Older adults with dementia including Alzheimer's disease may have difficulty communicating their treatment preferences and thus may receive intensive end-of-life (EOL) care that confers limited ...benefits.
This study compared the use of life-sustaining interventions during the last 90 days of life among Medicare beneficiaries with and without dementia.
This cohort study utilized population-based national survey data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. Our sample included Medicare fee-for-service beneficiaries aged 65 years or older deceased between 2000 and 2016. The main outcome was receipt of any life-sustaining interventions during the last 90 days of life, including mechanical ventilation, tracheostomy, tube feeding, and cardiopulmonary resuscitation. We used logistic regression, stratified by nursing home use, to examine dementia status (no dementia, non-advanced dementia, advanced dementia) and patient characteristics associated with receiving those interventions.
Community dwellers with dementia were more likely than those without dementia to receive life-sustaining treatments in their last 90 days of life (advanced dementia: OR = 1.83 1.42-2.35; non-advanced dementia: OR = 1.16 1.01-1.32). Advance care planning was associated with lower odds of receiving life-sustaining treatments in the community (OR = 0.84 0.74-0.96) and in nursing homes (OR = 0.68 0.53-0.86). More beneficiaries with advanced dementia received interventions discordant with their EOL treatment preferences.
Community dwellers with advanced dementia were more likely to receive life-sustaining treatments at the end of life and such treatments may be discordant with their EOL wishes. Enhancing advance care planning and patient-physician communication may improve EOL care quality for persons with dementia.
Background
Genome‐wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering ...gene–environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome‐wide by environment interaction study (GWEIS) of depressive symptoms.
Methods
Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome‐wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts.
Results
No SNPs achieved genome‐wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10−8) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10−7) and rs4542757 (intronic to DCC, P = 7.31 × 10−7). In the GEWIS with stressful life events, one interaction signal was genome‐wide significant in African Americans (rs4652467; P = 4.10 × 10−10; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self‐reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample.
Conclusions
Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.
The epigenome likely interacts with traditional and genetic risk factors to influence blood pressure. We evaluated whether 13 previously reported DNA methylation sites (CpGs) are associated with ...systolic (SBP) or diastolic (DBP) blood pressure, both individually and aggregated into methylation risk scores (MRS), in 3070 participants (including 437 African ancestry (AA) and 2021 European ancestry (EA), mean age = 70.5 years) from the Health and Retirement Study. Nine CpGs were at least nominally associated with SBP and/or DBP after adjusting for traditional hypertension risk factors (
< 0.05). MRS
was positively associated with SBP in the full sample (β = 1.7 mmHg per 1 standard deviation in MRS
;
= 2.7 × 10
) and in EA (β = 1.6;
= 0.001), and MRS
with DBP in the full sample (β = 1.1;
= 1.8 × 10
), EA (β = 1.1;
= 7.2 × 10
), and AA (β = 1.4;
= 0.03). The MRS and BP-genetic risk scores were independently associated with blood pressure in EA. The effects of both MRSs were weaker with increased age (
< 0.01), and the effect of MRS
was higher among individuals with at least some college education (
= 0.02). In AA, increasing MRS
was associated with higher SBP in females only (
= 0.01). Our work shows that MRS is a potential biomarker of blood pressure that may be modified by traditional hypertension risk factors.
Background
Older adults with dementia have difficulties communicating their treatment preferences and experience end‐of‐life burdensome interventions with discomfort and limited benefits. This study ...compared utilization of burdensome interventions during the last 90 days of life among Medicare fee‐for‐service (FFS) beneficiaries with no dementia, non‐advanced dementia, and advanced dementia.
Method
This study utilized data from 2000‐2016 Health and Retirement Study (HRS) linked with Medicare and Medicaid claims, and HRS Exit Interviews. We quantified rates of imaging tests and life‐sustaining treatments during the last 90 days of life among those with no dementia, non‐advanced dementia, and advanced dementia. Life‐sustaining treatments include tube feeding, intensive care unit care, cardiopulmonary resuscitation, and invasive mechanical ventilation. Among patients with a claims‐based diagnosis of dementia, we classified them as having advanced dementia if they had three or more activities of daily living limitations and any diagnosis of malnutrition, pressure ulcer, incontinence, or aspiration pneumonia. We used logistic regression to examine factors associated with end‐of‐life imaging tests and life‐sustaining treatments.
Result
A higher proportion of beneficiaries with non‐advanced dementia (68%) and advanced dementia (79%) had end‐of‐life imaging tests, compared to those without dementia (57%) (p<0.01). Beneficiaries with dementia were more likely than non‐dementia beneficiaries to receive these imaging tests, controlling for patient characteristics (non‐advanced dementia: OR = 2.2 95% CI 2.0‐2.5; advanced dementia: OR = 5.4 4.5‐6.5). The proportion of receiving end‐of‐life life‐sustaining treatments was lower among the non‐advanced dementia cohort (23%), compared to non‐dementia (27%) and advanced‐dementia (27%) individuals (p<0.01). After adjusting for patient characteristics, beneficiaries with dementia were more likely than those without dementia to receive at least one life‐sustaining treatment (non‐advanced dementia: OR = 1.1 1.0‐1.2; advanced dementia: OR = 1.9 1.6‐2.3). Younger age, survey self‐respondents, beneficiaries with fewer instrumental activities of daily living limitations and no advance care planning were more likely to have end‐of‐life imaging tests and life‐sustaining treatments.
Conclusion
Our findings suggest that older adults with dementia, especially advanced dementia, are more likely to receive end‐of‐life burdensome interventions compared to individuals without dementia. Advance care planning involving patients with dementia, their families, and physicians about end‐of‐life treatment may improve the quality of care.
Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index)-associated genetic loci identified ...through large-scale genome-wide association studies (GWAS) only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms) modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS). In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs) within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS). Childhood socioeconomic status (parental education) was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488) by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA) (
= 0.07).
The pool of studies examining ethnic and racial differences in hospice use and end-of-life hospitalizations among patients with dementia is limited and results are conflicting, making it difficult to ...assess health care needs of underresourced racial and ethnic groups.
To explore differences in end-of-life utilization of hospice and hospital services among patients with dementia by race and ethnicity.
This cohort study used national survey data from the Health and Retirement Study linked with Medicare and Medicaid claims that reflected a range of socioeconomic, health, and psychosocial characteristics. Eligible participants were Medicare fee-for-service beneficiaries aged 65 years or older diagnosed with dementia who died between 2000 and 2016. Analyses were performed from June to December 2021.
Race and ethnicity.
We examined the frequency and costs of hospice care, emergency department (ED) visits, and hospitalizations during the last 180 days of life among Medicare decedents with dementia. We analyzed the proportion of dementia decedents with advance care planning and their end-of-life care preferences.
The cohort sample included 5058 beneficiaries with dementia (mean SD age, 85.5 8.0 years; 3038 women 60.1%; 809 16.0% non-Hispanic Black, 357 7.1% Hispanic, and 3892 non-Hispanic White respondents 76.9%). In adjusted analysis, non-Hispanic Black decedents (odds ratio OR, 0.65; 95% CI, 0.55-0.78), nursing home residents (OR, 0.81; 95% CI, 0.71-0.93), and survey respondents represented by a proxy (OR, 0.84; 95% CI, 0.71-0.99) were less likely to use hospice, whereas older decedents (age 75-84 vs 65-74 years: OR, 1.39; 95% CI, 1.12-1.72; age ≥85 vs 65-74 years: OR, 1.39; 95% CI, 1.13-1.71), women (OR, 1.19; 95% CI, 1.05-1.35), and decedents with higher education (high school vs less than high school: OR, 1.17; 95% CI, 1.01-1.36; more than high school vs less than high school: OR, 1.32; 95% CI, 1.13-1.54), more severe cognitive impairment (OR, 1.51; 95% CI, 1.02-2.23), and more instrumental activities of daily living limitations (OR, 1.07; 95% CI, 1.01-1.12) were associated with higher hospice enrollment. A higher proportion of Black and Hispanic decedents with dementia used ED (645 of 809 79.7% and 274 of 357 76.8% vs 2753 of 3892 70.7%; P < .001) and inpatient services (625 of 809 77.3% and 275 of 357 77.0% vs 2630 of 3892 67.5%; P < .001) and incurred roughly 60% higher inpatient expenditures at the end of life compared with White decedents (estimated mean: Black, $23 279; 95% CI, $20 690-$25 868; Hispanic, $23 471; 95% CI, $19 532-$27 410 vs White, $14 609; 95% CI, $13 800-$15 418). A higher proportion of Black and Hispanic than White beneficiaries with dementia who were enrolled in hospice were subsequently admitted to the ED (56 of 309 18.1% and 22 of 153 14.4% vs 191 of 1967 9.7%; P < .001) or hospital (48 of 309 15.5% and 17 of 153 11.1% vs 119 of 1967 6.0%; P < .001) before death. The proportion of dementia beneficiaries completing advance care planning was lower among Black (146 of 704 20.7%) and Hispanic (66 of 308 21.4%) beneficiaries compared with White beneficiaries (1871 of 3274 57.1%). A higher proportion of Black and Hispanic decedents with dementia had written instructions choosing all care possible to prolong life (30 of 144 20.8% and 12 of 65 18.4% vs 72 of 1852 3.9%), whereas a higher proportion of White decedents preferred to limit care in certain situations (1708 of 1840 92.8% vs 114 of 141 80.9% and 51 of 64 79.7%), withhold treatments (1448 of 1799 80.5% vs 87 of 140 62.1% and 41 of 62 66.1%), and forgo extensive life-prolonging measures (1712 of 1838 93.1% vs 120 of 138 87.0% and 54 of 65 83.1%).
The results of this cohort study highlight unique end-of-life care utilization and treatment preferences across racial and ethnic groups among patients with dementia. Medicare should consider alternative payment models to promote culturally competent end-of-life care and reduce low-value interventions and costs among the population with dementia.
Telomere length (TL) is a widely used marker of biological aging and is associated with an increased risk of morbidity and mortality. Recently, there has been evidence for an association between TL ...and socioeconomic status (SES), particularly for measures of education and childhood SES. Individual differences in TL are also influenced by genetic factors, with heritability estimates from twin and sibling studies ranging from 34 to 82 percent. Yet the additive heritability of TL as a result of measured genetic variations and the extent to which heritability is modified by SES is still unknown. Data from the Health and Retirement Study, a nationally representative cohort of older adults (mean age 69 years), were used to provide the first estimates of molecular-based heritability of TL using genome-wide complex trait analysis (GCTA). We found that additive genetic variance contributed 28 percent (p = .012) of total phenotypic variance of TL in the European American sample (n = 3,290). Estimation using the GCTA and KING Robust relationship inference methods did not differ significantly in this sample. None of the variance from the gene-by-SES interactions examined contributed significantly to the total TL variance. Estimation of heritability and genetic interaction with SES in the African American sample (n = 442) was too unstable to provide reliable estimates.
Cognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive ...impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K, FRMD4B, the HLA gene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, including IFT122 in the hippocampus for SIS, SNX31 in the basal ganglia for B-SEVLT, RPS6KB2 in the frontal cortex for WFT, and CSPG5 in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.
Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of ...coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e.,
< 4.7 × 10
), including two common SNPs in
that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare in European Caucasians (MAF < 0.1%) and the associations were driven by African American samples. There was no evidence for replication of these associations in either TOPMed Stroke samples (
= 5613 cases) or UK Biobank (
= 5874 stroke cases), although power to replicate was very low given the low allele frequencies of the associated variants and a shortage of samples from diverse ancestries. Our study highlights the need for acquiring large, well-powered diverse cohorts to study rare variants, and the technical challenges using array-based genotyping technologies for rare variant genotyping.
Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the ...gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the
genomic region (
= 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the
genomic region (
= 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.
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