Patient-reported Cognitive Function Research Articles

Association between Cognitive Function and Physical Function, Frailty, and Quality of Life in Older Breast Cancer Survivors.

Older cancer survivors in general are at greater risk for cancer-related cognitive impairment (CRCI), yet few studies have explored its association with health outcomes. This study examined the association between subjective and objective measures of cognitive function and physical function, frailty, and quality of life (QoL) among older breast cancer survivors. Older breast cancer survivors who reported cognitive concerns completed surveys on patient-reported cognitive function, physical function, frailty, and QoL as well as objective tests of visuospatial working memory and sustained attention. Data were analyzed using descriptive statistics and separate linear regression models. A total of 219 female breast cancer survivors completed the study. Perceived cognitive abilities were associated with better physical function, frailty, and QoL (p ≤ 0.001) while cognitive concerns were negatively related with these metrics (p ≤ 0.001). Poorer visuospatial working memory and sustained attention were linked to increased frailty (p ≤ 0.001-0.01), whereas poorer sustained attention was associated with poorer physical function (p < 0.01). Older breast cancer survivors with perceived cognitive impairment and poorer cognitive performance reported poorer physical functioning, increased frailty, and poorer QoL. These findings underscore the importance of assessing cognitive concerns and their associated outcomes in older breast cancer survivors.

Patient-Reported Outcome Screens for Cognitive Dysfunction and Predicts Admissions in Cirrhosis

IntroductionHepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. Materials and MethodsWe studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. ResultsTwenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). ConclusionsA brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

Association between patient-reported cognitive function and location of glioblastoma

Objective cognitive function in patients with glioblastoma may depend on tumor location. Less is known about the potential impact of tumor location on cognitive function from the patients’ perspective. This study aimed to investigate the association between patient-reported cognitive function and the location of glioblastoma using voxel-based lesion-symptom mapping. Patient-reported cognitive function was assessed with the European Organisation for Research and Treatment (EORTC) QLQ-C30 cognitive function subscale preoperatively and 1 month postoperatively. Semi-automatic tumor segmentations from preoperative MRI images with the corresponding EORTC QLQ-C30 cognitive function score were registered to a standardized brain template. Student’s pooled-variance t-test was used to compare mean patient-reported cognitive function scores between those with and without tumors in each voxel. Both preoperative brain maps (n = 162) and postoperative maps of changes (n = 99) were developed. Glioblastomas around the superior part of the left lateral ventricle, the left lateral part of the thalamus, the left caudate nucleus, and a portion of the left internal capsule were significantly associated with reduced preoperative patient-reported cognitive function. However, no voxels were significantly associated with postoperative change in patient-reported cognitive function assessed 1 month postoperatively. There seems to be an anatomical relation between tumor location and patient-reported cognitive function before surgery, with the left hemisphere being the dominant from the patients’ perspective.

Phase 3 randomized placebo-controlled trial of donepezil for cancer-related cognitive impairment among breast cancer survivors: Results on patient-reported cognitive function from the wake forest nCI community oncology research program (NCORP) research base REMEMBER trial (WF97116).

12076 Background: Cancer-related cognitive impairment (CRCI) is prevalent and persistent among breast cancer survivors (BCS). The REMEMBER prospective, randomized, double-blind, placebo-controlled trial compared the efficacy of donepezil, an acetylcholine esterase inhibitor, versus placebo to reduce late CRCI among BCS. (Clinical Trials #: NCT02822573). Methods: Women ≥ 18 years of age, with a history of breast cancer who completed ≥ 4 cycles of cytotoxic chemotherapy 1 to 5 years prior to enrollment, self-reported CRCI, with evidence of a memory deficit on the Hopkins Verbal Learning Test were eligible. Women were randomized to a 24-week course of daily donepezil (5mg) or placebo. If tolerated, the donepezil/placebo oral daily dose was increased to two tablets (donepezil 10mg) Weeks 7-24. The Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) Version 3 patient-reported outcomes (PRO) measure was administered at Baseline and weeks 12, 24, and 36. Mixed effects repeated measures analysis of covariance (RMANCOVA) models were used to assess treatment differences in FACT-Cog subscale scores with model covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification and an unstructured covariance matrix to account for within participant correlation over time. Results: A total of 276 patients from 87 NCORP sites (mean age = 57.1 yr., SD = 10.5) an average of 29.6 months post-chemotherapy completion were randomized to donepezil (n = 140) or placebo (n = 136). Participants in both arms experienced an improvement in all FACT-Cog subscale scores from baseline to week 12 (e.g., FACT-Cog Perceived Cognitive Impairment change: Donepezil = 14.8, SD = 14.6; Placebo = 13.9, SD = 15.7), with a slight improvement in week 24 (Donepezil = 3.6, SD = 11.4; Placebo = 3.1, SD = 11.4) and slight decrease in week 36 (Donepezil = -1.7, SD = 12.4; Placebo = -1.2, SD = 12.2). The magnitude of change was comparable across treatments at all timepoints (week 12 p= 0.64; week 24 p= 0.75; week 36 p= 0.76). There were no statistically significant differences across treatments at 12, 24 and 36 weeks on any FACT-Cog subscale. Exploratory analyses adjusting for education, baseline fatigue and depression as well as independent analyses considering treatment interaction with endocrine therapy and menopausal status also did not result in group differences for any outcome. Conclusions: There were no differences in PRO-assessed cognitive function domains between donepezil or placebo. The magnitude of improvement in patient-rated cognitive function was comparable across treatment arms. These results underscore the importance of placebo controls for CRCI intervention trials. Funding: NIH/NCI 2UG1CA189824. Clinical trial information: NCT02822573 .

Patient-reported cognitive function before and after glioma surgery

BackgroundLittle is known about the extent to which glioma patients experience subjective changes in cognitive function following surgery. We sought to assess patient-reported cognitive function before and after glioma surgery and explore potential factors associated with cognitive change.MethodsIn a prospective population-based study, patient-reported cognitive function was measured in 182 patients undergoing primary surgery for diffuse glioma (141 high-grade gliomas (HGG) and 41 low-grade gliomas (LGG)) by using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 cognitive function subscale preoperatively and at 1 and 6 months postoperatively. Binomial logistic regression models were used to assess factors possibly associated with patient-reported cognitive changes.ResultsIn the HGG group, the mean cognitive function score increased from 70.9 (95% 66.6, 75.2) preoperatively to 85.1 (95% CI 81.2, 89.0) (p < 0.001) and 83.3 (95% CI 79.1, 87.6) (p < 0.001) at 1 and 6 months postoperatively, respectively. In the LGG group, the mean score was 80.9 (95% CI 74.4, 87.4) preoperatively and remained stable at postoperative follow-ups. Females reported lower scores than males. At an individual level, both improvement and deterioration in cognitive scores were frequently seen in LGG and HGG patients after surgery. Preoperative use of corticosteroids and large tumor volume were predictors for cognitive improvement at 1 month postoperatively. No predictors were identified for cognitive improvement at 6 months and worsening at 1 and 6 months.ConclusionMany glioma patients experience perioperative subjective changes in cognitive function after surgery. At group level, HGG patients reported improved cognitive function after surgery, while LGG patients reported stable cognitive function. Preoperative use of corticosteroids and large tumor volume were independently associated with postoperative improvement.

Protocol paper: Multi-site, cluster-randomized clinical trial for optimizing functional outcomes of older cancer survivors after chemotherapy

BackgroundCancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy. MethodsA cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months. DiscussionIf successful, GEMS would be an option for a standardized APP-led survivorship care intervention. Trial RegistrationClinicalTrials.govNCT05006482, registered on August 9, 2021.

Pretreatment patient-reported cognitive function in patients with diffuse glioma

PurposeCognitive function is frequently assessed with objective neuropsychological tests, but patient-reported cognitive function is less explored. We aimed to investigate the preoperative prevalence of patient-reported cognitive impairment in patients with diffuse glioma compared to a matched reference group and explore associated factors.MethodsWe included 237 patients with diffuse glioma and 474 age- and gender-matched controls from the general population. Patient-reported cognitive function was measured using the cognitive function subscale in the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The transformed scale score (0–100) was dichotomized, with a score of ≤ 75 indicating clinically important patient-reported cognitive impairment. Factors associated with preoperative patient-reported cognitive impairment were explored in a multivariable regression analysis.ResultsCognitive impairment was reported by 49.8% of the diffuse glioma patients and by 23.4% in the age- and gender-matched reference group (p < 0.001). Patients with diffuse glioma had 3.2 times higher odds (95% CI 2.29, 4.58, p < 0.001) for patient-reported cognitive impairment compared to the matched reference group. In the multivariable analysis, large tumor volume, left tumor lateralization, and low Karnofsky Performance Status score were found to be independent predictors for preoperative patient-reported cognitive impairment.ConclusionsOur findings demonstrate that patient-reported cognitive impairment is a common symptom in patients with diffuse glioma pretreatment, especially in patients with large tumor volumes, left tumor lateralization, and low functional levels. Patient-reported cognitive function may provide important information about patients’ subjective cognitive health and disease status and may serve as a complement to or as a screening variable for subsequent objective testing.

Do PROs Tell the Whole Story? Differential Outcomes Based on Patient-Reported Outcomes (PROs) Versus Performance-Based Metrics (PBM) on Cognition for Patients Receiving Chimeric Antigen Receptor (CAR)-T Cell Therapy

Do PROs Tell the Whole Story? Differential Outcomes Based on Patient-Reported Outcomes (PROs) Versus Performance-Based Metrics (PBM) on Cognition for Patients Receiving Chimeric Antigen Receptor (CAR)-T Cell Therapy

Self-reported cognitive concerns and abilities: two sides of one coin?

Patient-reported cognitive function can be measured using negatively worded items (concerns) and positively worded (abilities) items. It is possible that reporting abilities is less subject to the influence of emotional states. This study evaluated the relationship between cognitive concerns and cognitive abilities. Cancer patients (N = 509; mean age = 61 years; 50% men; 86% White) completed concerns and abilities items developed by the National Institutes of Health Patient-Reported Outcomes Information System (PROMIS). Confirmatory factor analysis was used to evaluate the extent to which items were loaded on one single factor (unidimensionality). Multidimensionality was evaluated using bi-factor analysis (local factors: concerns and abilities). Slope parameters from multidimensional item response theory (IRT) and unidimensional IRT were compared to evaluate which factor solution fits best. Acceptable fit indices were found in both one-factor confirmatory factor analysis (comparative fit index (CFI) = 0.96; root mean squared error of approximation (RMSEA) = 0.062) and bi-factor analysis (CFI = 0.98; RMSEA = 0.043). Thus, abilities and concerns could be considered as a single dimension. Yet, high loadings on the local factor in bi-factor analysis and slope discrepancies between unidimensional IRT and multidimensional IRT indicate that abilities should be considered as a separate factor from concerns. Concerns and abilities could be measured using one-unidimensional item bank. Results also support measuring each construct separately. We recommend a conservative approach by measuring and reporting concerns and abilities separately. We therefore recommend two separate but co-calibrated item banks in the PROMIS network: cognitive function item bank-concerns and cognitive function item bank-abilities. Both item banks showed good psychometric properties and are available for research and clinical purposes.

Cognitive function in breast cancer and lymphoma patients receiving chemotherapy: An ongoing nationwide University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) observational study with 1,200 patients and controls.

TPS9647 Background: Chemotherapy-related cognitive impairment (CRCI) is a major concern for up to 75% of cancer patients that can negatively affect quality of life. Studies which have objectively assessed cognitive function (CF) in patients suggest that chemotherapy is associated with declines in multiple domains. A large, prospective longitudinal study with age- and gender- paired healthy controls is needed to confirm and expand these findings, to identify etiological mechanisms of CRCI, and to identify the best assessment methods for detecting CRCI. Methods: We are conducting a nationwide prospective observational study (N=1,200), conducted through the URCC CCOP Research Base and 23 CCOPs. The primary aim is to test the hypothesis that breast cancer and lymphoma patients receiving chemotherapy will have greater impairments in CRCI over time than a control comparison group. Breast cancer (stage I-IIIc) and lymphoma patients (intermediate/high grade disease) meet the following eligibility: 1) chemotherapy naïve, 2) ≥21 years of age, 3) no CNS disease, 4) scheduled to receive a standard course of chemotherapy, and 5) no concurrent radiation. Healthy control participants meet eligibility criteria 1-3 and are the same gender and age as paired patients. CF is assessed at pre-chemotherapy (Assess. 1), post-chemotherapy (Assess. 2), and 6 months post-chemotherapy in patients; their paired controls are assessed at the same time intervals. CF is measured via: 1) Computer-based CANTAB neuropsychological (NP) battery (assessing memory (primary aim), verbal memory, sustained attention, processing speed, and executive function (secondary aims)), 2) paper-based objective NP assessment (secondary aims), 3) phone-based objective NP assessment (tertiary aims), and 4) Single item, patient-reported CF (tertiary aims). Blood is collected at Assess. 1 and 2 to explore inflammatory and genetic mechanisms. 807 participants have been enrolled in 21 months. Funding: U10CA037420-26 Supp. MCJ; U10CA037420, GRM; &amp; URCC/RPCI Grant, MCJ &amp; CBA. Clinical trial information: NCT01382082.

Abstract P2-12-02: Comorbidities and patient-reported cognitive function among women with stage I-II breast cancer randomized to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT) treated on the Trial Assigning IndividuaLized Options

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-02.

Decline in Tested and Patient-reported Cognitive Functioning Following Prophylactic Cranial Irradiation for Lung Cancer: Secondary Analysis of RTOG 0212 and 0214

To assess the impact of prophylactic cranial irradiation (PCI) on cognitive functioning, tested using the Hopkins Verbal Learning Test (HVLT) and patient-reported on the EORTC QLQ-C30 questionnaire, following curative-intent treatment for limited-disease small cell lung cancer (LD-SCLC) and locally advanced Non-small cell lung cancer (LA-NSCLC). Patients with LD-SCLC and LA-NSCLC were enrolled on RTOG trials 0212 and 0214, respectively. Recall (R) and delayed recall (DR) from HVLT and patient-reported cognitive functioning (PRCF) from EORTC QLQ-C30 were assessed as secondary endpoints at baseline (following locoregional therapy but before PCI or observation) and at 6 and 12 months follow-up. After pooling data from all enrolled patients, patients who developed brain relapse prior to follow-up evaluation were excluded. Deterioration in HVLT-R, HVLT-DR, and PRCF was defined compared to baseline using the reliable change index method and correlated with receipt of PCI using multivariate logistic regression at a significance level of p < 0.05 for HVLT-R and HVLT-DR correlations and p < 0.001 for PRCF correlations due to multiple testing of EORTC QLQ-C30. Covariates included age, gender, partner status, education level, Zubrod performance score, and PCI dose. Deterioration in HVLT-R and HVLT-DR was also correlated with deterioration in PRCF using Fisher's exact test at a significance level of p < 0.001. Five hundred fifty-two (91%) and 562 (93%) of the 604 eligible patients accrued to RTOG 0212 and RTOG 0214 had baseline EORTC QLQ-C30 and HVLT assessments, respectfully, and were included in this pooled analysis. Compliance was 59% at 6 months and 48% at 12 months for HVLT and 66% at 6 months and 54% at 12 months for EORTC QLQ-C30 and did not differ between RTOG 0212 and 0214. After adjusting for covariates, deterioration in HVLT-R, HVLT-DR and PRCF at 6 and 12 months follow-up was associated with receipt of PCI (Table). At 6 or 12 months, deterioration in PRCF was not correlated with deterioration in HVLT-R (p = 0.05 and p = 0.86, respectively) or HVLT-DR (p = 0.02 and p = 0.54, respectively). In lung cancer patients who do not develop brain relapse, receipt of PCI is associated with deterioration in HVLT-tested and patient-reported cognitive functioning. Decline in HVLT and decline in patient-reported cognitive functioning are not closely correlated.TableImpact of PCI (Referent Group: No PCI)Time to deterioration from baselineHVLT-recallHVLT-delayed recallPatient-reported cognitive functioning6 Months12 Months6 Months12 Months6 Months12 MonthsAdjusted odds ratio4.905.272.072.793.603.4495% Confidence interval1.87-12.871.98-14.021.04-4.121.08-7.162.34-6.371.84-6.44p value0.0010.00090.040.03<0.0001<0.0001 Open table in a new tab

Phase III Trial of Prophylactic Cranial Irradiation Compared With Observation in Patients With Locally Advanced Non–Small-Cell Lung Cancer: Neurocognitive and Quality-of-Life Analysis

There are scant data regarding the effects of prophylactic cranial irradiation (PCI) on neurocognitive function (NCF) and quality of life (QOL). Radiation Therapy Oncology Group trial 0214 showed no overall survival (OS) benefit for PCI in stage III non-small-cell lung cancer (NSCLC) at 1 year. However, there was a significant decrease in brain metastases (BM). This analysis focuses on the impact of PCI on NCF and QOL. Patients with stage III NSCLC who completed definitive therapy without progression were randomly assigned to PCI or observation. NCF was assessed with Mini-Mental Status Examination (MMSE), Activities of Daily Living Scale (ADLS), and Hopkins Verbal Learning Test (HVLT). QOL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) core tool (QOL Questionnaire-QLQC30) and brain module (QLQBN20). There were no statistically significant differences at 1 year between the two arms in any component of the EORTC-QLQC30 or QLQBN20 (P > .05), although a trend for greater decline in patient-reported cognitive functioning with PCI was noted. There were no significant differences in MMSE (P = .60) or ADLS (P = .88). However, for HVLT, there was greater decline in immediate recall (P = .03) and delayed recall (P = .008) in the PCI arm at 1 year. PCI in stage III NSCLC significantly decreases the risk of BM without improving 1-year OS. There were no significant differences in global cognitive function (MMSE) or QOL after PCI, but there was a significant decline in memory (HVLT) at 1 year. This study provides prospective data regarding the relative risks and benefits of PCI in this setting and the need to use sensitive cognitive assessments.