Effect of chemotherapy on hippocampal volume and shape in older long-term breast cancer survivors.

Purpose: The objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5-15 years prior. Methods: This study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C-), and healthy controls (HC). The participants were recruited 5-15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests. Results: At TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = -0.585, p = 0.007). Conclusion: The observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

Cognitive effects of long-term androgen deprivation therapy in older men with prostate cancer.

OBJECTIVE: Androgen deprivation therapy (ADT) is a common treatment for prostate cancer (PCa), with increasing numbers of men on ADT for longer. Limited evidence suggests ADT impacts cognition. This study addressed gaps in the literature by focusing on older men with PCa and assessing ADT usage longer than 1 year. METHODS: This study of 133 men ≥65 years of age with PCa included two groups: (1) men on ADT for 1-3 years (ADT-exposed), and (2) a comparison group of men with PCa not on ADT (ADT-unexposed). Group comparisons on individual neuropsychological test scores are reported, as well as effect sizes (Cohen's d). RESULTS: Half (n = 67) of the sample was ADT-exposed and half (n = 66) were unexposed. The average age was 72 years, most were White, and over 50% had at least secondary education. There were no statistically significant differences between groups by age, race, or education. Unadjusted analyses showed the ADT-exposed group, compared with the ADT-unexposed group, performed significantly lower in domains of verbal learning (d = 0.45-0.52, p = 0.01 to <0.01), verbal recall (d = 0.33-0.54, p = 0.06 to <0.01), and possible effects in visuospatial construction (d = 0.33, p = 0.08 to 0.06). When controlling for age and education, similar patterns emerged. The ADT exposed-group performed significantly lower in domains of verbal learning (d = 0.45-0.52, p = 0.06 to 0.03) and verbal recall (d = 0.33-0.54, p = 0.11 to 0.03), and possible effects in visuospatial construction d = 0.33, p = 0.18 to 0.13. CONCLUSIONS: This study suggests long-term ADT exposure impacts verbal learning, verbal recall, and possibly visuospatial abilities in older men (≥65) with PCa. The potential cognitive effects of ADT should be discussed with older patients considering long-term use of ADT.

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.

Hemichorea-hemiballismus associated with a case of cerebral toxoplasmosis in a hematopoietic stem cell transplant recipient.

Due to their immunocompromised state, recipients of hematopoietic stem cell transplants (HSCTs) are at a higher risk of opportunistic infections, such as that of toxoplasmosis. Toxoplasmosis is a rare but mortal infection that can cause severe neurological symptoms, including confusion. In immunosuppressed individuals, such as those with acquired immunodeficiency syndrome (AIDS), toxoplasmosis can cause movement disorders, including hemichorea-hemiballismus. We present the case of a 54-year-old Caucasian male with a history of hypertension and JAK-2-negative primary myelofibrosis who underwent an allogeneic peripheral blood stem cell transplant from a related donor. After the development of acute changes in mental status, left-sided weakness, and left-sided hemichorea-hemiballismus post-transplant, the patient was readmitted to the hospital. Subsequent testing included an magnetic resonance imaging (MRI) of the brain, which revealed multiple ring-enhancing lesions around the thalami and basal ganglia, as well as a cerebrospinal fluid tap that tested positive for toxoplasmosis. The patient was initially treated with intravenous clindamycin and oral pyrimethamine with leucovorin. The completion of treatment improved the patient's mental status but did not improve his hemichorea-hemiballismus. This case illustrates an uncommon complication associated with central nervous system (CNS) toxoplasmosis in stem cell transplant recipients. Due to its rarity, cerebral toxoplasmosis in immunocompromised patients often remains undetected, particularly in HSCT patients who are immunosuppressed to improve engraftment. Neurological and neuropsychiatric symptoms due to toxoplasmosis may be misidentified as psychiatric morbidities, delaying appropriate treatment. Polymerase chain reaction (PCR) assays offer methods that are sensitive and specific to detecting toxoplasmosis and provide opportunities for early intervention.

Brain white matter microstructural changes in chemotherapy-treated older long-term breast cancer survivors.

PURPOSE: To assess white matter microstructural changes in older long-term breast cancer survivors 5-15 years post-chemotherapy treatment. METHODS: Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C-) and age- and sex-matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract-based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. RESULTS: There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family-wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. CONCLUSIONS: Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.

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.

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

There is a paucity of research on treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high-dose chemotherapy (HDC) and autologous SCT (HDC/ASCT), despite the increasing use of this regimen. We examined resting state functional connectivity (RSFC), gray matter (GM) volume, neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Eighteen patients underwent MRI, NF tests, and serum PCy measurements prior to HDC/ASCT, and fifteen patients completed a follow up five-months post-HDC/ASCT. There were significant decreases in RSFC post-HDC/ASCT in (1) the central executive network (CEN) involving the left dorsolateral prefrontal cortex and right posterior parietal cortex (p = 0.022) and (2) the CEN involving the right posterior parietal cortex and the salience network involving the right dorsal anterior cingulate cortex (p = 0.029). There were no significant changes in GM or NF, except for improvements in attention (Digit Span Backward, p = 0.03). There were significant increases in several PCy post-HDC/ASCT (p ≤ 0.05). In conclusion, RSFC decreased in frontal, parietal, and cingulate cortices post-HDC/ASCT, NF was relatively stable, and several PCy increased. These findings are congruent with other studies in cancer patients and provide supporting evidence for the vulnerability of frontoparietal regions to chemotherapy's adverse effects.

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.

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

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.

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.

Cognitive Aging in Older Breast Cancer Survivors.

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.

Altered gyrification in chemotherapy-treated older long-term breast cancer survivors.

Purpose: The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long-term breast cancer survivors 5 to 15 years after chemotherapy treatment. Methods: Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C-) 5-15 years prior and age & sex-matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI. Results: The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C+ group, 12 participants for the C- group, and 13 participants for the HC group. The C+ group had increased gyrification in 6 local gyrus regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in 2 local gyrus regions from TP1 to TP2 (p < 0.05, Bonferroni corrected). The C- and HC groups showed decreased gyrification only (p < 0.05, Bonferroni corrected). In C+ group, changes in right paracentral gyrification and crystalized composite scores were negatively correlated (R = -0.76, p = 0.01). Conclusions: Altered gyrification could be the neural correlate of cognitive changes in older chemotherapy-treated long-term breast cancer survivors.

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

Background Many patients with hematological malignancies treated with stem cell transplantation (SCT) experience cognitive dysfunction. However, few studies have investigated treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high dose chemotherapy (HDC) and autologous SCT (HDC/ASCT). In this study, we examined gray matter (GM) volume, resting state functional connectivity (RSFC), neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Methods Eighteen MM patients underwent magnetic resonance imaging, neurocognitive tests, and serum PCy measurement prior to HDC/ASCT, and fifteen patients completed follow ups an average of five months post-HDC/ASCT. Results There were significant decreases in RSFC from pre- to post-HDC/ASCT in (1) the central executive network (CEN) involving the left dorsolateral prefrontal cortex and right posterior parietal cortex (p = 0.022), and (2) the CEN involving the right posterior parietal cortex and the salience network involving the right dorsal anterior cingulate cortex (p = 0.029); these comparisons were no longer significant after multiple comparisons correction. There were no significant changes in GM volumes or NF, except for improvement in attention (Digit Span Backward, p = 0.03). There were significant increases in several PCy post-HDC/ASCT (p ≤ 0.05). Conclusions This pilot study showed decreased RSFC involving the left frontal, right posterior parietal and right anterior cingulate cortices in MM patients post-HDC/ASCT, relatively stable NF, and increases in PCy. These findings are congruent with studies in patients with hematological malignancies and other cancers and provide supporting evidence for the vulnerability of frontoparietal regions to chemotherapy adverse effects.

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.

Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors.

PURPOSE: This study aims to examine whether cognitive function in older, long-term breast cancer survivors is both a direct effect of cancer and cancer treatments and an indirect effect mediated by deficit accumulation. PATIENTS AND METHODS: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 220) and age- and education-matched non-cancer controls (N = 123) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological tests and the comprehensive geriatric assessment which was used to calculate the deficit accumulation frailty index (DAFI). Blood or saliva samples for APOE genotyping were collected at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or and 50% were not exposed to chemotherapy. RESULTS: Latent variable mediation analysis revealed that cognitive performance was mediated by deficit accumulation for all three domains. The direct effect of cancer diagnosis and treatment history was significant for the Language domain (p = 0.04), a trend for the learning and memory domain (p = 0.054), and non-significant for the attention, processing speed, executive function (APE) domain. Carrying the APOE ε4 allele had a significant negative direct effect on the APE domain (p = 0.05) but no indirect effect through deficit accumulation. CONCLUSION: Cognitive function in older, long-term breast cancer survivors appears to be primarily mediated through deficit accumulation. IMPLICATIONS FOR CANCER SURVIVORS: These findings have important clinical implications suggesting that the most effective intervention to prevent or slow cognitive aging in older cancer survivors may be through prevention or management of comorbidities and interventions that maintain functional capacity (exercise, physical therapy) and social and mental health.

Remote, Computerised Cognitive Assessment for Breast Cancer- and Treatment-Related Cognitive Dysfunction: Psychometric Characteristics of the Cogsuite Neurocognitive Battery.

OBJECTIVE: Cancer-related cognitive dysfunction (CRCD) is a significant concern for breast cancer survivors. The Cogsuite battery was developed to improve sensitivity to CRCD with the use of cognitive experimental measures, clarify specific cognitive processes impacted and to be capable of being administered either in-office or remotely. METHODS: In sum, 357 breast cancer survivors and non-cancer controls completed the Cogsuite Battery in-office (n = 76) or remotely (n = 281). Measure validity, sensitivity to demographic factors, correlations with standard neuropsychological measures and intercorrelations of Cogsuite variables were assessed. Test-retest reliability was evaluated in-office (n = 24) and remotely (n = 80). RESULTS: Test-retest reliability for most variables assessed was adequate to strong. Internal validity, as indicated by the confirmation of expected condition effects within each measure, was established for all measures. Assessment of external validity found age, but not education, was a significant predictor in the majority of measures. Assessment of criterion validity found that Cogsuite variables were correlated with standard measures in psychomotor speed, working memory and executive function, but not associated with self-reported cognition or mood. CONCLUSIONS: Cogsuite is reliable and valid, and is sensitive to the effects of increasing age on cognition. The addition of the Cogsuite battery to standard assessment may improve sensitivity to CRCD and identify underlying processes that may be affected. Remote use of the Cogsuite battery in appropriate settings will lessen the burden for providers, researchers and survivors in research and clinical contexts.

Exercise Associated with Cognitive Function in Older Men with Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: To examine associations between exercise and cognitive function in older men undergoing hormone therapy for prostate cancer. METHOD: Men ≥ 65 years old with prostate cancer, currently undergoing androgen deprivation therapy for ≥ 6 months (n = 50), completed the Godin-Shephard Leisure-Time Physical Activity Questionnaire, and standard neuropsychological tests. Pearson's correlations and linear regressions were used to examine associations between exercise and cognitive performance. RESULTS: Exercise was significantly positively correlated with performance on tests of memory, attention, and executive function. Linear regressions showed that when controlling for age and education, exercise remained a significant predictor of attention and executive function performance (p < 0.05), and showed moderate, but statistically non-significant effects on memory performance (p < 0.10). CONCLUSION: Greater exercise is associated with better functioning in multiple cognitive domains in men with prostate cancer undergoing hormone therapy, providing proof-of-concept evidence that exercise may be a feasible intervention to limit cognitive dysfunction in prostate cancer patients.

Cortical thinning in chemotherapy-treated older long-term breast cancer survivors.

Cognitive decline is an increasing issue for cancer survivors, especially for older adults, as chemotherapy affects brain structure and function. The purpose of this single center study was to evaluate alterations in cortical thickness and cognition in older long-term survivors of breast cancer who had been treated with chemotherapy years ago. In this prospective cohort study, we enrolled 3 groups of women aged ≥ 65 years with a history of stage I-III breast cancer who had received adjuvant chemotherapy 5 to 15 years ago (chemotherapy group, C +), age-matched women with breast cancer but no chemotherapy (no-chemotherapy group, C-) and healthy controls (HC). All participants underwent brain magnetic resonance imaging and neuropsychological testing with the NIH Toolbox Cognition Battery at time point 1 (TP1) and again at 2 years after enrollment (time point 2 (TP2)). At TP1, there were no significant differences in cortical thickness among the 3 groups. Longitudinally, the C + group showed cortical thinning in the fusiform gyrus (p = 0.006, effect size (d) = -0.60 [ -1.86, -0.66]), pars triangularis (p = 0.026, effect size (d) = -0.43 [-1.68, -0.82]), and inferior temporal lobe (p = 0.026, effect size (d) = -0.38 [-1.62, -0.31]) of the left hemisphere. The C + group also showed decreases in neuropsychological scores such as the total composite score (p = 0.01, effect size (d) = -3.9726 [-0.9656, -6.9796], fluid composite score (p = 0.03, effect size (d) = -4.438 [-0.406, -8.47], and picture vocabulary score (p = 0.04, effect size (d) = -3.7499 [-0.0617, -7.438]. Our results showed that cortical thickness could be a candidate neuroimaging biomarker for cancer-related cognitive impairment and accelerated aging in older long-term cancer survivors.

The effect of visual target presence and age on antisaccade performance.

Antisaccade and prosaccade (PS) performance were studied in a large cohort of females (age range 42-74 yr). Antisaccade performance was assessed in two variants of the task, a "traditional" antisaccade (TA) task, in which no visual stimuli were present at the saccade goal, and a visually guided antisaccade (VGA) task, in which small visual stimuli were present at the possible saccade goals prior to the imperative visual stimulus. Directional error frequency was similar in the two antisaccade tasks. However, reaction time (RT) was ∼33 ms longer in the VGA task than in the TA task. Across participants, the average saccade amplitudes of prosaccades and TAs were both correlated with those of VGAs but not with each other. TAs had a hypermetria that increased with age. Saccade amplitude variability was much higher for TAs than for PSs and VGAs. Saccade polar angle variability was low for all three tasks. Age diminished performance with modest task dependence, except for an increase in TA hypermetria. These results suggest that the generation of antisaccade directional errors does not depend on visual target presence at the saccade goal, that antisaccade RT can be affected by target presence, that age can increase saccade hypermetria in the absence of visual guidance, and that visually guided antisaccades are governed by distinct voluntary and visually guided saccade mechanisms. Moreover, these results suggest that an understanding of human motor performance benefits from the use of a participant pool with a larger age range than that used in most studies.NEW & NOTEWORTHY This study uses a visually guided antisaccade (VGA) task to determine whether poor performance in a large middle-aged participant pool on an antisaccade task results from problems with executive control or voluntary saccade generation. Spatial and temporal attributes of saccade performance as a function of task and age are analyzed comprehensively. Correlational analysis is used to determine how VGAs are governed jointly by voluntary and visually guided movement mechanisms.

An Examination of the Longitudinal Relationship Between Cognitive Function and Physical Activity Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study.

BACKGROUND: Older cancer survivors are at risk for cognitive decline. Physical activity can improve cognition, and better cognitive function may facilitate greater physical activity. PURPOSE: We examined the potential bidirectional relationship between cognitive function and physical activity in older breast cancer survivors and controls. METHODS: The sample included women with newly diagnosed, nonmetastatic breast cancer (n = 395) and women without cancer (n = 374) ages 60-98. Participants were recruited as part of a larger multisite study, assessed prior to systemic therapy, and followed yearly for 36 months. Attention, processing speed, and executive function was measured using six neuropsychological tests, self-reported cognitive function using the Perceived Cognitive Impairments subscale of the Functional Assessment of Cancer Therapy-Cognitive Function , and physical activity using the International Physical Activity Questionnaire-Short Form. Separate random intercepts cross-lagged panel models were used to examine the between- and within-person effects for survivors and controls, controlling for age, education, and study site. RESULTS: Survivors reported significantly less physical activity than controls at baseline (1,284.92 vs. 2,085.98 MET min/week, p < .05). When survivors reported higher activity, they simultaneously had better objective cognition at 12 months (ß = 0.24, p = .04) and reported better perceived cognition at 12 and 24 months (ß = 0.25, p = .03), but this relationship was not seen in controls. Cognition did not predict subsequent physical activity or vice versa in either group. CONCLUSIONS: Cognition and physical activity are cross-sectionally associated in survivors, but the expected prospective relationships were not found.

Physical activity may improve cognitive function for older cancer survivors; however, cognitive function may also affect the ability to organize oneself to be physically active. We examined this potential bidirectional relationship in a sample of 395 women with newly diagnosed, nonmetastatic breast cancer, and 374 noncancer controls. These women completed cognitive tests and surveys yearly for 36 months. Surveys included their subjective cognitive function and physical activity. We examined the relationships between cognitive function (both objective and subjective) and physical activity over time (baseline, 12, 24, and 36 months). We found that when cancer survivors reported higher physical activity, they had better objective cognitive function at 12 months, and they reported better subjective cognitive function at 12 and 24 months. However, physical activity did not predict cognitive function at later time points, and cognitive function did not predict physical activity at later time points. In controls, better subjective cognitive function was related to higher physical activity overall, but there were not relationships over time or at specific time points. This was an observational study; therefore, future research should consider the potential impact of cognitive function when older cancer survivors are attempting to increase their physical activity.