Cognition and renal function: findings from a Brazilian population / Cognição e função renal: achados de uma população brasileira

ABSTRACT Introduction: The prevalence of chronic kidney disease (CKD) is increasing, with a potential impact in the risk of acceleration of dementia. The potential association between glomerular filtration rate (eGFR) and cognitive performance was scarcely studied. The aim of this study was to evaluate cognitive performance levels across different degrees of kidney function. Methods: We analyzed 240 outpatients in a nephrology service, classified according to eGFR: Advanced (≤ 30ml/min/1.73m2), Moderate (30,1ml/min/1.73m2 to ≤ 60ml/min/1.73m2), and Mild CKD (> 60ml/min/1.73m2). Word list memory, Semantic fluency, Mental State Mini Exam and Trail Making Test (TMT) were applied to evaluate cognitive performance. In the TMT, lower scores are associated with better cognition. In linear regression, cognitive function was considered as dependent variables while groups based on eGFR were considered explanatory variables. The group with eGFR > 60ml/min was the reference and models were adjusted for confounding factors. Results: In our population (n = 240) 64 patients (26.7%) were classified as having advanced, 98(40,8%) moderate, and 78(32,5%) mild. There was no statistical difference among them in MMSE or in the verbal fluency test. However, comparing to mild, patients with advanced CKD presented significantly worse cognitive performance measured by TMTA [50,8s ± 31.1s versus 66,6s ± 35,7s (p = 0.016)] and TMTB [92,7s ± 46,2s versus 162,4s ± 35,7s (p < 0.001)]. Significantly lower TMTB scores (CI95%) 33,0s (4,5-61,6s) were observed in patients with mild compared to advanced CKD in the multivariate analysis adjusting for age, education, sex, diabetes, and alcohol use. Conclusion: Advanced CKD is independently associated with poorer cognitive performance measured by an executive performance test compared to mild CKD.

RESUMO Introdução: A elevação da prevalência de doença renal crônica (DRC) traz consigo um impacto potencial sobre o risco de aceleração da demência. A possível associação entre taxa de filtração glomerular (TFGe) e desempenho cognitivo foi pouco estudada. O objetivo do presente estudo foi avaliar os níveis de desempenho cognitivo em indivíduos com diferentes graus de função renal. Métodos: Foram analisados 240 pacientes ambulatoriais atendidos em um serviço de nefrologia classificados segundo a TFGe em grupos com DRC avançada (≤ 30ml/min/1,73m2), moderada (30,1ml/min/1,73m2 a ≤ 60ml/min/1,73m2) ou leve (> 60ml/min/1,73m2). Testes de memória por listas de palavras, fluência semântica, o mini exame do estado mental e o teste das trilhas (TT) foram aplicados para avaliar o desempenho cognitivo. No TT, escores mais baixos representam melhor cognição. Na regressão linear, função cognitiva foi considerada como variável dependente, enquanto os grupos baseados na TFGe foram considerados como variáveis explicativas. O grupo com TFGe > 60ml/min foi utilizado como referência e os modelos foram ajustados para fatores de confusão. Resultados: Em nossa população (n = 240), 64 pacientes (26,7%) foram diagnosticados com DRC avançada, 98 (40,8%) com DRC moderada e 78 (32,5%) com DRC leve. Não houve diferença estatística entre eles no MEEM ou no teste de fluência verbal. Contudo, em relação aos indivíduos com DRC leve, os pacientes com DRC avançada apresentaram desempenho cognitivo significativamente pior medido pelo TT A [50,8s ± 31,1s x 66,6s ± 35,7s (p = 0,016)] e TT B [92,7s ± 46,2s x 162,4s ± 35,7s (p < 0,001)]. Escores significativamente mais baixos no TT B (IC95%) 33,0s (4,5-61,6s) foram observados nos pacientes com DRC leve em comparação com o grupo com DRC avançada na análise multivariada ajustada para idade, escolaridade, sexo, diabetes e uso de álcool. Conclusão: DRC avançada esteve independentemente associada a pior desempenho cognitivo medido por um teste de desempenho executivo em comparação à DRC leve.

Cognition and renal function: findings from a Brazilian population.

INTRODUCTION: The prevalence of chronic kidney disease (CKD) is increasing, with a potential impact in the risk of acceleration of dementia. The potential association between glomerular filtration rate (eGFR) and cognitive performance was scarcely studied. The aim of this study was to evaluate cognitive performance levels across different degrees of kidney function. METHODS: We analyzed 240 outpatients in a nephrology service, classified according to eGFR: Advanced (≤ 30ml/min/1.73m2), Moderate (30,1ml/min/1.73m2 to ≤ 60ml/min/1.73m2), and Mild CKD (> 60ml/min/1.73m2). Word list memory, Semantic fluency, Mental State Mini Exam and Trail Making Test (TMT) were applied to evaluate cognitive performance. In the TMT, lower scores are associated with better cognition. In linear regression, cognitive function was considered as dependent variables while groups based on eGFR were considered explanatory variables. The group with eGFR > 60ml/min was the reference and models were adjusted for confounding factors. RESULTS: In our population (n = 240) 64 patients (26.7%) were classified as having advanced, 98(40,8%) moderate, and 78(32,5%) mild. There was no statistical difference among them in MMSE or in the verbal fluency test. However, comparing to mild, patients with advanced CKD presented significantly worse cognitive performance measured by TMTA [50,8s ± 31.1s versus 66,6s ± 35,7s (p = 0.016)] and TMTB [92,7s ± 46,2s versus 162,4s ± 35,7s (p < 0.001)]. Significantly lower TMTB scores (CI95%) 33,0s (4,5-61,6s) were observed in patients with mild compared to advanced CKD in the multivariate analysis adjusting for age, education, sex, diabetes, and alcohol use. CONCLUSION: Advanced CKD is independently associated with poorer cognitive performance measured by an executive performance test compared to mild CKD.

GENETIC AND DEMOGRAPHIC FACTORS OF A BRAZILIAN POPULATION SAMPLE AT-RISK OF HEREDITARY BREAST AND OVARIAN CANCER / Fatores genéticos e demográficos de uma amostra da população brasileira sob risco de síndrome de câncer de mama e ovário hereditários

Objective: Genetic-related breast cancer has a tendency to manifest earlier and to be more aggressive than sporadic cancer. There are few studies evaluating the prevalence and incidence of hereditary breast and ovarian cancer (HBOC) among Brazilians. In order to improve assistance, efforts to characterize the population at risk of HBOC could help to formulate locally designed guidelines. Methodology: Descriptive retrospective study in Hospital Erasto Gaertner's service of Oncogenetics, in Curitiba, state of Paraná, Brazil. We included individuals at-risk for HBOC, according to the National Comprehensive Cancer Network (NCCN) criteria, who had performed genetic tests for HBOC. We collected complete family history, presented as heredograms. We excluded families with inappropriate family history. Results: Of the 27 patients analyzed (total of 25 families), 7% were asymptomatic, 8% had ovarian cancer and 85% had breast cancer. Mutations were found in 29.6%, 6 cases of BRCA1, 1 of BRCA2 and 1 of TP53. Triple negative was the most common reported subtype, representing 60% of breast cancers; among patients with identified pathogenic variants, 2 were BRCA2 mutated and 1 TP53 mutated. The mean age of diagnosis was 40 years for those identified as probands on heredograms; in the generation above, it was 52,5, and in the below, 33, suggesting the antecipation phenomena Two new mutations were identified in Brazilian population, both in BRCA1: c.4258 G>A and c.5345 G>A. The most frequent NCCN criteria were number 2, 9, 8 and 4. Estimated penetrance was 22%. Conclusion: This is the first descriptive study in the population at-risk for HBOC in the state of Paraná. We could identify two new pathogenic variants of BRCA1 in Brazilian population. A comprehensive family history was included in the study, depicted as heredograms of each family. Despite the low number of patients, the main results are in agreement with previous studies

Objetivo: Os carcinomas de mama hereditários têm a tendência de se manifestar precocemente e serem mais agressivos do que os esporádicos. São poucos os estudos que avaliam a prevalência e a incidência da síndrome de câncer de mama e ovário hereditário (SCMOH) na população brasileira. No intuito de melhorar a assistência prestada, a análise das características encontradas na população em risco para SCMOH ajudaria a formulação de protocolos regionais para a abordagem desses pacientes. Metodologia: Estudo descritivo retrospectivo realizado no serviço de Oncogenética do Hospital Erasto Gaertner em Curitiba, Paraná. Incluímos indivíduos em risco para SCMOH pelos critérios estabelecidos pela National Comprehensive Cancer Network (NCCN) e que realizaram testes genéticos para SCMOH. Coletamos o histórico familiar completo, apresentado na forma de heredograma. Foram excluídas famílias com histórico familiar inapropriado. Resultados: Das 27 pacientes analisadas (total de 25 famílias), 7% eram assintomáticas, 8% tiveram câncer de ovário e 85%, câncer de mama. Mutações foram encontradas em 29,6%, sendo 6 casos de BRCA1, 1 de BRCA2 e 1 de TP53. Tumores triplo negativos foram os mais encontrados entre os subtipos, representando 60% dos carcinomas de mama; dentre os pacientes com variantes patogênicas, 2 eram de mutações em BRCA2 e 1 em TP53. A média de idade entre as pacientes foi de 40 anos entre probandas dos heredogramas; na geração superior, foi de 52,5 anos e na inferior, de 33, sugerindo o fenômeno de antecipação. Duas novas mutações foram descritas na população brasileira, as duas sendo em BRCA1: c.4258 G>A e c.5345 G>A. Os critérios NCCN mais encontrados foram os de número 2, 9, 8 e 4. A penetrância estimada foi de 22%. Conclusão: Este foi o primeiro estudo descritivo de uma população em risco para SCMOH no estado do Paraná. Encontramos duas novas mutações que não haviam sido descritas na população brasileira até então. Foi realizada a análise detalhada do histórico familiar das pacientes, sendo descrita e detalhada em heredogramas para cada família. Apesar do baixo número de indivíduos analisados, os resultados principais foram de acordo com o encontrado em estudos prévios