There are prominent geographic disparities in the life expectancy (LE) of older US adults between the states with the highest (leading states) and lowest (lagging states) LE and their causes remain ...poorly understood. Heart failure (HF) has been proposed as a major contributor to these disparities. This study aims to investigate geographic disparities in HF outcomes between the leading and lagging states.
The study was a secondary data analysis of HF outcomes in older US adults aged 65+, using Center for Disease Control and Prevention sponsored Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and a nationally representative 5% sample of Medicare beneficiaries over 2000-2017. Empiric estimates of death certificate-based mortality from HF as underlying cause of death (CBM-UCD)/multiple cause of death (CBM-MCD); HF incidence-based mortality (IBM); HF incidence, prevalence, and survival were compared between the leading and lagging states. Cox regression was used to investigate the effect of residence in the lagging states on HF incidence and survival.
Between 2000 and 2017, HF mortality rates (per 100,000) were higher in the lagging states (CBM-UCD: 188.5-248.6; CBM-MCD: 749.4-965.9; IBM: 2656.0-2978.4) than that in the leading states (CBM-UCD: 79.4-95.6; CBM-MCD: 441.4-574.1; IBM: 1839.5-2138.1). Compared to their leading counterparts, lagging states had higher HF incidence (2.9-3.9% vs. 2.2-2.9%), prevalence (15.6-17.2% vs. 11.3-13.0%), and pre-existing prevalence at age 65 (5.3-7.3% vs. 2.8-4.1%). The most recent rates of one- (77.1% vs. 80.4%), three- (59.0% vs. 60.7%) and five-year (45.8% vs. 49.8%) survival were lower in the lagging states. A greater risk of HF incidence (Adjusted Hazards Ratio, AHR 95%CI: 1.29 1.29-1.30) and death after HF diagnosis (AHR: 1.12 1.11-1.13) was observed for populations in the lagging states. The study also observed recent increases in CBMs and HF incidence, and declines in HF prevalence, prevalence at age 65 and survival with a decade-long plateau stage in IBM in both leading and lagging states.
There are substantial geographic disparities in HF mortality, incidence, prevalence, and survival across the U.S.: HF incidence, prevalence at age 65 (age of Medicare enrollment), and survival of patients with HF contributed most to these disparities. The geographic disparities and the recent increase in incidence and decline in survival underscore the importance of HF prevention strategies.
Understanding the dynamics of epidemiologic trends in Alzheimer's disease (AD) and related dementias (ADRD) and their epidemiologic causes is vital to providing important insights into reducing the ...burden associated with these conditions.
To model the time trends in age-adjusted AD/ADRD prevalence and incidence-based mortality (IBM), and identify the main causes of the changes in these measures over time in terms of interpretable epidemiologic quantities.
Trend decomposition was applied to a 5%sample of Medicare beneficiaries between 1991 and 2017.
Prevalence of AD was increasing between 1992 and 2011 and declining thereafter, while IBM increased over the study period with a significant slowdown in its rate of growth from 2011 onwards. For ADRD, prevalence and IBM increased through 2014 prior to taking a downwards turn. The primary determinant responsible for declines in prevalence and IBM was the deceleration in the increase and eventual decrease in incidence rates though changes in relative survival began to affect the overall trends in prevalence/IBM in a noticeable manner after 2008. Other components showed only minor effects.
The prevalence and IBM of ADRD is expected to continue to decrease. The directions of these trends for AD are not clear because AD incidence, the main contributing component, is decreasing but at a decreasing rate suggesting a possible reversal. Furthermore, emerging treatments may contribute through their effects on survival. Improving ascertainment of AD played an important role in trends of AD/ADRD over the 1991-2009/10 period but this effect has exhausted itself by 2017.
Objectives
The regions with highest and lowest Alzheimer's disease (AD) mortality across the United States at state/county levels were identified and their contribution to the differences in total ...mortality rates between these regions was evaluated. The disease, disease group, sex, race/ethnicity, and place‐of‐death‐related inter‐region differences that engender the disparity in mortality were quantitatively described. The hypothesis that inter‐regional differences in filling out death certificates are a major contributor to differences in AD mortality was tested.
Design
Retrospective evaluation of death certificate data.
Setting
The United States.
Participants
Deceased US residents, 1999–2018.
Methods
Region‐specific age‐adjusted mortality rates and group‐specific rate decomposition.
Results
The county clusters with the highest and lowest AD mortality rates were in Washington (WA) and New York (NY), respectively, with other notable high‐mortality clusters on the border of Tennessee, Georgia, and Alabama as well as in North Dakota and South Dakota. These patterns were stable over the 1999–2018 period. AD had the highest contribution to total mortality difference between WA and NY (156%, higher in WA), in contrast circulatory diseases had a contribution of comparable magnitude (154%) but were higher in NY. Differences in cause‐of‐death certificate coding, either through coding of non‐AD dementias, or other conditions accompanying a potential AD death could not account for differences in AD mortality between NY and WA.
Conclusions
Inter‐regional differences in filling out death certificates were not a major contributor to variation in AD mortality between the regions with the highest and lowest rates. The respective mitigation of the effects of neural and circulatory diseases and several other high‐impact conditions would not negate the disparity in mortality between NY and WA.
Resilience Versus Robustness in Aging Ukraintseva, Svetlana; Yashin, Anatoliy I; Arbeev, Konstantin G
The journals of gerontology. Series A, Biological sciences and medical sciences,
11/2016, Letnik:
71, Številka:
11
Journal Article
Alzheimer's disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic ...inheritance. Despite discovering many susceptibility loci, a major proportion of AD genetic variance remains to be explained.
We investigated the genetic architecture of AD in four publicly available independent datasets through genome-wide association, transcriptome-wide association, and gene-based and pathway-based analyses. To explore differences in the genetic basis of AD between males and females, analyses were performed on three samples in each dataset: males and females combined, only males, or only females.
Our genome-wide association analyses corroborated the associations of several previously detected AD loci and revealed novel significant associations of 35 single-nucleotide polymorphisms (SNPs) outside the chromosome 19q13 region at the suggestive significance level of p < 5E-06. These SNPs were mapped to 21 genes in 19 chromosomal regions. Of these, 17 genes were not associated with AD at genome-wide or suggestive levels of associations by previous genome-wide association studies. Also, the chromosomal regions corresponding to 8 genes did not contain any previously detected AD-associated SNPs with p < 5E-06. Our transcriptome-wide association and gene-based analyses revealed that 26 genes located in 20 chromosomal regions outside chromosome 19q13 had evidence of potential associations with AD at a false discovery rate of 0.05. Of these, 13 genes/regions did not contain any previously AD-associated SNPs at genome-wide or suggestive levels of associations. Most of the newly detected AD-associated SNPs and genes were sex specific, indicating sex disparities in the genetic basis of AD. Also, 7 of 26 pathways that showed evidence of associations with AD in our pathway-bases analyses were significant only in females.
Our findings, particularly the newly discovered sex-specific genetic contributors, provide novel insight into the genetic architecture of AD and can advance our understanding of its pathogenesis.
Alzheimer's disease (AD) and related dementia (ADRD) risk is affected by multiple dependent risk factors; however, there is no consensus about their relative impact in the development of these ...disorders.
To rank the effects of potentially dependent risk factors and identify an optimal parsimonious set of measures for predicting AD/ADRD risk from a larger pool of potentially correlated predictors.
We used diagnosis record, survey, and genetic data from the Health and Retirement Study to assess the relative predictive strength of AD/ADRD risk factors spanning several domains: comorbidities, demographics/socioeconomics, health-related behavior, genetics, and environmental exposure. A modified stepwise-AIC-best-subset blanket algorithm was then used to select an optimal set of predictors.
The final predictive model was reduced to 10 features for AD and 19 for ADRD; concordance statistics were about 0.85 for one-year and 0.70 for ten-year follow-up. Depression, arterial hypertension, traumatic brain injury, cerebrovascular diseases, and the APOE4 proxy SNP rs769449 had the strongest individual associations with AD/ADRD risk. AD/ADRD risk-related co-morbidities provide predictive power on par with key genetic vulnerabilities.
Results confirm the consensus that circulatory diseases are the main comorbidities associated with AD/ADRD risk and show that clinical diagnosis records outperform comparable self-reported measures in predicting AD/ADRD risk. Model construction algorithms combined with modern data allows researchers to conserve power (especially in the study of disparities where disadvantaged groups are often grossly underrepresented) while accounting for a high proportion of AD/ADRD-risk-related population heterogeneity stemming from multiple domains.
•A recent symposium debate highlighted disagreements and confusion in aging biology.•Symposium participants followed up by completing an online survey.•Survey results show little common ground on ...most questions in aging biology.•However, there is a near-consensus that aging is heterogeneous and multifactorial.•Work is needed to achieve a common paradigm in aging biology.
At a recent symposium on aging biology, a debate was held as to whether or not we know what biological aging is. Most of the participants were struck not only by the lack of consensus on this core question, but also on many basic tenets of the field. Accordingly, we undertook a systematic survey of our 71 participants on key questions that were raised during the debate and symposium, eliciting 37 responses. The results confirmed the impression from the symposium: there is marked disagreement on the most fundamental questions in the field, and little consensus on anything other than the heterogeneous nature of aging processes. Areas of major disagreement included what participants viewed as the essence of aging, when it begins, whether aging is programmed or not, whether we currently have a good understanding of aging mechanisms, whether aging is or will be quantifiable, whether aging will be treatable, and whether many non-aging species exist. These disagreements lay bare the urgent need for a more unified and cross-disciplinary paradigm in the biology of aging that will clarify both areas of agreement and disagreement, allowing research to proceed more efficiently. We suggest directions to encourage the emergence of such a paradigm.
•Interactions between the GCN2/EIF2AK4 and APP genes were associated with AD in the analysis of human data.•Detection of these associations is a step forward in translation of evidence from ...experimental studies to humans.•Properties of newly constructed composite indices support an idea about involvement of stress related genes in AD.•Studies of candidate medications for AD might benefit from inclusion of stress related genes in the analyses.•Stress related conceptual framework can serve as a research guideline for studying multifactorial AD regulation.
Emerging evidence from experimental and clinical research suggests that stress-related genes may play key roles in AD development. The fact that genome-wide association studies were not able to detect a contribution of such genes to AD indicates the possibility that these genes may influence AD non-linearly, through interactions of their products. In this paper, we selected two stress-related genes (GCN2/EIF2AK4 and APP) based on recent findings from experimental studies which suggest that the interplay between these genes might influence AD in humans. To test this hypothesis, we evaluated the effects of interactions between SNPs in these two genes on AD occurrence, using the Health and Retirement Study data on white indidividuals. We found several interacting SNP-pairs whose associations with AD remained statistically significant after correction for multiple testing. These findings emphasize the importance of nonlinear mechanisms of polygenic AD regulation that cannot be detected in traditional association studies. To estimate collective effects of multiple interacting SNP-pairs on AD, we constructed a new composite index, called Interaction Polygenic Risk Score, and showed that its association with AD is highly statistically significant. These results open a new avenue in the analyses of mechanisms of complex multigenic AD regulation.
Trends in the prevalence of cognitive impairment (CI) based on cognitive assessment instruments are often inconsistent with those of neurocognitive disorders (ND) based on Medicare claims records.
We ...hypothesized that improved ascertainment and resulting decrease in disease severity at the time of diagnosis are responsible for this phenomenon.
Using Medicare data linked to the Health and Retirement Study (1992-2012), we performed a joint analysis of trends in CI and ND to test our hypothesis.
We identified two major contributors to the divergent directions in CI and ND trends: reductions in disease severity explained more than 60% of the differences between CI and ND prevalence over the study period; the remaining 40% was explained by a decrease in the fraction of undiagnosed individuals.
Improvements in the diagnoses of ND diseases were a major contributor to reported trends in ND and CI. Recent forecasts of CI and ND trends in the U.S. may be overly pessimistic.
Objectives
To use the Medicare Files of Service Use (MFSU) to evaluate patterns in the incidence of aging‐related diseases in the U.S. elderly population.
Design
Age‐specific incidence rates of 19 ...aging‐related diseases were evaluated using the National Long Term Care Survey (NLTCS) and the Surveillance, Epidemiology, and End Results (SEER) Registry data, both linked to MFSU (NLTCS‐M and SEER‐M, respectively), using an algorithm developed for individual date at onset evaluation.
Setting
A random sample from the entire U.S. elderly population (Medicare beneficiaries) was used in NLTCS, and the SEER Registry data covers 26% of the U.S. population.
Participants
Thirty‐four thousand seventy‐seven individuals from NLTCS‐M and 2,154,598 from SEER‐M.
Measurements
Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services and procedures, and Medicare enrollment and disenrollment.
Results
The majority of diseases (e.g., prostate cancer, asthma, and diabetes mellitus) had a monotonic decline (or decline after a short period of increase) in incidence with age. A monotonic increase in incidence with age with a subsequent leveling off and decline was observed for myocardial infarction, stroke, heart failure, ulcer, and Alzheimer's disease. An inverted U‐shaped age pattern was detected for lung and colon carcinomas, Parkinson's disease, and renal failure. The results obtained from the NLTCS‐M and SEER‐M were in agreement (excluding an excess for circulatory diseases in the NLTCS‐M). A sensitivity analysis proved the stability of the incidence rates evaluated.
Conclusion
The developed computational approaches applied to the nationally representative Medicare‐based data sets allow reconstruction of age patterns of disease incidence in the U.S. elderly population at the national level with unprecedented statistical accuracy and stability with respect to systematic biases.
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