Comparisons of disease cluster patterns, prevalence and health factors in the USA, Canada, England and Ireland.

BACKGROUND: Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland. METHODS: Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis. RESULTS: The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries. CONCLUSIONS: This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries.

Feasibility and Psychometric Integrity of Mobile Phone-Based Intensive Measurement of Cognition in Older Adults.

Background:There is a pressing need for assessment approaches that can be deployed remotely to measure cognitive outcomes in clinical trials and longitudinal aging cohorts. We evaluated the utility of a mobile phone-based intensive measurement study for this purpose. Method:A small cohort of healthy older adults (N = 17, mean age = 73) completed five assessment "bursts" over 12 months, with each measurement burst involving two assessments daily for five consecutive days. Each assessment included brief tests of visual short-term memory and information processing speed, as well as surveys measuring state factors that can affect cognition. Results:At study endpoint we had 94% retention, 97% compliance, and high participant satisfaction. Mobile cognitive test scores demonstrated good reliability, moderate correlations with in-person baseline neuropsychological testing, and significant associations with participant age and education level. Conclusions: Mobile phone-based intensive measurement designs represent a promising assessment approach for measuring cognition longitudinally in older adults.

The Dementias Platform UK (DPUK) Data Portal.

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

Optimizing Detection of True Within-Person Effects for Intensive Measurement Designs: A Comparison of Multilevel SEM and Unit-Weighted Scale Scores.

Intensive repeated measurement designs are frequently used to investigate within-person variation over relatively brief intervals of time. The majority of research utilizing these designs relies on unit-weighted scale scores, which assume that the constructs are measured without error. An alternative approach makes use of multilevel structural equation models (MSEM), which permit the specification of latent variables at both within-person and between-person levels. These models disaggregate measurement error from systematic variance, which should result in less biased within-person estimates and larger effect sizes. Differences in power, precision, and bias between multilevel unit-weighted models and MSEMs were compared through a series of Monte Carlo simulations. Results based on simulated data revealed that precision was consistently poorer in the MSEMs than the unit-weighted models, particularly when reliability was low. However, the degree of bias was considerably greater in the unit-weighted model than the latent variable model. Although the unit-weighted model consistently underestimated the effect of a covariate, it generally had similar power relative to the MSEM model due to the greater precision. Considerations for scale development and the impact of within-person reliability are highlighted.

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

An examination of the heterogeneity in the pattern and association between rates of change in grip strength and global cognition in late life. A multivariate growth mixture modelling approach.

Background: previous research has demonstrated how older adults exhibit different patterns of change in cognitive and physical functioning, suggesting differences in the underlying causal processes. Objective: to (i) identify subgroups of older adults that best account for different patterns of longitudinal change in performance on global cognition and grip strength, (ii) examine the interrelationship between global cognition and grip strength trajectories within these subgroups and (iii) identify demographic and health-related markers of class membership. Methods: multivariate growth mixture models (GMM) were used to identify groups of individuals with similar developmental trajectories of muscle strength measured by grip strength, and global cognition measured by Mini Mental State Examination (MMSE). Results: GMM analyses indicated high, moderate and low functioning groups. Individuals in the high and moderate classes demonstrated better cognitive and physical functioning at the start of the study and less decline than those in the low functioning group. Notably, cognitive performance was related to physical functioning at study entry only among individuals in the low functioning group. Conclusion: the study demonstrates the applicability of the multivariate GMM to achieve a better understanding of the heterogeneity of various aging related processes.

Transitions across cognitive states and death among older adults in relation to education: A multistate survival model using data from six longitudinal studies.

INTRODUCTION: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death. METHODS: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states. Life expectancies were estimated. RESULTS: Across most studies, a higher level of education was associated with a lower risk of transitioning from normal MMSE to mild MMSE impairment but was not associated with other transitions. Those with higher levels of education and socioeconomic status had longer nonimpaired life expectancies. DISCUSSION: This study highlights the importance of education in later life and that early life experiences can delay later compromised cognitive health. This study also demonstrates the feasibility and benefit in conducting coordinated analysis across multiple studies to validate findings.

An International Evaluation of Cognitive Reserve and Memory Changes in Early Old Age in 10 European Countries.

BACKGROUND: Cognitive reserve was postulated to explain individual differences in susceptibility to ageing, offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age. METHODS: Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe, were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models. Education was used as a marker of cognitive reserve and evaluated in association with memory performance and rate of change, while accounting for income, general health, smoking, body mass index, gender, and baseline age. RESULTS: In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 [SE = 0.003] and 0.006 [SE = 0.002]), and Switzerland for immediate recall (0.006 [SE = 0.003]). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 [SE = 0.003]). CONCLUSIONS: We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment.

V. DESIGN-BASED APPROACHES FOR IMPROVING MEASUREMENT IN DEVELOPMENTAL SCIENCE.

The study of change and variation within individuals, and the relative comparison of changes across individuals, relies on the assumption that observed measurements reflect true change in the construct being measured. Measurement properties that change over time, contexts, or people pose a fundamental threat to validity and lead to ambiguous conclusions about change and variation. We highlight such measurement issues from a within-person perspective and discuss the merits of measurement-intensive research designs for improving precision of both within-person and between-person analysis. In general, intensive measurement designs, potentially embedded within long-term longitudinal studies, provide developmental researchers an opportunity to more optimally capture within-person change and variation as well as provide a basis to understand changes in dynamic processes and determinants of these changes over time.

Comparison of Standardization Methods for the Harmonization of Phenotype Data: An Application to Cognitive Measures.

Standardization procedures are commonly used to combine phenotype data that were measured using different instruments, but there is little information on how the choice of standardization method influences pooled estimates and heterogeneity. Heterogeneity is of key importance in meta-analyses of observational studies because it affects the statistical models used and the decision of whether or not it is appropriate to calculate a pooled estimate of effect. Using 2-stage individual participant data analyses, we compared 2 common methods of standardization, T-scores and category-centered scores, to create combinable memory scores using cross-sectional data from 3 Canadian population-based studies (the Canadian Study on Health and Aging (1991-1992), the Canadian Community Health Survey on Healthy Aging (2008-2009), and the Quebec Longitudinal Study on Nutrition and Aging (2004-2005)). A simulation was then conducted to assess the influence of varying the following items across population-based studies: 1) effect size, 2) distribution of confounders, and 3) the relationship between confounders and the outcome. We found that pooled estimates based on the unadjusted category-centered scores tended to be larger than those based on the T-scores, although the differences were negligible when adjusted scores were used, and that most individual participant data meta-analyses identified significant heterogeneity. The results of the simulation suggested that in terms of heterogeneity, the method of standardization played a smaller role than did different effect sizes across populations and differential confounding of the outcome measure across studies. Although there was general consistency between the 2 types of standardization methods, the simulations identified a number of sources of heterogeneity, some of which are not the usual sources considered by researchers.

The role of cognitive reserve on terminal decline: a cross-cohort analysis from two European studies: OCTO-Twin, Sweden, and Newcastle 85+, UK.

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.

Correlated and Coupled Trajectories of Cancer-Related Worries and Depressive Symptoms among Long-Term Cancer Survivors.

The quality of life over time of long-term survivors has become an important part of both cancer and aging research. This paper examines individual differences in trajectories of cancer-related worries and depressive symptoms of 179 participants who completed four waves of annual interviews. Cancer-related worries were significantly associated with both initial level and trajectories of depressive symptoms. In a parallel process growth curve model, the initial level of depressive symptoms was significantly correlated with both the initial level and rate of change in cancer-related worry over time. Our findings indicate that cancer survivors are never completely removed from cancer's threats to quality of life, even as they survive into later life. These findings also suggest that older adults face the dual vulnerability of aging with its growing number of comorbidities and related symptoms along with the vulnerability conferred by cancer-related sequelae and the possibility of recurrence or new cancers.

Detecting short-term change and variation in health-related quality of life: within- and between-person factor structure of the SF-36 health survey.

BACKGROUND: A major goal of much aging-related research and geriatric medicine is to identify early changes in health and functioning before serious limitations develop. To this end, regular collection of patient-reported outcome measure (PROMs) in a clinical setting may be useful to identify and monitor these changes. However, existing PROMs were not designed for repeated administration and are more commonly used as one-time screening tools; as such, their ability to detect variation and measurement properties when administered repeatedly remain unknown. In this study we evaluated the potential of the RAND SF-36 Health Survey as a repeated-use PROM by examining its measurement properties when modified for administration over multiple occasions. METHODS: To distinguish between-person (i.e., average) from within-person (i.e., occasion) levels, the SF-36 Health Survey was completed by a sample of older adults (N = 122, M age = 66.28 years) daily for seven consecutive days. Multilevel confirmatory factor analysis (CFA) was employed to investigate the factor structure at both levels for two- and eight-factor solutions. RESULTS: Multilevel CFA models revealed that the correlated eight-factor solution provided better model fit than the two-factor solution at both the between-person and within-person levels. Overall model fit for the SF-36 Health Survey administered daily was not substantially different from standard survey administration, though both were below optimal levels as reported in the literature. However, individual subscales did demonstrate good reliability. CONCLUSIONS: Many of the subscales of the modified SF-36 for repeated daily assessment were found to be sufficiently reliable for use in repeated measurement designs incorporating PROMs, though the overall scale may not be optimal. We encourage future work to investigate the utility of the subscales in specific contexts, as well as the measurement properties of other existing PROMs when administered in a repeated measures design. The development and integration of new measures for this purpose may ultimately be necessary.

Guidelines for reporting methodological challenges and evaluating potential bias in dementia research.

Clinical and population research on dementia and related neurologic conditions, including Alzheimer's disease, faces several unique methodological challenges. Progress to identify preventive and therapeutic strategies rests on valid and rigorous analytic approaches, but the research literature reflects little consensus on "best practices." We present findings from a large scientific working group on research methods for clinical and population studies of dementia, which identified five categories of methodological challenges as follows: (1) attrition/sample selection, including selective survival; (2) measurement, including uncertainty in diagnostic criteria, measurement error in neuropsychological assessments, and practice or retest effects; (3) specification of longitudinal models when participants are followed for months, years, or even decades; (4) time-varying measurements; and (5) high-dimensional data. We explain why each challenge is important in dementia research and how it could compromise the translation of research findings into effective prevention or care strategies. We advance a checklist of potential sources of bias that should be routinely addressed when reporting dementia research.

The identification of regions of significance in the effect of multimorbidity on depressive symptoms using longitudinal data: an application of the Johnson-Neyman technique.

BACKGROUND: The investigation of multimorbidity and aging is complex and highly intertwined with aging-related changes in physical and cognitive capabilities, and mental health and is known to affect psychological distress and quality of life. Under these circumstances it is important to understand how the effects of chronic conditions evolve over time relative to aging-related and end-of-life changes. The identification of periods in time where multimorbidity impacts particular outcomes such as depressive symptoms, versus periods of time where this is not the case, reduces the complexity of the phenomenon. OBJECTIVE: We present the Johnson-Neyman (J-N) technique in the context of a curvilinear longitudinal model with higher-order terms to probe moderators and to identify regions of statistical significance. In essence, the J-N technique allows one to identify conditions under which moderators impact an outcome from conditions where these effects are not significant. METHODS: To illustrate the use of the J-N technique in a longitudinal sample, we used data from the Health and Retirement Study. Analyses were based on time-to-death models including participants who died within the study duration of 12 years. RESULTS: Multimorbidity differentially affects rates of change in depression. For some periods in time the effects are statistically significant while in other periods the same effects are not statistically different from zero. CONCLUSION: The J-N technique is useful to continuously probe moderating effects and to identify particular interactions with the model for time when certain effects are or are not statistically significant. In the context of multimorbidity this method is particularly useful for interpreting the complex interactions with differential change over time.

Fighting for Intelligence: A Brief Overview of the Academic Work of John L. Horn.

John L. Horn (1928-2006) was a pioneer in multivariate thinking and the application of multivariate methods to research on intelligence and personality. His key works on individual differences in the methodological areas of factor analysis and the substantive areas of cognition are reviewed here. John was also our mentor, teacher, colleague, and friend. We overview John Horn's main contributions to the field of intelligence by highlighting 3 issues about his methods of factor analysis and 3 of his substantive debates about intelligence. We first focus on Horn's methodological demonstrations describing (a) the many uses of simulated random variables in exploratory factor analysis; (b) the exploratory uses of confirmatory factor analysis; and (c) the key differences between states, traits, and trait-changes. On a substantive basis, John believed that there were important individual differences among people in terms of cognition and personality. These sentiments led to his intellectual battles about (d) Spearman's g theory of a unitary intelligence, (e) Guilford's multifaceted model of intelligence, and (f) the Schaie and Baltes approach to defining the lack of decline of intelligence earlier in the life span. We conclude with a summary of John Horn's unique approaches to dealing with common issues.

Developmental Change and Time-Specific Variation in Global and Specific Aspects of Self-Concept in Adolescence and Association with Depressive Symptoms.

Previous research has demonstrated that adolescents make differential self-evaluations in multiple domains that include physical appearance, academic competence, and peer acceptance. We report growth curve analyses over a seven year period from age 9 to age 16 on the six domains of the Harter Self-Perception Profile for Children. In general, we find little change in self-concept, on average, but do find substantial individual differences in level, rate of change, and time-specific variation in these self- evaluations. The results suggest that sex differences and adoptive status were related to only certain aspects of the participants' self-concept. Depressive symptoms were found to have significant effects on individual differences in rate of change and on time-specific variation in general self-concept, as well as on some of the specific domains of self-concept.

Multiple imputation of systematically missing data on gait speed in the Swedish National Study on Aging and Care.

BACKGROUND: There is insufficient investigation of multiple imputation for systematically missing discrete variables in individual participant data meta-analysis (IPDMA) with a small number of included studies. Therefore, this study aims to evaluate the performance of three multiple imputation strategies - fully conditional specification (FCS), multivariate normal (MVN), conditional quantile imputation (CQI) - on systematically missing data on gait speed in the Swedish National Study on Aging and Care (SNAC). METHODS: In total, 1 000 IPDMA were simulated with four prospective cohort studies based on the characteristics of the SNAC. The three multiple imputation strategies were analysed with a two-stage common-effect multivariable logistic model targeting the effect of three levels of gait speed (100% missing in one study) on 5-years mortality with common odds ratios set to OR1 = 0.55 (0.8-1.2 vs ≤0.8 m/s), and OR2 = 0.29 (>1.2 vs ≤0.8 m/s). RESULTS: The average combined estimate for the mortality odds ratio OR1 (relative bias %) were 0.58 (8.2%), 0.58 (7.5%), and 0.55 (0.7%) for the FCS, MVN, and CQI, respectively. The average combined estimate for the mortality odds ratio OR2 (relative bias %) were 0.30 (2.5%), 0.33 (10.0%), and 0.29 (0.9%) for the FCS, MVN, and CQI respectively. CONCLUSIONS: In our simulations of an IPDMA based on the SNAC where gait speed data was systematically missing in one study, all three imputation methods performed relatively well. The smallest bias was found for the CQI approach.

Longitudinal Quantiles of Frailty Trajectories Considering Death: New Insights into Sex and Cohort Differences in the Reference Curves for Frailty Progression of Older European.

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 (ß^a0.9 = 0.0229, p < .001; ß^a0.5 = 0.0067, p < .001; H0: ßa0.5=ßa0.9, p < .001). Education was consistently associated with a slower progression of the FI in all quantiles (ß^ae0.1 = -0.0001, p < .001; ß^ae0.5 =-0.0004, p < .001; ß^ae0.9 = -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.

Sleep disturbances and change in multiple cognitive domains among older adults: a multicenter study of five Nordic cohorts.

STUDY OBJECTIVES: We examined and compared cross-sectional and longitudinal associations between self-reported sleep disturbances and various cognitive domains in five separate Nordic European longitudinal aging studies (baseline N = 5631, mean age = 77.7, mean follow-up = 4.16 years). METHODS: Comparable sleep parameters across studies included reduced sleep duration/quality, insomnia symptoms (sleep latency, waking up at night, and early awakenings), short and long sleep duration, and daytime napping. The cognitive domains were episodic memory, verbal fluency, perceptual speed, executive functioning, and global cognition (aggregated measure). A series of mixed linear models were run separately in each study and then compared to assess the level and rate of change in cognitive functioning across each sleep disturbance parameter. Models were adjusted for age, sex, education, hypnotic usage, depressive symptoms, lifestyle factors, cardiovascular, and metabolic conditions. By using a coordinated analytic approach, comparable construct-level measurements were generated, and results from identical statistical models were qualitatively compared across studies. RESULTS: While the pattern of statistically significant results varied across studies, subjective sleep disturbances were consistently associated with worse cognition and steeper cognitive decline. Insomnia symptoms were associated with poorer episodic memory and participants sleeping less or more than 7-8 hours had a steeper decline in perceptual speed. In addition, daytime napping (>2 hours) was cross-sectionally and longitudinally associated with all examined cognitive domains. Most observed associations were study-specific (except for daytime napping), and a majority of association estimates remained significant after adjusting for covariates. CONCLUSION: This rigorous multicenter investigation further supports the importance of sleep disturbance, including insomnia, long and short sleep duration, and daytime napping on baseline cognitive functioning and rate of change among older adults. These sleep factors may be targeted in future lifestyle interventions to reduce cognitive decline.