Cancer-Related Neuropathic Pain, Chemotherapy-Induced Peripheral Neuropathy and Cognitive Decline in a 5-Year Prospective Study of Patients with Breast Cancer-NEON-BC.

This study aims to estimate the prevalence and to identify the determinants of cancer-related neuropathic pain (CRNP), chemotherapy-induced peripheral neuropathy (CIPN) and cognitive decline among patients with breast cancer over five years after diagnosis. Women with an incident breast cancer (n = 462) and proposed for surgery were recruited at the Portuguese Institute of Oncology-Porto in 2012 and underwent systematic neurological examinations and evaluations with the Montreal Cognitive Assessment (MoCA) before treatment and after one, three, and five years. Multivariate logistic regression was used to assess the determinants of CRNP and CIPN, and multivariate linear regression for the variation in MoCA scores. Prevalence of CRNP and CIPN decreased from the first to the fifth year after diagnosis (CRNP: from 21.1% to 16.2%, p = 0.018; CIPN: from 22.0% to 16.0% among those undergoing chemotherapy, p = 0.007). Cognitive impairment was observed in at least one assessment in 17.7% of the women. Statistically significant associations were observed between: cancer stage III and both CRNP and CIPN; triple negative breast cancer, chemotherapy, axillary node dissection, older age, higher education, and being single and CRNP; taxanes and fruit and vegetable consumption and CIPN. Anxiety, depression and poor sleep quality at baseline were associated with decreases in MoCA values from pre- to post-treatment and with CRNP. Follow-up protocols should consider the persistence of CRNP, CIPN, and cognitive impairment for several years following diagnosis.

Interpersonal Values of Patients Participating in Phase II-III Clinical Trials: Implications for Clinical Trial Representativeness.

BACKGROUND: An individual's personal values strongly influence their immediate and long-term decisions. Psychological heterogeneity in clinical trial populations contributes to selection bias and may affect treatment outcomes and inevitably trial results. OBJECTIVES: The objective of this study was to characterize for the first time the main interpersonal values of patients who participated in Phase II and III clinical trials. METHODS: This multicenter observational study included 200 participants from 4 different hospitals who participated in a Phase II or III clinical trial. Patients from different therapeutic areas were included in this study. The patients' interpersonal values were studied using the Survey of Interpersonal Values (SIV). The SIV scale is grouped into six subscales that assess specific personal values: (1) support, the need to be treated with kindness and to receive encouragement from other people; (2) conformity, the extent to which one does what is acceptable and considered socially correct; (3) recognition, the need to be highly regarded and admired, to be considered important and recognized by others; (4) independence, the extent to which individuals feel free to make their own decisions; (5) benevolence, the capacity to understand and show generosity towards the less fortunate; and (6) leadership, the value ascribed to coordinating the work of others, being selected for a leadership position, and being in a position to tell others what to do. The results obtained from the patient population were classified using the following categories: "very high" (P95-P99), "high" (P70-90), "medium" (P35-65) low" (P10-30), or "very low" (P1-5), and subsequently compared with those of the Portuguese normative population. RESULTS: Compared with the normative population, regardless of the patient's underlying disease, the percentile frequency distributions were significantly higher for the independence (p < 0.001) and benevolence (p < 0.001) subscales, and significantly lower for the leadership (p < 0.001) and recognition (p < 0.001) subscales in the patient population. Patient distribution according to underlying disease differed significantly relative differences in distribution relative to the normative population for the majority of subscales. Non-alcoholic steatohepatitis (NASH), heart failure, myocardial infarction, lung cancer, and rheumatoid arthritis patients were those for which the greatest differences were observed across diseases, while stroke, multiple sclerosis, and HIV patients showed the least differences relative to the normative population. CONCLUSIONS: This novel analysis of the interpersonal values of patients that participate in Phase II and III clinical trials revealed that the patients' interpersonal values largely differed from those of the Portuguese normative population. Better understanding the implications of these findings for clinical trial representativeness and outcomes is of crucial importance.

Alzheimer's Disease Diagnosis Based on the Amyloid, Tau, and Neurodegeneration Scheme (ATN) in a Real-Life Multicenter Cohort of General Neurological Centers.

BACKGROUND: The ATN scheme was proposed as an unbiased biological characterization of the Alzheimer's disease (AD) spectrum, grouping biomarkers into three categories: brain Amyloidosis-A, Tauopathy-T, Neurodegeneration-N. Although this scheme was mainly recommended for research, it is relevant for diagnosis. OBJECTIVE: To evaluate the ATN scheme performance in real-life cohorts reflecting the inflow of patients with cognitive complaints and different underlying disorders in general neurological centers. METHODS: We included patients (n = 1,128) from six centers with their core cerebrospinal fluid-AD biomarkers analyzed centrally. A was assessed through Aß42/Aß40, T through pTau-181, and N through tTau. Association between demographic features, clinical diagnosis at baseline/follow-up and ATN profiles was assessed. RESULTS: The prevalence of ATN categories was: A-T-N-: 28.3%; AD continuum (A + T-/+N-/+): 47.8%; non-AD (A- plus T or/and N+): 23.9%. ATN profiles prevalence was strongly influenced by age, showing differences according to gender, APOE genotype, and cognitive status. At baseline, 74.6% of patients classified as AD fell in the AD continuum, decreasing to 47.4% in mild cognitive impairment and 42.3% in other neurodegenerative conditions. At follow-up, 41% of patients changed diagnosis, and 92% of patients that changed to AD were classified within the AD continuum. A + was the best individual marker for predicting a final AD diagnosis, and the combinations A + T+ (irrespective of N) and A + T+N+ had the highest overall accuracy (83%). CONCLUSION: The ATN scheme is useful to guide AD diagnosis in real-life neurological centers settings. However, it shows a lack of accuracy for patients with other types of dementia. In such cases, the inclusion of other markers specific for non-AD proteinopathies could be an important aid to the differential diagnosis.

Interchangeability of two versions of the Montreal Cognitive Assessment for the longitudinal evaluation of patients with breast cancer.

PURPOSE: The cognitive performance of patients with breast cancer (BCa) may be affected by cancer and its treatments. The Montreal Cognitive Assessment (MoCA) is a widely used cognitive impairment screening tool, but practice effects must be considered for longitudinal assessments. Since learning effects could be overcome through the alternate use of two versions of the MoCA, we aimed to explore their interchangeability by comparing their overall, and domain- and task-specific, scores among patients with BCa. METHODS: BCa patients from the NEON-BC cohort were evaluated with the MoCA, version 7.1, after diagnosis and after 1 year. At the 3-year follow-up (n = 422), the 7.1 and 7.3 versions were applied at the beginning and at the end (approximately 1 h later) of this evaluation, respectively. Agreements between versions, regarding total, sub-domain, and task scores, were assessed using Bland-Altman plots and intraclass correlation coefficients (ICC). RESULTS: The mean total scores were not statistically different between versions and the ICC was 0.890. The Bland-Altman limits of agreement were - 3.70 to 3.88. For women with midrange scores, total scores were significantly higher in version 7.1. There were significant differences in the percentage of correct answers in 7 out of 12 tasks, being the highest for the copy of a geometric figure (more than twofold higher with version 7.3). In version 7.1, the language and memory domains presented higher scores and lower visuospatial ability. CONCLUSION: Despite similar overall scores being obtained with the two versions of the MoCA, there were item-specific differences that may compromise their interchangeable use.

Transthyretin amyloid-related transitory events (TARTEs): Descriptive analysis of clinical, imagiological, and neurophysiological features.

Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) is a multisystemic disorder inherited as an autosomal dominant trait. Transitory events in ATTR-FAP patients are a feature of this disorder and remain poorly depicted in the literature. We aimed to describe a case series of ATTR-FAP patients who presented to our department with transitory events and document the clinical, neuroimaging and neurophysiological characteristics of the events. We collected data from eight patients carrying the Val30Met ATTR-FAP variant. We registered a total of 23 events. Of the eight patients, seven had been submitted to hepatic transplant. The events were either TIA-like or seizures, often followed by prolonged language, motor or sensory impairment. In 9 (39%) of the events, the patients presented with fever, but an infection was only found in 5 (21%). Cerebrospinal fluid analysis was performed in 5 patients. EEG was abnormal in at least 1 event in 7 of the 8 patients. Brain MRI was performed in 3 patients during the acute stage and showed no acute lesions. Although the etiology of these events remains unclear, brain MRI performed in the acute phase of acute TIA-like events and the EEG abnormalities, argues in favor of regional brain dysfunction due to amyloid deposition. Focal neurological episodes should be considered in long-term duration Val30Met ATTR-FAP patients, who present with acute neurological deficits or seizures.

Trajectories of cognitive performance over five years in a prospective cohort of patients with breast cancer (NEON-BC).

PURPOSE: To identify trajectories of cognitive performance up to five years since diagnosis and their predictors, in a cohort of patients with breast cancer (BCa). METHODS: A total of 464 women with BCa admitted to the Portuguese Institute of Oncology, Porto, during 2012, were evaluated with the Montreal Cognitive Assessment (MoCA) before any treatment, and after one, three and five years. Probable cognitive impairment (PCI) at baseline was defined based on normative age- and education-specific reference values. Mclust was used to define MoCA trajectories. Receiver Operating Characteristic curves were used to assess the predictive accuracy for cognitive trajectories. RESULTS: Two trajectories were identified, one with higher scores and increasing overtime, and the other, including 25.9% of the participants, showing a continuous decline. To further characterize each trajectory, participants were also classified as scoring above or below the median baseline MoCA scores. This resulted in four groups: 1) highest baseline scores, stable overtime (0.0% with PCI); 2) lowest baseline scores (29.5% with PCI); 3) mid-range scores at baseline, increasing overtime (10.5% with PCI); 4) mid-range scores at baseline, decreasing overtime (0.0% with PCI). Adding the change in MoCA during the first year to baseline variables significantly increased the accuracy to predict the downward trajectory (area under the curve [AUC] = 0.732 vs. AUC = 0.841, P < 0.001). CONCLUSION: Four groups of patients with BCa with different cognitive performance trends were identified. The assessment of cognitive performance before treatments and after one year allows for the identification of patients more likely to have cognitive decline in the long term.

Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC.

INTRODUCTION: Prostate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline. METHODS: Participants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants' cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.