Estudo longitudinal de um programa de reabilitação neuropsicológica dirigido a pacientes com doença de Alzheimer

Our aim was to study the duration of benefits derived from a neuropsychological rehabilitation program (NRP) for dementia patients. METHOD: The participants in this study were three patients diagnosed as probable Alzheimer's disease in the initial-to-moderate phase; the three were taking anticholinesterases. They were submitted to a neuropsychological evaluation (NE) before the NRP and then revaluated after 12 and 24 months of treatment. The aim of our intervention was to do practical work with implicit and explicit residual memory by training them in everyday life activities, and using compensatory strategies and their intact cognitive abilities. RESULTS: Analysis of quantitative NE data (descriptive measures) after the first year of NRP showed cognitive improvement, functional stabilization and fewer behavioral problems. However, this improvement did not continue in the second year, and the disease maintained its characteristic progression.OBJETIVO: Estudar a duração do beneficio de um programa de reabilitação neuropsicológica (PRN) dirigido a pacientes demenciados. MÉTODO: Participaram deste estudo, três pacientes com diagnóstico de provável doença de Alzheimer em fase inicial a moderada. Todos faziam uso de anti-colinesterásicos e passaram por uma avaliação neuropsicológica (AN) antes de começar o PRN e reavaliação após 12 e 24 meses do tratamento. O alvo de nossa intervenção foi trabalhar de forma prática a memória explicita residual e implícita, através do treino das atividades da vida diária, uso de estratégias compensatórias e habilidades cognitivas ainda preservadas. RESULTADOS: A análise dos dados quantitativos (medidas descritivas) da AN mostrou, que após o primeiro ano do PRN houve uma melhora cognitiva, estabilização funcional e redução dos problemas comportamentais nos pacientes. No entanto, observamos que essa melhora não se estendeu para o segundo ano, mostrando a doença sua característica progressiva.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Centro Paulista de NeuropsicologiaUNIFESP, EPM, Centro Paulista de NeuropsicologiaSciEL

Impact of SCHOLAR-1 Criteria on Chimeric Antigen Receptor T Cell Therapy Efficacy in Aggressive B Lymphoma: A Real-World GELTAMO/GETH Study

In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real -world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we ana-lyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diag-nosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable dis-ease as the best response to >4 cycles of first-line therapy or >2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognos-tic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era.(c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc

Short-Term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice

Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models

Applicability of the abbreviated neuropsychologic battery (NEUROPSI) in Alzheimer disease patients

NEUROPSI is a brief neuropsychologic battery developed to briefly assess a wide spectrum of cognitive functions. The aim of this study was to examine the applicability of a Portuguese version of this battery and verify the efficacy in detecting cognitive impairment in Alzheimer disease (AD) patients. NEUROPSI was applied to 75 elderly people, 25 patients with probable AD in mild stage (AD1), 25 patients in moderate stage (AD2), and 25 healthy elderly persons (control group), matched with the AD patients for age and schooling. Before testing all participants were applied the Mini-Mental State Examination. Results showed significant differences in total scores of the tests; NEUROPSI (P<0.001) and Mini-Mental State Examination (P < 0.001), and the control group scored highest in both of the tests followed by groups AD1 and AD2. Differences were also found between the initial phase and the moderate phase. Results indicate that NEUROPSI is an efficient instrument for detecting AD patients in the initial stage of the disease.Univ Fed Sao Paulo, Dept Psychobiol, Escola Paulista Med, BR-04024002 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Neurol & Neurosurg, Escola Paulista Med, BR-04024002 Sao Paulo, BrazilUniv Nacl Autonoma Mexico, Psychophysiol Dept, Mexico City 04510, DF, MexicoUniv Fed Sao Paulo, Dept Psychobiol, Escola Paulista Med, BR-04024002 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Neurol & Neurosurg, Escola Paulista Med, BR-04024002 Sao Paulo, BrazilWeb of Scienc