Cancer-related Cognitive Impairment in Patients With Newly Diagnosed Aggressive Lymphoma Undergoing Standard Chemotherapy: a Longitudinal Feasibility Study

Abstract PurposeCancer-related cognitive impairment (CRCI) is a recognised adverse consequence of cancer and its treatment. This study assessed the feasibility of collecting longitudinal data on cognition in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent via self-report, neuropsychological assessment, peripheral markers of inflammation and neuroimaging. An exploration and description of patterns of cancer-related cognitive impairment over the course of treatment and recovery was also explored. MethodsEligible participants completed repeated measures of cognition including self-report, neuropsychological assessment, blood cell–based inflammatory markers, and neuroimaging at three pre-specified time-points, Time 1 (T1) – pre-treatment (treatment naïve), Time 2 (T2) – mid-treatment, and Time 3 (T3) – six to eight weeks post-completion of treatment. ResultsOf 33 eligible participants, 30 (91%, 95% CI: 76%, 97%) were recruited over 10 months. The recruitment rate was 3 patients/month (95% CI: 2.0, 4.3 patients/month). Reasons for declining included feeling overwhelmed and rapid treatment commencement. Mean age was 57 years (SD=17 years) and 16/30 (53%) were male. Most patients (20/30, 67%) had diffuse large B cell lymphoma or Hodgkin lymphoma (4/30, 13%). The neuroimaging sub-study was optional, 11/30 participants (37%) were eligible to take part, and all agreed. Retention and compliance with all assessments was very high at all time-points. Only one patient was withdrawn from the study due to disease progression.ConclusionsFindings from this study demonstrate that it is feasible to longitudinally assess cognitive status and impairment in people with newly diagnosed aggressive lymphoma during their initial treatment and recovery and larger studies should be undertaken within other cancer groups.

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Longitudinal exploration of cancer-related cognitive impairment in patients with newly diagnosed aggressive lymphoma: protocol for a feasibility study

BMJ Open ◽

10.1136/bmjopen-2020-038312 ◽

2020 ◽

Vol 10 (9) ◽

pp. e038312

Author(s):

Priscilla Gates ◽

Karla Gough ◽

Haryana Dhillon ◽

Carlene Wilson ◽

Eliza Hawkes ◽

...

Keyword(s):

Cognitive Impairment ◽

Longitudinal Data ◽

Feasibility Study ◽

Verbal Learning ◽

Cognitive Change ◽

Self Report ◽

Aggressive Lymphoma ◽

Newly Diagnosed ◽

Markers Of Inflammation ◽

Prospective Longitudinal

IntroductionCancer-related cognitive impairment (CRCI) is a distressing and disabling side-effect of cancer treatments affecting up to 75% of patients. For some patients, their cognitive impairment may be transient, but for a subgroup, these symptoms can be long-standing and have a major impact on the quality of life. This paper describes the protocol for a study: (1) to assess the feasibility of collecting longitudinal data on cognition via self-report, neuropsychological testing, peripheral markers of inflammation and neuroimaging and (2) to explore and describe patterns of cancer-related cognitive impairment over the course of treatment and recovery in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent.Methods and analysisThis is a prospective, longitudinal, feasibility study in which 30 newly diagnosed, treatment-naive patients with aggressive lymphoma will be recruited over a 12-month period. Patients will complete comprehensive assessments at three time points: baseline (time 1, pre-treatment) and two post-baseline follow-up assessments (time 2, mid-treatment and time 3, 6–8 weeks post-treatment completion). All patients will be assessed for self-reported cognitive difficulties and objective cognitive function using Stroop Colour and Word, Trail Making Test Part A and B, Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association and Digit Span. Blood cell-based inflammatory markers and neuroimaging including a positron emission tomography (PET) with 18F-labelled fluoro-2-deoxyglucose (18F-FDG) and CT (18F-FDG-PET/CT) and a MRI will explore potential inflammatory and neuroanatomical or functional mechanisms and biomarkers related to CRCI. The primary intent of analysis will be to assess the feasibility of collecting longitudinal data on cognition using subjective reports and objective tasks from patients during treatment and recovery for lymphoma. These data will inform the design of a larger-scale investigation into the patterns of cognitive change over the course of treatment and recovery, adding to an underexplored area of cancer survivorship research.Ethics and disseminationEthical approval has been granted by Austin Health Human Rights Ethics Committee (HREC) in Victoria Australia. Peer reviewed publications and conference presentations will report the findings of this novel study.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619001649101).

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Frequency of But Not Capacity for Participation in Everyday Activities Is Associated With Cognitive Impairment in Late Life

Journal of Applied Gerontology ◽

10.1177/0733464820984283 ◽

2021 ◽

pp. 073346482098428

Author(s):

Chao-Yi Wu ◽

Juleen Rodakowski ◽

Lauren Terhorst ◽

Mary Amanda Dew ◽

Meryl Butters ◽

...

Keyword(s):

Cognitive Impairment ◽

Late Life ◽

Cognitive Status ◽

Computerized Adaptive Test ◽

Time Points ◽

Everyday Activities ◽

Neuropsychological Status ◽

Activity Frequency ◽

Test Version ◽

Life Function

We examined features of everyday activities (capacity and frequency) between older adults with and without cognitive impairment over 12 months. Participants aged ≥60 years and at risk for depression were included (n = 260); 26% ( n = 69) had an acquired cognitive impairment at baseline. Cognitive impairment was defined as one standard deviation below norms on the Repeatable Battery for the Assessment of Neuropsychological Status. Features of everyday activities were measured by a computerized adaptive test version of Late-Life Function and Disability Instrument (LLFDI) at six time points (baseline, 6 weeks, 3, 6, 9, 12 months). There were significant between-group differences in activity frequency ( p = .04), but not activity capacity ( p = .05). The group difference in activity frequency exceeded minimal detectable changes (MDC90 = 3.7) and reached moderate clinical meaningfulness (∆ at six time points = 3.7–4.7). Generalized linear mixed models revealed no Group × Time interactions on activity capacity and frequency ( p = .65 and p = .98). Practitioners may assess changes in activity frequency to monitor cognitive status of clients even when there is no loss of activity capacity.

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Two-year course of cognitive function and instrumental activities of daily living in older adults with bipolar disorder: evidence for neuroprogression?

Psychological Medicine ◽

10.1017/s0033291712001614 ◽

2012 ◽

Vol 43 (4) ◽

pp. 801-811 ◽

Cited By ~ 47

Author(s):

A. G. Gildengers ◽

D. Chisholm ◽

M. A. Butters ◽

S. J. Anderson ◽

A. Begley ◽

...

Keyword(s):

Older Adults ◽

Bipolar Disorder ◽

Cognitive Impairment ◽

Cognitive Function ◽

Activities Of Daily Living ◽

Cognitive Aging ◽

Repeated Measures ◽

Daily Living ◽

Time Points ◽

Instrumental Activities

BackgroundWhile bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD.MethodWe recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects (‘controls’) were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs.ResultsThe BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years.ConclusionsOver 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.

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Subjective Cognitive Complaints in Newly-Diagnosed Parkinson’s Disease With and Without Mild Cognitive Impairment

Frontiers in Neuroscience ◽

10.3389/fnins.2021.761817 ◽

2021 ◽

Vol 15 ◽

Author(s):

Chenxi Pan ◽

Jingru Ren ◽

Ping Hua ◽

Lei Yan ◽

Miao Yu ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Logistic Regression ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Status ◽

Newly Diagnosed ◽

Cognitive Complaints ◽

Subjective Cognitive Complaints

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson’s disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI.Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC).Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115−1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009−1.119, p = 0.016).Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.

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Risk-Adapted Therapy of Aggressive Lymphoma Based on FDG-PET Performed after 2 or 3 Cycles of Initial Chemotherapy.

Blood ◽

10.1182/blood.v110.11.1894.1894 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1894-1894 ◽

Cited By ~ 1

Author(s):

Yvette L. Kasamon ◽

Richard L. Wahl ◽

Harvey A. Ziessman ◽

Caroline Fidyk ◽

Kathryn Rogers ◽

...

Keyword(s):

Early Treatment ◽

Fdg Pet ◽

Standard Therapy ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Blood Pool ◽

Aggressive Lymphoma ◽

Newly Diagnosed ◽

Treatment Intensification

Abstract Background: [18F] FDG-PET after only 2–3 cycles of chemotherapy is highly prognostic in newly diagnosed aggressive non-Hodgkin’s lymphoma (NHL), with reported relapse rates of 71–100% after standard therapy if midtreatment PET remains positive. We hypothesized that early treatment intensification, based on individualized risk assessment by PET, would improve outcome. Methods: A phase II, single center trial was activated in 2/2004 for patients (pts) with newly diagnosed aggressive NHL. PET-CT was performed between days 11 and 20 of cycle 2 or 3 of CHOP + rituximab (R). Pts whose PET scan was considered positive on semiquantitative visual interpretation, irrespective of stage or international prognostic index (IPI), received 2 cycles of (R)ESHAP or (R)ICE, followed by autologous stem cell transplantation (SCT) with busulfan-cyclophosphamide conditioning. Biopsies of FDG positive areas were not performed. Pts with negative midtreatment PET completed standard therapy. Tumor FDG uptake was graded on a 5-point scale: 0, no tumor activity (cold); 1+, minimal; 2+, equivocal (equal to mediastinal blood pool); 3+, moderately greater than blood pool; 4+, strong. Scores of 3+ or 4+ were considered positive. Results: As of 8/16/2007, 58 evaluable pts have been accrued, 55 with large B-cell lymphoma. Median age at diagnosis was 51 (20–78); 39 pts had stage III or IV disease. Thirty-two pts (55%) had positive midtreatment PET (17 with score of 3+, 15 with score of 4+). Twenty-six pts (45%) had negative midtreatment PET (10 with score of 0, 3 with score of 1+, 13 with score of 2+). PET was positive in 23 of 38 pts (61%) with IPI 0–2 and in 9 of 18 pts (50%) with IPI 3-5; 2 pts had undetermined IPI. Twenty-eight of 32 pts with positive midtreatment PET have completed SCT; 3 were ineligible because of early disease progression; 1 withdrew consent. At a median follow-up of 20.4 months, their actuarial 2-year event-free survival (EFS) after SCT is 67% (figure). Overall, 19 of 28 transplant recipients are alive and without evidence of relapse or secondary cancers: 6 relapsed at a median of 3.6 months (< 1–17 months) after SCT; 1 died of venoocclusive disease (1.4 months); 1 developed MDS (24.8 months); 1 had an unrelated death (9.9 months). On intent-to-treat analysis, the actuarial 2-year EFS from the time of midtreatment imaging is 60% if PET positive (including pts not eligible for transplant), 86% if PET negative. Of the PET negative pts, 2 have relapsed and 1 developed AML. Conclusion: These data confirm the strong prognostic value of negative midtreatment PET scans, with excellent outcomes in such pts treated with (R)CHOP alone. Early treatment intensification for poor-risk pts, as identified by midtreatment PET, results in a significantly better outcome than that achieved historically. Outcome for midtreatment PET positive pts Outcome for midtreatment PET positive pts

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The Cardioprotective Role of Flaxseed in the Prevention of Doxorubicin- and Trastuzumab-Mediated Cardiotoxicity in C57BL/6 Mice

Journal of Nutrition ◽

10.1093/jn/nxaa144 ◽

2020 ◽

Vol 150 (9) ◽

pp. 2353-2363 ◽

Cited By ~ 1

Author(s):

Chantal Y Asselin ◽

Amy Lam ◽

David Y C Cheung ◽

Cameron R Eekhoudt ◽

Antonia Zhu ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Repeated Measures ◽

B Cell Lymphoma ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Prophylactic Administration ◽

Markers Of Inflammation ◽

Regular Control

ABSTRACT Background Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. Objective We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ–mediated cardiotoxicity in a chronic in vivo female murine model. Methods Wild-type C57BL/6 female mice (10–12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures. Results In the RC + DOX + TRZ–treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ–treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase–1 and the ratio of BCL2-associated X protein to B-cell lymphoma–extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways. Conclusion In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ–mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.

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Comparison of Informant Reports and Neuropsychological Assessment in Mild Cognitive Impairment

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317511429323 ◽

2011 ◽

Vol 26 (7) ◽

pp. 528-534 ◽

Cited By ~ 2

Author(s):

Carlo Abbate ◽

Pietro D. Trimarchi ◽

Paola Nicolini ◽

Luigi Bergamaschini ◽

Carlo Vergani ◽

...

Keyword(s):

Cognitive Impairment ◽

Retrospective Study ◽

Mild Cognitive Impairment ◽

Neuropsychological Assessment ◽

Neuropsychological Tests ◽

Subjective Evaluation ◽

Structured Interview ◽

Cognitive Status ◽

Cognitive Profile ◽

The One

The aim of this retrospective study was to investigate the accuracy of informant reports on cognitive status in mild cognitive impairment (MCI) by comparing the subjective evaluation made by patients’ relatives with the objective results of neuropsychological assessment. We enrolled 119 MCI outpatients and their relatives. Cognitive impairment was assessed by a battery of standardized neuropsychological tests. Informant reports on cognitive functioning were obtained by means of a structured interview. Subjective and objective evaluations of cognitive status were rated according to the same scoring system in order to enable comparison. All but one relative reported cognitive dysfunctions at the interview, but the kind of cognitive profile emerging from their reports was quite different from the one highlighted by neuropsychological assessment. A subjective evaluation of cognitive status based on informant reports could therefore be useful to identify patients with MCI but is unable to define MCI subtypes.

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Mixed-methods and Repeated Measures in Substance Use Research: Implications for Informant Accuracy

Field Methods ◽

10.1177/1525822x19871945 ◽

2019 ◽

Vol 31 (4) ◽

pp. 344-358

Author(s):

Caitlyn D. Placek ◽

Vijaya Srinivas ◽

Poornima Jayakrishna ◽

Purnima Madhivanan

Keyword(s):

Substance Use ◽

Mixed Methods ◽

Repeated Measures ◽

Self Report ◽

Time Points ◽

Sensitive Topics ◽

The Social ◽

Reported Data ◽

Study Participants ◽

Informant Accuracy

Informant accuracy is a pervasive issue in the social sciences and persists through the ongoing use of self-report measures of behaviors that are subject to recall errors. The current study reports findings from methods we used to measure substance use among adolescents in South India. We used a repeated-measures, mixed-methods design that began with semistructured interviews ( N = 60) to determine the substances used by adolescents. Next, adolescents were recruited to participate in a four-week study that assessed self-reported substance use at three time points and urinary cotinine, a nicotine metabolite, at two time points. Fifty-six participants completed the study protocol. Findings revealed that during the last phase of the study, participants were more willing to admit using substances. Our results add to existing literature that demonstrates the need to move beyond self-reported data of consumption, and to consider using repeated measures, direct observation of behavior, and biometric markers of behavior to ensure more accurate assessments of sensitive topics.

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Pain and Cognitive Status among Nursing Home Residents in Canada

Pain Research and Management ◽

10.1155/2001/978130 ◽

2001 ◽

Vol 6 (3) ◽

pp. 119-125 ◽

Cited By ~ 104

Author(s):

Wendey R Proctor ◽

John P Hirdes

Keyword(s):

Nursing Home ◽

Cognitive Impairment ◽

Regional Differences ◽

Cognitive Impairments ◽

Nursing Home Residents ◽

Cognitive Status ◽

Self Report ◽

Health Conditions ◽

Nursing Home Admission ◽

Elderly Persons

BACKGROUND: There is little information available on the rates of pain in institutionalized elderly persons, and this is particularly true for Canada.OBJECTIVES: To provide information about the prevalence and clinical correlates of pain in a sample of Canadian nursing homes, to determine whether residents with cognitive impairment experience lower rates of health conditions associated with pain (eg, arthritis) than residents without cognitive impairment and to determine whether the associations (ie, odds ratios) for pain with such health conditions vary as a function of cognitive status.DESIGN: The study is based on a secondary analysis of data collected with the minimum data set (MDS 2.0).SETTING AND PARTICIPANTS: The study comprised 3195 nursing home residents in Ontario, Manitoba and Saskatchewan.SUBJECTS AND METHODS: All residents were assessed with the MDS 2.0 by trained clinicians (usually nurses). Pain was documented if it had occurred within the seven days before the assessment. Assessors were trained to look for overt signs of discomfort, such as wincing or verbalizations. Self-report ratings were obtained when possible.RESULTS: The overall prevalence of pain in this sample was 49.7%, and 23.7% of residents experienced pain daily. Persons with and persons without cognitive impairments did not differ with respect to the prevalence of conditions likely to cause pain and the associations of pain with such health conditions. Regional differences were found, with Ontario residents having a higher frequency and intensity of pain than their counterparts in Saskatchewan and Manitoba. This may be due, at least in part, to regional differences in nursing home admission criteria.CONCLUSIONS: The findings suggest that the prevalence of identified pain is lower among nursing home residents with higher levels of cognitive impairment. These results do not support the notion that this is a function of lower prevalence rates of pain-causing conditions in nursing home residents with dementia. Furthermore, the results do not support the view that residents with cognitive impairments are less sensitive to pain. This study highlights the need for more comprehensive tools to assess pain in persons with cognitive impairments. Nonetheless, the MDS may be a useful instrument for detecting pain in such populations, because it does not rely exclusively on self-report.

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Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: A systematic review and meta-analysis

10.1101/2021.08.17.21262190 ◽

2021 ◽

Author(s):

Alexandra L Whittaker ◽

Rebecca P George ◽

Lucy O’Malley

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Neuropsychological Tests ◽

Negative Impact ◽

Self Report ◽

Screening Tools ◽

Low Grade ◽

Chemotherapy Treatment ◽

Time Points

AbstractBreast cancer survival rates have markedly improved. Consequently, survivorship issues have received increased attention. One common sequela of treatment is chemotherapy- induced cognitive impairment (CICI). CICI causes a range of impairments that can have a significant negative impact on quality of life. Knowledge of the prevalence of this condition is required to inform survivorship plans, and ensure adequate resource allocation and support is available for sufferers.ObjectiveTo estimate the prevalence of cognitive impairment following chemotherapy treatment for breast cancer.MethodsMedline, Scopus, CINAHL and PSYCHInfo were searched for eligible studies which included prevalence data on CICI, as ascertained though the use of self-report, or neuropsychological tests. Methodological quality of included studies was assessed. Findings were synthesised narratively, with meta-analyses being used to calculate pooled prevalence when impairment was assessed by neuropsychological tests.Results and discussionThe review included 52 studies. Time-points considered ranged from the chemotherapy treatment period to greater than 10 years after treatment cessation. Summary prevalence figures (across time-points) using self-report, short cognitive screening tools and neuropsychological test batteries were 44%, 16% and 21-34% respectively (very low GRADE evidence).ConclusionSynthesised findings demonstrate that 1 in 3 breast cancer survivors may have clinically significant cognitive impairment. Prevalence is higher when self-report based on patient experience is considered. This review highlights a number of study design issues that may have contributed to the low certainty rating of the evidence. Future studies should take a more consistent approach to the criteria used to assess impairment. Larger studies are urgently needed.Summary of Findings Table

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