Identifying risk factors for brain atrophy during the aging process can help direct new preventive approaches for dementia and cognitive decline. The association of neighborhood socioeconomic ...disadvantage with brain volume in this context is not well known.
To test whether neighborhood-level socioeconomic disadvantage is associated with decreased brain volume in a cognitively unimpaired population enriched for Alzheimer disease risk.
This study, conducted from January 6, 2010, to January 17, 2019, at an academic research neuroimaging center, used cross-sectional data on 951 participants from 2 large, ongoing cohort studies of Alzheimer disease (Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center clinical cohort). Participants were cognitively unimpaired based on National Institute on Aging-Alzheimer's Association workgroup diagnostic criteria for mild cognitive impairment and Alzheimer disease, confirmed through a consensus diagnosis panel. The cohort was enriched for Alzheimer disease risk based on family history of dementia. Statistical analysis was performed from April 3 to September 27, 2019.
The Area Deprivation Index, a geospatially determined index of neighborhood-level disadvantage, and cardiovascular disease risk indices were calculated for each participant. Linear regression models were fitted to test associations between relative neighborhood-level disadvantage (highest 20% based on state of residence) and hippocampal and total brain tissue volume, as assessed by magnetic resonance imaging.
In the primary analysis of 951 participants (637 women 67.0%; mean SD age, 63.9 8.1 years), living in the 20% most disadvantaged neighborhoods was associated with 4.1% lower hippocampal volume (β = -317.44; 95% CI, -543.32 to -91.56; P = .006) and 2.0% lower total brain tissue volume (β = -20 959.67; 95% CI, -37 611.92 to -4307.43; P = .01), after controlling for intracranial volume, individual-level educational attainment, age, and sex. Robust propensity score-matched analyses determined that this association was not due to racial/ethnic or demographic characteristics. Cardiovascular risk score, examined in a subsample of 893 participants, mediated this association for total brain tissue but not for hippocampal volume.
For cognitively unimpaired individuals, living in the most disadvantaged neighborhoods was associated with significantly lower cerebral volumes, after controlling for maximal premorbid (total intracranial) volume. This finding suggests an association of community socioeconomic context, distinct from individual-level socioeconomic status, with brain volume during aging. Cardiovascular risk mediated this association for total brain tissue volume but not for hippocampal volume, suggesting that neighborhood-level disadvantage may be associated with these 2 outcomes via distinct biological pathways.
Social determinants of health, such as income, education, housing quality, and employment, are associated with disparities in Alzheimer disease and health generally, yet these determinants are rarely ...incorporated within neuropathology research.
To establish the feasibility of linking neuropathology data to social determinants of health exposures using neighborhood disadvantage metrics (the validated Area Deprivation Index) and to evaluate the association between neighborhood disadvantage and Alzheimer disease-related neuropathology.
This cross-sectional study consisted of decedents with a known home address who donated their brains to 1 of 2 Alzheimer disease research center brain banks in California and Wisconsin between January 1, 1990, and December 31, 2016. Neither site had preexisting social metrics available for their decedents. Neuropathologic features were obtained from each site for data collected using the standardized Neuropathology Data Set form and from autopsy reports. Data were analyzed from June 7 to October 10, 2019.
Geocoded decedent addresses linked to neighborhood disadvantage as measured by the Area Deprivation Index calculated for the year of death.
Presence of Alzheimer disease neuropathology. The association between neighborhood disadvantage and Alzheimer disease neuropathology was evaluated via logistic regression, adjusting for age, sex, and year of death.
The sample consisted of 447 decedents (249 men 56%; mean SD age, 80.3 9.5 years; median year of death, 2011) spanning 24 years of donation. Fewer decedents (n = 24 5.4%) originated from the top 20% most disadvantaged neighborhood contexts. Increasing neighborhood disadvantage was associated with an 8.1% increase in the odds of Alzheimer disease neuropathology for every decile change on the Area Deprivation Index (adjusted odds ratio, 1.08; 95% CI, 1.07-1.09). As such, living in the most disadvantaged neighborhood decile was associated with a 2.18 increased odds of Alzheimer disease neuropathology (adjusted odds ratio, 2.18; 95% CI, 1.99-2.39).
The findings of this cross-sectional study suggest that social determinants of health data can be linked to preexisting autopsy samples as a means to study sociobiological mechanisms involved in neuropathology. This novel technique has the potential to be applied to any brain bank within the United States. To our knowledge, this is the first time Alzheimer disease neuropathology has been associated with neighborhood disadvantage.
Thermostable enzymes and thermophilic cell factories may afford economic advantages in the production of many chemicals and biomass-based fuels. Here we describe and compare the genomes of two ...thermophilic fungi, Myceliophthora thermophila and Thielavia terrestris. To our knowledge, these genomes are the first described for thermophilic eukaryotes and the first complete telomere-to-telomere genomes for filamentous fungi. Genome analyses and experimental data suggest that both thermophiles are capable of hydrolyzing all major polysaccharides found in biomass. Examination of transcriptome data and secreted proteins suggests that the two fungi use shared approaches in the hydrolysis of cellulose and xylan but distinct mechanisms in pectin degradation. Characterization of the biomass-hydrolyzing activity of recombinant enzymes suggests that these organisms are highly efficient in biomass decomposition at both moderate and high temperatures. Furthermore, we present evidence suggesting that aside from representing a potential reservoir of thermostable enzymes, thermophilic fungi are amenable to manipulation using classical and molecular genetics.
Perineural invasion (PNI) is a pathologic finding observed across a spectrum of solid tumors, typically with adverse prognostic implications. Little is known about how the presence of PNI influences ...locoregional recurrence (LRR) among breast cancers. We evaluated the association between PNI and LRR among an unselected, broadly representative cohort of breast cancer patients, and among a propensity-score matched cohort. We ascertained breast cancer patients seen at our institution from 2008 to 2019 for whom PNI status and salient clinicopathologic features were available. Fine-Gray regression models were constructed to evaluate the association between PNI and LRR, accounting for age, tumor size, nodal involvement, estrogen receptor (ER), progesterone receptor (PR), HER2 status, histologic tumor grade, presence of lymphovascular invasion (LVI), and receipt of chemotherapy and/or radiation. Analyses were then refined by comparing PNI-positive patients to a PNI-negative cohort defined by propensity score matching. Among 8864 invasive breast cancers, 1384 (15.6%) were noted to harbor PNI. At a median follow-up of 6.3 years, 428 locoregional recurrence events were observed yielding a 7-year LRR of 7.1% (95% CI 5.5-9.1) for those with PNI and 4.7% (95% CI 4.2-5.3; p = 0.01) for those without. On univariate analysis throughout the entire cohort, presence of PNI was significantly associated with an increased risk of LRR (HR 1.39, 95% CI 1.08-1.78, p < 0.01). Accounting for differences in salient clinicopathologic and treatment parameters by multivariable Fine-Gray regression modeling, the association between PNI and LRR was potentiated (HR 1.57, 95% CI 1.2-2.07, p = 0.001). We further conducted propensity score matching to balance clinicopathologic parameters and treatments between the two groups (PNI vs not), again showing a similar significant association between PNI and LRR (HR 1.46, 95% CI 1.03-2.08, p = 0.034). PNI is significantly associated with LRR following the definitive treatment of invasive breast cancer. The excess risk conferred by PNI is similar in magnitude to that observed with LVI, or by ER/PR negativity. Breast cancer prognostication and therapeutic decision-making should consider the presence of PNI among other salient risk factors. Larger studies among more uniform breast cancer presentations may elucidate the extent to which these findings apply across breast cancer subtypes and stages.
Clostridioides difficile infection (CDI) is commonly associated with outcomes like recurrence and readmission. The effect of social determinants of health, such as 'neighborhood' socioeconomic ...disadvantage, on a CDI patient's health outcomes is unclear. Living in a disadvantaged neighborhood could interfere with a CDI patient's ability to follow post-discharge care recommendations and the success probability of these recommendations, thereby increasing risk of readmission. We hypothesized that neighborhood disadvantage was associated with 30-day readmission risk in Medicare patients with CDI. In this retrospective cohort study, odds of 30-day readmission for CDI patients are evaluated controlling for patient sociodemographics, comorbidities, and hospital and stay-level variables. The cohort was created from a random 20% national sample of Medicare patients during the first 11 months of 2014. From the cohort of 19,490 patients (39% male; 80% white; 83% 65 years or older), 22% were readmitted within 30 days of an index stay. Unadjusted analyses showed that patients from the most disadvantaged neighborhoods were readmitted at a higher rate than those from less disadvantaged neighborhoods (26% vs. 21% rate: unadjusted OR = 1.32 1.20, 1.45). This relationship held in adjusted analyses, in which residence in the most disadvantaged neighborhoods was associated with 16% increased odds of readmission (adjusted OR = 1.16 1.04, 1.28). Residence in disadvantaged neighborhoods poses a significantly increased risk of readmission in CDI patients. Further research should focus on in-depth assessments of this population to better understand the mechanisms underlying these risks and if these findings apply to other infectious diseases.
Background
Readmissions contribute to excessive care costs and burden for people living with dementia. Assessments of racial disparities in readmissions among dementia populations are lacking, and ...the role of social and geographic risk factors such as individual‐level exposure to greater neighborhood disadvantage is poorly understood. We examined the association between race and 30‐day readmissions in a nationally representative sample of Black and non‐Hispanic White individuals with dementia diagnoses.
Methods
This retrospective cohort study used 100% Medicare fee‐for‐service claims from all 2014 hospitalizations nationwide among Medicare enrollees with dementia diagnosis linked to patient, stay, and hospital factors. The sample consisted of 1,523,142 hospital stays among 945,481 beneficiaries. The relationship between all cause 30‐day readmissions and the explanatory variable of self‐reported race (Black, non‐Hispanic White) was examined via generalized estimating equations approach adjusting for patient, stay, and hospital‐level characteristics to model 30‐day readmission odds.
Results
Black Medicare beneficiaries had 37% higher readmission odds compared to White beneficiaries (unadjusted OR 1.37, CI 1.35–1.39). This heightened readmission risk persisted after adjusting for geographic factors (OR 1.33, CI 1.31–1.34), social factors (OR 1.25, CI 1.23–1.27), hospital characteristics (OR 1.24, CI 1.23–1.26), stay‐level factors (OR 1.22, CI 1.21–1.24), demographics (OR 1.21, CI 1.19–1.23), and comorbidities (OR 1.16, CI 1.14–1.17), suggesting racially‐patterned disparities in care account for a portion of observed differences. Associations varied by individual‐level exposure to neighborhood disadvantage such that the protective effect of living in a less disadvantaged neighborhood was associated with reduced readmissions for White but not Black beneficiaries. Conversely, among White beneficiaries, exposure to the most disadvantaged neighborhoods associated with greater readmission rates compared to White beneficiaries residing in less disadvantaged contexts.
Conclusions
There are significant racial and geographic disparities in 30‐day readmission rates among Medicare beneficiaries with dementia diagnoses. Findings suggest distinct mechanisms underlying observed disparities differentially influence various subpopulations.
To determine whether neighborhood socioeconomic disadvantage, as determined by the Area Deprivation Index, increases 30-day hospital re-observation risk.
This retrospective study of 20% Medicare ...fee-for-service beneficiary observation stays from January 1, 2014, to November 30, 2014, included 319,980 stays among 273,308 beneficiaries. We evaluated risk for a 30-day re-observation following an index observation stay for those living in the 15% most disadvantaged compared with the 85% least disadvantaged neighborhoods.
Overall, 4.5% (270,600 of 6,080,664) of beneficiaries had index observation stays, which varied by disadvantage (4.3% 232,568 of 5,398,311 in the least disadvantaged 85% compared with 5.6% 38,032 of 682,353 in the most disadvantaged 15%). Patients in the most disadvantaged neighborhoods had a higher 30-day re-observation rate (2857 of 41,975; 6.8%) compared with least disadvantaged neighborhoods (13,543 of 278,005; 4.9%); a 43% increased risk (unadjusted odds ratio OR, 1.43; 95% CI, 1.31 to 1.55). After adjustment, this risk remained (adjusted OR, 1.13; 95% CI, 1.04 to 1.22). Discharge to a skilled nursing facility reduced 30-day re-observation risk (OR, 0.63; 95% CI, 0.57 to 0.69), whereas index observation length of stay of 4 or more days (3 midnights) conferred increased risk (OR, 1.29; 95% CI, 1.09 to 1.52); those living in disadvantaged neighborhoods were less likely to discharge to skilled nursing facilities and more likely to have long index stays. Beneficiaries with more than one 30-day re-observation (chronic re-observation) had progressively greater disadvantage by number of stays (adjusted incident rate ratio, 1.08; 95% CI, 1.02 to 1.14). Observation prevalence varied nationally.
Thirty-day re-observation, especially chronic re-observation, is highly associated with socioeconomic neighborhood disadvantage, even after accounting for factors such as race, disability, and Medicaid eligibility. Beneficiaries least able to pay are potentially most vulnerable to costs from serial re-observations and challenges of Medicare observation policy, which may discourage patients from seeking necessary care.
Objective
In systemic lupus erythematosus, poor disease outcomes occur in young adults, patients identifying as Black or Hispanic, and socioeconomically disadvantaged patients. These identities and ...social factors differentially shape care access and quality that contribute to lupus health disparities in the US. Thus, our objective was to measure markers of care access and quality, including rheumatology visits (longitudinal care retention) and lupus-specific serology testing, by race and ethnicity, neighborhood disadvantage, and geographic context.
Methods
This cohort study used a geo-linked 20% national sample of young adult Medicare beneficiaries (ages 18–35) with lupus-coded encounters and a 1-year assessment period. Retention in lupus care required a rheumatology visit in each 6-month period, and serology testing required ≥1 complement or dsDNA antibody test within the year. Multivariable logistic regression models were fit for visit-based retention and serology testing to determine associations with race and ethnicity, neighborhood disadvantage, and geography.
Results
Among 1,036 young adults with lupus, 39% saw a rheumatologist every 6 months and 28% had serology testing. White beneficiaries from the least disadvantaged quintile of neighborhoods had higher visit-based retention than other beneficiaries (64% vs 30%–60%). Serology testing decreased with increasing neighborhood disadvantage quintile (aOR 0.80; 95% CI 0.71, 0.90) and in the Midwest (aOR 0.46; 0.30, 0.71).
Conclusion
Disparities in care, measured by rheumatology visits and serology testing, exist by neighborhood disadvantage, race and ethnicity, and region among young adults with lupus, despite uniform Medicare coverage. Findings support evaluating lupus care quality measures and their impact on US lupus outcomes.
PDF
