An Early and Unequal Decline: Life Course Trajectories of Cognitive Aging in the United States.

Objectives: Cognitive aging is a lifelong process with implications for Alzheimer's disease and dementia. This study aims to fill major gaps in research on the natural history of and social disparities in aging-related cognitive decline over the life span. Methods: We conducted integrative data analysis of four large U.S. population-based longitudinal studies of individuals aged 12 to 105 followed over two decades and modeled age trajectories of cognitive function in multiple domains. Results: We found evidence for the onset of cognitive decline in the 4th decade of life, varying gender differences with age, and persistent disadvantage among non-Hispanic Blacks, Hispanics, and those without college education. We further found improvement in cognitive function across 20th century birth cohorts but widening social inequalities in more recent cohorts. Discussion: These findings advance an understanding of early life origins of dementia risk and invite future research on strategies for promoting cognitive health for all Americans.

Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Male Veterans: A Twin Study.

BACKGROUND AND OBJECTIVES: Traumatic brain injuries (TBIs) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions after TBI may improve cognitive trajectories and delay dementia. Because twins share many genes and environmental factors, we capitalize on the twin study design to examine the association between lifetime TBI and cognitive decline. METHODS: Participants were members of the National Academy of Sciences-National Research Council's Twin Registry of male veterans of World War II with self or proxy-reported history of TBI and with up to 4 observations over 12 years of the modified Telephone Interview for Cognitive Status (TICS-m). We used linear random-effects mixed models to analyze the association between TBI and TICS-m in the full sample and among co-twins discordant for TBI. Additional TBI predictor variables included number of TBIs, severity (loss of consciousness [LOC]), and age of first TBI (age <25 vs 25+ years [older age TBI]). Models were adjusted for age (centered at 70 years), age-squared, education, wave, twin pair, lifestyle behaviors, and medical conditions. RESULTS: Of 8,662 participants, 25% reported TBI. History of any TBI (ß = -0.56, 95% CI -0.73 to -0.39), TBI with LOC (ß = -0.51, 95% CI -0.71 to -0.31), and older age TBI (ß = -0.66, 95% CI -0.90 to -0.42) were associated with lower TICS-m scores at 70 years. TBI with LOC (ß = -0.03, 95% CI -0.05 to -0.001), more than one TBI (ß = -0.05, 95% CI -0.09 to -0.002,), and older age TBI (ß = -0.06, 95% CI -0.09 to -0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), history of any TBI (ß = -0.55, 95% CI -0.91 to -0.19) and older age TBI (ß = -0.74, 95% CI -1.22 to -0.26) were associated with lower TICS-m scores at 70 years. Those with more than one TBI (ß = -0.13, 95% CI -0.23 to -0.03) and older age TBI (ß = -0.07, 95% CI -0.13 to -0.002) showed greater cognitive decline compared with their co-twin without TBI. DISCUSSION: These findings support an association of the effect of TBI on cognitive score and the rapidity of cognitive decline in later life. The results in monozygotic pairs, who share all genes and many exposures, particularly in early life, provide additional evidence of a causal relationship between TBI and poorer late-life cognitive outcomes.

The Preventing Alzheimer's with Cognitive Training (PACT) randomized clinical trial.

BACKGROUND: To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma ß-amyloid level or apolipoprotein E e4 (APOE e4) allele status. METHODS/DESIGN: This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score > 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer's disease related biomarkers. DISCUSSION: The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health. REGISTRATION: The PACT study is registered at http://Clinicaltrials.govNCT03848312.

Traumatic brain injury and dementia risk in male veteran older twins-Controlling for genetic and early life non-genetic factors.

INTRODUCTION: This study leveraged the twin study design, which controls for shared genetic and early life exposures, to investigate the association between traumatic brain injury (TBI) and dementia. METHODS: Members of the National Academy of Sciences-National Research Council's Twins Registry of World War II male veterans were assigned a cognitive outcome based on a multi-step assessment protocol. History of TBI was obtained via interviews. RESULTS: Among 8302 individuals, risk of non-Alzheimer's disease (non-AD) dementia was higher in those with TBI (hazard ratio [HR] = 2.00, 95% confidence interval [CI], 0.97-4.12), than for AD (HR = 1.23, 95% CI, 0.76-2.00). To add more control of genetic and shared environmental factors, we analyzed 100 twin pairs discordant for both TBI and dementia onset, and found TBI-associated risk for non-AD dementia increased further (McNemar odds ratio = 2.70; 95% CI, 1.27-6.25). DISCUSSION: These findings suggest that non-AD mechanisms may underlie the association between TBI and dementia, potentially providing insight into inconsistent results from prior studies.

Sex Differences in the Association Between Metabolic Dysregulation and Cognitive Aging: The Health and Retirement Study.

BACKGROUND: Dysregulation of some metabolic factors increases the risk of dementia. It remains unclear if overall metabolic dysregulation, or only certain components, contribute to cognitive aging and if these associations are sex specific. METHODS: Data from the 2006-2016 waves of the Health and Retirement Study (HRS) was used to analyze 7 103 participants aged 65 and older at baseline (58% women). We created a metabolic-dysregulation risk score (MDRS) composed of blood pressure/hypertension status, glycosylated hemoglobin (HbA1c)/diabetes status, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and waist circumference, and assessed cognitive trajectories from repeated measures of the HRS-Telephone Interview for Cognitive Status (HRS-TICS) over 10 years of follow-up. Linear mixed-effects models estimated associations between MDRS or individual metabolic factors (biomarkers) with mean and change in HRS-TICS scores and assessed sex-modification of these associations. RESULTS: Participants with higher MDRSs had lower mean HRS-TICS scores, but there were no statistically significant differences in rate of decline. Sex stratification showed this association was present for women only. MDRS biomarkers revealed heterogeneity in the strength and direction of associations with HRS-TICS. Lower HRS-TICS levels were associated with hypertension, higher HbA1c/diabetes, and lower HDL-C and TC, whereas faster rate of cognitive decline was associated with hypertension, higher HbA1c/diabetes, and higher TC. Participants with higher HbA1c/diabetes presented worse cognitive trajectories. Sex differences indicated that women with higher HbA1c/diabetes to have lower HRS-TICS levels, whereas hypertensive males presented better cognitive trajectory. CONCLUSIONS: Our results demonstrate that metabolic dysregulation is more strongly associated with cognition in women compared with men, though sex differences vary by individual biomarker.

Life-course trajectories of body mass index from adolescence to old age: Racial and educational disparities.

No research exists on how body mass index (BMI) changes with age over the full life span and social disparities therein. This study aims to fill the gap using an innovative life-course research design and analytic methods to model BMI trajectories from early adolescence to old age across 20th-century birth cohorts and test sociodemographic variation in such trajectories. We conducted the pooled integrative data analysis (IDA) to combine data from four national population-based NIH longitudinal cohort studies that collectively cover multiple stages of the life course (Add Health, MIDUS, ACL, and HRS) and estimate mixed-effects models of age trajectories of BMI for men and women. We examined associations of BMI trajectories with birth cohort, race/ethnicity, parental education, and adult educational attainment. We found higher mean levels of and larger increases in BMI with age across more recent birth cohorts as compared with earlier-born cohorts. Black and Hispanic excesses in BMI compared with Whites were present early in life and persisted at all ages, and, in the case of Black-White disparities, were of larger magnitude for more recent cohorts. Higher parental and adulthood educational attainment were associated with lower levels of BMI at all ages. Women with college-educated parents also experienced less cohort increase in mean BMI. Both race and education disparities in BMI trajectories were larger for women compared with men.

Racially diverse participant registries to facilitate the recruitment of African Americans into presymptomatic Alzheimer's disease studies.

INTRODUCTION: The Alzheimer's Disease Prevention Registry (ADPR) of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center at Duke University has been successful in achieving a racially diverse and "research ready" cohort of cognitively healthy volunteers. METHODS: The ADPR is based on an infrastructure that includes: (1) an administrative leadership team; (2) a coordinating center; (3) an IT management team; (4) a community engagement team; and (5) collaborations with study partners across disciplines. RESULTS: The ADPR currently has more than 4677 members, 26% of whom are African American. The ADPR has supported 21 studies including 8 biomarker studies, 7 clinical trials, 4 cognitive neuroscience studies, and 2 studies assessing novel computerized measures. DISCUSSION: We describe our experiences establishing and maintaining a diverse ADPR as well as insights on recruitment strategies to increase the representation of African Americans in Alzheimer's disease studies.

The NAS-NRC Twin Registry and Duke Twins Study of Memory in Aging: An Update.

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917-1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson's disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).

The Impact of Multiple Dimensions of Socioeconomic Status on Physical Functioning Across the Life Course.

Objective: We used the Physical Performance Across the LifeSpan Study to investigate the relationships of multiple indicators of socioeconomic status (SES), both in early life and late life, with physical function. Method: We examined associations between multiple early and late life SES indicators with physical function measured by aerobic endurance, gait speed, and lower body strength. Results: Higher participant education and household income were associated with increased physical function. In our age-stratified analysis, we observed widening SES disparities with increasing age among those in the two younger strata with lower SES associated with worse physical function. Finally, we observed an association between socioeconomic trend and gait speed, aerobic endurance, and lower body strength. There was also an association between lower aerobic endurance and being in a downward socioeconomic trend. Discussion: These findings highlight the significance of considering multiple dimensions of the social environment as important correlates of physical functioning across the life course.

The Association Between Lipoproteins, Disability, and Physical Function Among Older Costa Rican Adults.

OBJECTIVE: To examine the relationship between total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) with disability and physical performance. METHOD: Wave 1 data were from Costa Rican Longevity and Healthy Aging Study ( n = 2,827). Lipoprotein profiles were measured using blood samples. Disability and physical functioning were measured with activities of daily living/instrumental activities of daily living (ADLs/IADLs) and objective assessment of physical performance. RESULTS: Lower HDL-C was associated with greater ADL disability, and lower TC with longer time to pick-a-pencil and Time-Up-Go (TUG) test. Age interacted between (a) TG and lung function, chair stands, and pick-a-pencil, and (b) HDL-C and TUG. Stratification showed lower TG and longer time picking up a pencil only for those above 84 years. Based on significant interactions with sex, lower TC was associated with slower chair stand time in women and higher HDL-C with slower chair stand time in men. DISCUSSION: Lower levels of lipoproteins may suggest worse physical function, but the association may differ by sex.

The relationship between phytoestrogens and speed of processing.

OBJECTIVE: This study examined the cross-sectional association between phytoestrogens and speed of processing. We hypothesized that higher levels of phytoestrogens would be related to better cognitive performance among older women. METHODS: Participants were from the National Health and Nutrition Examination Survey and consisted of 200 older women (M = 74.4 y). Stepwise regressions examined indicators of speed of processing, measured by the Digit Symbol Substitution Test. Isoflavones, lignans, and individual phytoestrogens were added to the regression after including covariates of age, education, race, smoking, and creatinine. Isoflavones were further broken into quartiles among the sample to further evaluate the nature of the curvilinear association. RESULTS: Results showed a relationship between cognition and lignans, explaining 3.8% of the variance after including the covariates, indicating fewer lignans were associated with better speed of processing (P < 0.001). A significant curvilinear relationship with isoflavones explained 1.3% additional variance (P < 0.001). The moderate-high, low-moderate, and the lowest quartile of isoflavones were associated with better cognition, whereas the highest amount was associated with worse speed of processing. Among the individual phytoestrogens, only enterodiol accounted for 4.4% additional variance after taking into account covariates and indicated a negative association with cognition (P = 0.03). CONCLUSIONS: Results suggest that moderate levels of isoflavones, but not lignans, may be associated with better speed of processing. Caution must remain for high isoflavone amounts due to the negative association with cognition. Given the results, phytoestrogens have the potential to be an intervention target for older females' cognition. To become a viable intervention, further research is needed.

Cholesterol and cognitive performance among community volunteers from the Czech Republic.

BACKGROUND: Research shows that lipid levels may be associated with cognitive function, particularly among women. We aimed to examine total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein (HDL), and HDL/LDL ratio in relation to cognitive performance, measured with six well-established cognitive domains and a composite cognitive score (CCS). METHODS: In this cross-sectional study, biomarkers and neuropsychological assessment were available for 141 adults with MMSE scores ≥ 24 (mean age = 69 years, 47% female, mean education = 14.4 years) attending a neuropsychological evaluation. Ordinary least squares regressions were adjusted for age, gender, education, and depressive symptoms in Model 1 and also for apolipoprotein E4 (APOE4) status in Model 2. RESULTS: High-density lipoprotein cholesterol (HDL-C) was associated with better CCS (ß = 0.24; p = 0.014). This association was significant among women (ß = 0.30; p = 0.026) and not among men (ß = 0.20; p = 0.124). HDL-C was also related to attention/working memory (ß = 0.24; p = 0.021), again only among women (ß = 0.37; p = 0.012) and not men (ß = 0.15; p = 0.271). Adjusting for APOE4 yielded significance for high HDL-C and CCS (ß = 0.24; p = 0.022). CONCLUSIONS: HDL-C was the main lipoprotein affecting cognitive function, with results somewhat more pronounced among women. Research should investigate the possibility of finding ways to boost HDL-C levels to potentially promote cognitive function.

Dementia: a barrier to receiving percutaneous coronary intervention for elderly patients with ST-elevated myocardial infarction.

OBJECTIVE: Percutaneous coronary intervention (PCI) is the first line of treatment for ST-elevated myocardial infarction (STEMI). This study evaluates the role of dementia in diagnostic cardiac catheterization (to receive PCI) in STEMI patients ≥65 years old admitted to high annual volume PCI hospitals. METHODS: Participants were registered in Florida's comprehensive inpatient surveillance system for the years 2006-2007 with principal diagnosis of STEMI. Dementia was defined using ICD-9 codes for presenile, senile, and Alzheimer's type dementia. RESULTS: Data from 8331 STEMI patients were used. Of these, 77.2% were catheterized, 67.2% received PCI, and 9.3% had coronary artery bypass graft (CABG). The mean age of the cohort was 76.3 years (SD 7.8 years.); with 43.3% female, 83.4% white, 4.6% black, and 12% Hispanic/other. Of the 248 (3%) patients with dementia, 42% were catheterized. After adjustment for age, gender, and race/ethnicity, patients with dementia were less likely to be catheterized (RR 0.30, 95% CI 0.30-0.50) than non-demented patients. However, among patients who were catheterized, there was no difference in the use of PCI or CABG for patients with versus without dementia (p = 0.56). Of those with dementia, being older and arriving to the hospital in the afternoon were associated with lower likelihood of being catheterized (RR 0.08, 95% CI 0.02-0.28, and RR 0.30, 95% CI 0.10-0.88, respectively). However, having hyperlipidemia increased the probability of catheterization (RR 3.60, 95% CI 1.86-6.98). CONCLUSION: ST-elevated myocardial infarction patients with dementia were much less likely to receive diagnostic cardiac catheterization, thereby limiting the possibility for receiving optimal care including PCI or CABG.