Genetic associations with dementia-related proteinopathy: Application of item response theory.

INTRODUCTION: Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete. METHODS: We applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aß, tau, α-synuclein, and TDP-43. RESULTS: Final included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aß/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility. DISCUSSION: A novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies. HIGHLIGHTS: Latent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Evaluating ChatGPT's Accuracy in Providing Screening Mammography Recommendations among Older Women: Artificial Intelligence and Cancer Communication.

Abstract Objective: The U.S. Preventive Services Task Force (USPSTF) recommends biennial screening mammography through age 74. Guidelines vary as to whether or not they recommended mammography screening to women aged 75 and older. This study aims to determine the ability of ChatGPT to provide appropriate recommendations for breast cancer screening in patients aged 75 years and older. Methods: 12 questions and 4 clinical vignettes addressing fundamental concepts about breast cancer screening and prevention in patients aged 75 years and older were created and asked to ChatGPT three consecutive times to generate 3 sets of responses. The responses were graded by a multi-disciplinary panel of experts in the intersection of breast cancer screening and aging . The responses were graded as 'appropriate', 'inappropriate', or 'unreliable' based on the reviewer's clinical judgment, content of the response, and whether the content was consistent across the three responses . Appropriateness was determined through a majority consensus. Results: The responses generated by ChatGPT were appropriate for 11/17 questions (64%). Three questions were graded as inappropriate (18%) and 2 questions were graded as unreliable (12%). A consensus was not reached on one question (6%) and was graded as no consensus. Conclusions: While recognizing the limitations of ChatGPT, it has potential to provide accurate health care information and could be utilized by healthcare professionals to assist in providing recommendations for breast cancer screening in patients age 75 years and older. Physician oversight will be necessary, due to the possibility of ChatGPT to provide inappropriate and unreliable responses, and the importance of accuracy in medicine.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Racial and socioeconomic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy.

PURPOSE: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. METHODS: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. RESULTS: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03-1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05-1.21). CONCLUSIONS: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance.

Food insecurity is associated with chronic pain and high-impact chronic pain in the USA.

OBJECTIVE: This study evaluated whether food insecurity (US Adult Food Security Survey) was associated with chronic pain (≥ 3 months) and high-impact chronic pain (i.e. pain that limits work and life) among US adults. DESIGN: Cross-sectional analysis. SETTING: Nationally representative sample of non-institutionalised adults in the USA. PARTICIPANTS: 79 686 adults from the National Health Interview Survey (2019-2021). RESULTS: Marginal, low and very low food security were associated with increased prevalence odds of chronic pain (OR: 1·58 (95 % CI 1·44, 1·72), 2·28 (95 % CI 2·06, 2·52) and 3·37 (95 % CI 3·01, 3·78), respectively) and high-impact chronic pain (OR: 1·28 (95 % CI 1·14, 1·42), 1·55 (95 % CI 1·37, 1·75) and 1·90 (95 % CI 1·65, 2·18), respectively) in a dose-response fashion (P-trend < 0·0001 for both), adjusted for sociodemographic, socio-economic and clinically relevant factors. Participation in Supplemental Nutrition Assistance Program (SNAP) and age modified the association between food insecurity and chronic pain. CONCLUSIONS: These findings illustrate the impact of socio-economic factors on chronic pain and suggest that food insecurity may be a social determinant of chronic pain. Further research is needed to better understand the complex relationship between food insecurity and chronic pain and to identify targets for interventions. Moreover, the consideration of food insecurity in the clinical assessment of pain and pain-related conditions among socio-economically disadvantaged adults may be warranted.

Allostatic load and risk of all-cause, cancer-specific, and cardiovascular mortality in older cancer survivors: an analysis of the National Health and Nutrition Examination Survey 1999-2010.

Background: Allostatic load has been linked to an increased risk of death in various populations. However, to date, there is no research specifically investigating the effect of allostatic load on mortality in older cancer survivors. Aims: To investigate the association between allostatic load (AL) and mortality in older cancer survivors. Method: A total of 1,291 adults aged 60 years or older who survived for ≥1 year since cancer diagnoses were identified from the 1999-2010 National Health and Nutrition Examination Survey. AL was the exposure of interest incorporating 9 clinical measures/biomarkers; one point was added to AL if any of the measures/biomarkers exceeded the normal level. The sum of points was categorized as an ordinal variable to reflect low, moderate, and high AL. Our outcomes of interest were all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. Death was identified by linkage to the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (CI) of mortality by AL category. Results: Overall, 53.6% of participants were male and 78.4% were white. The mean age of study participants at interview was 72.8 years (SD=7.1). A total of 546 participants died during the follow-up (median follow-up time: 8.0 years). Among them, 158 died of cancer and 106 died of cardiovascular events. Results from multivariable Cox proportional hazards models showed that higher ALS was positively associated with higher all-cause mortality (ALS=4-9 vs. ALS =0-1: aHR=1.52, 95% CI =1.17-1.98, p-trend<0.01) and higher cancer-specific mortality (ALS=4-9 vs. ALS =0-1: aHR=1.80, 95% CI =1.12-2.90, p-trend=0.01). The association between ALS and cardiovascular mortality was positive but non-significant (ALS=4-9 vs. ALS =0-1: aHR=1.59, 95% CI =0.86-2.94, p-trend=0.11). Conclusions: Our study suggests that older cancer survivors can have a higher risk of death if they have a high burden of AL.

Clinician and patient perspectives on screening mammography among women age 75 and older: A pilot study of a novel decision aid.

Objective: Supporting patient-clinician communication is key to implementing tailored, risk-based screening for older adults. Objectives of this multiphase mixed methods study were to identify factors that primary care clinicians consider influential when making screening mammography recommendations for women ≥ 75 years, develop a patient decision aid that incorporates these factors, and gather feasibility and acceptability from the patients' perspective. Methods: Clinicians from a Mid-Atlantic practice network completed online surveys. Women in the same network completed surveys before and after receiving a tailored booklet that included information about the benefits and harms of screening for women ≥ 75 years, a breast cancer risk-estimate, and a question prompt list to support patient-clinician communication. Results: Clinicians (N = 21) were primarily women [57.1%] and practiced family medicine [81.0%]. They cited patients' age ≥ 75 years [95.4%], comorbidity [86.4%], functional status [77.3%], cancer family history [63.6%], U.S. Preventive Services Task Force guidelines [81.8%] and new research [77.3%] as factors influencing their recommendations. Fourteen women completed baseline surveys and received personalized decision aids (Mean age = 79.1 years). Eleven completed the post-intervention survey. All were satisfied with the booklet length, 81.8% found the booklet easy to understand and 72.7% helpful in decision-making Perceived lifetime breast cancer risk decreased significantly from pre- to post-intervention (p = 0.02). Conclusions: Results suggest this decision aid, which incorporates key decisional factors from the clinician's perspective, is feasible and acceptable to patients. Innovation: A tailored decision aid booklet is innovative as it provides information on personalized risk and potential benefits and harms to older women considering screening.

Socioeconomic disparities in immunotherapy use among advanced-stage non-small cell lung cancer patients: analysis of the National Cancer Database.

Socioeconomic and racial disparities exist in access to care among patients with non-small cell lung cancer (NSCLC) in the United States. Immunotherapy is a widely established treatment modality for patients with advanced-stage NSCLC (aNSCLC). We examined associations of area-level socioeconomic status with receipt of immunotherapy for aNSCLC patients by race/ethnicity and cancer facility type (academic and non-academic). We used the National Cancer Database (2015-2016), and included patients aged 40-89 years who were diagnosed with stage III-IV NSCLC. Area-level income was defined as the median household income in the patient's zip code, and area-level education was defined as the proportion of adults aged ≥ 25 years in the patient's zip code without a high school degree. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) using multi-level multivariable logistic regression. Among 100,298 aNSCLC patients, lower area-level education and income were associated with lower odds of immunotherapy treatment (education: aOR 0.71; 95% CI 0.65, 0.76 and income: aOR 0.71; 95% CI 0.66, 0.77). These associations persisted for NH-White patients. However, among NH-Black patients, we only observed an association with lower education (aOR 0.74; 95% CI 0.57, 0.97). Across all cancer facility types, lower education and income were associated with lower immunotherapy receipt among NH-White patients. However, among NH-Black patients, this association only persisted with education for patients treated at non-academic facilities (aOR 0.70; 95% CI 0.49, 0.99). In conclusion, aNSCLC patients residing in areas of lower educational and economic wealth were less likely to receive immunotherapy.

Survival Differences by Comorbidity Burden among Patients with Stage I/II Non-Small-Cell Lung Cancer after Thoracoscopic Resection.

We sought to compare overall survival (OS) by comorbidity burden among patients with stage I/II non-small cell lung cancer (NSCLC) who received thoracoscopic resection. Utilizing data from the National Cancer Database, we conducted a survival analysis among patients aged 50+ with stage I/II NSCLC who received thoracoscopic resection between 2010 and 2017. The comorbidity burden was measured by the Charlson comorbidity index (CCI, 0, 1, 2+). Multivariable Cox proportional hazard models were used to compare overall survival relative to the CCI (CCI of 0 as the referent). Subgroup analyses were conducted considering sex, age groups, days from diagnosis to surgery, facility type, laterality, and type of surgery. For this study, 61,760 patients were included, with a mean age of 69.1 years (SD: 8.5). Notably, 51.2% had a CCI of 0, 31.8% had a CCI of 1, and 17.0% had a CCI of 2+. Most participants were non-Hispanic White (87.5%), and 56.9% were female. We found that an increase in the CCI was associated with a higher risk of all-cause mortality (CCI 1 vs. 0 aHR: 1.24, 95% CI: 1.20-1.28; CCI 2+ vs. 0 aHR: 1.51, 95% CI: 1.45-1.57; p-trend < 0.01). Our subgroup analysis according to sex suggested that the association between CCI and risk of death was stronger in women.

The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study.

BACKGROUND: Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES. METHODS: Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated. RESULTS: 76,095 patients were included in the analysis: 63.2% were <65 years, 73.4% male, and 11.3% non-Hispanic (NH) Black. Most patients (58.3%) were diagnosed at regional or distant stages and 20.6% died of HNC. The five-year relative survival rate increased with SES group, with 51.6% in the lowest SES group, and 74.1% in the highest SES group. NH-Black patients had higher risk of all-cause and HNC-specific mortality than NH-White patients, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of HNC-specific mortality in some SES groups. CONCLUSIONS: NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities. IMPACT: The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.

Associations of Total Body Fat Mass and Skeletal Muscle Index with All-Cause and Cancer-Specific Mortality in Cancer Survivors.

Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m2 for males and less than 5.45 kg/m2 for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06-1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22-1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23-2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39-6.06) compared to White people (aHR = 1.53, 95% CI = 1.19-1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.

Low muscle mass is associated with a higher risk of all-cause and cardiovascular disease-specific mortality in cancer survivors.

OBJECTIVES: Individuals with prior cancer diagnosis are more likely to have low muscle mass (LMM) than their cancer-free counterparts. Understanding the effects of LMM on the prognosis of cancer survivors can be clinically important. The aim of this study was to investigate whether risks for all-cause and cardiovascular disease (CVD)-specific mortality differ by status of LMM in cancer survivors and a matched cohort without cancer history. METHODS: We used cohort data from the 1999-2006 and 2011-2014 National Health and Nutrition Examination Survey. Participants included 946 adults surviving for ≥1 since cancer diagnosis and a matched cohort (by age, sex, and race) without cancer history (N = 1857). LMM was defined by appendicular lean mass and body height (men <7.26 kg/m2, women <5.45 kg/m2). Death was ascertained via the National Death Index and cause of death was assessed via International Classification of Diseases, Tenth Revision. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI) of LMM. RESULTS: The mean age of cancer survivors and matched cohort was 60.6 y (SD 15) and 60.2 y (SD 14.9), respectively. The median follow-up was 10.5 y for survivors and 10.9 y for matched cohort. Overall, 22.2% of cancer survivors and 19.7% of the matched cohort had LMM, respectively. In all, 321 survivors (33.9%) and 495 participants (26.7%) in the matched cohort died during follow-up. CVD-specific deaths were identified in 58 survivors (6.1%) and 122 participants in the matched cohort (6.6%). The multivariable Cox model suggested that LMM was positively associated with all-cause (aHR, 1.73; 95% CI, 1.31-2.29) and CVD-specific (aHR, 2.13; 95% CI, 1.14-4.00) mortality in cancer survivors. The associations between LMM and risk for all-cause (aHR, 1.24; 95% CI, 0.98-1.56) and CVD-specific (aHR, 1.21; 95% CI, 0.75-1.93) mortality were not statistically significant in the matched cohort. CONCLUSION: Cancer survivors with LMM have an increased risk for all-cause and CVD-specific mortality. This increase appears to be larger than that in counterparts without cancer history.

Personalised Lung Cancer Screening (PLuS) study to assess the importance of coexisting chronic conditions to clinical practice and policy: protocol for a multicentre observational study.

INTRODUCTION: Lung cancer is the leading cause of cancer death in the USA and worldwide, and lung cancer screening (LCS) with low-dose CT (LDCT) has the potential to improve lung cancer outcomes. A critical question is whether the ratio of potential benefits to harms found in prior LCS trials applies to an older and potentially sicker population. The Personalised Lung Cancer Screening (PLuS) study will help close this knowledge gap by leveraging real-world data to fully characterise LCS recipients. The principal goal of the PLuS study is to characterise the comorbidity burden of individuals undergoing LCS and quantify the benefits and harms of LCS to enable informed decision-making. METHODS AND ANALYSIS: PLuS is a multicentre observational study designed to assemble an LCS cohort from the electronic health records of ~40 000 individuals undergoing annual LCS with LDCT from 2016 to 2022. Data will be integrated into a unified repository to (1) examine the burden of multimorbidity by race/ethnicity, socioeconomic status and age; (2) quantify potential benefits and harms; and (3) use the observational data with validated simulation models in the Cancer Intervention and Surveillance Modeling Network (CISNET) to provide LCS outcomes in the real-world US population. We will fit a multivariable logistic regression model to estimate the adjusted ORs of comorbidity, functional limitations and impaired pulmonary function adjusted for relevant covariates. We will also estimate the cumulative risk of LCS outcomes using discrete-time survival models. To our knowledge, this is the first study to combine observational data and simulation models to estimate the long-term impact of LCS with LDCT. ETHICS AND DISSEMINATION: The study was approved by the Kaiser Permanente Southern California Institutional Review Board and VA Portland Health Care System. The results will be disseminated through publications and presentations at national and international conferences. Safety considerations include protection of patient confidentiality.

An evaluation of injurious falls and Fall-Risk-Increasing-Drug (FRID) prescribing in ambulatory care in older adults.

BACKGROUND: Falls are a major public health problem affecting millions of older adults each year. Little is known about FRID prescribing behaviors after injurious falls occur. The primary objective of this study was to investigate whether an injurious fall is associated with being prescribed a new FRID. METHODS: We conducted a cross-sectional analysis using data from the National Ambulatory Medical Care Survey (2016). We included visits from patients age ≥ 65 years and classified visits based on presence of an injurious fall. The outcome of interest was prescription of new FRID between those with and without an injurious fall. Multivariable logistic regression weighted for sampling and adjusted for demographics, health history and other medications was used. Age and Alzheimer's disease were examined as potential effect measure modifiers. Odds ratios and 95% confidence intervals were reported. Bayes factor upper bounds were also reported to quantify whether the data were better predicted by the null hypothesis or the alternative hypothesis. RESULTS: The sample included 239,016,482 ambulatory care visits. 5,095,734 (2.1%) of the visits were related to an injurious fall. An injurious fall was associated with a non-statistically significant increase in odds of at least one new FRID prescription: adjusted OR = 1.6 (95% CI 0.6, 4.0). However, there was non-statistically significant evidence that the association depended on patient age, with OR = 2.6 (95% CI 0.9, 7.4) for ages 65-74 versus OR = 0.4 (95% CI 0.1, 1.6) for ages ≥ 75. In addition to age, Alzheimer's disease was also identified as a statistically significant effect measure modifier, but stratum specific estimates were not determined due to small sample sizes. CONCLUSIONS: Ambulatory care visits involving an injurious fall showed a non-statistically significant increase in odds of generating a new FRID prescription, but this association may depend on age.

Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer's-type neuropathology.

Cancer and Alzheimer's disease are common diseases in ageing populations. Previous research has reported a lower incidence of Alzheimer's disease-type (amnestic) dementia among individuals with a diagnosis of cancer. Both cancer and amnestic dementia are prevalent and potentially lethal clinical syndromes. The current study was conducted to investigate the association of cancer diagnosis with neuropathological and cognitive features of dementia. Data were analysed from longitudinally evaluated participants in a community-based cohort study of brain ageing who came to autopsy at the University of Kentucky Alzheimer's Disease Research Center. These data were linked to the Kentucky Cancer Registry, a population-based state cancer surveillance system, to obtain cancer-related data. We examined the relationship between cancer diagnosis, clinical dementia diagnosis, Mini-Mental State Examination scores and neuropathological features using inverse probability weighting to address bias due to confounding and missing data. To address bias due to inclusion of participants with dementia at cohort baseline, we repeated all analyses restricted to the participants who were cognitively normal at baseline. Included participants (n = 785) had a mean ± standard deviation age of death of 83.8 ± 8.6 years; 60.1% were female. Cancer diagnosis was determined in 190 (24.2%) participants, and a diagnosis of mild cognitive impairment or dementia was determined in 539 (68.7%). APOE ɛ4 allele dosage was lower among participants with cancer diagnosis compared to cancer-free participants overall (P = 0.0072); however, this association was not observed among those who were cognitively normal at baseline. Participants with cancer diagnosis had lower odds of mild cognitive impairment or dementia, and higher cognitive test scores (e.g. Mini-Mental State Examination scores evaluated 6 and ≤2 years ante-mortem, P < 0.001 for both comparisons). Cancer diagnosis also associated with lower odds of higher Braak neurofibrillary tangle stages (III/IV) or (V/VI), moderate/frequent neuritic plaques, moderate/frequent diffuse plaques and moderate/severe cerebral amyloid angiopathy (all P < 0.05). By contrast, TDP-43, α-synuclein and cerebrovascular pathologies were not associated with cancer diagnosis. Cancer diagnosis was associated with a lower burden of Alzheimer's disease pathology and less cognitive impairment. These findings from a community-based cohort with neuropathological confirmation of substrates support the hypothesis that there is an inverse relationship between cancer and Alzheimer's disease.

Racial Differences in Survival Among Advanced-stage Non-small-Cell Lung Cancer Patients Who Received Immunotherapy: An Analysis of the US National Cancer Database (NCDB).

Lung cancer is the most common cause of cancer death among men and women in the United States, with significant racial disparities in survival. It is unclear whether these disparities persist upon equal utilization of immunotherapy. The purpose of this study was to evaluate the association between race and all-cause mortality among non-small-cell lung cancer (NSCLC) patients who received immunotherapy. We obtained data from the 2016 National Cancer Database on patients diagnosed with advanced-stage (III-IV) NSCLC from 2015 to 2016. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) by race/ethnicity. A total of 2940 patients were included. Non-Hispanic (NH)-Black patients had a lower risk of death relative to NH-White patients (HR: 0.85; 95% CI: 0.73, 0.98) after adjusting for sociodemographic, clinical, and treatment factors. Formal tests of interaction evaluating race with Charlson-Deyo comorbidity score and race with area-level median income were nonsignificant. However, in stratified analyses, NH-Black versus NH-White patients had a lower risk of death in models adjusted for sociodemographic factors among those with at least 1 comorbidity (HR: 0.75; 95% CI: 0.57, 0.97), and those living in regions within the 2 lowest quartiles of median income (HR: 0.82; 95% CI: 0.68, 0.99). Among advanced-stage NSCLC patients who received immunotherapy, NH-Black patients experienced higher survival compared with NH-White patients. We urge the implementation of policies and interventions that seek to equalize access to care as a means of addressing differences in overall NSCLC survival by race.

Inflammation in Relation to Sarcopenia and Sarcopenic Obesity among Older Adults Living with Chronic Comorbidities: Results from the National Health and Nutrition Examination Survey 1999-2006.

Loss of muscle mass and waning in muscle strength are common in older adults, and inflammation may play a key role in pathogenesis. This study aimed to examine associations of C-reactive protein (CRP) and systemic immune-inflammation index (SII) with sarcopenia and sarcopenic obesity in older adults with chronic comorbidities. Cross-sectional data from the National Health and Nutrition Examination Survey (1999-2006) were obtained for participants aged ≥60 years. Sarcopenia was defined by a lean mass and body height (males < 7.26 kg/m2, females < 5.45 kg/m2). Sarcopenic obesity was defined by the concurrent presence of sarcopenia and obesity (defined by relative fat mass). Logistic regression was used to assess the associations of CRP and SII with sarcopenia and sarcopenic obesity. The dose-response relationship was examined via restricted cubic splines. Of the participants (n = 2483), 23.1% (n = 574) and 7.7% (n = 190) had sarcopenia and sarcopenic obesity, respectively. The multivariable logistic regression models suggested a positive association of SII with sarcopenia and sarcopenic obesity, but a positive statistically significant association was not consistently observed for CRP. Dose-response curves suggested similar association patterns for these biomarkers. In clinical practice, measures to prevent sarcopenia and sarcopenic obesity are needed for older vulnerable people with high systemic inflammation.

Four Common Late-Life Cognitive Trajectories Patterns Associate with Replicable Underlying Neuropathologies.

BACKGROUND: Late-life cognitive function is heterogeneous, ranging from no decline to severe dementia. Prior studies of cognitive trajectories have tended to focus on a single measure of global cognition or individual tests scores, rather than considering longitudinal performance on multiple tests simultaneously. OBJECTIVE: The current study aimed to examine cognitive trajectories from two independent datasets to assess whether similar patterns might describe longitudinal cognition in the decade preceding death, as well as what participant characteristics were associated with trajectory membership. METHODS: Data were drawn from autopsied longitudinally followed participants of two cohorts (total N = 1,346), community-based cohort at the University of Kentucky Alzheimer's Disease Research Center (n = 365) and National Alzheimer's Coordinating Center (n = 981). We used group-based multi-trajectory models (GBMTM) to identify cognitive trajectories over the decade before death using Mini-Mental State Exam, Logical Memory-Immediate, and Animal Naming performance. Multinomial logistic and Random Forest analyses assessed characteristics associated with trajectory groups. RESULTS: GBMTM identified four similar cognitive trajectories in each dataset. In multinomial models, death age, Braak neurofibrillary tangles (NFT) stage, TDP-43, and α-synuclein were associated with declining trajectories. Random Forest results suggested the most important trajectory predictors were Braak NFT stage, cerebral atrophy, death age, and brain weight. Multiple pathologies were most common in trajectories with moderate or accelerated decline. CONCLUSION: Cognitive trajectories associated strongly with neuropathology, particularly Braak NFT stage. High frequency of multiple pathologies in trajectories with cognitive decline suggests dementia treatment and prevention efforts must consider multiple diseases simultaneously.