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BackgroundAdverse childhood socioeconomic status (cSES) predicts higher late-life risk of memory loss and dementia. Veterans of U.S. wars are eligible for educational and economic benefits that may offset cSES disadvantage. We test whether cSES disparities in late-life memory and dementia are smaller among veterans than non-veterans.MethodsData came from US-born men in the 1995-2014 biennial surveys of the Health and Retirement Study (n=7916 born 1928-1956, contributing n=38 381 cognitive assessments). Childhood SES was represented by maternal education. Memory and dementia risk were assessed with brief neuropsychological assessments and proxy reports. Military service (veteran/non-veteran) was evaluated as a modifier of the effect of maternal education on memory and dementia risk. We employed linear or logistic regression models to test whether military service modified the effect of maternal education on memory or dementia risk, adjusted for age, race, birthplace and childhood health.ResultsLow maternal education was associated with worse memory than high maternal education (β = -0.07 SD, 95% CI -0.08 to -0.05), while veterans had better memory than non-veterans (β = 0.03 SD, 95% CI 0.02 to 0.04). In interaction analyses, maternal education disparities in memory were smaller among veterans than non-veterans (difference in disparities = 0.04 SD, 95% CI 0.01 to 0.08, p = 0.006). Patterns were similar for dementia risk.ConclusionsDisparities in memory by maternal education were smaller among veterans than non-veterans, suggesting military service and benefits partially offset the deleterious effects of low maternal education on late-life cognitive outcomes.

BackgroundIn middle age, stroke incidence is higher among black than white Americans. For unknown reasons, this inequality decreases and reverses with age. We conducted simulations to evaluate whether selective survival could account for observed age patterning of black-white stroke inequalities.MethodsWe simulated birth cohorts of 20,000 blacks and 20,000 whites with survival distributions based on US life tables for the 1919-1921 birth cohort. We generated stroke incidence rates for ages 45-94 years using Reasons for Geographic and Racial Disparities in Stroke (REGARDS) study rates for whites and setting the effect of black race on stroke to incidence rate difference (IRD) = 20/10,000 person-years at all ages, the inequality observed at younger ages in REGARDS. We compared observed age-specific stroke incidence across scenarios, varying effects of U, representing unobserved factors influencing mortality and stroke risk.ResultsDespite a constant adverse effect of black race on stroke risk, the observed black-white inequality in stroke incidence attenuated at older age. When the hazard ratio for U on stroke was 1.5 for both blacks and whites, but U only directly influenced mortality for blacks (hazard ratio for U on mortality =1.5 for blacks; 1.0 for whites), stroke incidence rates in late life were lower among blacks (average observed IRD = -43/10,000 person-years at ages 85-94 years versus causal IRD = 20/10,000 person-years) and mirrored patterns observed in REGARDS.ConclusionsA relatively moderate unmeasured common cause of stroke and survival could fully account for observed age attenuation of racial inequalities in stroke.

Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline.

ObjectiveNumerous studies show that depressive symptoms measured at a single assessment predict greater future stroke risk. Longer-term symptom patterns, such as variability across repeated measures or worst symptom level, might better reflect adverse aspects of depression than a single measurement. This prospective study compared five approaches to operationalizing depressive symptoms at annual assessments as predictors of stroke incidence.DesignCohort followed for incident stroke over an average of 6.4 years.SettingThe Adult Changes in Thought cohort follows initially cognitively intact, community- dwelling older adults from a population base defined by membership in Group Health, a Seattle-based nonprofit healthcare organization.Participants3,524 individuals aged 65 years and older.MeasurementsWe identified 665 incident strokes using ICD codes. We considered both baseline Center for Epidemiologic Studies-Depression scale (CES-D) score and, using a moving window of three most recent annual CES-D measurements, we compared most recent, maximum, average, and intra-individual variability of CES-D scores as predictors of subsequent stroke using Cox proportional hazards models.ResultsGreater maximum (hazard ratio [HR]: 1.18; 95% CI: 1.07-1.30), average (HR: 1.20; 95% CI: 1.05-1.36) and intra-individual variability (HR: 1.15; 95% CI: 1.06-1.24) in CES-D were each associated with elevated stroke risk, independent of sociodemographics, cardiovascular risks, cognition, and daily functioning. Neither baseline nor most recent CES-D was associated with stroke. In a combined model, intra-individual variability in CES-D predicted stroke, but average CES-D did not.ConclusionsCapturing the dynamic nature of depression is relevant in assessing stroke risk. Fluctuating depressive symptoms may reflect a prodrome of reduced cerebrovascular integrity.

IntroductionWe hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality.MethodsWe used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years.ResultsHigher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00, P = .05).DiscussionNon-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.

Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality is a common effect of exposure and an unmeasured determinant of cognitive decline and in similar settings. This potential is often represented as collider-stratification bias in directed acyclic graphs, but it is difficult to anticipate the magnitude of bias. In this paper, we present a flexible simulation platform with which to quantify the expected bias in longitudinal studies of determinants of cognitive decline. We evaluated potential survival bias in naive analyses under several selective survival scenarios, assuming that exposure had no effect on cognitive decline for anyone in the population. Compared with the situation with no collider bias, the magnitude of bias was higher when exposure and an unmeasured determinant of cognitive decline interacted on the hazard ratio scale to influence mortality or when both exposure and rate of cognitive decline influenced mortality. Bias was, as expected, larger in high-mortality situations. This simulation platform provides a flexible tool for evaluating biases in studies with high mortality, as is common in cognitive aging research.

BackgroundIndividual-level modifiers can delay onset of limitations in basic activities of daily living (ADLs) among cognitively impaired individuals. We assessed whether these modifiers also delayed onset of limitations in instrumental ADLs (IADLs) among individuals at elevated dementia risk.ObjectivesTo determine whether modifiable individual-level factors delay incident IADL limitations among adults stratified by dementia risk.MethodsHealth and Retirement Study participants aged 65+ without activity limitations in 1998 or 2000 (n = 5,219) were interviewed biennially through 2010. Dementia probability, categorized in quartiles, was used to predict incident IADL limitations with Poisson regression. We estimated relative (risk ratio) and absolute (number of limitations) effects from models including dementia, individual-level modifiers (physical inactivity, smoking, no alcohol consumption, and depression) and interaction terms between dementia and individual-level modifiers.ResultsDementia probability quartile predicted incident IADL limitations (relative risk for highest versus lowest quartile = 0.44; 95% CI: 0.28-0.70). Most modifiers did not significantly increase risk of IADL limitations among the cognitively impaired. Physical inactivity (RR = 1.60; 95% CI: 1.16, 2.19) increased the risk of IADL limitations among the cognitively impaired. The interaction between physical inactivity and low dementia probability was statistically significant (p = 0.009) indicating that physical inactivity had significantly larger effects on incident IADLs among cognitively normal than among those with high dementia probability.ConclusionPhysical activity may protect against IADL limitations while not smoking, alcohol consumption, and not being depressed do not afford substantial protection among the cognitively impaired. RESULTS highlight the need for extra support for IADLs among individuals with cognitive losses.

ObjectiveTo identify modifying factors that preserve functional independence among individuals at high dementia risk.MethodsHealth and Retirement Study participants aged 65 years or older without baseline activities of daily living (ADL) limitations (n = 4,922) were interviewed biennially for up to 12 years. Dementia probability, estimated from direct and proxy cognitive assessments, was categorized as low (i.e., normal cognitive function), mild, moderate, or high risk (i.e., very impaired) and used to predict incident ADL limitations (censoring after limitation onset). We assessed multiplicative and additive interactions of dementia category with modifiers (previously self-reported physical activity, smoking, alcohol consumption, depression, and income) in predicting incident limitations.ResultsSmoking, not drinking, and income predicted incident ADL limitations and had larger absolute effects on ADL onset among individuals with high dementia probability than among cognitively normal individuals. Smoking increased the 2-year risk of ADL limitations onset from 9.9% to 14.9% among the lowest dementia probability category and from 32.6% to 42.7% among the highest dementia probability category. Not drinking increased the 2-year risk of ADL limitations onset by 2.1 percentage points among the lowest dementia probability category and 13.2 percentage points among the highest dementia probability category. Low income increased the 2-year risk of ADL limitations onset by 0.4% among the lowest dementia probability category and 12.9% among the highest dementia probability category.ConclusionsSmoking, not drinking, and low income predict incident dependence even in the context of cognitive impairment. Regardless of cognitive status, reducing these risk factors may improve functional outcomes and delay institutionalization.

In this retrospective cohort study, data from an integrated US healthcare system containing both electronic medical record data and linked claims data (from 01/2004 to 12/2020) were used to evaluate the clinical burden, treatment patterns, and healthcare resource use (HRU) in patients with von Willebrand disease (VWD). Two patient cohorts were analyzed: the overall VWD population (n = 396) and a subset of these patients (n = 75) who were considered potentially eligible for prophylaxis treatment with von Willebrand factor (VWF) based on a history of severe and frequent bleeding. HRU (hospitalizations, outpatient visits, and emergency department visits) were measured in patients with linked claims data (n = 110, overall VWD patients; n = 23 potentially VWF-prophylaxis-eligible VWD patients). In general, patients with VWD experienced a substantial burden of bleeding events, comorbidities, and HRU. Patients with VWD who were considered potentially eligible for prophylaxis owing to severe and frequent bleeds suffered from a higher clinical burden and HRU than the overall VWD population, and thus may benefit from VWF prophylactic treatment. The findings from this study could help improve clinical outcomes and manage HRU for patients with VWD. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that, like apolipoprotein E ( APOE ), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality., Methods: We used a weighted genetic risk score (GRS) from 21 non- APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years., Results: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10, P  = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00, P  = .05)., Discussion: Non- APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.