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PURPOSE: Frailty predicts poor outcomes in older adults with cancer, but how it differs between different cancer types is unknown. We examined differences in pretreatment frailty between colorectal (CRC), pancreatic, and hepatobiliary cancers. METHODS: We included older adults age 60 years or older with the above cancer types enrolled in the Cancer and Aging Resilience Evaluation registry. Frailty was defined using a 44-item Cancer and Aging Resilience Evaluation frailty index constructed on the basis of the principles of deficit accumulation (including several geriatric assessment impairments encompassing malnutrition, functional status, comorbidities, anxiety, depression, cognitive complaints, health-related quality of life, falls, ability to walk one block, interference in social activities, and polypharmacy). Multivariable logistic regression models were used to examine the adjusted odds ratio (aOR) of frailty between cancer types. RESULTS: A total of 505 patients were included (mean age 70 years, 59% male): 211 (41.8%) CRC, 178 (35.2%)pancreatic cancer, and 116 (23.0%) hepatobiliary cancer. Patients with pancreatic cancer had the highest prevalence of frailty (23.3% CRC, 40.6% pancreatic, 34.3% hepatobiliary; P = .001). Both pancreatic (aOR, 2.18; 95% CI, 1.38 to 3.45), and hepatobiliary cancer (aOR, 1.73; 95% CI, 1.03 to 2.93) were independently associated with higher odds of frailty relative to CRC. Frailty was driven by higher rates of malnutrition and instrumental activities of daily living impairments in patients with pancreatic cancer and higher number of comorbidities in patients with hepatobiliary cancer. CONCLUSION: Older adults with pancreatic and hepatobiliary cancers are at high-risk of pretreatment frailty. Early interventions to improve nutritional and functional status and optimization of comorbidities may help improve outcomes.

Background: Cancer-related cognitive impairment (CRCI), a frequent effect of cancer and its treatments, shares common cognitive symptoms with dementia syndromes. Cross-sectional studies demonstrate an inverse relationship between cancer and dementia. However, the longitudinal relationship between dementia decline and cancer has not been investigated. Objective: To evaluate the association between cancer and longitudinal progression of dementia. Methods: We extracted electronic health record data from July 2003 to February 2020 from a single academic medical center. We identified dementia and cancer history prior to dementia using ICD-9/10 codes. We measured cognitive decline with the Alabama Brief Cognitive Screener (ABCs). We used adjusted linear mixed models to estimate baseline cognition and rate of progression by cancer history, including differences by race. Results: The study included 3,809 participants with dementia, of which 672 (17.6%) had cancer history. Those with cancer history had higher baseline cognition (β: 1.07, 95% CI: 0.45, 1.69), but similar rate of decline. Non-Hispanic Blacks had lower cognitive scores at baseline and throughout follow-up regardless of cancer status compared to non-Hispanic Whites and other races/ethnicities with and without cancer history. Conclusion: In this longitudinal retrospective study, participants with cancer history demonstrate better cognition at dementia diagnosis and no difference in cognitive decline than those without cancer history. Smoking and comorbidities attenuate this association and results indicate non-Hispanic Blacks have worse cognitive outcomes in dementia regardless of cancer history than other race/ethnicity groups. Further exploration of the role of smoking, comorbidities, and race/ethnicity on cancer and dementia-related cognitive decline is needed.

Longitudinal change in patient-reported cognitive complaints (CC) in older adults with cancer is poorly understood. The purpose of this study was to evaluate early longitudinal CC and predictors among older adults with cancer.We examined early CC change on the PROMIS® Short Form4a Cognitive Function among adults ≥ 60 years with GI cancer enrolled in the Cancer and Aging Resilience Evaluation (CARE) undergoing geriatric assessment (GA) at baseline and one 3-6-month follow-up. Multivariable linear regression examined associations of demographics, socioeconomics, GA domains, baseline cognitive score, and treatment toxicities on follow-up cognitive score. Bayesian analysis of covariance (ANCOVA) determined best fitting model.A total of 218 participants were included. The median follow-up was 3.7 months, the mean age was 69.2 ± 7.1, and 57.3% were male. The most common cancer was colorectal (30.7%) with most stage III/IV (73.7%). About half (51.8%) had stable cognition baseline to follow-up (follow-up t-score ± 5 points of baseline), 20.6% improved (≥ 5 increase), and 27.5% declined (≥ 5 decrease). After adjustment, there were no significant baseline predictors of follow-up cognitive t-score. Baseline t-score was the best-fitting predictor of follow-up t-score.In this first study, examining early change in CC among older adults with cancer, ~ 28% exhibited cognitive decline. Baseline cognition is the most important early predictor of follow-up cognition. Longer follow-up is needed to identify long-term predictors of CC change in cancer survivors.Cognitive decline, even early, may occur in many older adults with cancer. Baseline and regular follow-up assessments of cognitive symptoms are an important component of survivorship care.

Background Cross-sectional studies suggest self-reported cancer history is associated with decreased risk of Alzheimer's disease (AD). However, little is known about how self-reported cancer affects longitudinal AD progression, the primary outcome in clinical trials and observational studies. Objective To determine self-reported cancer history's effect on longitudinal AD progression in an observational study. Methods We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to evaluate progression to AD by self-reported all-cancer, breast, prostate, colorectal, or non-melanoma skin cancer history. Linear mixed effects models were used to examine baseline differences and rates of progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) by self-reported cancer history. Age at AD onset was examined using consensus clinical diagnoses with Cox proportional hazards regression. Results Among 1,271 participants, models revealed no significant differences in progression over time but did reveal significantly lower baseline ADAS-Cog score, indicating better cognition at a given age in those with self-reported cancer history. Cox models indicated those with self-reported cancer history had significantly later age of AD onset (HR: 0.67, 95% CI: 0.53-0.85) after adjustment for covariates. Conclusion Participants with self-reported cancer history entered ADNI with better cognition and later age of AD onset, but progressed similarly to participants without such history, indicating differences in AD between those with and without self-reported cancer history emerge early in the disease course. Such differences in longitudinal progression by self-reported cancer history could affect AD trials and observational studies, given the current focus on early disease course. Further investigation is warranted with detailed longitudinal assessment of cancer and AD.

Objective To evaluate the ability of persons with metastatic cancer to self‐assess their medical decision‐making capacity (MDC). To investigate this, we compared an objective measure of MDC with self‐ratings and evaluated predictors of agreement. Methods Data were obtained from a cross‐sectional study of metastatic cancer patients at a large academic medical center. Across all standards of MDC, sensitivity, specificity, and reliability using Gwet's AC1 statistic were calculated using the objective measure as the gold standard. Logistic regression was used to evaluate predictors of agreement between the measures across all MDC standards. Results In those with brain metastases, high sensitivity (greater than 0.7), but low specificity was observed for all standards. Poor reliability was observed across all standards. Higher age resulted in higher odds of disagreement for Standard 3 (appreciation) (OR: 1.07, 95% CI: 1.00, 1.15) and Standard 4 (reasoning) (OR: 1.05, 95% CI: 1.00, 1.10). For Standard 3, chemotherapy use and brain metastases compared to other metastases resulted in higher odds of disagreement (Chemotherapy: OR: 5.62, 95% CI: 1.37, 23.09, Brain Metastases: OR: 5.93, 95% CI: 1.28, 27.55). For Standard 5 (understanding), no predictors were associated with disagreement. Conclusions For less cognitively complex standards (e.g., appreciation), self‐report may be more valid and reliable than more cognitively complex standards (e.g., reasoning or understanding). However, overall, MDC self‐report in the current sample is suboptimal. Thus, the need for detailed assessment of MDC, especially when patients are older or used chemotherapy, is indicated. Other studies should be conducted to assess MDC agreement longitudinally.

Highlights • Racial disparities exist in CRC screening by history of CVD in the ACA era. • Hispanics, Whites and women with CVD are more likely to be screened for CRC. • CRC screening in Hispanics with CVD was higher in the stable phase of the ACA era. • CRC screening needs to improve for Blacks, who also bear higher risk of CVD., Colorectal cancer (CRC) and cardiovascular diseases (CVD) share several risk factors. We examined the relationships between CRC screening and CVD history by race/ethnicity and sex. Data from 15 states across the United States with high age-adjusted CVD rates from the 2012–2016 Behavioral Risk Factor Surveillance System were used to examine prevalence of self-reported screening for CRC among 179,276 adults ages 50–75 years with and without history of CVD. Multivariable logistic regression was used to evaluate the association between socio-demographics and CRC screening in the expansion and stable phases of the Affordable Care Act (ACA) era. Prevalence of CRC screening was high among those with history of CVD. After multivariable adjustment, Whites and Hispanics with CVD had 19% (95%[CI]: 1.13–1.26) and 50% (95%[CI]: 1.10–2.06) higher odds for CRC screening, respectively, versus those without CVD. Individuals in both sexes with CVD had higher odds for CRC screening compared those without CVD. Strikingly, the odds for CRC screening in Hispanics with history of CVD were 72% higher in the stable phase of the ACA era for the fully adjusted model. Whites and Hispanics with history of CVD are more likely to undergo CRC screening, perhaps due to greater exposure to the healthcare system due to CVD. This association was not observed in Blacks. Interventions are needed to improve CRC screening rates among Blacks, especially due to their well-documented higher risk of CVD.

Metastatic cancer patients undergo numerous treatment strategies with known cognitive side effects. It is unclear how medical decision-making capacity (MDC) is impacted by cognitive deficits in metastatic cancer. This study examines reliability of an objective measure of MDC compared with self-report. Participants with newly diagnosed metastasis to the brain and other sites were enrolled at the University of Alabama at Birmingham over seven years. At the study visit, participants completed a comprehensive neuropsychological battery including memory and executive functioning, and the Capacity to Consent to Treatment Instrument (CCTI) assessing medico-legal domains of MDC. The CCTI is a reliable and valid instrument containing two vignettes of hypothetical medical situations assessing four standards of consent. We examined reliability between the CCTI and self-reported MDC using Gwet’s AC1 statistic. Participants with brain metastasis with impairment on the CCTI demonstrated significantly lower executive functioning and memory skills than those without impairment (Trails B Raw: 158.20±86.82 vs. 118.90±77.98 p: 0.0248; Digit-Span Raw Forward: 9.13±2.30 vs. 10.12±2.03 p: 0.0254). There were no significant differences between intact and impaired participants with other metastases. Low reliability was observed between self-report and all medico-legal standards on the CCTI across both metastatic groups [Gwet’s AC1 Appreciation: 0.70 (0.58, 0.81); Reasoning: 0.34 (0.16, 0.52); Understanding: 0.44, (0.27, 0.60)]. Self-rating of MDC is unreliable in metastatic cancer patients. Patients with metastases (particularly brain metastases) may lack awareness of deficits in their MDC, so providers must affirm proper autonomy in their decisions.

Background Ovarian cancer remains a leading cause of death from gynecological malignancies. Race, socioeconomic status (SES), and access to health care are important predictors of quality treatment and survival. We provide a systematic review and meta-analysis on the role of these predictors on disparities in ovarian cancer treatment and mortality. Methods Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched PubMed, EMBASE, and Scopus for relevant articles published between January 2000 and March 2017. We selected studies published in the United States that evaluated the role of race, SES, or health-care access on disparities in ovarian cancer treatment or survival. Pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated for each outcome using a random-effects model. Results A total of 41 studies met the inclusion criteria for systematic review. In meta-analysis, there was a 25% decrease (RR = 0.75, 95% CI = 0.66 to 0.84) in receipt of adherent ovarian cancer treatment and 18% increased risk (RR = 1.18, 95% CI = 1.11 to 1.26) of mortality for blacks compared to whites. Receipt of adherent ovarian cancer treatment was 15% lower (RR = 0.85, 95% CI = 0.77 to 0.94) in the lowest vs highest SES group and 30% lower (RR = 0.70, 95% CI = 0.58 to 0.85) among patients at lower vs higher hospital volumes. Conclusion We found consistent and strong evidence for continued lack of quality ovarian cancer treatment and higher mortality among ovarian cancer patients who are black, are of low SES, and/or have poor access to care. Interventions focused on these groups targeting specific barriers to care are needed to reduce disparities in ovarian cancer treatment and mortality.

OBJECTIVES: Hospital-associated disability (HAD), defined as loss of independence in activities of daily living (ADL) following acute hospitalization, is observed among older adults. The study objective is to determine overall prevalence of HAD among older adults hospitalized in acute care, and to assess the impact of study initiation year in moderation of prevalence. DESIGN: Meta-analysis of data collected from randomized trials, quasi-experimental and prospective cohort studies. English-language searches to identify included studies were completed February 2018 and updated May 2018 of electronic databases and reference lists of studies and reviews. Included studies were human subjects investigations that measured ADL ≥ 2 time points before/during and after hospitalization and reported prevalence of ADL decline among older adults. SETTING: Acute care hospital units. PARTICIPANTS: Adults aged ≥ 65 years hospitalized in medical-surgical acute care. Total sample size across all included studies was 7,375. METHODS: Independence in ADL was assessed using the Katz Index of Independence in Activities of Daily Living and Barthel Index of Independence in Activities of Daily Living. RESULTS: Random effects meta-analysis across included studies identified combined prevalence of HAD as 30% (95% CI: 24%, 33%; p < 0.001). The effect of study initiation year on prevalence rate was minimal. A large amount of heterogeneity was observed between studies, which may be due in part to non-standardized measurement of ADL impairment or other methodological differences. CONCLUSIONS AND IMPLICATIONS: Hospitalization in acute care poses a significant risk to functional independence of older adults and this risk is unchanged despite shorter lengths of stay. The evidence supports the continued need for hospital-based programs that provide assessment of functional ability and identification of at risk older adults in order to better treat and prevent HAD.

Objective To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials. Methods Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation. Results The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects. Conclusion Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects.

Delirium, or acute confusional state, affects up to 7 million hospitalized older adults annually, and is associated with increased risk of mortality, institutionalization, and cognitive and functional impairment. There has been a proliferation of both pharmacological and nonpharmacological clinical trials to reduce the incidence and sequelae of delirium. In other neuropsychiatric disorders, exclusion criteria prevent up to 75% of individuals with the condition under study from participating. It is unclear how well these trial samples represent the population of older adults with delirium. We selected all intervention trials registered at ClinicalTrials.gov containing the keyword “delirium” (N=131), regardless of type of intervention. We manually examined study descriptions to restrict analysis to studies with delirium as a primary or secondary outcome (N=92). Of these 92 studies, 76% enrolled only adults, with 45% enrolling only older adults. 38% of studies were restricted to surgical units, 27% to intensive care units, and 7.6% to medical units. Only 1 study examined nursing homes and 4 studies examined palliative care. 50% of studies excluded individuals with pre-existing dementia, 28% excluded individuals with psychiatric disorders, and 30% excluded individuals with neurological disorders. 34% of studies excluded individuals with alcohol or drug abuse. Overall, many intervention studies for delirium are limited to the surgical and ICU populations, and they exclude individuals with common comorbidities associated with an increased risk of delirium. Similar to other neuropsychiatric disorders, these findings raise significant concerns about the generalizability of clinical trials in delirium to the hospitalized older adult population.

Proinflammatory dietary patterns have been associated with increased cancer risk and mortality. We present a systematic review and meta-analysis of the current published literature on a dietary inflammatory index (DII) score and its association with cancer risk and mortality outcomes. Published articles from online databases (PubMed, Scopus, and Embase) examining the association between DII and any cancer risk, incidence, or mortality between 1980 and November 2016 were selected for review. Results of studies meeting inclusion criteria were summarized and meta-analyzed using STATA to generate summary measures of association across studies. Sixty-three published articles were identified from the search, and following title, abstract and full-text review, twenty-four studies met inclusion criteria. All articles calculated DII scores based on study-specific food-frequency questionnaires using methodology from the same article. Of the 24 included studies, 13 were case-control, 6 were prospective cohort, 1 was a retrospective cohort, 3 were RCTs, and 1 did not specify study design. The most common cancers examined were colorectal, breast, lung, and prostate. Individuals in the highest versus lowest DII categories had 25% increased risk of overall cancer incidence (RR: 1.25, 95% CI: 1.16-1.35), 75% higher odds of cancer (OR: 1.75, 95% CI: 1.43-2.16) and 67% increased risk of cancer mortality (RR: 1.67, 95% CI: 1.13-2.48). Upon stratification for cancer type, positive associations remained (RRbreast : RR: 1.12, 95% CI: 1.03-1.22) (RRcolorectal : 1.33, 95% CI: 1.22-1.46) (RRlung : 1.30, 95% CI: 1.13-1.50). There were consistent and significant positive associations between higher DII and cancer incidence and mortality across cancer types, study populations, and study design.

Small-area geographic disparities in health care delivery have been observed across multiple disorders, but remain poorly studied for Alzheimer’s disease (AD) and other dementias. While national and state estimates of the prevalence and incidence of AD are available, estimates across finer geographic regions offer an opportunity to tailor programs to the needs of the local population. We estimated prevalence of AD at the county level across the continental United States. We used prevalence rates of AD by age category and race among Medicare fee-for-service beneficiaries published by the Centers for Disease Control (CDC). These prevalence rates were projected onto bridged-race county-level population data for 2017 from the National Center for Health Statistics, with empirical Bayes spatial smoothing to reduce variability in rates due to small population sizes. Estimated prevalence of AD varied more than threefold across counties, from a low of 51.8 per 1,000 persons in Loving County, Texas to a high of 169.6 per 1,000 persons in Kalawao County, Hawaii. Higher prevalence of AD was seen in the Southeastern and Midwestern United States. However, we observed specific counties with low prevalence of AD within regions with high prevalence of AD, and vice versa. These small-area geographic variations may provide vital information about social and environmental influences on dementia care, yet little data have been available to date. Understanding geographic disparities in prevalence will be critical for addressing practice variation in the prevention and diagnosis of dementia.

Importance Clinical trials in Alzheimer disease (AD) generally allow participants to continue receiving concomitant medications, including cholinesterase inhibitors (ChEIs) and memantine, if the dose is stable. Previous analysis of observational studies indicates such individuals experience greater rate of decline on cognitive testing than those not receiving such medications. Objective To investigate whether concomitant use of ChEIs or memantine is associated with cognitive outcomes in AD clinical trials. Data Sources Meta-database of 18 studies from the Alzheimer Disease Cooperative Study and Alzheimer Disease Neuroimaging Initiative. Study Selection All studies with data on ChEI and memantine use that included assessment of specified outcome measures. Data Extraction and Synthesis The analysis estimated annual rate of decline on the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) using linear mixed-effects models, and compared rates for participants receiving ChEIs and memantine, alone and combined, with participants not receiving either medication using random-effects meta-analysis. Main Outcomes and Measures Annual rate of change on the ADAS-cog. Results Across 10 studies, of 2714 participants, the mean (SD) age was 75.0 (8.2) years, 58% were female, and 9% were racial/ethnic minorities. There were 906 participants (33.4%) receiving ChEIs, 143 (5.3%) receiving memantine, 923 (34.0%) receiving both, and 742 (27.3%) receiving neither. Meta-analysis showed those receiving ChEIs or memantine were associated with significantly greater annual rate of decline on the ADAS-cog than those receiving neither medication (1.4 points/y; 95% CI, 0.1-2.7). Conclusions and Relevance Similar to observational studies, many participants in AD clinical trials receiving ChEIs or memantine experience greater cognitive decline. This difference is nearly as large as the hypothesized effect sizes of the treatments investigated in the trials. Concomitant use of ChEIs or memantine may be confounded with outcomes on the ADAS-cog and should be considered in design of clinical trials of potential therapeutic agents for AD. Post hoc analyses stratifying by ChEIs or memantine must be interpreted cautiously given the potential for confounding.