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.

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.

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.

Transitions Between Mild Cognitive Impairment, Dementia, and Mortality: The Importance of Olfaction.

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.

Personality traits, cognitive states, and mortality in older adulthood.

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. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Review of selected databases of longitudinal aging studies.

One of the recommendations of the 2010 Leon Thal Symposium, organized to develop strategies to prevent Alzheimer's disease, was to build a global database of longitudinal aging studies. Although several databases of longitudinal aging studies exist, none of these are comprehensive or complete. In this article, we review selected databases of longitudinal aging studies. We also make recommendations on future steps to create a comprehensive database. Additionally, we discuss issues related to data harmonization.

Coordinated data analysis: Knowledge accumulation in lifespan developmental psychology.

Coordinated analysis is a powerful form of integrative analysis, and is well suited in its capacity to promote cumulative scientific knowledge, particularly in subfields of psychology that focus on the processes of lifespan development and aging. Coordinated analysis uses raw data from individual studies to create similar hypothesis tests for a given research question across multiple datasets, thereby making it less vulnerable to common criticisms of meta-analysis such as file drawer effects or publication bias. Coordinated analysis can sometimes use random effects meta-analysis to summarize results, which does not assume a single true effect size for a given statistical test. By fitting parallel models in separate datasets, coordinated analysis preserves the heterogeneity among studies, and provides a window into the generalizability and external validity of a set of results. The current article achieves three goals: First, it describes the phases of a coordinated analysis so that interested researchers can more easily adopt these methods in their labs. Second, it discusses the importance of coordinated analysis within the context of the credibility revolution in psychology. Third, it encourages the use of existing data networks and repositories for conducting coordinated analysis, in order to enhance accessibility and inclusivity. Subfields of research that require time- or resource- intensive data collection, such as longitudinal aging research, would benefit by adopting these methods. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Trajectories of Frailty With Aging: Coordinated Analysis of Five Longitudinal Studies.

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

The Importance of Engaging in Physical Activity in Older Adulthood for Transitions Between Cognitive Status Categories and Death: A Coordinated Analysis of 14 Longitudinal Studies.

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.

A Coordinated Multi-study Analysis of the Longitudinal Association Between Handgrip Strength and Cognitive Function in Older Adults.

OBJECTIVE: Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis. METHODS: We performed coordinated analysis on 9 cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis. RESULTS: After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44-0.56). We also found a high level of heterogeneity in this association across studies. DISCUSSION: Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers.

Variability and Coupling of Olfactory Identification and Episodic Memory in Older Adults.

OBJECTIVES: To determine whether assessment-to-assessment fluctuations in episodic memory (EM) reflect fluctuations in olfaction over time. METHODS: Within-person coupled variation in EM and the Brief Smell Identification Test (BSIT) was examined in 565 participants aged 58-106 with autopsy data from the Rush Memory and Aging Project. A growth model for up to 15 years of EM data, with BSIT as time-varying covariate, was estimated accounting for main effects of sex, education, ε4 allele, and Alzheimer's disease (AD) pathology, BSIT and time-varying BSIT, as well as the interaction between AD pathology and time-varying BSIT. RESULTS: Individuals with higher BSIT scores (b = .01, standard error [SE] = .004, p = .009) had slower declines in EM. High AD pathology (b = -.06, SE = .02, p = .001) was associated with more rapid declines in EM. The association between time-specific fluctuations in EM and BSIT differed by level of AD pathology (b = .08, SE = .034, p = .028), with a higher EM-BSIT association at higher levels of pathology. DISCUSSION: BSIT and EM fluctuate together over measurement occasions, particularly for individuals with AD pathology. Repeated intraindividual measurements provide information that could lead to early detection and inexpensive monitoring of accumulating AD pathology.

Memory Decline and Depression Onset in U.S. and European Older Adults.

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.

Systematic Review of Pulmonary Function and Cognition in Aging.

BACKGROUND: Substantial research is dedicated to understanding the aging-related dynamics among individual differences in level, change, and variation across physical and cognitive abilities. Evaluating replicability and synthesizing findings has been limited by differences in measurements, samples, study design, and statistical analyses that confound between-person differences with within-person changes. Here, we systematically reviewed longitudinal results on the aging-related dynamics linking pulmonary function and cognitive performance. METHODS: Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were used to systematically review longitudinal studies of pulmonary function and cognition. RESULTS: Only four studies thoroughly investigating cognitive and pulmonary longitudinal associations (three or more measurement occasions) were identified. Expanded review criteria identified three studies reporting two measurement occasions, and seven studies reporting one measurement of pulmonary function or cognition and two or more measurements of the other. We identified numerous methodological quality and risk for bias issues across studies. CONCLUSIONS: Despite documented correlational associations between pulmonary function and cognition, these results show there is very limited research thoroughly investigating their longitudinal associations. This highlights the need for longitudinal data, rigorous methodological design including key covariates, and clear communication of methods and analyses to facilitate replication across an array of samples. We recommend systematic study of outcome measures and covariates, inclusion of multiple measures (e.g., peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity), as well as application of the same analytic approach across multiple datasets.

Increases in Neuroticism May Be an Early Indicator of Dementia: A Coordinated Analysis.

OBJECTIVES: Although personality change is typically considered a symptom of dementia, some studies suggest that personality change may be an early indication of dementia. One prospective study found increases in neuroticism preceding dementia diagnosis (Yoneda, T., Rush, J., Berg, A. I., Johansson, B., & Piccinin, A. M. (2017). Trajectories of personality traits preceding dementia diagnosis. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 72, 922-931. doi:10.1093/geronb/gbw006). This study extends this research by examining trajectories of personality traits in additional longitudinal studies of aging. METHODS: Three independent series of latent growth curve models were fitted to data from the Longitudinal Aging Study Amsterdam and Einstein Aging Study to estimate trajectories of personality traits in individuals with incident dementia diagnosis (total N = 210), in individuals with incident Mild Cognitive Impairment (N = 135), and in individuals who did not receive a diagnosis during follow-up periods (total N = 1740). RESULTS: Controlling for sex, age, education, depressive symptoms, and the interaction between age and education, growth curve analyses consistently revealed significant linear increases in neuroticism preceding dementia diagnosis in both datasets and in individuals with mild cognitive impairment. Analyses examining individuals without a diagnosis revealed nonsignificant change in neuroticism overtime. DISCUSSION: Replication of our previous work in 2 additional datasets provides compelling evidence that increases in neuroticism may be early indication of dementia, which can facilitate development of screening assessments.

Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Is Healthy Neuroticism Associated with Longevity? A Coordinated Integrative Data Analysis.

Individual differences in the Big Five personality traits have emerged as predictors of health and longevity. Although there are robust protective effects for higher levels of conscientiousness, results are mixed for other personality traits. In particular, higher levels of neuroticism have significantly predicted an increased risk of mortality, no-risk at all, and even a reduced risk of dying. The current study hypothesizes that one potential reason for the discrepancy in these findings for neuroticism is that interactions among neuroticism and other key personality traits have largely been ignored. Thus, in the current study we focus on testing whether the personality traits neuroticism and conscientiousness interact to predict mortality. Specifically, we borrow from recent evidence of "healthy neuroticism" to explore whether higher levels of neuroticism are only a risk factor for increased mortality risk when conscientiousness levels are low. We conducted a pre-registered integrative data analysis using 12 different cohort studies (total N = 44,702). Although a consistent pattern emerged of higher levels of conscientiousness predicting a reduced hazard of dying, neuroticism did not show a consistent pattern of prediction. Moreover, no study provided statistical evidence of a neuroticism by conscientiousness interaction. The current findings do not support the idea that the combination of high conscientiousness and high neuroticism can be protective for longevity. Future work is needed to explore different protective factors that may buffer the negative effects of higher levels of neuroticism on health, as well as other behaviors and outcomes that may support the construct of healthy neuroticism.