid (CSF) levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), and amyloid positivity in a cohort of older adults at various severities of AD. A secondary aim was to explore which AD risk factors were associated with cognitive dispersion scores.Methods: Linear and logistic regression analyses explored the associations between dispersion and CSF levels of Aβ42, t-tau, and p-tau and amyloid positivity (Aβ42 < 1000 pg/ml). Relationships between sociodemographics, APOEɛ4 status, family history of dementia, and levels of depression and dispersion were also assessed.Results: Dispersion did not emerge as associated with any of the analytes nor amyloid positivity. Older (β= -0.007, SE = 0.002, p = 0.001) and less educated (β= -0.009, SE = 0.003, p = 0.009) individuals showed greater dispersion.Conclusion: Dispersion was not associated with AD pathology, but was associated with age and years of education, highlighting individual differences in cognitive aging. The use of this metric as a screening tool for existing AD pathology is not supported by our analyses. Follow-up work will determine if dispersion scores can predict changes in biomarker levels and/or positivity status longitudinally. [ABSTRACT FROM AUTHOR]

Objectives: We explore the association between different patterns of change in depressive symptoms and memory trajectories in US and European Mediterranean (Spain, France, Italy, and Israel) and non-Mediterranean (Sweden, Denmark, Netherlands, Germany, Belgium, Switzerland, and Austria) older adults. Methods: Samples consisted of 3,466 participants from the Health Retirement Study (HRS) and 3,940 participants from the Survey of Health, Aging and Retirement (SHARE). Individuals were grouped as follows: non-case depression (NO DEP), persistent depression (DEP), depression onset (ONSET), depression recovery (RECOV), and fluctuating (FLUCT). Memory was measured using immediate and delayed recall tests. Linear mixed models were used. Results: DEP and RECOV had significantly lower baseline memory scores compared to NO DEP, at intercept level. At slope level, ONSET had a significantly faster decline in both tasks compared to NO DEP. Discussion: Cross-cohort robust and consistent new empirical evidence on the association between depression onset and faster decline in memory scores is provided. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity (the co-occurrence of multiple chronic conditions) is increasingly common, especially among people with dementia. Few neuroimaging studies have explored amyloid biomarkers in people with multimorbidity.Objective: We aimed to conduct the first study of the association between multimorbidity and cerebrospinal fluid amyloid-β42 (CSF Aβ).Method: The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study V500.0 dataset includes volunteers aged ≥50 years from 12 sites. Participants undergo detailed phenotyping, including CSF measures and a self-reported medical history. Using logistic and linear regression analyses, we explored the association between multimorbidity and continuous chronic condition count with CSF Aβ positivity (Aβ42 <1000pg/ml) and continuous CSF Aβ concentration. All models were adjusted for age, sex, APOE status, education, and family history of dementia.Results: Among 447 eligible participants without dementia, the mean (SD) age was 66.6 (6.6) years, 234 (52.3%) were women, and 157 (35.1%) were amyloid positive. With chronic conditions regarded as pseudo-continuous, each additional condition carried a decreased likelihood of amyloid positivity (OR = 0.82, 95% CI: 0.68-0.97; p = 0.026). With CSF Aβ as a continuous variable, each additional condition was associated with an increase of 54.2 pg/ml (95% CI: 9.9-98.5, p = 0.017). Having ≥2 conditions was inversely associated with amyloid positivity (OR 0.59, 95% CI: 0.37-0.95, p = 0.030) compared to one or none.Conclusion: Our findings suggest that the established association between multimorbidity and dementia may be due to a pathway other than amyloid. However, this cross-sectional study does not allow us to make causal inferences. Longitudinal work is required to confirm the inverse association found. [ABSTRACT FROM AUTHOR]

A model is presented that describes bivariate longitudinal count data by conditioning on a progressive illness-death process where the two living states are latent. The illness-death process is modelled in continuous time, and the count data are described by a bivariate extension of the binomial distribution. The bivariate distributions for the count data approach include the correlation between two responses even after conditioning on the state. An illustrative data analysis is discussed, where the bivariate data consist of scores on two cognitive tests, and the latent states represent two stages of underlying cognitive function. By including a death state, possible association between cognitive function and the risk of death is accounted for. [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]

Background: International comparisons of trajectories of depressive symptoms in older adults are scarce and longitudinal associations with co-morbid conditions not fully understood. Objective: To compare trajectories of depressive symptoms from participants living in 10 European Countries and identify ages at which the associations of co-morbid conditions with these trajectories become more relevant. Methods: Latent growth curve models were fitted to depressive symptoms scores from participants of the Survey of Health and Retirement in Europe (SHARE) initiative (combined n = 21,253) and co-morbid conditions modelled as time varying covariates. To identify the ages at which the association between co-morbid conditions and depressive symptoms was significant the Johnson-Neyman (JN) technique was used. Results: The shape of depressive symptoms trajectories varied between countries, and was highly dependent on modelling decisions. The association between the average number of co-morbidities reported over time and depressive symptoms was consistent and positive across countries and ages. Conclusion: International differences in ageing-related trajectories of depressive symptoms emerged. The longitudinal association of co-morbid conditions with trajectories of depressive symptoms was found, but the results overall suggest that modelling decisions could greatly influence the outcomes, and should thus be interpreted with caution. [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]

Objective: Cognitive performance shows a marked deterioration in close proximity to death, as postulated by the terminal decline hypothesis. The effect of education on the rate of terminal decline in the oldest people (i.e. persons 85+ years) has been controversial and not entirely understood. In the current study, we investigated the rate of decline prior to death with a special focus on the role of education and socioeconomic position, in two European longitudinal studies of ageing: the Origins of Variance in the Old-Old: Octogenarian Twins (OCTO-Twin) and the Newcastle 85+ study.Methods: A process-based approach was used in which individuals' cognitive scores were aligned according to distance to death. In a coordinated analysis, multilevel models were employed to examine associations between different markers of cognitive reserve (education and socioeconomic position) and terminal decline using the mini-mental state examination (MMSE), controlling for age at baseline, sex, dementia incidence and time to death from the study entry to the time of death within each cohort.Results: The current findings suggest that education was positively associated with higher MMSE scores prior to death in the OCTO-Twin, but not in the Newcastle 85+ study, independent of socioeconomic position and other factors such as baseline age, sex and time to death from the study entry. However, education was not associated with the rate of terminal decline in both of these studies.Conclusions: Our results offer only partial support to the cognitive reserve hypothesis and cognitive performance prior to death. [ABSTRACT FROM AUTHOR]

Background: The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group.Methods: Baseline and 5-year follow-up data from the Newcastle 85+ Study were used (N = 845, mean age = 85.5, 38% male). A Cognitive Reserve Index (CRI) was created, including: education, social class, marital status, engagement in mental activities, social participation, and physical activity. Global (Mini-Mental State Examination) and domain specific (Cognitive Drug Research Battery subtests assessing memory, attention, and speed) cognitive functions were assessed. Dementia diagnosis was determined by health records. Logistic regression analysis examined the association between CRI scores and incident dementia. Mixed effects models investigated baseline and longitudinal associations between the CRI scores and cognitive function. Analyses controlled for sex, age, depression, and cardiovascular disease history.Results: Higher reserve associated with better cognitive performance on all baseline measures, but not 5-year rate of change. The CRI associated with prevalent, but not incident dementia.Conclusions: In the oldest-old, higher reserve associated with better baseline global and domain-specific cognitive function and reduced risk of prevalent dementia; but not cognitive decline or incident dementia. Increasing reserve could promote cognitive function in the oldest-old. The results suggest there would be little impact on trajectories, but replication is needed. Development of preventative strategies would benefit from identifying the role of each factor in building reserve and why rate of change is not affected. [ABSTRACT FROM AUTHOR]

Background: We aimed to identify the hierarchy of rates of decline in 16 physical functioning measures in U.S. and English samples, using a systematic and integrative coordinated data analysis approach.Methods: The U.S. sample consisted of 13,612 Health and Retirement Study participants, and the English sample consisted of 5,301 English Longitudinal Study of Ageing participants. Functional loss was ascertained using self-reported difficulties performing 6 activities of daily living and 10 mobility tasks. The variables were standardized, rates of decline were computed, and mean rates of decline were ranked. Mann-Whitney U tests were performed to compare rates of decline between studies.Results: In both studies, the rates of decline followed a similar pattern; difficulty with eating was the activity that showed the slowest decline and climbing several flights of stairs and stooping, kneeling, or crouching the fastest declines. There were statistical differences in the speed of decline in all 16 measures between countries. American women had steeper declines in 10 of the measures than English women. Similar differences were found between American and English men.Conclusions: Reporting difficulties climbing several flights of stairs without resting, and stooping, kneeling, or crouching are the first indicators of functional loss reported in both populations. [ABSTRACT FROM AUTHOR]

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated.Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia.Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors.Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed.Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death.Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE points per year (95% CI, -0.57 to -0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional -0.16 MMSE points per year (95% CI, -0.29 to -0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level-matched controls.Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia. [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]

Given the aging population in the UK, statistical modelling of cognitive function in the older population is of interest. Joint models are formulated for survival and cognitive function in the older population. Because tests of cognitive function often result in discrete outcomes, binomial and beta--binomial mixed effects regression models are applied to analyse longitudinal measurements. Dropout due to death is accounted for by parametric survival models, where the choice of a Gompertz baseline hazard and the specification of the random-effects structure are of specific interest. The measurement model and the survival model are combined in a shared parameter joint model. Estimation is by marginal likelihood. The methods are used to analyse data from the Cambridge City over-75s cohort study and the English Longitudinal Study of Ageing. [ABSTRACT FROM AUTHOR]

A mixed-effects regression model with a bent-cable change-point predictor is formulated to describe potential decline of cognitive function over time in the older population. For the individual trajectories, cognitive function is considered to be a latent variable measured through an item response theory model given longitudinal test data. Individual-specific parameters are defined for both cognitive function and the rate of change over time, using the change-point predictor for non-linear trends. Bayesian inference is used, where the Deviance Information Criterion and the L-criterion are investigated for model comparison. Special attention is given to the identifiability of the item response parameters. Item response theory makes it possible to use dichotomous and polytomous test items, and to take into account missing data and survey-design change during follow-up. This will be illustrated in an application where data stem from the Cambridge City over-75s Cohort Study. [ABSTRACT FROM AUTHOR]

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability.Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures.Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10(-3) to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits.Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up. [ABSTRACT FROM AUTHOR]

Background: criteria for mild cognitive impairment (MCI) capture an intermediate cognitive state between normal ageing and dementia, associated with increased dementia risk. Whether criteria for MCI are applicable in the context of stroke and can be used to predict dementia in stroke cases is not known.Objectives: to determine the prevalence of MCI in individuals with stroke and identify predictors of 2-year incident dementia in stroke cases.Methods: individuals were from the Medical Research Council Cognitive Function and Ageing Study. MCI prevalence in individuals with stroke was determined. Logistic regression, with receiver operating characteristic curve analysis, was used to identify variables associated with risk of dementia in stroke cases including MCI criteria, demographic, health and lifestyle variables.Findings: of 2,640 individuals seen at the first assessment, 199 reported stroke with no dementia. In individuals with stroke, criteria for MCI are not appropriate, with less than 1% of stroke cases being classified as having MCI. However, in individuals with stroke two components of the MCI definition, subjective memory complaint and cognitive function (memory and praxis scores) predicted 2-year incident dementia (area under the curve = 0.85, 95% CI: 0.77–0.94, n = 113).Conclusion: criteria for MCI do not appear to capture risk of dementia in the context of stroke in the population. In stroke cases, subjective and objective cognitive performance predicts dementia and these variables could possibly be incorporated into dementia risk models for stroke cases. Identifying individuals with stroke at greatest risk of dementia has important implications for treatment and intervention. [ABSTRACT FROM PUBLISHER]

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]

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.

Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood. • Five approaches to creating composite scores of cumulative stress were examined. • The strength of these approaches to predict different health outcomes was tested. • Area under the curve with respect to ground outperformed alternative approaches. • The effects of cumulative stress varied across age groups and health outcomes. [ABSTRACT FROM AUTHOR]

Age-related decline in processing speed has long been considered a key driver of cognitive aging. While the majority of empirical evidence for the processing speed hypothesis has been obtained from analyses of between-person age differences, longitudinal studies provide a direct test of within-person change. Using recent developments in longitudinal mediation analysis, we examine the speed-mediation hypothesis at both the within-and between-person levels in two longitudinal studies. Longitudinal Aging Study Amsterdam (LASA) and Origins of Variance in the Oldest-Old (OCTO-Twin). We found significant within-person indirect effects of change in age, such that increasing age was related to lower speed, which in turn relates to lower performance across repeated measures on other cognitive outcomes. Although between-person indirect effects were also significant in LASA, they were not in OCTO-Twin which is not unexpected given the age homogeneous nature of the OCTO-Twin data. A more in-depth examination through measures of effect size suggests that, for the LASA study, the within-person indirect effects were small and between-person indirect effects were consistently larger. These differing magnitudes of direct and indirect effects across levels demonstrate the importance of separating between- and within-person effects in evaluating theoretical models of age-related change. [ABSTRACT FROM AUTHOR]

Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40–3.07; LASA: HR = 1.33, 95%CI = 1.01–1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74–6.28; LASA: HR = 1.70, 95%CI = 1.30–2.21). Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore. • There has been an increasing interest in slow gait speed as risk factor for cognitive decline. • Very few studies have investigated the competing risk of death. • This study shows that slow gait speed predicts transitions into cognitive impairment and death. • Once in the stage of more advanced cognitive impairment, slow gait does not predict death anymore. [ABSTRACT FROM AUTHOR]