Well-being trajectories in breast cancer and their predictors: A machine-learning approach.

OBJECTIVE: This study aimed to describe distinct trajectories of anxiety/depression symptoms and overall health status/quality of life over a period of 18 months following a breast cancer diagnosis, and identify the medical, socio-demographic, lifestyle, and psychological factors that predict these trajectories. METHODS: 474 females (mean age = 55.79 years) were enrolled in the first weeks after surgery or biopsy. Data from seven assessment points over 18 months, at 3-month intervals, were used. The two outcomes were assessed at all points. Potential predictors were assessed at baseline and the first follow-up. Machine-Learning techniques were used to detect latent patterns of change and identify the most important predictors. RESULTS: Five trajectories were identified for each outcome: stably high, high with fluctuations, recovery, deteriorating/delayed response, and stably poor well-being (chronic distress). Psychological factors (i.e., negative affect, coping, sense of control, social support), age, and a few medical variables (e.g., symptoms, immune-related inflammation) predicted patients' participation in the delayed response and the chronic distress trajectories versus all other trajectories. CONCLUSIONS: There is a strong possibility that resilience does not always reflect a stable response pattern, as there might be some interim fluctuations. The use of machine-learning techniques provides a unique opportunity for the identification of illness trajectories and a shortlist of major bio/behavioral predictors. This will facilitate the development of early interventions to prevent a significant deterioration in patient well-being.

Criterion and construct validity of the Beck Depression Inventory (BDI-II) to measure depression in patients with cancer: The contribution of somatic items

Background/Objective: Screening for depression in patients with cancer can be difficult due to overlap between symptoms of depression and cancer. We assessed validity of the Beck Depression Inventory (BDI-II) in this population. Method: Data was obtained in an outpatient neuropsychiatry unit treating patients with and without cancer. Psychometric properties of the BDI-II Portuguese version were assessed separately in 202 patients with cancer, and 376 outpatients with mental health complaints but without cancer. Results: Confirmatory factor analysis suggested a three-factor structure model (cognitive, affective and somatic) provided best fit to data in both samples. Criterion validity was good for detecting depression in oncological patients, with an area under the ROC curve (AUC) of 0.85 (95% confidence interval [CI], 0.76–0.91). A cut-off score of 14 had sensitivity of 87% and specificity of 73%. Excluding somatic items did not significantly change the ROC curve for BDI-II (difference AUCs = 0.002, p=0.9). A good criterion validity for BDI-II was also obtained in the non-oncological population (AUC = 0.87; 95% CI 0.81–0.91), with a cut-off of 18 (sensitivity=84%; specificity=73%). Conclusions: The BDI-II demonstrated good psychometric properties in patients with cancer, comparable to a population without cancer. Exclusion of somatic items did not affect screening accuracy. (AU)

Criterion and construct validity of the Beck Depression Inventory (BDI-II) to measure depression in patients with cancer: The contribution of somatic items.

Background/Objective: Screening for depression in patients with cancer can be difficult due to overlap between symptoms of depression and cancer. We assessed validity of the Beck Depression Inventory (BDI-II) in this population. Method: Data was obtained in an outpatient neuropsychiatry unit treating patients with and without cancer. Psychometric properties of the BDI-II Portuguese version were assessed separately in 202 patients with cancer, and 376 outpatients with mental health complaints but without cancer. Results: Confirmatory factor analysis suggested a three-factor structure model (cognitive, affective and somatic) provided best fit to data in both samples. Criterion validity was good for detecting depression in oncological patients, with an area under the ROC curve (AUC) of 0.85 (95% confidence interval [CI], 0.76-0.91). A cut-off score of 14 had sensitivity of 87% and specificity of 73%. Excluding somatic items did not significantly change the ROC curve for BDI-II (difference AUCs = 0.002, p=0.9). A good criterion validity for BDI-II was also obtained in the non-oncological population (AUC = 0.87; 95% CI 0.81-0.91), with a cut-off of 18 (sensitivity=84%; specificity=73%). Conclusions: The BDI-II demonstrated good psychometric properties in patients with cancer, comparable to a population without cancer. Exclusion of somatic items did not affect screening accuracy.

A prospective observational study for a Federated Artificial Intelligence solution for moniToring mental Health status after cancer treatment (FAITH): study protocol.

BACKGROUND: Depression is a common condition among cancer patients, across several points in the disease trajectory. Although presenting higher prevalence rates than the general population, it is often not reported or remains unnoticed. Moreover, somatic symptoms of depression are common in the oncological context and should not be dismissed as a general symptom of cancer. It becomes even more challenging to track psychological distress in the period after the treatment, where connection with the healthcare system typically becomes sporadic. The main goal of the FAITH project is to remotely identify and predict depressive symptoms in cancer survivors, based on a federated machine learning (ML) approach, towards optimization of privacy. METHODS: FAITH will remotely analyse depression markers, predicting their negative trends. These markers will be treated in distinct categories, namely nutrition, sleep, activity and voice, assessed in part through wearable technologies. The study will include 300 patients who have had a previous diagnosis of breast or lung cancer and will be recruited 1 to 5 years after the end of primary cancer. The study will be organized as a 12-month longitudinal prospective observational cohort study, with monthly assessments to evaluate depression symptoms and quality of life among cancer survivors. The primary endpoint is the severity of depressive symptoms as measured by the Hamilton Depression Rating Scale (Ham-D) at months 3, 6, 9 and 12. Secondary outcomes include self-reported anxiety and depression symptoms (HADS scale), and perceived quality of life (EORTC questionnaires), at baseline and monthly. Based on the predictive models gathered during the study, FAITH will also aim at further developing a conceptual federated learning framework, enabling to build machine learning models for the prediction and monitoring of depression without direct access to user's personal data. DISCUSSION: Improvements in the objectivity of psychiatric assessment are necessary. Wearable technologies can provide potential indicators of depression and anxiety and be used for biofeedback. If the FAITH application is effective, it will provide healthcare systems with a novel and innovative method to screen depressive symptoms in oncological settings. TRIAL REGISTRATION: Trial ID: ISRCTN10423782 . Date registered: 21/03/2022.

Predicting Effective Adaptation to Breast Cancer to Help Women BOUNCE Back: Protocol for a Multicenter Clinical Pilot Study.

BACKGROUND: Despite the continued progress of medicine, dealing with breast cancer is becoming a major socioeconomic challenge, particularly due to its increasing incidence. The ability to better manage and adapt to the entire care process depends not only on the type of cancer but also on the patient's sociodemographic and psychological characteristics as well as on the social environment in which a person lives and interacts. Therefore, it is important to understand which factors may contribute to successful adaptation to breast cancer. To our knowledge, no studies have been performed on the combination effect of multiple psychological, biological, and functional variables in predicting the patient's ability to bounce back from a stressful life event, such as a breast cancer diagnosis. Here we describe the study protocol of a multicenter clinical study entitled "Predicting Effective Adaptation to Breast Cancer to Help Women to BOUNCE Back" or, in short, BOUNCE. OBJECTIVE: The aim of the study is to build a quantitative mathematical model of factors associated with the capacity for optimal adjustment to cancer and to study resilience through the cancer continuum in a population of patients with breast cancer. METHODS: A total of 660 women with breast cancer will be recruited from five European cancer centers in Italy, Finland, Israel, and Portugal. Biomedical and psychosocial variables will be collected using the Noona Healthcare platform. Psychosocial, sociodemographic, lifestyle, and clinical variables will be measured every 3 months, starting from presurgery assessment (ie, baseline) to 18 months after surgery. Temporal data mining, time-series prediction, sequence classification methods, clustering time-series data, and temporal association rules will be used to develop the predictive model. RESULTS: The recruitment process stared in January 2019 and ended in November 2021. Preliminary results have been published in a scientific journal and are available for consultation on the BOUNCE project website. Data analysis and dissemination of the study results will be performed in 2022. CONCLUSIONS: This study will develop a predictive model that is able to describe individual resilience and identify different resilience trajectories along the care process. The results will allow the implementation of tailored interventions according to patients' needs, supported by eHealth technologies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05095675; https://clinicaltrials.gov/ct2/show/NCT05095675. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34564.

Cross-Cultural Adaptation and Psychometric Evaluation of the Perceived Ability to Cope With Trauma Scale in Portuguese Patients With Breast Cancer.

BACKGROUND: The impact of a cancer diagnosis may be traumatic, depending on the psychological resources used by patients. Appropriate coping strategies are related to better adaptation to the disease, with coping flexibility, corresponding to the ability to replace ineffective coping strategies, demonstrated to be highly related with self-efficacy to handle trauma. The Perceived Ability to Cope with Trauma (PACT) scale is a self-rated questionnaire that assesses the perceived ability to cope with potentially traumatic events, providing a measure of coping flexibility. The current study aimed at examining the psychometric properties of the PACT Scale in Portuguese patients with breast cancer. METHODS: The study included 172 patients recently diagnosed with early breast cancer. Participants completed a Portuguese version of the PACT scale, and instruments of self-efficacy for coping with cancer (Cancer Behavior Inventory-Brief Version-CBI-B), of quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30-QLQ-C30), and of psychological distress (Hospital Anxiety and Depression Scale-HADS) that were used as convergent and divergent measures, thus assessing construct validity. A confirmatory factor analysis (CFA) was performed to test the factor structure of the Portuguese version of PACT scale and reliabilities were examined. RESULTS: Results from the CFA confirmed the two-factor structure, consistent with the original Forward and Trauma focus subscales. The two subscales demonstrated high internal consistencies. Convergent and divergent validities were confirmed: the PACT scale was related to high self-efficacy to cope with cancer (CBI-B), to high perceived quality of life (QLQ-C30), and to low psychological distress (HADS). DISCUSSION: Overall, the current results support and replicate the psychometric properties of the PACT scale. The scale was found to be a valid and reliable self-reported measure to assess Portuguese breast cancer patients regarding beliefs about their capabilities in managing the potentially traumatic sequelae of cancer. The PACT is a simple and brief measure of coping flexibility to trauma, with potential relevance for application in clinical and research settings.

Cross-cultural adaptation and psychometric evaluation of the Portuguese version of the family resilience questionnaire - short form (FaRE-SF-P) in women with breast cancer.

Background: A diagnosis of cancer, and the resulting treatment process, can be perceived as a life-threatening event, affecting not only patients but also their social network and, more specifically, their relatives. While the ability to cope and adjust to difficult health situations may be challenging, family resilience may optimize a positive adaptation to adversity and contribute to enhance the patient's quality of life. The Family Resilience Questionnaire (FaRE) is a self-report measure of family resilience that assesses this construct systematically. We aimed to validate the Portuguese version of a short form of the FaRE (FaRE-SF-P) in a sample of women with breast cancer. Methods: 147 women recently diagnosed with early breast cancer were recruited at the Champalimaud Clinical Centre in Lisbon. Participants completed psychometric assessment including the Portuguese version of the FaRE-SF-P, composed by two subscales of the original version - the FaRE Perceived Family Coping (FaRE-PFC) and the FaRE Communication and Cohesion (FaRE-CC). Confirmatory factor analysis (CFA) was performed to assess the factor structure of the FaRE-SF-P. Construct validity was assessed using the Hospital Anxiety and Depression Scale (HADS) for divergent validity, and the Modified Medical Outcomes Study Social Support Survey (mMOS-SS) as well as the social functioning subscale from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) for convergent validity. Results: The CFA results confirmed a correlated two-factor structure model consistent with the Perceived Family Coping and the Communication and Cohesion subscales. Internal consistency reliability indicated good values both for Perceived Family Coping and Communication and Cohesion subscales. The results for construct validity showed acceptable convergent and divergent validity. Discussion: The FaRE-SF-P showed good psychometric properties demonstrating to be a valid and reliable family resilience measure to use in Portuguese women diagnosed with breast cancer. Since FaRE-SF-P is a short instrument it may be a useful screening tool in an oncological clinical practice routine.

Acoustic analysis of swallowing sounds in tracheostomized patients affected by traumatic brain injury / Análise acústica de sons da deglutição em pacientes traqueostomizados acometidos por traumatismo cranioencefálico

ABSTRACT Purpose: to demonstrate the feasibility of using the acoustic analysis of swallowing sounds as a combined method in the clinical assessment of tracheostomized patients affected by traumatic brain injury. Methods: an observational, cross-sectional study. A total of 10 adult patients, in the mean age of 43.6 years, participated. They were hospitalized in wards, semi-intensive, or intensive care units, from May to July 2016. The inclusion criterion involved being affected by traumatic brain injury, confirmed with a CT scan. The Speech Therapy Tracheal Decannulation Protocol was used in the clinical assessment, as well as the cervical auscultation with the Doppler sonar. Fisher's test was used, resulting in no significant relationship (p > 0.05) between the variables analyzed in the two consistencies and decannulation. Results: the presence of an acoustic signal of laryngeal elevation was observed, as well as noise between the swallowings, and acoustic signal suggestive of residue in 50% of the patients for the consistencies tested. When the peak frequency, mean wave time, presence of residue in between swallowings, and acoustic signal suggestive of residues were correlated with decannulation (Table 5), no significant correlation was verified (p > 0.05) between the variables analyzed in the two consistencies and the decannulation. Conclusion: the study suggests that it is feasible to use the Doppler sonar as a combined method in the clinical assessment of dysphagia for the decannulation of patients affected by traumatic brain injury.

RESUMO Objetivo: demonstrar a viabilidade do uso da análise acústica dos sons da deglutição como método conjugado à avaliação clínica em pacientes traqueostomizados acometidos por traumatismo cranioencefálico. Métodos: estudo observacional do tipo transversal. Participaram deste estudo 10 pacientes adultos, com idade média de 43,6 anos internados em leito hospitalar, unidades de terapias intensivas ou semi-intensivas, no período de maio a julho de 2016. O critério para inclusão foi ser acometido por traumatismo cranioencefálico, confirmado por tomografia axial computadorizada. Foi aplicado o Protocolo Fonoaudiológico de Decanulação Traqueal para a avaliação clínica e a ausculta cervical por meio do Sonar Doppler. Foi aplicado o Test Fischer e não foi encontrada relação significante (p>0,05), entre as variáveis analisadas nas duas consistências e na decanulação. Resultados: foi observada a presença de sinal acústico de elevação laríngea, presença de ruído entre as deglutições, presença de sinal acústico sugestivo de resíduo em 50% dos pacientes, para as consistências testadas. Quando correlacionados a relação entre frequência de pico, tempo médio da onda, presença de resíduo entre as deglutições, sinal acústico sugestivo de resíduos e decanulação (Tabela 5), verificou-se que não existe correlação significante (p>0,05) entre as variáveis analisadas nas duas consistências e a decanulação. Conclusão: o estudo sugere que o uso do Sonar Doppler é viável como método conjugado na avaliação clínica das disfagias para a decanulação de pacientes acometidos por traumatismo cranioencefálico.

Medical therapy using omeprazole in 12 hydrocephalic dogs: clinical, diagnostic, and therapeutic findings / Terapia médica utilizando omeprazol em 12 cães hidrocefálicos: achados clínicos, diagnósticos e terapêuticos

According to experimental studies with healthy dogs, omeprazole might decrease the CSF production by about 26%; therefore, book texts have been suggested the usage of omeprazole in medical protocols for hydrocephalus treatment. However, to the best knowledge of the authors, the usage and medical response of the omeprazole with substantial group of illness dogs, such as hydrocephalic animals, was lacking. This report describes clinical, diagnostic, and therapeutic findings in 12 dogs with hydrocephalus in which omeprazole were used for medical treatment. The diagnosis of hydrocephalus was accomplished by transcranial sonography (TCS) and/or computed tomography. The ventricular measurement was assessed periodically by TCS during medical treatment. Six dogs were diagnosed with non-obstrutive hydrocephalus and in the other 6 cases hydrocephalus occurred with other concomitant anomalous encephalic disease often related with obstructive hysdrocephalus, such as quadrigeminal cist, arachnoid cyst, chiary-like malformation, and syringomyelia. All of them had medical improvement after the use of omeprazole and the most of the cases had ventricular size reduction. In 10 dogs, the omeprazole was used as single drug, and in 2 dogs medical treatment with steroids and/or diuretics was previously being performed, and omeprazole was added because conventional treatment was resulting in mild to unsatisfactory medical control of the neurological status. The results of this paper shown that omeprazole may be used to ameliorate the neurological status in symptomatic hydrocephalic dogs. This work may represent the first description about the use of omeprazole in order to treat a substantial group of affected dogs with suspected increased intracranial pressure by hydrocephalus, probably due to limitation of CSF production.(AU)

O omeprazol diminui a produção do fluido cerebrospinal (FCE) por cerca de 26% de acordo com estudos experimentais em cães saudáveis. Segundo o conhecimento dos autores, embora utilizado na prática clínica e recomendado em livros textos, não há até o momento estudos clínicos em um grupo substancial de animais avaliando a resposta terapêutica ao uso do omeprazol em pacientes enfermos, tais como cães hidrocefálicos sintomáticos. Este trabalho descreve os achados clínicos, diagnósticos e terapêuticos em 12 cães com hidrocefalia que foram submetidos ao tratamento com omeprazol para o manejo médico de hidrocefalia. O diagnóstico de hidrocefalia e doenças neurológicas concomitantes foi realizado por ultrassonografia transcraniana (USTC) e/ou tomografia computadorizada. A mensuração do tamanho ventricular foi realizada pela USTC durante o tratamento médico. Seis cães foram diagnosticados com hidrocefalia não obstrutiva e os outros 6 casos apresentaram hidrofalia concomitante com outras afecções encefálicas anômalas comumente associada à hidrocefalia obstrutiva, tal como cisto quadrigêmio, cisto aracnóide, síndrome de chiari-like e seringomegalia. Em 10 cães o omeprazol foi utilizado como droga única e em 2 cães a terapia inicial foi a convencional utilizando esteroides e diuréticos, e o omeprazol foi adicionado, pois a resposta clínica a terapia convencional foi insatisfatória. Todos os animais obtiveram melhora dos parâmetros neurológicos e a maioria teve uma redução do tamanho ventricular após o uso do omeprazol. Os resultados deste estudo demonstram que o omeprazol pode ser utilizado para melhorar o estado neurológico em cães com hidrocefalia. Este estudo representa a primeira descrição clínica usando o omeprazol para tratar uma série de cães com suspeita de aumento da pressão intracraniana devido à hidrocefalia, provavelmente pela capacidade do fármaco em limitar a produção do FCE.(AU)

Association between Adipokines and Biomarkers of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Adipose tissue dysfunction has been implicated in the pathophysiology of Alzheimer's disease. However, the involvement of adipokines, particularly adiponectin, remains unclear. OBJECTIVE: To compare serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin and leptin-to-adiponectin ratio in patients within the spectrum of Alzheimer's disease and evaluate their relationship with classical biomarkers and their value as markers of progression. METHODS: Amnestic mild cognitive impairment (MCI, n = 71) and Alzheimer's dementia (AD, n = 53) subjects were consecutively recruited for serum and CSF adiponectin and leptin determination using an analytically validated commercial enzyme-linked immunosorbent assay (ELISA). Correlations were explored using adjusted Spearman's correlation coefficients. A logistic regression model and ROC analysis were performed to evaluate the staging predictive value of adipokines. RESULTS: Serum adiponectin was 33% higher in AD when compared to MCI patients. Adiponectin CSF levels, similar in both groups, were positively correlated with Aß42 and cognitive function, though only in women. The area under the ROC curve was 0.673 (95% CI:0.57-0.78) for serum adiponectin as predictor of dementia stage and the cut-off 10.85µg/ml maximized the sum of specificity (87%) and sensitivity (44%). CONCLUSION: Although longitudinal studies are required, we hypothesize that higher serum adiponectin in AD patients constitutes a strategy to compensate possible central signaling defects. In addition, adiponectin might be specifically assigned to neuroprotective functions in women and eventually involved in the female-biased incidence of Alzheimer's disease.

Concomitant myeloproliferative and lymphoproliferative neoplasms, distinct progenitors: A case report and review of the literature.

Patients with a Philadelphia chromosome-negative myeloproliferative neoplasm may develop a lymphoproliferative disorder; however, the clinical and molecular determinants and the chronological onset of the two events remain unknown. We herein report the case of a 64-year-old man with concomitant diagnosis of high-risk essential thrombocythemia with evidence of a thrombotic event and high-count monoclonal B-cell lymphocytosis (high-count MBL). The patient harbored a JAK2V617F mutation and one of the most common genetic alterations found in chronic lymphocytic leukemia (CLL) (del 13q), which may represent a sign of disease progression. He was initiated on cytoreductive therapy with hydroxyurea 500 mg 3 times per week and hypocoagulation treatment, and is currently under regular surveillance of MBL without CLL criteria.

The free and cued selective reminding test for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: A prospective longitudinal study.

Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow-up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker.

Three-Dimensional Face Recognition in Mild Cognitive Impairment: A Psychophysical and Structural MR Study.

OBJECTIVES: Mild cognitive impairment (MCI) has been associated with a high risk of conversion to Alzheimer's dementia. In addition to memory complaints, impairments in the visuospatial domain have been reported in this condition. We have previously shown that deficits in perceiving structure-from-motion (SFM) objects are reflected in functional reorganization of brain activity within the visual ventral stream. Here we aimed to identify structural correlates of psychophysical complex face and object recognition performance in amnestic MCI patients (n=30 vs. n=25 controls). This study was, therefore, motivated by evidence from recent studies showing that a combination of visual information across dorsal and ventral visual streams may be needed for the perception of three-dimensional (3D) SFM objects. METHODS: In our experimental paradigm, participants had to discriminate 3D SFM shapes (faces and objects) from 3D SFM meaningless (scrambled) shapes. RESULTS: Morphometric analysis established neuroanatomical evidence for impairment in MCI as demonstrated by smaller hippocampal volumes. We found association between cortical thickness and face recognition performance, comprising the occipital lobe and visual ventral stream fusiform regions (overlapping the known location of face fusiform area) in the right hemisphere, in MCI. CONCLUSIONS: We conclude that impairment of 3D visual integration exists at the MCI stage involving also the visual ventral stream and contributing to face recognition deficits. The specificity of such observed structure-function correlation for faces suggests a special role of this processing pathway in health and disease. (JINS, 2016, 22, 744-754).

[Mini-Mental State Examination: Screening and Diagnosis of Cognitive Decline, Using New Normative Data]. / Mini-Mental State Examination: Avaliação dos Novos Dados Normativos no Rastreio e Diagnóstico do Défice Cognitivo.

INTRODUCTION: The Mini-Mental State Examination is the most commonly used cognitive screening test. In Portugal, the cut-off scores are defined according to literacy groups, but different proposals have been recommended by more representative studies. We therefore propose to confirm the influence of demographical variables, such as age and education, in the subjectâs performance; evaluating the discriminant ability of the new normative data; and to further examine the diagnostic acuity of the validated cut-off scoring for mild cognitive impairment and for the most prevalent types of dementia. MATERIAL AND METHODS: Our study includes 1 441 educated subjects, divided into seven subgroups: Mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, vascular dementia, dementia with Lewy bodies, community-controls and memory clinic-controls. RESULTS: Altogether age and education explain 10.4% of the Mini-Mental State Examination results variance, with both variables contributing significantly to the resultsâ prediction. The diagnostic acuity based on the most recent normative data was always higher than the one obtained through the validation cut-off scoring, revealing an overall excellent specificity (superior to 90%) and different sensitivity values: excellent for mild Alzheimer's disease (91%), good for dementia with Lewy Bodies (78%) and low for mild cognitive impairment (65%), frontotemporal dementia and vascular dementia (55%). DISCUSSION AND CONCLUSIONS: The performance on the Mini-Mental State Examination is influenced by age and education, supporting the use of normative data that consider those variables. With this approach, the Mini-Mental State Examination could be a sensitive and specific instrument for the Alzheimer's disease screening among all healthcare levels. Nevertheless, its diagnostic acuity is limited in other conditions frequently seen in memory clinics, such as Mild Cognitive Impairment and other types of dementia.

Introdução: O Mini-Mental State Examination é o teste de rastreio de défice cognitivo/demência mais difundido. No nosso país têm-se utilizado pontuações de corte definidas por grupos de literacia, mas existem novas propostas sustentadas por estudos mais representativos. Propomo-nos confirmar a influência da idade e da escolaridade no desempenho, avaliar a capacidade discriminativa dos novos dados normativos e testar a acuidade diagnóstica das pontuações de corte validadas para o défice cognitivo ligeiro e para as formas mais prevalentes de demência. Material e Métodos: O estudo incluiu 1 441 participantes escolarizados, divididos em sete subgrupos: Défice cognitivo ligeiro, doença de Alzheimer, demência fronto-temporal, demência vascular, demência com corpos de Lewy, controlo-comunidade e controlo-clínica- memória. Resultados: Em conjunto, idade e escolaridade explicam 10,4% da variância dos resultados no Mini-Mental State Examination, com ambas contribuindo significativamente para a predição dos resultados. A acuidade diagnóstica com base nos dados normativos mais recentes foi sempre superior à conseguida com as pontuações de corte de validação, revelando uma especificidade excelente (superior a 90%) e uma sensibilidade também excelente para a doença de Alzheimer ligeira (91%), boa para demência com corpos de Lewy (78%), baixa para o défice cognitivo ligeiro (65%) e demência fronto-temporal e demência vascular (55%). Discussão e Conclusões: O desempenho no Mini-Mental State Examination é influenciado pela idade e pela escolaridade, apoiando a utilização de dados normativos que considerem estas variáveis. Com esta abordagem, o Mini-Mental State Examination poderá ser um instrumento sensível e específico para o rastreio da doença de Alzheimer em todos os níveis de cuidados de saúde, mas a acuidade de diagnóstico é limitada noutras situações frequentes em consultas especializadas, como o défice cognitivo ligeiro ou outras formas de demência.

Construct and diagnostic validities of the Free and Cued Selective Reminding Test in the Alzheimer's disease spectrum.

INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is a memory test that controls attention and acquisition, by providing category cues in the learning process. Because it enables an assessment of memory not confounded by normal age-related changes in cognition and a high accuracy on Alzheimer's disease (AD) evaluation, it has been suggested by the International Working Group on AD. Our aim was to assess the construct related validity of the FCSRT in the AD spectrum disorders. METHOD: Patients were classified in two groups according to standard criteria: amnestic mild cognitive impairment (n = 100) and AD (n = 70). A matched control group (n = 101) of cognitively healthy subjects was included. The factorial structure of two models and respective construct and diagnostic validities were analyzed. RESULTS: Both models revealed adequate fit values. The appropriated convergent validity and the lack of discriminant validity support the two factors as measuring the same construct (memory ability). The recalls of the FCSRT enabled high classification accuracy and diagnostic validity for both pathological groups. CONCLUSIONS: This study represents a novel contribution regarding the adequacy of the FCSRT in terms of construct and diagnostic validities and shows the interest of including both immediate (learning) and delayed (retention) recalls. It gives also new possibilities regarding the use of the FCSRT in the memory assessment of AD spectrum disorders.

Selective Reminding and Free and Cued Selective Reminding in Mild Cognitive Impairment and Alzheimer Disease.

The Selective Reminding Test (SRT) and the Free and Cued Selective Reminding Test (FCSRT) are multitrial memory tests that use a common "selective reminding" paradigm that aims to facilitate learning by presenting only the missing words from the previous recall trial. While in the FCSRT semantic cues are provided to elicit recall, in the SRT, participants are merely reminded of the missing items by repeating them. These tests have been used to assess age-related memory changes and to predict dementia. The performance of healthy elders on these tests has been compared before, and results have shown that twice as many words were retrieved from long-term memory in the FCSRT compared with the SRT. In this study, we compared the tests' properties and their accuracy in discriminating amnestic mild cognitive impairment (aMCI; n = 20) from Alzheimer disease (AD; n = 18). Patients with AD performed significantly worse than patients with aMCI on both tests. The percentage of items recalled during the learning trials was significantly higher for the FCSRT in both groups, and a higher number of items were later retrieved, showing the benefit of category cueing. Our key finding was that the FCSRT showed higher accuracy in discriminating patients with aMCI from those with AD.

Cerebrospinal fluid Aß40 is similarly reduced in patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease.

Cerebrospinal fluid (CSF) biomarkers have been increasingly studied for dementia diagnosis, however the accuracy to distinguish between different forms of dementia is still unsatisfactory. In this study, the added value of another CSF Aß-peptide (Aß40), along with the core CSF markers t-Tau, p-Tau, and Aß42, in the discrimination between two large dementia groups of Frontotemporal Lobar Degeneration (FTLD; n=107), Alzheimer's Disease (AD; n=107) and non-demented subjects (n=33) was evaluated. In FTLD, t-Tau and p-Tau were significantly increased in relation to controls, but lower than in AD, while Aß42 was similar in FTLD and controls, but higher than in AD. Equally reduced Aß40 levels were seen in both dementia groups, and therefore the combination of Aß40 with core CSF biomarkers optimally discriminated FTLD and AD patients from controls. Aß42 and t-Tau were selected as the best biomarker subset to differentiate FTLD from AD, with no added value of Aß40 to the model. Diagnostic accuracy between FTLD and AD was still sub-optimal, with a significant percentage (23%) of FTLD patients, in particularly women, carrying an ApoE-ε4 allele, showing a CSF-AD biomarkers profile. Although CSF Aß40 does not appear to have an additional value in the distinction between FTLD and AD, it increases the discrimination between subjects with dementia from controls. A CSF-AD biomarker profile can be seen in patients with a clinical phenotype of FTLD, reinforcing the need for autopsy confirmation.

Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage.

Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.

Free and Cued Selective Reminding Test is superior to the Wechsler Memory Scale in discriminating mild cognitive impairment from Alzheimer's disease.

AIM: The Logical Memory (LM) and the Verbal Paired Associative Learning (VPAL) are subtests from the Wechsler Memory Scale commonly used to characterize the memory deficit of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). The Free and Cued Selective Reminding Test (FCSRT) was suggested to assess the memory impairment of AD spectrum patients by the International Working Group on AD. In the present study, we compared the properties of the tests and their accuracy in classifying aMCI and AD. METHODS: A group of aMCI patients (n = 85) and AD patients (n = 43) were included. The reliability and the validity of the three tests were analyzed. RESULTS: AD patients showed a significant pattern of worse impairment on all tests than aMCI. The FCSRT was able to classify more patients as having memory impairment in the aMCI group rather than the WMS subtests. The FCSRT proved to be good in discriminating the two groups in both lower and higher educational levels, whereas the LM was more useful in higher educated patients. CONCLUSIONS: Although the instruments had good results, the FCSRT was more accurate in discriminating MCI from AD, and less influenced by the educational level.

The free and cued selective reminding test: Validation for mild cognitive impairment and Alzheimer's disease.

The International Working Group on Alzheimer's disease (AD) suggested the free and cued selective reminding test (FCSRT) to assess memory, as it showed high sensitivity and specificity in the differentiation of AD from healthy controls and other dementias. The FCSRT involves the use of selective reminding with semantic cueing in memory assessment. This study aims to validate the FCSRT for mild cognitive impairment (MCI) and AD through the analysis of the diagnostic accuracy and the suggestion of cut-off scores. Patients were classified into two groups according to standard criteria: MCI (n = 100) and AD (n = 70). A matched control group (n = 101) of cognitively healthy subjects was included. The reliability and the validity of the FCSRT were analysed on the immediate (IR) and delayed (DR) recalls. The Cronbach's alpha was 0.915 for the IR and 0.879 for the DR. The total recall measures revealed good areas under the curve for MCI (IR: .818; DR: .828) and excellent for AD (IR: .987; DR: .991). Furthermore, the MCI group was subdivided with respect to a non-similar/similar AD pattern of impairment, with almost half of the subjects showing an AD-like decline. This analysis represents a novel contribution regarding the properties of the FCSRT in illustrating the heterogeneity of MCI at baseline. The FCSRT has proved to be a very useful tool in the characterization of the memory impairment of the AD spectrum.