Alzheimer's disease-related biomarkers and cancer-related cognitive decline: the thinking and living with cancer study.

PURPOSE: We evaluated whether plasma Alzheimer's Disease (AD)-related biomarkers were associated with cancer-related cognitive decline (CRCD) among older breast cancer survivors. METHODS: We included survivors 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched non-cancer controls (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (pre-systemic therapy) and annually for up to 60-months. Cognition was measured using tests of attention, processing speed and executive function (APE) and learning and memory (LM); perceived cognition was measured by the FACT-Cog PCI. Baseline plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), beta-amyloid 42/40 (Aß42/40) and phosphorylated tau (p-tau181) were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD-biomarkers, time, group (survivor vs control) and their two- and three-way interactions, controlling for age, race, WRAT4 Word Reading score, comorbidity and BMI; two-sided 0.05 p-values were considered statistically significant. RESULTS: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline NfL levels than controls (p = .013). Survivors had lower adjusted longitudinal APE than controls starting from baseline and continuing over time (p = <0.002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except controls had lower APE scores with higher GFAP levels (p = .008). CONCLUSION: The results do not support a relationship between baseline AD-related biomarkers and CRCD. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers and examine other mechanisms and factors affecting cognition pre-systemic therapy.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

PURPOSE: To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories. METHODS: Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories. RESULTS: Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F = 4.13; p = 0.0006) and tangible (F = 2.86; p = 0.01) social support over time, was associated with recovery from depressive symptoms. CONCLUSIONS: Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

Validating the PROMIS cognitive function short form in cancer survivors.

PURPOSE: The Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a  (PROMIS Cog) could provide a shorter, useful alternative to the often used Functional Assessment of Cancer Therapy - Cognition (FACT-Cog) in research and clinical care. This study aimed to determine the convergent validity and internal reliability of the PROMIS Cog in 3 separate samples of breast cancer survivors and to explore clinical cut points. METHODS: Data from three samples of breast cancer survivors were used for this secondary analysis. Convergent validity was determined by evaluating correlation strength among the derived PROMIS Cog and measures of depression, anxiety, stress, fatigue, sleep, loneliness, the FACT-Cog . Clinical cut-points for the PROMIS Cog were determined by plotting the receiver operating characteristic curves. RESULTS: 3 samples of breast cancer survivors (N = 471, N = 132, N = 90) were included. Absolute values of correlations demonstrating convergent validity ranged from 0.21 to 0.82, p's < 0.001, and were comparable to correlations with the full FACT-Cog 18 item perceived cognitive impairments (PCI) scale. ROC curve plots indicated a clinical cut off < 34 for the combined sample. CONCLUSION: The 8-item PROMIS Cog demonstrated good convergent validity and internal reliability in breast cancer survivors, comparable to the 18-item FACT-Cog PCI. The PROMIS Cog 8a is a brief self-report measure that can be easily incorporated into cancer-related cognitive impairment research designs or used in clinical settings.

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.

BACKGROUND: Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. METHODS: Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. RESULTS: Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001-.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001-.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. CONCLUSION: Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

BACKGROUND: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. METHODS: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. RESULTS: Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. CONCLUSIONS: Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.

A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects.

BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.

Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.

PURPOSE: To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls. METHODS: English-speaking women age ≥ 60 years, newly diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect-lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results. RESULTS: There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years; range, 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor-positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all P < .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls (P interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance (v controls), with significant interactions with CRP only for the Trails B test. CONCLUSION: Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.

Longitudinal Analysis of Patient-Reported Cognitive Function in Multiple Myeloma.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has been largely unstudied in patients with multiple myeloma (MM). This study describes patient-reported cognition over time and patient factors associated with adverse cognitive outcomes in MM. METHODS: Participants enrolled in a registry in which they completed a geriatric assessment at study entry, and 3 & 6 months after entry. Cognitive function was assessed using the EORTC QLQ-C30 Cognitive Function subscale, with CRCI defined as scores < 75. Generalized estimating equation (GEE) models were used to fit longitudinal models to investigate differences by group and differences in changes over time by group, with adjustment for time since diagnosis. RESULTS: One hundred and four adults with MM had mean age of 67 years and 30% identified as Black. Patient-reported CRCI was present in 18% of participants at enrollment, 21% at 3 months, and 30% at 6 months. Worse cognitive function was reported in those with impairments in physical function (P = .002), IADLs (P = .02), and performance status (P = .04), as well as in those who were prefrail/frail (P = .02) and depressed (P = .049). Greater cognitive decline over time was observed in patients without CRCI at enrollment (P < .0001) and those with lower levels of education (P = .04). CONCLUSION: This is one of the first studies to describe longitudinal changes in patient-reported cognition in patients with MM. Several potentially intervenable factors, including physical function impairment and depression, were associated with worse cognition at study entry, but only baseline CRCI status and education level were predictive of future decline.

Associating persistent self-reported cognitive decline with neurocognitive decline in older breast cancer survivors using machine learning: The Thinking and Living with Cancer study.

INTRODUCTION: Many cancer survivors report cognitive problems following diagnosis and treatment. However, the clinical significance of patient-reported cognitive symptoms early in survivorship can be unclear. We used a machine learning approach to determine the association of persistent self-reported cognitive symptoms two years after diagnosis and neurocognitive test performance in a prospective cohort of older breast cancer survivors. MATERIALS AND METHODS: We enrolled breast cancer survivors with non-metastatic disease (n = 435) and age- and education-matched non-cancer controls (n = 441) between August 2010 and December 2017 and followed until January 2020; we excluded women with neurological disease and all women passed a cognitive screen at enrollment. Women completed the FACT-Cog Perceived Cognitive Impairment (PCI) scale and neurocognitive tests of attention, processing speed, executive function, learning, memory and visuospatial ability, and timed activities of daily living assessments at enrollment (pre-systemic treatment) and annually to 24 months, for a total of 59 individual neurocognitive measures. We defined persistent self-reported cognitive decline as clinically meaningful decline (3.7+ points) on the PCI scale from enrollment to twelve months with persistence to 24 months. Analysis used four machine learning models based on data for change scores (baseline to twelve months) on the 59 neurocognitive measures and measures of depression, anxiety, and fatigue to determine a set of variables that distinguished the 24-month persistent cognitive decline group from non-cancer controls or from survivors without decline. RESULTS: The sample of survivors and controls ranged in age from were ages 60-89. Thirty-three percent of survivors had self-reported cognitive decline at twelve months and two-thirds continued to have persistent decline to 24 months (n = 60). Least Absolute Shrinkage and Selection Operator (LASSO) models distinguished survivors with persistent self-reported declines from controls (AUC = 0.736) and survivors without decline (n = 147; AUC = 0.744). The variables that separated groups were predominantly neurocognitive test performance change scores, including declines in list learning, verbal fluency, and attention measures. DISCUSSION: Machine learning may be useful to further our understanding of cancer-related cognitive decline. Our results suggest that persistent self-reported cognitive problems among older women with breast cancer are associated with a constellation of mild neurocognitive changes warranting clinical attention.

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.

PURPOSE: Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant therapy and tumor aggressivity in older breast cancer patients. METHODS: Women diagnosed with non-metastatic breast cancer (n = 705) ages 60-98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score < 54 or having 2 tests < 1.5 SD or 1 test < 2 SD from the mean APE or LM domain score). RESULTS: HER2 positivity and the hormone receptor negative/HER2 + molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values < .05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM. CONCLUSIONS: Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to confirm these results and assess potential mechanisms and clinical management strategies.

Prevalence and clinical correlates of cognitive impairment in adults with plasma cell disorders.

INTRODUCTION: Older adults with plasma cell disorders (PCDs) experience cognitive dysfunction that may be attributable to the disease and associated therapies. Yet, this has seldom been reported in the literature. Our objectives were to describe cognitive function (objective and patient-reported) in adults with PCDs and to explore clinical correlates of cognitive impairment. MATERIALS AND METHODS: Participants completed a geriatric assessment between March 2018 and February 2020. Cognitive function was evaluated using two objective measures - Montreal Cognitive Assessment (MoCA, cutpoint <26) and Blessed Orientation Memory Concentration Test (BOMC, cutpoint >4) - and two patient-reported outcome (PRO) measures - Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF, cutpoint <45) and European Organization for Research and Treatment of Cancer Cognitive Functioning subscale (EORTC-CF, cutpoint <75). Spearman correlations examined relationships among these measures and log binomial regression was used to examine characteristics associated with cognitive impairment, as defined by the MoCA and PROMIS-CF measures. RESULTS: Among 86 participants with a mean age of 69 (range: 46-91), the prevalence of cognitive dysfunction was between 20% (BOMC) and 63% (MoCA). There was moderate correlation among objective measures (r = 0.51, p < 0.0001), moderate to high correlation among PRO measures (r = 0.69, p < 0.0001), but no correlation between objective and PRO measures. Factors associated with objective impairment included ≤ high school education (RR 1.46, p = 0.009), living alone (RR 1.42, p = 0.02), relapsed/refractory disease (RR 1.39, p = 0.04), empirically de-intensified induction therapy (RR 1.62, p = 0.008), frailty (RR 1.49, p = 0.04), and peripheral vascular disease (RR 1.54, p = 0.002). Factors associated with PRO impairment included social isolation (RR 3.43, p = 0.003), depression (RR 3.30, p = 0.004) and anxiety (RR 4.43, p = 0.0002), frailty (RR 3.60, p = 0.02), falls in the previous 6 months (RR 2.53, p = 0.02), and deficits in physical function (RR 4.44, p = 0.01). Older age was not associated with either objective or PRO impairment. DISCUSSION: Cognitive impairment, using objective and PRO screening measures, was relatively common in adults with PCDs. Cancer-related factors and medical comorbidities were associated with objective cognitive impairment whereas psychosocial and functional factors were associated with PRO impairment.

Associations between longitudinal changes in sleep disturbance and depressive and anxiety symptoms during the COVID-19 virus pandemic among older women with and without breast cancer in the thinking and living with breast cancer study.

PURPOSE: Several studies have reported sleep disturbances during the COVID-19 virus pandemic. Little data exist about the impact of the pandemic on sleep and mental health among older women with breast cancer. We sought to examine whether women with and without breast cancer who experienced new sleep problems during the pandemic had worsening depression and anxiety. METHODS: Breast cancer survivors aged ≥60 years with a history of nonmetastatic breast cancer (n = 242) and frequency-matched noncancer controls (n = 158) active in a longitudinal cohort study completed a COVID-19 virus pandemic survey from May to September 2020 (response rate 83%). Incident sleep disturbance was measured using the restless sleep item from the Center for Epidemiological Studies-Depression Scale (CES-D). CES-D score (minus the sleep item) captured depressive symptoms; the State-Anxiety subscale of the State Trait Anxiety Inventory measured anxiety symptoms. Multivariable linear regression models examined how the development of sleep disturbance affected changes in depressive or anxiety symptoms from the most recent prepandemic survey to the pandemic survey, controlling for covariates. RESULTS: The prevalence of sleep disturbance during the pandemic was 22.3%, with incident sleep disturbance in 10% and 13.5% of survivors and controls, respectively. Depressive and anxiety symptoms significantly increased during the pandemic among women with incident sleep disturbance (vs. no disturbance) (ß = 8.16, p < 0.01 and ß = 6.14, p < 0.01, respectively), but there were no survivor-control differences in the effect. CONCLUSION: Development of sleep disturbances during the COVID-19 virus pandemic may negatively affect older women's mental health, but breast cancer survivors diagnosed with the nonmetastatic disease had similar experiences as women without cancer.

Anticipating mental health needs after chemotherapy in early-stage breast cancer using patient-reported symptom screening.

PURPOSE: Many patients with breast cancer experience depression and anxiety for years after completing systemic chemotherapy, which negatively impact overall symptom burden, quality of life, and treatment outcomes. The objective of this study was to examine the utility of patient-reported outcome (PRO) measures to predict mental health needs in patients with breast cancer during post-chemotherapy follow-up care. METHODS: In a sample of women with non-metastatic breast cancer, associations between patient-reported depression and anxiety at end of chemotherapy and post-chemotherapy mental health needs were evaluated using log-binomial regression adjusted for functional status, social activity limitations, and time from chemotherapy. RESULTS: In a sample of 149 women, 40% reported at least mild depressive symptoms and 52% reported at least mild anxiety at the end of chemotherapy. Over an average 3.2 years post-chemotherapy (range: 0.7-5.6 years), 23% received new psychiatric diagnoses, 21% engaged in mental health specialty care, and 62% were prescribed psychotropic medications. End of chemotherapy depression and anxiety were associated with future prescription of psychotropic medications (RR 1.52; 95% CI 1.14-2.03), as well as greater number of psychotropics. Associations were strongest with serotonin-norepinephrine reuptake inhibitors [(depression: RR 4.75; 95% CI 2.06-10.95); (anxiety: RR 3.68; 95% CI 1.62-8.36); (depression and anxiety: RR 2.98; 95% CI 1.65-5.36)]. CONCLUSION: Diagnosis of and treatment for depression and anxiety are common among women with breast cancer after completing chemotherapy. Prescriptions for psychotropic medications during the initial years after systemic chemotherapy can be anticipated by depression and anxiety screening at end of chemotherapy.

Loneliness and mental health during the COVID-19 pandemic in older breast cancer survivors and noncancer controls.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had wide-ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. METHODS: The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web-based or telephone COVID-19 survey, between May 27 and September 11, 2020. Mixed-effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies-Depression [CES-D] scale) from before to during the pandemic in survivors versus controls and to test survivor-control differences in the associations between changes in loneliness and changes in mental health, including depression (CES-D, excluding the loneliness item), anxiety (the State-Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID-19 death rates, and time between assessments. RESULTS: Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor-control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor-control differences. CONCLUSIONS: Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic.

A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To determine if high dose intravenous (IV) thiamine can prevent delirium during hospitalization following allogeneic HSCT. Secondarily, we evaluated the effects of high dose IV thiamine on thiamine levels and explored risk factors for delirium. METHODS: Randomized, double-blind, placebo-controlled trial in patients undergoing allogeneic HSCT at a U.S. academic medical center between October 2017 and March 2020. 64 participants were randomized 1:1 to thiamine 200 mg IV three times daily for 7 days or placebo. We used the Delirium Rating Scale to assess for delirium. Delirium incidence was compared between groups using the chi-square test. Group differences in time to onset and duration of delirium were compared using the Kaplan-Meier method. Fisher's Exact and Wilcoxon Rank Sum tests were used to examine associations between pre-transplantation variables and delirium. RESULTS: 61 participants were analyzed. Delirium incidence (25% vs. 21%, Chi-square (df = 1) = 0.12, p = 0.73), time to onset, duration, and severity were not different between study arms. Immediately following the intervention, thiamine levels were higher in the thiamine arm (275 vs. 73 nmol/L, t-test (df = 57) = 13.63, p < 0.0001), but not predictive of delirium. Variables associated with delirium in our sample included disease severity, corticosteroid exposure, infection, and pre-transplantation markers of nutrition. CONCLUSION: High dose IV thiamine did not prevent delirium in patients receiving allogeneic HSCT. Given the multiple contributors to delirium in this population, further research regarding the efficacy of multicomponent interventions may be needed. TRIAL REGISTRATION: Clinical Trials NCT03263442. FUNDING: Rising Tide Foundation for Clinical Cancer Research.

Neuropsychiatric Complications of COVID-19.

PURPOSE OF REVIEW: To describe the presentation, etiologies, and suggested management of post-acute COVID-19 neuropsychiatric symptoms. RECENT FINDINGS: Over 30% of patients hospitalized with COVID-19 may exhibit cognitive impairment, depression, and anxiety that persist for months after discharge. These symptoms are even more common in patients who required intensive care for severe effects of the virus. In addition to the pandemic-related psychological stress, multiple biological mechanisms have been proposed to understand the neuropsychiatric symptoms observed with COVID-19. Given limited research regarding effective interventions, we recommend pharmacologic and behavioral strategies with established evidence in other medically-ill populations. Long-term, neuropsychiatric complications of COVID-19 are common and consequential. Because these are likely to co-occur with other medical problems, patients recovering from COVID-19 are best managed in clinics with highly coordinated care across disciplines and medical specialties. Future research is needed to inform appropriate interventions.

Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer.

BACKGROUND: Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. MATERIALS AND METHODS: Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. RESULTS: In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36-3.45) and anxiety (RR, 1.48; 95% CI, 1.05-2.09). CONCLUSION: Oncologists frequently underestimate patients' depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. IMPLICATIONS FOR PRACTICE: In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients' mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients' psychological health.