RESUMEN
BACKGROUND: Androgen-deprivation therapy (ADT) has been associated with cognitive decline, but results are conflicting. This study describes changes in cognitive performance in patients with prostate cancer, according to ADT, during the first year after prostate cancer diagnosis. PATIENTS AND METHODS: Patients with prostate cancer treated at the Portuguese Institute of Oncology of Porto (n = 366) were evaluated with the Montreal Cognitive Assessment (MoCA), before treatment and after 1 year. All baseline evaluations were performed before the coronavirus disease 2019 (COVID-19) pandemic and 69.7% of the 1-year assessments were completed after the first lockdown. Cognitive decline was defined as the decrease in MoCA from baseline to the 1-year evaluation below 1.5 standard deviations of the distribution of changes in the whole cohort. Participants scoring below age- and education-specific normative reference values in the MoCA were considered to have cognitive impairment. Age- and education-adjusted odds ratios (aORs) were computed for the association between ADT and cognitive outcomes. RESULTS: Mean MoCA scores increased from baseline to the 1-year evaluation (22.3 versus 22.8, P < 0.001). Cognitive decline was more frequent in the ADT group, and even more after the onset of the COVID-19 pandemic (aOR 6.81 versus 1.93, P for interaction = 0.233). The 1-year cumulative incidence of cognitive impairment was 6.9% (9.1% before and 3.7% after the pandemic onset), which was higher among patients receiving ADT, but only after the pandemic (aOR 5.53 versus 0.49, P for interaction = 0.044). CONCLUSIONS: ADT was associated with worse cognitive performance of patients with prostate cancer, mostly among those evaluated after the first COVID-19 lockdown.
Asunto(s)
COVID-19 , Disfunción Cognitiva , Neoplasias de la Próstata , Antagonistas de Andrógenos/efectos adversos , Andrógenos , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/etiología , Control de Enfermedades Transmisibles , Humanos , Masculino , Neón , Pandemias , Estudios Prospectivos , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
OBJECTIVES: The hereditary spastic paraplegias (HSP) are a genetically and clinically heterogeneous group of neurodegenerative disorders, mainly characterized by a progressive spasticity and weakness of the lower limbs. Mutations in the SPG4 and SPG3A genes are responsible for approximately 50% of autosomal dominant HSP. To genetically diagnose the Portuguese families with HSP, mutation analysis was performed for the SPG4 and SPG3A genes. PATIENTS AND METHODS: Analysis was performed by polymerase chain reaction, followed by denaturing high performance liquid chromatography (DHPLC), in 61 autosomal dominant (AD)-HSP families and 19 unrelated patients without family history. RESULTS: Ten novel mutations were identified: one in the SPG3A and nine in the SPG4 genes; three known mutations in the SPG4 were also found. Most of the novel mutations were frameshift or nonsense (80%), resulting in a dysfunctional protein. CONCLUSIONS: The SPG4 and SPG3A analysis allowed the identification of 10 novel mutations and the genetic diagnosis of approximately a quarter of our AD-HSP families.
Asunto(s)
Adenosina Trifosfatasas/genética , GTP Fosfohidrolasas/genética , Paraplejía/genética , Edad de Inicio , Secuencia de Aminoácidos , Cromatografía Líquida de Alta Presión , Familia , Femenino , Proteínas de Unión al GTP , Genes Dominantes , Humanos , Masculino , Proteínas de la Membrana , Datos de Secuencia Molecular , Mutación , Paraplejía/epidemiología , Linaje , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de Proteína , EspastinaRESUMEN
Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by progressive spasticity of the lower limbs. Here, we performed a genome-wide linkage analysis on a consanguineous family presenting an autosomal recessive form of HSP associated with mild mental retardation, brainstem dysraphia, and clinically asymptomatic cerebellar atrophy. We have mapped the disease locus SPG32 to chromosome 14q12-q21 within a 30-cM interval, which excludes the atlastin gene.
Asunto(s)
Cromosomas Humanos Par 14/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Paraplejía Espástica Hereditaria/genética , Adulto , Tronco Encefálico/anomalías , Tronco Encefálico/metabolismo , Tronco Encefálico/fisiopatología , Cerebelo/anomalías , Cerebelo/metabolismo , Cerebelo/fisiopatología , Mapeo Cromosómico , Consanguinidad , Análisis Mutacional de ADN , Femenino , GTP Fosfohidrolasas/genética , Proteínas de Unión al GTP , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Patrón de Herencia/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/fisiopatología , Masculino , Proteínas de la Membrana , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/fisiopatología , Linaje , Paraplejía Espástica Hereditaria/metabolismo , Paraplejía Espástica Hereditaria/fisiopatologíaRESUMEN
The authors identified a missense mutation in the FTL gene (474G>A; A96T) in a 19-year-old man with parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit, and episodic psychosis. This mutation was also present in his asymptomatic mother and younger brother, who had abnormally low levels of ferritin in the serum. The patient and his mother displayed bilateral involvement of the pallidum.
