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15 pages, 937 KiB

Open AccessArticle

Association of Radiation Dose to the Amygdala–Orbitofrontal Network with Emotion Recognition Task Performance in Patients with Low-Grade and Benign Brain Tumors

by Sara J. Hardy, Alan Finkelstein, Michael T. Milano, Giovanni Schifitto, Hongying Sun, Koren Holley, Kenneth Usuki, Miriam T. Weber, Dandan Zheng, Christopher L. Seplaki and Michelle Janelsins

Cancers 2023, 15(23), 5544; https://doi.org/10.3390/cancers15235544 - 23 Nov 2023

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Abstract

Background: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala–orbitofrontal network can impact social cognition. Methods: We prospectively enrolled 51 patients with [...] Read more.

Background: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala–orbitofrontal network can impact social cognition. Methods: We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala–orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH). Results: The RT dose to the amygdala–orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT. Discussion: This is, to our knowledge, the first study to show that off-target RT dose to the amygdala–orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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11 pages, 587 KiB

Open AccessArticle

Symptom Clusters in Survivorship and Their Impact on Ability to Work among Cancer Survivors

by Joanna E. Fardell, Sim Yee (Cindy) Tan, Kim Kerin-Ayres, Haryana M. Dhillon and Janette L. Vardy

Cancers 2023, 15(21), 5119; https://doi.org/10.3390/cancers15215119 - 24 Oct 2023

Cited by 2 | Viewed by 2403

Abstract

Background: Cancer survivors often experience a range of symptoms after treatment which can impact their quality of life. Symptoms may cluster or co-occur. We aimed to investigate how symptoms and symptom clusters impact the ability to work among cancer survivors. Methods: We used [...] Read more.

Background: Cancer survivors often experience a range of symptoms after treatment which can impact their quality of life. Symptoms may cluster or co-occur. We aimed to investigate how symptoms and symptom clusters impact the ability to work among cancer survivors. Methods: We used symptom severity data and ability to work data routinely collected from cancer survivors attending a survivorship clinic after primary treatment with curative intent. We defined symptom clusters using single linkage and a threshold on the rescaled distances of <10. We then conducted a logistic regression to examine how symptoms and symptom clusters were related to the ability to work. Results: We analysed data from 561 cancer survivors, mean age 58 years and 1.5 years post diagnosis, with mixed diagnoses including breast (40.5%), colorectal (32.3%), and haematological cancers (15.3%). Limitations to work ability were reported by 34.9% of participants. Survivors experiencing pain, emotional, and cognitive symptom clusters were 14–17% more likely to report limitations in their ability to work. Older survivors and those with a higher stage disease were more likely to report limitations in their ability to work. Conclusion: A better understanding and management of symptom severity and symptom clusters may help the sizable proportion of cancer survivors experiencing symptoms to participate in work after treatment. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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16 pages, 1287 KiB

Open AccessArticle

Using Single-Case Experimental Design and Patient-Reported Outcome Measures to Evaluate the Treatment of Cancer-Related Cognitive Impairment in Clinical Practice

by Robert J. Ferguson, Lauren Terhorst, Benjamin Gibbons, Donna M. Posluszny, Hsuan Chang, Dana H. Bovbjerg and Brenna C. McDonald

Cancers 2023, 15(18), 4643; https://doi.org/10.3390/cancers15184643 - 20 Sep 2023

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Abstract

Cancer-related cognitive impairment (CRCI) affects a large proportion of cancer survivors and has significant negative effects on survivor function and quality of life (QOL). Treatments for CRCI are being developed and evaluated. Memory and attention adaptation training (MAAT) is a cognitive-behavioral therapy (CBT) [...] Read more.

Cancer-related cognitive impairment (CRCI) affects a large proportion of cancer survivors and has significant negative effects on survivor function and quality of life (QOL). Treatments for CRCI are being developed and evaluated. Memory and attention adaptation training (MAAT) is a cognitive-behavioral therapy (CBT) demonstrated to improve CRCI symptoms and QOL in previous research. The aim of this article is to describe a single-case experimental design (SCED) approach to evaluate interventions for CRCI in clinical practice with patient-reported outcome measures (PROs). We illustrate the use of contemporary SCED methods as a means of evaluating MAAT, or any CRCI treatment, once clinically deployed. With the anticipated growth of cancer survivorship and concurrent growth in the number of survivors with CRCI, the treatment implementation and evaluation methods described here can be one way to assess and continually improve CRCI rehabilitative services. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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23 pages, 1367 KiB

Open AccessArticle

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship

by Annelise A. Madison, Rebecca Andridge, Anthony H. Kantaras, Megan E. Renna, Jeanette M. Bennett, Catherine M. Alfano, Stephen P. Povoski, Doreen M. Agnese, Maryam Lustberg, Robert Wesolowski, William E. Carson III, Nicole O. Williams, Raquel E. Reinbolt, Sagar D. Sardesai, Anne M. Noonan, Daniel G. Stover, Mathew A. Cherian, William B. Malarkey and Janice K. Kiecolt-Glaser

Cancers 2023, 15(17), 4414; https://doi.org/10.3390/cancers15174414 - 4 Sep 2023

Cited by 2 | Viewed by 1968

Abstract

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression—another vulnerability for cognitive decline. The current study tested whether depression accompanied by [...] Read more.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression—another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein—a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239–246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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18 pages, 1639 KiB

Open AccessArticle

The Impact of Mindfulness on Functional Brain Connectivity and Peripheral Inflammation in Breast Cancer Survivors with Cognitive Complaints

by Michelle Melis, Gwen Schroyen, Jeroen Blommaert, Nicolas Leenaerts, Ann Smeets, Katleen Van Der Gucht, Stefan Sunaert and Sabine Deprez

Cancers 2023, 15(14), 3632; https://doi.org/10.3390/cancers15143632 - 15 Jul 2023

Cited by 2 | Viewed by 1582

Abstract

Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer [...] Read more.

Background: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. Methods: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. Results: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1β, and IL-8). Conclusion: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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12 pages, 289 KiB

Open AccessArticle

Research Attitude and Interest among Cancer Survivors with or without Cognitive Impairment

by Ding Quan Ng, Daniella Chan, Munjal M. Acharya, Joshua D. Grill and Alexandre Chan

Cancers 2023, 15(13), 3409; https://doi.org/10.3390/cancers15133409 - 29 Jun 2023

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Abstract

Background: We examined the research attitudes and willingness to participate in clinical research among cancer survivors with varying degrees of cognitive function. Methods: This is a secondary analysis of data collected through the University of California Irvine Consent-to-Contact registry. Cancer survivors completed the [...] Read more.

Background: We examined the research attitudes and willingness to participate in clinical research among cancer survivors with varying degrees of cognitive function. Methods: This is a secondary analysis of data collected through the University of California Irvine Consent-to-Contact registry. Cancer survivors completed the Cognitive Function Instrument (CFI), the Research Attitudes Questionnaire (RAQ), and willingness to participate (WTP) in certain research procedures. Perceived cognitive impairment (CI) was defined as the worst 20% CFI scores. Results: Here, 265 CI and 909 cognitively non-impaired (CNI) participants’ data were analyzed. Mean age and sex distribution were similar, with fewer non-Hispanic Whites and education years among CI participants. More CI participants self-reported past diagnoses of Alzheimer’s disease, mild cognitive impairment, stroke, depression, post-traumatic stress disorder, and alcohol abuse (all p < 0.05). CI participants were significantly more interested in studies investigating approved medications (92% vs. 87%, p = 0.030), lumbar puncture (47% vs. 38%, p = 0.027), and autopsy (78% vs. 69%, p = 0.022). After removing survivors with co-existing neuropsychiatric conditions, interest in autopsy studies remained statistically higher among CI (79% vs. 69%, p = 0.022). Conclusions: Participants with cancer and CI are open to research procedures and interventions that are traditionally less utilized, which may facilitate the discovery of the pathogenesis and interventions for cancer-related cognitive impairment (CRCI). Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

14 pages, 1308 KiB

Open AccessArticle

Cognitive Aging in Older Breast Cancer Survivors

by James C. Root, Yuelin Li, Elizabeth Schofield, Irene Orlow, Elizabeth Ryan, Tiffany Traina, Sunita K. Patel and Tim A. Ahles

Cancers 2023, 15(12), 3208; https://doi.org/10.3390/cancers15123208 - 16 Jun 2023

Cited by 1 | Viewed by 1233

Abstract

Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but the extant studies are limited in their intervals of assessment (two–five years). We studied the cognitive performance of a cohort of survivors and controls aged from 60 [...] Read more.

Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but the extant studies are limited in their intervals of assessment (two–five years). We studied the cognitive performance of a cohort of survivors and controls aged from 60 to 89 years utilizing cross-sectional cognitive performance data as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5- to 15-year survivors (N = 328) and non-cancer controls (N = 158) were assessed at enrollment and at 8, 16, and 24 months with standard neuropsychological tests and comprehensive geriatric assessment. Results: A cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower overall than controls in learning and memory (LM). Younger survivors, i.e., those under 75 years of age, exhibited lower performance in both LM and attention, and processing speed and executive function (APE), compared to controls, with no differences being observed between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Cognitive differences between the survivors and controls for the LM and APE domains were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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11 pages, 1294 KiB

Open AccessArticle

Intolerance of Uncertainty and Cognition in Breast Cancer Survivors: The Mediating Role of Anxiety

by Yesol Yang, Stephanie M. Gorka, Michael L. Pennell, Kellie Weinhold and Tonya Orchard

Cancers 2023, 15(12), 3105; https://doi.org/10.3390/cancers15123105 - 8 Jun 2023

Cited by 2 | Viewed by 1410

Abstract

Cancer-related cognitive impairment (CRCI) is one of the most prevalent symptoms that breast cancer survivors experience. While cancer treatments are established contributors to CRCI, inter-individual differences in CRCI are not well understood. Individual differences in sensitivity to uncertainty are potential contributors to CRCI; [...] Read more.

Cancer-related cognitive impairment (CRCI) is one of the most prevalent symptoms that breast cancer survivors experience. While cancer treatments are established contributors to CRCI, inter-individual differences in CRCI are not well understood. Individual differences in sensitivity to uncertainty are potential contributors to CRCI; however, no prior studies have attempted to examine this link in the context of breast cancer. To address the gap, we used preliminary findings from an ongoing cross-sectional study. A total of 38 women with stage I–III breast cancer (1–4 years post-treatment) were included in this study. Intolerance of uncertainty (IU) was assessed using the Intolerance of Uncertainty Scale. Self-reported cognitive function was assessed with the Neuro-QoL questionnaire. Anxiety was assessed using the Patient-Reported Outcomes Measurement System Bank. From this study, we found that anxiety mediates the association between IU and cognitive function of survivors. In other words, among post-menopausal breast cancer survivors, those with higher IU showed higher anxiety and consequently had lower cognitive function. This finding suggests that assessing IU may help predict the risk of CRCI. This study expands the current knowledge that addresses the importance of IU as a factor associated with cognitive health. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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15 pages, 2963 KiB

Open AccessArticle

Genetic Variants Associated with Longitudinal Cognitive Performance in Older Breast Cancer Patients and Controls

by Kelly Nudelman, Kwangsik Nho, Michael Zhang, Brenna C. McDonald, Wanting Zhai, Brent J. Small, Claire E. Wegel, Paul B. Jacobsen, Heather S. L. Jim, Sunita K. Patel, Deena M. A. Graham, Tim A. Ahles, James C. Root, Tatiana Foroud, Elizabeth C. Breen, Judith E. Carroll, Jeanne S. Mandelblatt and Andrew J. Saykin

Cancers 2023, 15(11), 2877; https://doi.org/10.3390/cancers15112877 - 23 May 2023

Cited by 1 | Viewed by 1416

Abstract

Background: There have been no published genome-wide studies of the genetics of cancer- and treatment-related cognitive decline (CRCD); the purpose of this study is to identify genetic variants associated with CRCD in older female breast cancer survivors. Methods: Analyses included white non-Hispanic women [...] Read more.

Background: There have been no published genome-wide studies of the genetics of cancer- and treatment-related cognitive decline (CRCD); the purpose of this study is to identify genetic variants associated with CRCD in older female breast cancer survivors. Methods: Analyses included white non-Hispanic women with non-metastatic breast cancer aged 60+ (N = 325) and age-, racial/ethnic group-, and education-matched controls (N = 340) with pre-systemic treatment and one-year follow-up cognitive assessment. CRCD was evaluated using longitudinal domain scores on cognitive tests of attention, processing speed, and executive function (APE), and learning and memory (LM). Linear regression models of one-year cognition included an interaction term for SNP or gene SNP enrichment*cancer case/control status, controlling for demographic variables and baseline cognition. Results: Cancer patients carrying minor alleles for two SNPs, rs76859653 (chromosome 1) in the hemicentin 1 (HMCN1) gene (p = 1.624 × 10⁻⁸), and rs78786199 (chromosome 2, p = 1.925 × 10⁻⁸) in an intergenic region had lower one-year APE scores than non-carriers and controls. Gene-level analyses showed the POC5 centriolar protein gene was enriched for SNPs associated with differences in longitudinal LM performance between patients and controls. Conclusions: The SNPs associated with cognition in survivors, but not controls, were members of the cyclic nucleotide phosphodiesterase family, that play important roles in cell signaling, cancer risk, and neurodegeneration. These findings provide preliminary evidence that novel genetic loci may contribute to susceptibility to CRCD. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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12 pages, 2067 KiB

Open AccessArticle

Normal Pressure Hydrocephalus Following Cranial Radiation: Identification of Shunting Responders

by Nuria Cayuela, Manuel Domínguez-Lizarbe, Gerard Plans, Montserrat Alemany, Juan José Sánchez, Begoña Andrés, Anna Lucas, Jordi Bruna and Marta Simó

Cancers 2023, 15(7), 1949; https://doi.org/10.3390/cancers15071949 - 24 Mar 2023

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Abstract

Background: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). Methods: Patients who completed cranial RT at least [...] Read more.

Background: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). Methods: Patients who completed cranial RT at least 2 years before with clinically suspected NPH and an Evans’ index (EI) ≥ 0.30 underwent a cognitive and a cerebrospinal fluid (CSF) volumetric (MRI) analysis (n = 36). For those in whom VPS was placed (n = 14), we explored whether adding a CSF volumetric analysis to classical MRI and LIT (Tap Test) features would better identify VPS responders. Results: Nearly 80% exhibited cognitive impairment. The CSF volume at NPH diagnoses was significantly larger in the group of VPS responders (p = 0.04). The addition of CSF volume to NPH diagnoses increased accuracy to 93%, with a positive and negative predictive value of 91% and 100%, respectively. Conclusion: The addition of a quantitative MRI analysis of CSF volume to classical MRI and LIT NPH criteria, along with a high clinical suspicion of NPH, may help to identify VPS responders, thus improving the clinical management and prognosis of long-term survivors. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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17 pages, 832 KiB

Open AccessArticle

Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study

by Lisa E. Mash, Lisa S. Kahalley, Kimberly P. Raghubar, Naomi J. Goodrich-Hunsaker, Tracy J. Abildskov, Luz A. De Leon, Marianne MacLeod, Heather Stancel, Kelley Parsons, Brian Biekman, Nilesh K. Desai, David R. Grosshans, Arnold C. Paulino, Zili D. Chu, William E. Whitehead, Mehmet Fatih Okcu, Murali Chintagumpala and Elisabeth A. Wilde

Cancers 2023, 15(6), 1844; https://doi.org/10.3390/cancers15061844 - 19 Mar 2023

Cited by 6 | Viewed by 2118

Abstract

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study [...] Read more.

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging >7 years post-radiotherapy. A healthy comparison group (n = 23) was also recruited. Participants completed age-appropriate measures of intellectual functioning, visual-motor integration, and motor coordination. Tractography was conducted using automated fiber quantification (AFQ). Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 12 tracts of interest. Overall, both white matter integrity (FA) and neuropsychological performance were lower in XRT patients while PRT patients were similar to healthy control participants with respect to both FA and cognitive functioning. These findings support improved long-term outcomes in PRT versus XRT. This exploratory study is the first to directly support for white matter integrity as a mechanism of cognitive sparing in PRT. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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18 pages, 766 KiB

Open AccessArticle

First-Line Immunotherapy with Check-Point Inhibitors: Prospective Assessment of Cognitive Function

by Jamie S. Myers, Adam C. Parks, Jonathan D. Mahnken, Kate J. Young, Harsh B. Pathak, Rajni V. Puri, Amber Unrein, Phyllis Switzer, Yazan Abdulateef, Samantha Sullivan, John F. Walker, David Streeter and Jeffrey M. Burns

Cancers 2023, 15(5), 1615; https://doi.org/10.3390/cancers15051615 - 6 Mar 2023

Cited by 1 | Viewed by 1965

Abstract

Approximately 40% of patients with cancer are eligible for check-point inhibitor (CPI) therapy. Little research has examined the potential cognitive impact of CPIs. First-line CPI therapy offers a unique research opportunity without chemotherapy-related confounders. The purpose of this prospective, observational pilot was to [...] Read more.

Approximately 40% of patients with cancer are eligible for check-point inhibitor (CPI) therapy. Little research has examined the potential cognitive impact of CPIs. First-line CPI therapy offers a unique research opportunity without chemotherapy-related confounders. The purpose of this prospective, observational pilot was to (1) demonstrate the feasibility of prospective recruitment, retention, and neurocognitive assessment for older adults receiving first-line CPI(s) and (2) provide preliminary evidence of changes in cognitive function associated with CPI(s). Patients receiving first-line CPI(s) (CPI Group) were assessed at baseline (n = 20) and 6 months (n = 13) for self-report of cognitive function and neurocognitive test performance. Results were compared to age-matched controls without cognitive impairment assessed annually by the Alzheimer’s Disease Research Center (ADRC). Plasma biomarkers were measured at baseline and 6 months for the CPI Group. Estimated differences for CPI Group scores prior to initiating CPIs (baseline) trended to lower performance on the Montreal Cognitive Assessment-Blind (MOCA-Blind) test compared to the ADRC controls (p = 0.066). Controlling for age, the CPI Group’s 6-months MOCA-Blind performance was lower than the ADRC control group’s 12-months performance (p = 0.011). No significant differences in biomarkers were detected between baseline and 6 months, although significant correlations were noted for biomarker change and cognitive performance at 6 months. IFNγ, IL-1β, IL-2, FGF2, and VEGF were inversely associated with Craft Story Recall performance (p < 0.05), e.g., higher levels correlated with poorer memory performance. Higher IGF-1 and VEGF correlated with better letter-number sequencing and digit-span backwards performance, respectively. Unexpected inverse correlation was noted between IL-1α and Oral Trail-Making Test B completion time. CPI(s) may have a negative impact on some neurocognitive domains and warrant further investigation. A multi-site study design may be crucial to fully powering prospective investigation of the cognitive impact of CPIs. Establishment of a multi-site observational registry from collaborating cancer centers and ADRCs is recommended. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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19 pages, 3416 KiB

Open AccessArticle

Associations between Lifestyle Factors and Neurocognitive Impairment among Chinese Adolescent and Young Adult (AYA) Survivors of Sarcoma

by Yin Ting Cheung, Chung Tin Ma, Michael Can Heng Li, Keary Rui Zhou, Herbert Ho Fung Loong, Agnes Sui Yin Chan, Kwok Chuen Wong and Chi Kong Li

Cancers 2023, 15(3), 799; https://doi.org/10.3390/cancers15030799 - 28 Jan 2023

Cited by 3 | Viewed by 2011

Abstract

Background: The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes (specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15–39 years) of sarcoma. Methods: [...] Read more.

Background: The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes (specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15–39 years) of sarcoma. Methods: This study recruited 116 AYA survivors (age 28.2 (SD = 8.2) years), who were diagnosed with osteosarcoma (49%) or soft-tissue sarcoma (51%) at age 13.3 (SD = 7.2) years. The neurocognitive battery included measures of attention, memory, motor-processing speed, and cognitive flexibility. Survivors reported health-damaging practices, which included: physical inactivity, smoking, alcohol intake, inadequate sleep (<7 h of actual sleep/day), sleep-related fatigue (Multidimensional Fatigue Scale) and long working hours (>9 h/day). General linear modeling was conducted to examine the association between lifestyle factors and neurocognitive outcomes, adjusting for age at diagnosis, sex, education attainment and clinical/treatment variables. Results: At 14.9 (SD = 7.6) years post-diagnosis, survivors demonstrated impairment in attentiveness (4.3–13.0%), processing speed (34.5%) and cognitive flexibility (18.1%). Nearly half (45.7%) had developed a chronic health condition (CHC). Low physical activity (estimate = −0.97, p = 0.003) and sleep-related fatigue (estimate = −0.08, p = 0.005) were associated with inattention. Survivors who worked >9 h/day (n = 15) demonstrated worse attention (estimate = 5.42, p = 0.023) and cognitive flexibility (estimate = 5.22, p = 0.005) than survivors who worked ≤9 h/day (n = 66). Interaction analysis (CHCs*physical activity) showed that survivors who developed CHCs and reported low physical activity had worse attention (p = 0.032) and cognitive-flexibility (p = 0.019) scores than other subgroups. Conclusion: Treatment-related CHCs, coupled with continued physical inactivity, may exacerbate inattention and executive dysfunction among survivors. Long working hours and sleep-related fatigue are associated with worse functioning; this finding should be validated with prospective assessment of work-related stressors and objective sleep measures. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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35 pages, 1157 KiB

Open AccessSystematic Review

A Systematic Review on the Potential Acceleration of Neurocognitive Aging in Older Cancer Survivors

by Charlotte Kerstens, Hans P. M. W. Wildiers, Gwen Schroyen, Mercedes Almela, Ruth E. Mark, Maarten Lambrecht, Sabine Deprez and Charlotte Sleurs

Cancers 2023, 15(4), 1215; https://doi.org/10.3390/cancers15041215 - 14 Feb 2023

Cited by 7 | Viewed by 3250

Abstract

As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer [...] Read more.

As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer survivors (>65 years), based on three databases (Pubmed, Web of Science and Medline). Ninety-six studies were included. Evidence was found for functional and structural brain changes (frontal regions, basal ganglia, gray and white matter), compared to healthy controls. Cognitive decline was mainly found in memory functioning. Anti-hormonal treatments were repeatedly associated with cognitive decline (tamoxifen) and sometimes with an increased risk of Alzheimer’s disease (androgen deprivation therapy). Chemotherapy was inconsistently associated with later development of cognitive changes or dementia. Radiotherapy was not associated with cognition in patients with non-central nervous system cancer but can play a role in patients with central nervous system cancer, while neurosurgery seemed to improve their cognition in the short-term. Individual risk factors included cancer subtypes (e.g., brain cancer, hormone-related cancers), treatment (e.g., anti-hormonal therapy, chemotherapy, cranial radiation), genetic predisposition (e.g., APOE, COMT, BDNF), age, comorbidities (e.g., frailty, cognitive reserve), and psychological (e.g., depression, (post-traumatic) distress, sleep, fatigue) and social factors (e.g., loneliness, limited caregiver support, low SES). More research on accelerated aging is required to guide intervention studies. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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