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Objectives An emerging literature suggests that fertility history, which includes measures of parity and birth timing, may influence cognitive health in older ages, especially among women given their differential exposure to pregnancy and sex hormones. Yet, few studies have examined associations between measures of fertility history and incident dementia in population-based samples. Method We examined the associations between parity, younger age at first birth, and older age at last birth with incident dementia over a 16-year period in a prospective sample of 15,361 men and women aged 51–100 years at baseline drawn from the Health and Retirement Study. We used Cox regression and the Fine and Gray model to obtain cause-specific hazard ratios (csHRs) and subdistribution hazard ratios for incident dementia from gender-stratified models, with the latter method accounting for the semicompeting risk of death. Results During the follow-up period (median 13.0 years), the crude incidence rate for dementia was 16.6 and 19.9 per 1,000 person-years for men and women, respectively. In crude models estimating csHRs, higher parity (vs parity 2) and younger age at first birth were associated with increased risk of dementia for both genders. These associations did not persist after adjusting for sociodemographic characteristics, smoking status, and health conditions, with much of the attenuation in estimates occurring after adjustment for sociodemographic characteristics. Discussion In this population-based, multiethnic cohort, we observed limited evidence for an association between measures of fertility history and incident dementia among men and women after adjusting for potential confounders. [ABSTRACT FROM AUTHOR]

Microbial agents including periodontal pathogens have recently appeared as important actors in Alzheimer's disease (AD) pathology. We examined associations of clinical periodontal and bacterial parameters with incident all-cause and AD dementia as well as AD mortality among US middle-aged and older adults. Clinical [Attachment Loss (AL); probing pocket depth (PPD)] and bacterial [pathogen immunoglobulin G (IgG)] periodontal markers were investigated in relation to AD and all-cause dementia incidence and to AD mortality, using data from the third National Health and Nutrition Examination Surveys (NHANES III, 1988-1994) linked longitudinally with National Death Index and Medicare data through January 1, 2014, with up to 26 years of follow-up. Sex- and age-specific multivariable-adjusted Cox proportional hazards models were conducted. Among those ≥65 years, AD incidence and mortality were consistently associated with PPD, two factors and one cluster comprised of IgG titers against Porphyromonas gingivalis (P. gingivalis), Prevotella melaninogenica (P. melaninogenica) and Campylobacter rectus (C. rectus) among others. Specifically, AD incidence was linked to a composite of C. rectus and P. gingivalis titers (per SD, aHR = 1.22; 95% CI, 1.04-1.43, p = 0.012), while AD mortality risk was increased with another composite (per SD, aHR = 1.46; 95% CI, 1.09-1.96, p = 0.017) loading highly on IgG for P. gingivalis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, C. rectus, Streptococcus intermedius, Capnocylophaga Ochracea, and P. melaninogenica. This study provides evidence for an association between periodontal pathogens and AD, which was stronger for older adults. Effectiveness of periodontal pathogen treatment on reducing sequelae of neurodegeneration should be tested in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Introduction: Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined., Methods: Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]., Results: Hepatitis C (hazard ratio = 3.33, p = 0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample., Discussion: Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes., Highlights: Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Despite the high burden of Alzheimer's disease and other dementias among the Hispanic population worldwide, little is known about how dementia affects healthcare utilizations among this population outside of the US, in particular among those in the Caribbean region., Objective: This study examines healthcare utilization associated with Alzheimer's disease and other dementias among older adults in the Caribbean as compared to the US., Methods: We conducted harmonized analyses of two population-based surveys, the 10/66 Dementia Group Research data collected in Dominican Republic, Cuba, and Puerto Rico, and the US-based Health and Retirement Study. We examined changes in hospital nights and physician visits in response to incident and ongoing dementias., Results: Incident dementia significantly increased the risk of hospitalization and number of hospital nights in both populations. Ongoing dementia increased the risk of hospitalization and hospital nights in the US, with imprecise estimates for the Caribbean. The number of physician visits was elevated in the US but not in the Caribbean., Conclusions: The concentration of increased healthcare utilization on hospital care and among patients with incident dementia suggests an opportunity for improved outpatient management of new and existing dementia patients in the Caribbean.

Differential racial and socioeconomic disparities in dementia incidence across income groups and their underlying mechanisms remain largely unknown. A retrospective cohort study examining all-cause dementia incidence across income groups was conducted linking third National Health and Nutrition Examination Surveys (NHANES III) to Centers for Medicare and Medicaid Services-Medicare data over ≤26 y of follow-up (1988-2014). Cox regression and generalized structural equations models (GSEM) were constructed among adults aged≥60 y at baseline (N = 4,592). Non-Hispanic Black versus White (NHW) adults had higher risk of dementia in age and sex-adjusted Cox regression models (HR = 1.34, 95%CI: 1.15-1.55, P < 0.001), an association that was attenuated in the SES-adjusted model (HR = 1.15, 95%CI: 1.01-1.34, P = 0.092). SES was inversely related to dementia risk overall (per Standard Deviation, HR = 0.80, 95% CI:0.69-0.92, P = 0.002, Model 2), mainly within the middle-income group. Within the lowest and middle-income groups and in socio-economic status (SES)-adjusted models, Mexican American participants were at lower all-cause dementia risk compared with their NHW counterparts. GSEM models further detected 3 pathways explaining >55% of the total effect of SES on dementia risk (Total effect = -0.160 ± 0.067, p = 0.022), namely SES→LIFESTYLE→DEMENTIA (Indirect effect (IE) = -0.041 ± 0.014, p = 0.004), SES→LIFESTYLE→COGN→DEMENTIA (IE = -0.006 ± 0.001, p < 0.001), SES→COGN→DEMENTIA(IE = -0.040 ± 0.008, p < 0.001), with the last two remaining significant or marginally significant in the uppermost income groups. Diet and social support were among key lifestyle factors involved in socio-economic disparities in dementia incidence. We provide evidence for modifiable risk factors that may delay dementia onset differentially across poverty-income ratio groups, underscoring their importance for future observational and intervention studies., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objectives: Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and Alzheimer disease (AD) dementia among US middle-aged and older adults., Methods: Using data from the third National Health and Nutrition Examination Surveys (1988-1994), linked with Centers for Medicare & Medicaid follow-up data, we tested associations and interactions of serum vitamins A, C, and E and total and individual serum carotenoids and interactions with incident AD and all-cause dementia. Cox proportional hazards regression models were conducted., Results: After ≤26 years follow-up (mean 16-17 years, 7,283 participants aged 45-90 years at baseline), serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia (65+ age group), even in the lifestyle-adjusted model (per SD: hazard ratio [HR] 0.93, 95% CI 0.87-0.99; p = 0.037), but attenuated in comparison with a socioeconomic status (SES)-adjusted model (HR 0.92, 95% CI 0.86-0.93; p = 0.013). An inverse relationship was detected between serum β-cryptoxanthin (per SD increase) and all-cause dementia (45+ and 65+) for age- and sex-adjusted models (HR 0.86, 95% CI 0.80-0.93; p < 0.001 for 45+; HR 0.86, 95% CI 0.80-0.93; p = 0.001 for 65+), a relationship remaining strong in SES-adjusted models (HR 0.89, 95% CI 0.82-0.96; p = 0.006 for 45+; HR 0.88, 95% CI 0.81-0.96; p = 0.007 for 65+), but attenuated in subsequent models. Antagonistic interactions indicate putative protective effects of 1 carotenoid may be observed at lower levels other carotenoids or antioxidant vitamin., Discussion: Incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and β-cryptoxanthin levels. Further studies with time-dependent exposures and randomized trials are needed to test neuroprotective effects of supplementing the diet with select carotenoids., Classification of Evidence: This study provides Class II evidence that incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and β-cryptoxanthin levels., (© 2022 American Academy of Neurology.)

Background: To identify key socio-demographic, lifestyle, and health predictors of self-reported coronavirus disease 2019 (Covid-19) history, examine cardiometabolic health characteristics as predictors of self-reported Covid-19 history and compare groups with and without a history of Covid-19 on trajectories in cardiometabolic health and blood pressure measurements over time, among United States (U.S.) older adults., Methods: Nationally representative longitudinal data on U.S. older adults from the 2006-2020 Health and Retirement Study were analyzed using logistic and mixed-effects logistic regression models., Results: Based on logistic regression, number of household members (OR=1.26, 95% CI: 1.05, 1.52), depressive symptoms score (OR = 1.21, 95% CI: 1.04, 1.42) and number of cardiometabolic risk factors or chronic conditions ("1-2" vs "0") (OR = 0.27, 95% CI: 0.11, 0.67) were significant predictors of self-reported Covid-19 history. Based on mixed-effects logistic regression, several statistically significant predictors of Covid-19 history were identified, including female sex (OR = 3.06, 95% CI: 1.57, 5.96), other race (OR = 5.85, 95% CI: 2.37, 14.43), Hispanic ethnicity (OR = 2.66, 95% CI: 1.15, 6.17), number of household members (OR = 1.25, 95% CI: 1.10, 1.42), moderate-to-vigorous physical activity (1-4 times per month vs never) (OR = 0.38, 95% CI: 0.18, 0.78) and number of cardiometabolic risk factors or chronic conditions ("1-2" vs "0") (OR = 0.34, 95% CI: 0.19, 0.60)., Conclusions: Number of household members, depressive symptoms and number of cardiometabolic risk factors or chronic conditions may be key predictors for self-reported Covid-19 history among U.S. older adults. In-depth analyses are needed to confirm preliminary findings., (Published by Elsevier Inc.)

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US., Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017., Design, Setting, and Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus., Exposures: Any of the 14 listed neurological diseases., Main Outcome and Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated., Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus., Conclusions and Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.

Importance: Vital statistics are the primary source of data used to understand the mortality burden of dementia in the US, despite evidence that dementia is underreported on death certificates. Alternative estimates, drawing on population-based samples, are needed., Objective: To estimate the percentage of deaths attributable to dementia in the US., Design, Setting, and Participants: A prospective cohort study of the Health and Retirement Study of noninstitutionalized US individuals with baseline exposure assessment in 2000 and follow-up through 2009 was conducted. Data were analyzed from November 2018 to May 2020. The sample was drawn from 7489 adults aged 70 to 99 years interviewed directly or by proxy. Ninety participants with missing covariates or sample weights and 57 participants lost to follow-up were excluded. The final analytic sample included 7342 adults., Exposure: Dementia and cognitive impairment without dementia (CIND) were identified at baseline using Health and Retirement Study self- or proxy-reported cognitive measures and the validated Langa-Weir score cutoff., Main Outcomes and Measures: Hazard ratios relating dementia and CIND status to all-cause mortality were estimated using Cox proportional hazards regression models, accounting for covariates, and were used to calculate population-attributable fractions. Results were compared with information on cause of death from death certificates., Results: Of the 7342 total sample, 4348 participants (60.3%) were women. At baseline, 4533 individuals (64.0%) were between ages 70 and 79 years, 2393 individuals (31.0%) were between 80 and 89 years, and 416 individuals (5.0%) were between 90 and 99 years; percentages were weighted. The percentage of deaths attributable to dementia was 13.6% (95% CI, 12.2%-15.0%) between 2000 and 2009. The mortality burden of dementia was significantly higher among non-Hispanic Black participants (24.7%; 95% CI, 17.3-31.4) than non-Hispanic White participants (12.2%; 95% CI, 10.7-13.6) and among adults with less than a high school education (16.2%; 95% CI, 13.2%-19.0%) compared with those with a college education (9.8%; 95% CI, 7.0%-12.5%). Underlying cause of death recorded on death certificates (5.0%; 95% CI, 4.3%-5.8%) underestimated the contribution of dementia to US mortality by a factor of 2.7. Incorporating deaths attributable to CIND revealed an even greater underestimation., Conclusions and Relevance: The findings of this study suggest that the mortality burden associated with dementia is underestimated using vital statistics, especially when considering CIND in addition to dementia.

Background: Studies examining risk factors for dementia have typically focused on testing a priori hypotheses within specific risk factor domains, leaving unanswered the question of what risk factors across broad and diverse research fields may be most important to predicting dementia. We examined the relative importance of 65 sociodemographic, early-life, economic, health and behavioral, social, and genetic risk factors across the life course in predicting incident dementia and how these rankings may vary across racial/ethnic (non-Hispanic white and black) and gender (men and women) groups., Methods and Findings: We conducted a prospective analysis of dementia and its association with 65 risk factors in a sample of 7,908 adults aged 51 years and older from the nationally representative US-based Health and Retirement Study. We used traditional survival analysis methods (Fine and Gray models) and a data-driven approach (random survival forests for competing risks) which allowed us to account for the semi-competing risk of death with up to 14 years of follow-up. Overall, the top five predictors across all groups were lower education, loneliness, lower wealth and income, and lower self-reported health. However, we observed variation in the leading predictors of dementia across racial/ethnic and gender groups such that at most four risk factors were consistently observed in the top ten predictors across the four demographic strata (non-Hispanic white men, non-Hispanic white women, non-Hispanic black men, non-Hispanic black women)., Conclusions: We identified leading risk factors across racial/ethnic and gender groups that predict incident dementia over a 14-year period among a nationally representative sample of US aged 51 years and older. Our ranked lists may be useful for guiding future observational and quasi-experimental research that investigates understudied domains of risk and emphasizes life course economic and health conditions as well as disparities therein., Competing Interests: The authors have declared that no competing interests exist.

Behavioral and social scientists have identified many nonbiological predictors of mortality. An important limitation of much of this research, however, is that risk factors are not studied in comparison with one another or from across different fields of research. It therefore remains unclear which factors should be prioritized for interventions and policy to reduce mortality risk. In the current investigation, we compare 57 factors within a multidisciplinary framework. These include ( i ) adverse socioeconomic and psychosocial experiences during childhood and ( ii ) socioeconomic conditions, ( iii ) health behaviors, ( iv ) social connections, ( v ) psychological characteristics, and ( vi ) adverse experiences during adulthood. The current prospective cohort investigation with 13,611 adults from 52 to 104 y of age (mean age 69.3 y) from the nationally representative Health and Retirement Study used weighted traditional (i.e., multivariate Cox regressions) and machine-learning (i.e., lasso, random forest analysis) statistical approaches to identify the leading predictors of mortality over 6 y of follow-up time. We demonstrate that, in addition to the well-established behavioral risk factors of smoking, alcohol abuse, and lack of physical activity, economic (e.g., recent financial difficulties, unemployment history), social (e.g., childhood adversity, divorce history), and psychological (e.g., negative affectivity) factors were also among the strongest predictors of mortality among older American adults. The strength of these predictors should be used to guide future transdisciplinary investigations and intervention studies across the fields of epidemiology, psychology, sociology, economics, and medicine to understand how changes in these factors alter individual mortality risk., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Concerned about potentially increased risk of neurodegenerative disease, several health professionals and policy makers have proposed limiting or banning youth participation in American-style tackle football. Given the large affected population (over 1 million boys play high school football annually), careful estimation of the long-term health effects of playing football is necessary for developing effective public health policy. Unfortunately, existing attempts to estimate these effects tend not to generalize to current participants because they either studied a much older cohort or, more seriously, failed to account for potential confounding. We leverage data from a nationally representative cohort of American men who were in grades 7-12 in the 1994-95 school year to estimate the effect of playing football in adolescent on depression in early adulthood. We control for several potential confounders related to subjects' health, behavior, educational experience, family background, and family health history through matching and regression adjustment. We found no evidence of even a small harmful effect of football participation on scores on a version of the Center for Epidemiological Studies Depression scale (CES-D) nor did we find evidence of adverse associations with several secondary outcomes including anxiety disorder diagnosis or alcohol dependence in early adulthood. For men who were in grades 7-12 in the 1994-95 school year, participating or intending to participate in school football does not appear to be a major risk factor for early adulthood depression., Competing Interests: The authors have declared that no competing interests exist.

Background: Prior work has established sociodemographic, lifestyle, and behavioral risk factors for diabetes but the contribution of these factors to the onset of diabetes remains unclear when accounting for genetic propensity for diabetes. We examined the contribution of a diabetes polygenic score (PGS) to the onset of diabetes in the context of modifiable known risk factors for diabetes., Methods: Our sample consisted of 15,190 respondents in the United States-based Health and Retirement Study, a longitudinal study with up to 22 years of follow-up. We performed multivariate Cox regression models stratified by race (non-Hispanic white and non-Hispanic black) with time-varying covariates., Results: We observed 4217 (27.76%) cases of incident diabetes over the survey period. The diabetes PGS was statistically significantly associated with diabetes onset for both non-Hispanic whites (hazard ratio [HR] = 1.38, 95% confidence interval [CI] = 1.30, 1.46) and non-Hispanic blacks (HR = 1.22, 95% CI = 1.06, 1.40) after adjusting for a range of known risk factors for diabetes, highlighting the critical role genetic endowment might play. Nevertheless, genetics do not downplay the role that modifiable characteristics could still play in diabetes management; even with the inclusion of the diabetes PGS, several behavioral and lifestyle characteristics remained significant for both race groups., Conclusions: The effects of genetic and lifestyle characteristics should be taken into consideration for both future studies and diabetes management.