Volunteering and instrumental support during the first phase of the pandemic in Europe: the significance of COVID-19 exposure and stringent country's COVID-19 policy.

BACKGROUND: The COVID-19 control policies might negatively impact older adults' participation in volunteer work, instrumental support provision, and the likelihood of receiving instrumental support. Studies that quantify changes in these activities and the related factors are limited. The current study aimed to examine the level of volunteering, instrumental support provision and receipt before and during the first phase of the COVID-19 pandemic in Europe and to determine whether older adults' volunteering, instrumental support provision and receipt were associated with individual exposure to COVID-19 and the stringency of country's COVID-19 control policy during the first phase of the COVID-19 pandemic. METHODS: A cross-sectional survey using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) Corona Survey 1 was designed to focus on community-dwelling Europeans aged ≥50 years. History of participation in volunteering work and instrumental support provision or receipt was assessed from the previous SHARE Wave data. The country's COVID-19 control policy stringency index (S-Index) was from the Oxford COVID-19 Government Response Tracker database. A total of 45,669 respondents from 26 European countries were included in the volunteering analysis. Seventeen European countries were included in the analyses of instrumental support provision (N = 36,518) and receipt (N = 36,526). The multilevel logistic regression model was fitted separately to analyse each activity. RESULTS: The level of volunteering and instrumental support provision was lower during the pandemic, but instrumental support receipt was higher. The country S-Index was positively associated with support provision (OR:1.13;95%CI:1.02-1.26) and negatively associated with support receipt (OR:0.69;95%CI:0.54-0.88). Exposure to COVID-19 was positively associated with support receipt (OR:1.64;95%CI:1.38-1.95). COVID-19 exposure on close ones positively associated with volunteering (OR:1.47;95%CI:1.32-1.65), support provision (OR:1.28;95%CI:1.19-1.39), and support receipt (OR:1.25;95%CI:1.15-1.35). CONCLUSIONS: The COVID-19 pandemic impacted older Europeans' volunteering, instrumental support provision, and instrumental support receipt from outside their household. When someone close to them was exposed to COVID-19, older Europeans were likely to receive instrumental support and to volunteer and provide instrumental support. A stricter country's COVID-19 control policy might motivate older adults to provide instrumental support, but it prevents them from receiving instrumental support from outside their households.

Sufficient Dimension Reduction for Feasible and Robust Estimation of Average Causal Effect.

When estimating the treatment effect in an observational study, we use a semiparametric locally efficient dimension reduction approach to assess both the treatment assignment mechanism and the average responses in both treated and non-treated groups. We then integrate all results through imputation, inverse probability weighting and double robust augmentation estimators. Double robust estimators are locally efficient while imputation estimators are super-efficient when the response models are correct. To take advantage of both procedures, we introduce a shrinkage estimator to automatically combine the two, which retains the double robustness property while improving on the variance when the response model is correct. We demonstrate the performance of these estimators through simulated experiments and a real dataset concerning the effect of maternal smoking on baby birth weight.

Causal inference accounting for unobserved confounding after outcome regression and doubly robust estimation.

Causal inference with observational data can be performed under an assumption of no unobserved confounders (unconfoundedness assumption). There is, however, seldom clear subject-matter or empirical evidence for such an assumption. We therefore develop uncertainty intervals for average causal effects based on outcome regression estimators and doubly robust estimators, which provide inference taking into account both sampling variability and uncertainty due to unobserved confounders. In contrast with sampling variation, uncertainty due to unobserved confounding does not decrease with increasing sample size. The intervals introduced are obtained by modeling the treatment assignment mechanism and its correlation with the outcome given the observed confounders, allowing us to derive the bias of the estimators due to unobserved confounders. We are thus also able to contrast the size of the bias due to violation of the unconfoundedness assumption, with bias due to misspecification of the models used to explain potential outcomes. This is illustrated through numerical experiments where bias due to moderate unobserved confounding dominates misspecification bias for typical situations in terms of sample size and modeling assumptions. We also study the empirical coverage of the uncertainty intervals introduced and apply the results to a study of the effect of regular food intake on health. An R-package implementing the inference proposed is available.

Influenza Casts a Lung Shadow.

This commentary highlights the article by Pociask et al that provides new insights into the lingering effects of influenza infection.

Sensitivity analysis for unobserved confounding of direct and indirect effects using uncertainty intervals.

To estimate direct and indirect effects of an exposure on an outcome from observed data, strong assumptions about unconfoundedness are required. Since these assumptions cannot be tested using the observed data, a mediation analysis should always be accompanied by a sensitivity analysis of the resulting estimates. In this article, we propose a sensitivity analysis method for parametric estimation of direct and indirect effects when the exposure, mediator, and outcome are all binary. The sensitivity parameters consist of the correlations between the error terms of the exposure, mediator, and outcome models. These correlations are incorporated into the estimation of the model parameters and identification sets are then obtained for the direct and indirect effects for a range of plausible correlation values. We take the sampling variability into account through the construction of uncertainty intervals. The proposed method is able to assess sensitivity to both mediator-outcome confounding and confounding involving the exposure. To illustrate the method, we apply it to a mediation study based on the data from the Swedish Stroke Register (Riksstroke). An R package that implements the proposed method is available.

Childhood family structure and women's adult overweight risk: A longitudinal study.

AIM: The aim of this study was to investigate whether women's adult overweight and obesity risk was associated with their childhood family structure, measured as their mothers' marital status history, during the women's first 18 years of life. METHODS: Using linked register data, we analyzed 30,584 primiparous women born in Sweden in 1975 who were between 19-35 years of age when their height and pre-pregnancy weight was recorded. The outcomes were women's overweight/obesity (body mass index (BMI) ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) and the predictor was mothers' marital status history, which was summarized using sequence analysis. We carried out nested logistic regression models adjusting for women's age and maternal sociodemographic characteristics. RESULTS: Mothers' marital status history was summarized into six clusters: stable marriage, stable cohabitation, married then divorcing, cohabiting then separating, varied transitions, and not with father. In fully adjusted models and compared with women whose mothers belonged to the stable marriage cluster: (1) women whose mothers belonged to the other marital status clusters had higher odds of overweight/obesity (odds ratio (OR) ranging 1.15-1.19; p < 0.05); and (2) women whose mothers belonged to the stable cohabitation (OR = 1.31; 95% confidence interval (CI) = 1.14-1.52), cohabiting then separating (OR = 1.23; 95% CI = 1.01-1.49), varied transitions (OR = 1.24; 95% CI = 1.11-1.39), and not with father (OR = 1.24; 95% CI = 1.00-1.54) clusters had higher odds of obesity. CONCLUSIONS: Women whose mothers were not in stable marriage relationships had higher odds of being overweight or obese in adulthood. The finding that even women raised in the context of stable cohabitation had higher odds of being overweight or obese is intriguing as these relationships are socially accepted in Sweden.

Regional inequalities in pre-pregnancy overweight and obesity in Sweden, 1992, 2000, and 2010.

AIMS: To investigate regional differences and time trends in women's overweight and obesity in Sweden. METHODS: Using data from the Swedish Medical Birth Register (women aged ⩾18 years, first pregnancy only) and the Total Population Register accessed through the Umeå SIMSAM Lab, age-standardized prevalence of pre-pregnancy overweight/obesity (BMI ⩾ 25 kg/m(2)) and obesity (BMI ⩾ 30 kg/m(2)) were estimated by county for the years 1992, 2000, and 2010. Maps were created using ArcMap v10.2.2 to display regional variations over time and logistic regression analyses were used to assess if the observed trends were significant. RESULTS: The prevalence of pre-pregnancy overweight/obesity and obesity increased significantly in all Swedish counties between 1992, and 2010. In 2010, Södermanland and Gotland exhibited the highest age-standardized overweight/obesity (39.7%) and obesity (15.1%) prevalence, respectively. The sharpest increases between 1992 and 2010 were observed in Västerbotten for overweight/obesity (75% increase) and in Gotland for obesity (233% increase). Across the years, Stockholm had the lowest prevalence of overweight/obesity (26.3% in 2010) and obesity (7.3% in 2010) and one of the least steep increases in prevalence of both between 1992 and 2010. CONCLUSIONS: Substantial regional differences in pre-pregnancy overweight and obesity prevalence are apparent in Sweden. Further research should elucidate the mechanisms causing these differences.

Brain characteristics of individuals resisting age-related cognitive decline over two decades.

Some elderly appear to resist age-related decline in cognitive functions, but the neural correlates of successful cognitive aging are not well known. Here, older human participants from a longitudinal study were classified as successful or average relative to the mean attrition-corrected cognitive development across 15-20 years in a population-based sample (n = 1561). Fifty-one successful elderly and 51 age-matched average elderly (mean age: 68.8 years) underwent functional magnetic resonance imaging while performing an episodic memory face-name paired-associates task. Successful older participants had higher BOLD signal during encoding than average participants, notably in the bilateral PFC and the left hippocampus (HC). The HC activation of the average, but not the successful, older group was lower than that of a young reference group (n = 45, mean age: 35.3 years). HC activation was correlated with task performance, thus likely contributing to the superior memory performance of successful older participants. The frontal BOLD response pattern might reflect individual differences present from young age. Additional analyses confirmed that both the initial cognitive level and the slope of cognitive change across the longitudinal measurement period contributed to the observed group differences in BOLD signal. Further, the differences between the older groups could not be accounted for by differences in brain structure. The current results suggest that one mechanism behind successful cognitive aging might be preservation of HC function combined with a high frontal responsivity. These findings highlight sources for heterogeneity in cognitive aging and may hold useful information for cognitive intervention studies.

Regional differences in initial labour market conditions and dynamics in lifetime income trajectories.

We use longitudinal register data from Sweden to study patterns and dynamics in lifetime income trajectories. We examine divergences in these income trajectories by local economic conditions at labour market entry, in combination with other factors such as gender, education level and socio-economic background. We cannot assume that these relationships are constant over the course of individuals' working lives. Therefore, we use methods from functional data analysis, allowing for a time-varying relationship between income and the explanatory variables. Our results show a large degree of heterogeneity in how lifetime income trajectories develop for different subgroups. We find that, for men, entering the labour market in an urban area is associated with higher cumulative lifetime income, especially later in life. The exception is men with only primary education, for whom those starting their working lives in a large city have lower incomes on average. This divergence increases in size over time. Women who enter into a large urban labour market receive higher lifetime income at all education levels. This relationship is strongest for women with primary education but decreases in strength over time for these women.

Frailty and types of social relationships among older adults in 17 European countries: A latent class analysis.

BACKGROUND: Frailty is a syndrome commonly associated with old age. Social relationships are an essential determinant of frailty progression, and frailty can negatively affect social relationships. OBJECTIVES: To identify social relationship types among older adults in Europe; to evaluate whether social relationship types differ across European regions; and to assess the association between frailty status and social relationship type. METHODS: We used data from 56,226 individuals from 17 European countries who participated in Wave 6 of the Survey of Health, Ageing and Retirement in Europe. We constructed social relationship types from social relationship variables (contacts frequency, perceived emotional support, participation in social activities, providing and receiving instrumental support) using latent class analysis (LCA). Associations between social relationship types and frailty were examined using multinomial regression analyses integrated with LCA. RESULTS: We identified four social relationship types: 'poor'; 'frequent and emotionally close'; 'frequent, emotionally close, and supportive'; and 'frequent, emotionally close, and active'. Type 3 is also characterised by participation in sport/social clubs (in the northern region) or receiving support (in the eastern region). Participation in volunteering/charity activities (in the central and northern regions) and instrumental support provision (in the northern region) are Type 4's characteristics as well. In all regions, being frail was associated with less active social relationships (Types 1, 2, and 3) relative to the more 'active' type (Type 4). CONCLUSION: Frailty status was associated with social relationship types. The identified types may help tailor intervention programmes for older adults to prevent worsening frailty.

A longitudinal study on social support, social participation, and older Europeans' Quality of life.

The association between quality of life (QoL) and social relationships is well established. This paper further analyses whether and how participation in social activities as well as providing and receiving social support, independently, are associated with QoL among the older population in 16 European countries. QoL was measured using the CASP-12 scale. The baseline data came from Wave 6 and the outcome from Wave 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). The associations of interest were analysed using multivariable linear regression. The effect of possible non-ignorable dropout was tested. Then, doubly robust estimation and sensitivity analyses for unobserved confounding were performed to evaluate the possible causal interpretation of the associations found. Our findings show that participation in at least one of the socially productive activities was positively associated with QoL at two-year follow-up (Average Causal Effect, ACE: 0.474; 95%CI: 0.361, 0.587). The association was stronger among women, people aged 75+, and those in the Southern European region. Providing social support had a positive association with QoL, but only among people aged 75+ (ACE: 0.410; 95%CI: 0.031, 0.789). Conversely, receiving social support had a negative association (ACE: -0.321; 95%CI: -0.448, -0.195) with QoL, especially for men, people aged 75+, and those in Eastern European countries. Sensitivity analyses for unobserved confounders showed that the associations found cannot be attributed to causal effects.

Effects of serum amyloid protein A on influenza A virus replication and viral interactions with neutrophils.

Innate immunity is vital for the early control of influenza A virus (IAV) infection. Serum amyloid A (SAA1) is an acute phase reactant produced in the liver and lung that rises dramatically during IAV infection. The potential role of SAA1 in host defense against IAV is unknown. SAA1 has been reported to directly activate neutrophils and to recruit them to the lung during infectious and inflammatory processes. Neutrophils are the most abundant cell recruited to the lung in the early phase of IAV infection. There are different forms and preparations of SAA1 that have found to have different effects on phagocyte responses, through various receptors. In this paper, we test the direct effects of various preparations of serum derived or recombinant SAA on IAV and how it modulates the interactions of IAV with neutrophils. All SAA preparations bound to IAV in vitro but caused minimal hemagglutination inhibition or viral aggregation. The human serum-derived SAA1 or the complex of SAA1 with HDL did have IAV neutralizing activity in vitro, whereas the recombinant SAA1 preparations did not. We found that different SAA preparations also had markedly different effects on neutrophil functions, with E. coli-derived SAA1 triggering some responses in neutrophils on its own or in presence of IAV whereas mammalian cell-derived SAA1 did not. This discrepancy could be explained by the reported contamination of the former preparation with bacterial components. Of interest, however, serum SAA alone, serum SAA complexed with HDL, or HDL alone potentiated some neutrophil responses to IAV. Our results suggest that SAA may play some role in host response to IAV, but further work needs to be done to clarify the role of different variants of SAA alone or complexed with HDL.

A Hierarchical Bayesian Mixture Model Approach for Analysis of Resting-State Functional Brain Connectivity: An Alternative to Thresholding.

This article proposes a Bayesian hierarchical mixture model to analyze functional brain connectivity where mixture components represent "positively connected" and "non-connected" brain regions. Such an approach provides a data-informed separation of reliable and spurious connections in contrast to arbitrary thresholding of a connectivity matrix. The hierarchical structure of the model allows simultaneous inferences for the entire population as well as for each individual subject. A new connectivity measure, the posterior probability of a given pair of brain regions of a specific subject to be connected given the observed correlation of regions' activity, can be computed from the model fit. The posterior probability reflects the connectivity of a pair of regions relative to the overall connectivity pattern of an individual, which is overlooked in traditional correlation analyses. This article demonstrates that using the posterior probability might diminish the effect of spurious connections on inferences, which is present when a correlation is used as a connectivity measure. In addition, simulation analyses reveal that the sparsification of the connectivity matrix using the posterior probabilities might outperform the absolute thresholding based on correlations. Therefore, we suggest that posterior probability might be a beneficial measure of connectivity compared with the correlation. The applicability of the introduced method is exemplified by a study of functional resting-state brain connectivity in older adults.

Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study.

BACKGROUND: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC. METHODS: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period. RESULTS: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29. CONCLUSION(S): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

Predictors of decline in self-reported health: addressing non-ignorable dropout in longitudinal studies of aging.

Predictors of decline in health in older populations have been investigated in multiple studies before. Most longitudinal studies of aging, however, assume that dropout at follow-up is ignorable (missing at random) given a set of observed characteristics at baseline. The objective of this study was to address non-ignorable dropout in investigating predictors of declining self-reported health (SRH) in older populations (50 years or older) in Sweden, the Netherlands, and Italy. We used the SHARE panel survey, and since only 2895 out of the original 5657 participants in the survey 2004 were followed up in 2013, we studied whether the results were sensitive to the expectation that those dropping out have a higher proportion of decliners in SRH. We found that older age and a greater number of chronic diseases were positively associated with a decline in self-reported health in the three countries studies here. Maximum grip strength was associated with decline in self-reported health in Sweden and Italy, and self-reported limitations in normal activities due to health problems were associated with decline in self-reported health in Sweden. These results were not sensitive to non-ignorable dropout. On the other hand, although obesity was associated with decline in a complete case analysis, this result was not confirmed when performing a sensitivity analysis to non-ignorable dropout. The findings, thereby, contribute to the literature in understanding the robustness of longitudinal study results to non-ignorable dropout while considering three different population samples in Europe.

The Role and Molecular Mechanism of Action of Surfactant Protein D in Innate Host Defense Against Influenza A Virus.

Influenza A viruses (IAVs) continue to pose major risks of morbidity and mortality during yearly epidemics and periodic pandemics. The genomic instability of IAV allows it to evade adaptive immune responses developed during prior infection. Of particular concern are pandemics which result from wholesale incorporation of viral genome sections from animal sources. These pandemic strains are radically different from circulating human strains and pose great risk for the human population. For these reasons, innate immunity plays a strong role in the initial containment of IAV infection. Soluble inhibitors present in respiratory lining fluids and blood provide a level of early protection against IAV. In general, these inhibitors act by binding to the viral hemagglutinin (HA). Surfactant protein D (SP-D) and mannose-binding lectin (MBL) attach to mannosylated glycans on the HA in a calcium dependent manner. In contrast, surfactant protein A, ficolins, and other inhibitors present sialic acid rich ligands to which the HA can bind. Among these inhibitors, SP-D seems to be the most potent due to its specific mode of binding to viral carbohydrates and its ability to strongly aggregate viral particles. We have studied specific properties of the N-terminal and collagen domain of SP-D that enable formation of highly multimerized molecules and cooperative binding among the multiple trimeric lectin domains in the protein. In addition, we have studied in depth the lectin activity of SP-D through expression of isolated lectin domains and targeted mutations of the SP-D lectin binding site. Through modifying specific residues around the saccharide binding pocket, antiviral activity of isolated lectin domains of SP-D can be markedly increased for seasonal strains of IAV. Wild-type SP-D causes little inhibition of pandemic IAV, but mutated versions of SP-D were able to inhibit pandemic IAV through enhanced binding to the reduced number of mannosylated glycans present on the HA of these strains. Through collaborative studies involving crystallography of isolated lectin domains of SP-D, glycomics analysis of the HA, and molecular modeling, the mechanism of binding of wild type and mutant forms of SP-D have been determined. These studies could guide investigation of the interactions of SP-D with other pathogens.

Critical role of C-terminal residues of the Alzheimer's associated ß-amyloid protein in mediating antiviral activity and modulating viral and bacterial interactions with neutrophils.

Recent studies have shown that the Alzheimer's associated ß-amyloid protein (ßA) can inhibit growth of bacteria, fungi and viruses. We reported that the 42 amino acid ßA protein inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro and modulates activation of neutrophils and monocytes exposed IAV. We here show that fragments composed of the N and C terminal domain of ßA42, including ßA22-42 and the 8 amino acid ßA35-42, retain viral neutralizing and viral aggregating activity, whereas fragments lacking the C-terminal amino acids 41 and 42 (e.g. ßA1-40, ßA1-34, ßA1-28, ßA22-40 or ßA33-40) have markedly diminished activities on these assays. ßA22-42 also increased viral uptake, and virus induced respiratory burst responses, by human neutrophils, while peptides lacking residues 41 and 42 did not. Similar results were obtained with regard to bacterial aggregation, or promotion of bacterial uptake by neutrophils. Published structural studies have shown that ßA1-42 has a greater propensity to form neurotoxic oligomers than ßA1-40 due to a molecular interaction between Met35 and Ala42. Our findings suggest that there is a relationship between neurotoxic and antimicrobial activities of ßA1-42. Truncated peptides containing the last 8 C-terminal amino acids of ßA1-42 retain antimicrobial and opsonizing activities likely resulting from their ability to induce viral or bacterial aggregation.

Longitudinal association between hippocampus atrophy and episodic-memory decline.

There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age.

Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline.

In this paper we develop a model to estimate the causal effect of living arrangement (living alone versus living with someone) on cognitive decline based on a 15-year prospective cohort study, where episodic memory function is measured every five years. One key feature of the model is the combination of propensity score matching to balance confounding variables between the two living arrangement groups -in order to reduce bias due to unbalanced covariates at baseline, with a pattern mixture model for longitudinal data -in order to deal with non-ignorable drop-out. A fully Bayesian approach allows us to convey the uncertainty in the estimation of the propensity score and subsequent matching in the inference of the causal effect of interest. The analysis conducted here adds to previous studies in the literature concerning the protective effect of living with someone, by proposing a modeling approach treating living arrangement as an exposure.

Genetic and lifestyle predictors of 15-year longitudinal change in episodic memory.

OBJECTIVES: To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. DESIGN: Prospective cohort study. SETTING: The Betula Project, Umeå, Sweden. PARTICIPANTS: One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. MEASUREMENTS: Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. RESULTS: Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ~4 allele was more frequent in decliners. CONCLUSION: Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.