Associations Between Blood-Based Biomarkers and Cognitive and Functional Trajectories Among Participants of the MEMENTO Cohort.

BACKGROUND AND OBJECTIVES: Elevated levels of Alzheimer disease (AD) blood-based biomarkers are associated with accelerated cognitive decline. However, their distinct relationships with specific cognitive and functional domains require further investigation. We aimed at estimating the associations between AD blood-based biomarkers and the trajectories of distinct cognitive and functional domains over a 5-year follow-up period. METHODS: We conducted a clinic-based prospective study using data from the MEMENTO study, a nationwide French cohort. We selected dementia-free individuals at baseline aged 60 years or older. Baseline measurements of ß-amyloid (Aß) 40 and 42, phosphorylated tau (p-tau181), and neurofilament light chain (NfL) concentrations were obtained using the Simoa HD-X analyzer. Mini-Mental State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT), animal fluency, Trail Making Tests A and B, Short Physical Performance Battery (SPPB), and Instrumental Activities of Daily Living were administered annually for up to 5 years. We used linear mixed models, adjusted for potential confounders, to model AD biomarkers' relation with cognitive and functional decline. RESULTS: A total of 1,938 participants were included in this study, with a mean (SD) baseline age of 72.8 (6.6) years, and 62% were women. Higher baseline p-tau181 and NfL were associated with significantly faster decline in most cognitive, physical, and functional outcomes (+1 SD p-tau181: ßMMSE = -0.055, 95% CI -0.067 to -0.043, ßFCSRT = -0.034, 95% CI -0.043 to -0.025, ßfluency = -0.029, 95% CI -0.038 to -0.020, ßSPPB = -0.040, 95% CI -0.057 to -0.022, and ß4IADL = -0.115, 95% CI 0.091-0.140. +1 SD NfL: ßMMSE = -0.039, 95% CI -0.053 to -0.025, ßFCSRT = -0.022, 95% CI -0.032 to -0.012, ßfluency = -0.014, 95% CI -0.024 to -0.004, and ß4IADL = 0.077, 95% CI 0.048-0.105). A multiplicative association of p-tau181 and NfL with worsening cognitive and functional trajectories was evidenced. Lower Aß42/40 ratio was only associated with slightly faster cognitive decline in FCSRT and semantic fluency (+1 SD: ß = 0.011, 95% CI 0.002-0.020, and ß = 0.011, 95% CI 0.003-0.020, respectively). These associations were not modified by APOE ε4, sex, nor education level. DISCUSSION: In a memory clinic sample, p-tau181 and NfL, both independently and jointly, are linked to more pronounced cognitive, physical and functional declines. Blood-based biomarker measurement in AD research may provide useful insights regarding biological processes underlying cognitive, physical, and functional declines in at-risk individuals.

Understanding the relationship between type-2 diabetes, MRI markers of neurodegeneration and small vessel disease, and dementia risk: a mediation analysis.

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk. The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels. Dementia status was assessed every 2 to 3 years, during up to 12 years of follow-up. Brain parenchymal fraction (BPF) and white matter hyperintensities volume (WMHV) were selected as markers of neurodegeneration and cerebral SVD respectively. We performed a mediation analysis of the effect of baseline BPF and WMHV (mediators) on the association between diabetes and dementia risk using linear and Cox models adjusted for age, sex, education level, hypertension, hypercholesterolemia, BMI, smoking and alcohol drinking status, APOE-ε4 status, and study site. At baseline, 8.8% of the participants had diabetes. Diabetes (yes vs. no) was associated with higher WMHV (ßdiab = 0.193, 95% CI 0.040; 0.346) and lower BPF (ßdiab = -0.342, 95% CI -0.474; -0.210), as well as with an increased risk of dementia over 12 years of follow-up (HRdiab = 1.65, 95% CI 1.04; 2.60). The association between diabetes status and dementia risk was statistically mediated by higher WMHV (HRdiab=1.05, 95% CI 1.01; 1.11, mediated part = 10.8%) and lower BPF (HRdiab = 1.12, 95% CI 1.05; 1.20, mediated part = 22.9%). This study showed that both neurodegeneration and cerebral SVD statistically explained almost 30% of the association between diabetes and dementia.

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies.

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Understanding factors associated with the trajectory of subjective cognitive complaints in groups with similar objective cognitive trajectories.

BACKGROUND: Cognitive complaints are often regarded as an early sign of Alzheimer's disease (AD) but may also occur in several other conditions and contexts. This study examines the correlates of cognitive complaint trajectories over a 5-year period in individuals who shared similar objective cognitive trajectories. METHODS: We analyzed a subsample (n = 1748) of the MEMENTO cohort, consisting of individuals with subjective cognitive decline or mild cognitive impairment at baseline. Participants were stratified based on their latent MMSE trajectory over a 5-year period: "high and increasing," "subtle decline," and "steep decline." Within each of the three strata, we used a latent-class longitudinal approach to identify distinct trajectories of cognitive complaints. We then used multiple logistic regressions to examine the association between these complaint trajectories and several factors, including AD biomarkers (blood pTau/Aß42 ratio, cortical thickness, APOE genotype), anxiety, depression, social relationships, a comorbidity-polypharmacy score, and demographic characteristics. RESULTS: Among participants with high and increasing MMSE scores, greater baseline comorbidity-polypharmacy scores (odds ratio (OR) = 1.30, adjusted p = 0.03) were associated with higher odds of moderate and increasing cognitive complaints (as opposed to mild and decreasing complaints). Baseline depression and social relationships also showed significant associations with the complaint pattern but did not survive correction for multiple comparisons. Among participants with subtle decline in MMSE scores, greater baseline depression (OR = 1.76, adjusted p = 0.02) was associated with higher odds of moderate and increasing cognitive complaints (versus mild and decreasing). Similarly, baseline comorbidity-polypharmacy scores and pTau/Aß42 ratio exhibited significant associations, but they did not survive correction. Among participants with a steep decline in MMSE scores, greater baseline comorbidity-polypharmacy scores increased the odds of moderate complaints (versus mild, OR = 1.38, unadjusted p = 0.03, adjusted p = 0.32), but this effect did not survive correction for multiple comparisons. CONCLUSIONS: Despite similar objective cognitive trajectory, there is heterogeneity in the subjective perception of these cognitive changes. This perception was explained by both AD-related and, more robustly, non-AD-related factors. These findings deepen our understanding of the multifaceted nature of subjective cognitive complaints in individuals at risk for dementia and underscore the importance of considering a range of factors when interpreting cognitive complaints.

Physical activity, biomarkers of brain pathologies and dementia risk: Results from the Memento clinical cohort.

INTRODUCTION: This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. METHODS: From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self-reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aß)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow-up, and interactions with biomarkers of brain pathologies were tested. RESULTS: Physical activity moderated the association between MTA and plasma Aß42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aß42/40 on dementia risk were attenuated in participants with high physical activity. DISCUSSION: Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. HIGHLIGHTS: Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity.

How Traumatic Brain Injury History Relates to Brain Health MRI Markers and Dementia Risk: Findings from the 3C Dijon Cohort.

BACKGROUND: The long-term effects of traumatic brain injury (TBI) with loss of consciousness (LOC) on magnetic resonance imaging (MRI) markers of brain health and on dementia risk are still debated. OBJECTIVE: To investigate the associations of history of TBI with LOC with incident dementia and neuroimaging markers of brain structure and small vessel disease lesions. METHODS: The analytical sample consisted in 4,144 participants aged 65 and older who were dementia-free at baseline from the Three City -Dijon study. History of TBI with LOC was self-reported at baseline. Clinical Dementia was assessed every two to three years, up to 12 years of follow-up. A subsample of 1,675 participants <80 years old underwent a brain MRI at baseline. We investigated the associations between history of TBI with LOC and 1) incident all cause and Alzheimer's disease (AD) dementia using illness-death models, and 2) neuroimaging markers at baseline. RESULTS: At baseline, 8.3% of the participants reported a history of TBI with LOC. In fully-adjusted models, participants with a history of TBI with LOC had no statistically significant differences in dementia risk (HR = 0.90, 95% CI = 0.60-1.36) or AD risk (HR = 1.03, 95% CI = 0.69-1.52), compared to participants without TBI history. History of TBI with LOC was associated with lower white matter volume (ß= -4.58, p = 0.048), but not with other brain volumes, white matter hyperintensities volume, nor covert brain infarct. CONCLUSION: This study did not find evidence of an association between history of TBI with LOC and dementia or AD dementia risks over 12-year follow-up, brain atrophy, or markers of small vessel disease.

Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort.

BACKGROUND: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. METHODS: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. RESULTS: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct ß = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total ß = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct ß = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect ß = 0.066 (0.042; 0.090) and direct ß = - 0.116 (- 0.153; - 0.079)), but not through AD pathology nor SVD. CONCLUSIONS: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.

Racial Residential Segregation in Young Adulthood and Brain Integrity in Middle Age: Can We Learn From Small Samples?

Racial residential segregation is associated with multiple adverse health outcomes in Black individuals. Yet, the influence of structural racism and racial residential segregation on brain aging is less understood. In this study, we investigated the association between cumulative exposure to racial residential segregation over 25 years (1985-2010) in young adulthood, as measured by the Getis-Ord Gi* statistic, and year 25 measures of brain volume (cerebral, gray matter, white matter, and hippocampal volumes) in midlife. We studied 290 Black participants with available brain imaging data who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort study. CARDIA investigators originally recruited 2,637 Black participants aged 18-30 years from 4 field centers across the United States. We conducted analyses using marginal structural models, incorporating inverse probability of treatment weighting and inverse probability of censoring weighting. We found that compared with low/medium segregation, greater cumulative exposure to a high level of racial residential segregation throughout young adulthood was associated with smaller brain volumes in general (e.g., for cerebral volume, ß = -0.08, 95% confidence interval: -0.15, -0.02) and with a more pronounced reduction in hippocampal volume, though results were not statistically significant. Our findings suggest that exposure to segregated neighborhoods may be associated with worse brain aging.

Statins and Cognitive Decline in the Cardiovascular Health Study: A Comparison of Different Analytical Approaches.

BACKGROUND: Despite their well-established benefits for the prevention of cardiovascular disease, robust evidence on the effects of statins on cognition is largely inconclusive. We apply various study designs and analytical approaches to mimic randomized controlled trial effects from observational data. METHODS: We used observational data from 5 580 participants enrolled in the Cardiovascular Health Study from 1989/1990 to 1999/2000. We conceptualized the cohort as an overlapping sequence of nonrandomized trials. We compared multiple selection (eligible population, prevalent users, new users) and analytic approaches (multivariable adjustment, inverse-probability treatment weights, propensity score matching) to evaluate the association between statin use and 5-year change in global cognitive function, assessed using the Modified Mini-Mental State Examination (3MSE). RESULTS: When comparing prevalent users to nonusers (N = 2 772), statin use was associated with slower cognitive decline over 5 years (adjusted annual change in 3MSE = 0.34 points/year; 95% CI: 0.05-0.63). Compared to prevalent user design, estimates from new user designs (eg, comparing eligible statin initiators to noninitiators) were attenuated showing either null or negative association, though not significant. For example, in a propensity score-matched sample of statin-eligible individuals (N = 454), the annual 3MS change comparing statin initiators to noninitiators was -0.21 points/year (95% CI: -0.81 to 0.39). CONCLUSIONS: The association of statin use and cognitive decline is attenuated toward the null when using rigorous analytical approaches that more closely mimic randomized controlled trials. Point estimates, even within the same study, may vary depending on the analytical methods used. Further studies that leverage natural or quasi experiments around statin use are needed to replicate our findings.

Associations Between 20-Year Lipid Variability Throughout Young Adulthood and Midlife Cognitive Function and Brain Integrity.

BACKGROUND: Little is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife. METHOD: We studied 3 328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high-density lipoprotein (LDL and HDL) variability as the intraindividual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored. RESULTS: Mean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (ß = -0.25, 95% CI: -0.42, -0.08), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (ß = -0.80, 95% CI: -1.18, -0.41) and brain integrity, for example, smaller total brain volume (ß = -0.58, 95% CI: -0.82, -0.34) and worse total brain fractional anisotropy (ß = -1.13, 95% CI: -1.87, -0.39). CONCLUSIONS: Higher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.

Estimating the effects of Mexico to U.S. migration on elevated depressive symptoms: evidence from pooled cross-national cohorts.

PURPOSE: Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health. METHODS: We pooled data from the Mexican Health and Aging Study (N = 17,771) and Mexican-born U.S. Health and Retirement Study (N = 898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration. RESULTS: Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count = 1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood. CONCLUSIONS: In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.

Body mass index in early adulthood and dementia in late life: Findings from a pooled cohort.

INTRODUCTION: To examine the independent association of body mass index (BMI) in early adulthood with dementia incidence among men and women. METHODS: We studied 5104 older adults from the Cardiovascular Health Study (CHS) and the Health, Aging, and Body Composition (Health ABC) study. We imputed early adulthood and midlife BMI using a pooled parent cohort with complete adult lifespan coverage and previously established methods. Dementia was ascertained using criteria such as neuropsychological test battery, medical records, and dementia-related drug use. Pooled logistic regression (PLR) models were used. RESULTS: Compared to women with normal BMI in early adulthood, the odds of dementia were higher among both overweight (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.31 to 2.54) and obese (OR = 2.45; 95% CI = 1.47 to 4.06) women, independent of mid- and late-life BMI. Similar relationship was observed in men. CONCLUSIONS: With the growing obesity epidemic among US adults, efforts aimed at reducing dementia may need to begin obesity prevention and treatment early in the life course.

Quantifying Lifecourse Drivers of International Migration: A Cross-national Analysis of Mexico and the United States.

BACKGROUND: Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health. METHODS: We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW. RESULTS: Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models. CONCLUSIONS: Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium.

OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.

Association of High-Density Lipoprotein Cholesterol With Cognitive Function: Findings From the PROspective Study of Pravastatin in the Elderly at Risk.

Objective: We aimed to examine whether variability in high-density lipoprotein cholesterol (HDL-c) over time was associated with cognitive function. Method: We conducted a post hoc analysis of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. Our sample included 4,428 participants with at least two repeated HDL-c measures between Months 3 and 24 postbaseline and with cognitive assessments at Month 30. HDL-c variability was defined as the intraindividual standard deviation over each person's repeated measurements. Results: Higher HDL-c variability was associated with worse performance on the Letter-Digit Coding Test (ß [95% confidence interval] [CI] = -4.39 [-7.36, -1.43], p = .004), immediate recall on the 15-Picture Learning Test (ß [95% CI] = -0.98 [-1.86, -0.11], p = .027), and delayed recall on the 15-Picture Learning Test (ß [95% CI] = -1.90 [-3.14, -0.67], p = .002). The associations did not vary by treatment group. Discussion: Our findings suggest that variability in HDL-c may be associated with poor cognitive function among older adults.

Association of traumatic brain injury with dementia and memory decline in older adults in the United States.

INTRODUCTION: To examine associations of history of traumatic brain injuries (TBIs) with loss of consciousness (LOC) with dementia incidence and memory decline. METHODS: We studied 2718 participants from the 1992 enrollment cohort of the Health and Retirement Study (HRS) aged 65 years or older in 2000. History of TBI with LOC was self-reported in 1992. Dementia was assessed using four algorithms established in HRS. Participants were followed from 2000 to 2014 with repeated measures of dementia and memory performance. Cox models and linear mixed-effects models were used. RESULTS: In 1992, 11.9% of the participants reported a history of TBI with LOC. In fully adjusted models for all four algorithms, participants with a history of TBI with LOC had no statistically significant difference in dementia incidence nor in memory decline, compared to participants without TBI history. DISCUSSION: Our study did not find evidence of a long-term association between history of TBI with LOC (of unknown frequency and severity) and dementia incidence or memory decline.

Relation between 20-year income volatility and brain health in midlife: The CARDIA study.

OBJECTIVE: Income volatility presents a growing public health threat. To our knowledge, no previous study examined the relationship among income volatility, cognitive function, and brain integrity. METHODS: We studied 3,287 participants aged 23-35 years in 1990 from the Coronary Artery Risk Development in Young Adults prospective cohort study. Income volatility data were created using income data collected from 1990 to 2010 and defined as SD of percent change in income and number of income drops ≥25% (categorized as 0, 1, or 2+). In 2010, cognitive tests (n = 3,287) and brain scans (n = 716) were obtained. RESULTS: After covariate adjustment, higher income volatility was associated with worse performance on processing speed (ß = -1.09, 95% confidence interval [CI] -1.73 to -0.44) and executive functioning (ß = 2.53, 95% CI 0.60-4.50) but not on verbal memory (ß = -0.02, 95% CI -0.16 to 0.11). Similarly, additional income drops were associated with worse performance on processing speed and executive functioning. Higher income volatility and more income drops were also associated with worse microstructural integrity of total brain and total white matter. All findings were similar when restricted to those with high education, suggesting reverse causation may not explain these findings. CONCLUSION: Income volatility over a 20-year period of formative earning years was associated with worse cognitive function and brain integrity in midlife.

Sociodemographic Disparities in Long-Term Mortality Among Stroke Survivors in the United States.

Background and Purpose- It is unclear whether disparities in mortality among stroke survivors exist long term. Therefore, the purpose of the current study is to describe rates of longer term mortality among stroke survivors (ie, beyond 30 days) and to determine whether socioeconomic disparities exist. Methods- This analysis included 1329 black and white participants, aged ≥45 years, enrolled between 2003 and 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) who suffered a first stroke and survived at least 30 days after the event. Long-term mortality among stroke survivors was defined in person-years as time from 30 days after a first stroke to date of death or censoring. Mortality rate ratios (MRRs) were used to compare rates of poststroke mortality by demographic and socioeconomic characteristics. Results- Among adults who survived ≥30 days poststroke, the age-adjusted rate of mortality was 82.3 per 1000 person-years (95% CI, 75.4-89.2). Long-term mortality among stroke survivors was higher in older individuals (MRR for 75+ versus <65, 3.2; 95% CI, 2.6-4.1) and among men than women (MRR, 1.3; 95% CI, 1.1-1.6). It was also higher among those with less educational attainment (MRR for less than high-school versus college graduate, 1.5; 95% CI, 1.1-1.9), lower income (MRR for <$20k versus >50k, 1.4; 95% CI, 1.1-1.9), and lower neighborhood socioeconomic status (SES; MRR for low versus high neighborhood SES, 1.4; 95% CI, 1.1-1.7). There were no differences in age-adjusted rates of long-term poststroke mortality by race, rurality, or US region. Conclusions- Rates of long-term mortality among stroke survivors were higher among individuals with lower SES and among those residing in neighborhoods of lower SES. These results emphasize the need for improvements in long-term care poststroke, especially among individuals of lower SES.

Secular trends of mortality and dementia-free life expectancy over a 10-year period in France.

The aim of this paper was to investigate the evolution of mortality and life expectancy according to dementia in two French populations 10 years apart. Two different populations of subjects aged 65 or older included in PAQUID from 1988 to 1989 (n = 1342) and 3C from 1999 to 2000 (n = 1996) and initially not demented were followed over 10 years. Dementia was assessed using an algorithmic approach, and participants were considered to have dementia if they had an MMSE score < 24 AND a 4IADL score > 1. Illness-death models were used to compare mortality with and without dementia and to provide total life expectancy (LE), dementia-free life expectancy (DemFreeLE), life expectancy with dementia (DemLE), and survival with dementia. Mortality without dementia has decreased between the two populations among men [HR = 0.63 (0.49-0.81)] and women [HR = 0.67 (0.50-0.90)], whereas mortality with dementia has decreased for women only [HR = 0.59 (0.41-0.87)]. Total LE and DemFreeLE have increased between the 1990s and the 2000s populations (total LE: + 2.5 years; DemFreeLE: + 2.2 years); DemLE only slightly increased between the populations (DemLE: + 0.3 years). For survival with dementia, an increase in survival has been evidenced (mean survival: + 1.3 years) for women only. The improvement in DemFreeLE is promising. However, as the duration of life with dementia tends to increase for women, efforts to delay the onset of dementia should be reinforced.

Evolution of dementia diagnosis over time (1988-2013): Evidence from French and English cohorts. Implication for secular trends analyses.

INTRODUCTION: The aims of this study are to examine the evolution of clinical dementia diagnosis over 3 decades and to investigate secular trends of dementia. METHODS: Four cohorts covering a period from 1988 to 2013 were used: the Personnes Agées Quid and Three-City-Bordeaux studies, and the Cognitive Function and Aging Study (CFAS) I and II. Mini-Mental State Examination scores at clinical diagnosis were evaluated over a 24-year follow-up period in French studies. An algorithmic approach was applied to CFAS I and II to provide dementia prevalence and incidence estimates. RESULTS: A significant increase of the Mini-Mental State Examination score at diagnosis was observed until 2000 and a significant decrease after. We reported a prevalence of 8.8% for CFAS I (1990-1993) compared with a prevalence of 6.5% in CFAS II (2008-2011). The 2-year incidence rate was estimated at 31.2/1000 (95% confidence interval = 28.0-34.8) for CFAS I and 15.0/1000 (95% confidence interval = 13.5-16.7) for CFAS II. DISCUSSION: Applying a stable algorithm to different cohorts across time can provide a robust method for time trends estimation.