RESUMO
PURPOSE: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD). METHODS: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92). RESULTS: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees. CONCLUSION: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure.
Assuntos
Doença de Alzheimer , Sequenciamento do Exoma , Predisposição Genética para Doença , Testes Genéticos , Glicoproteínas de Membrana , Presenilina-2 , Receptores Imunológicos , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/diagnóstico , Testes Genéticos/métodos , Feminino , Masculino , Idoso , Fatores de Risco , Estudos Prospectivos , Pessoa de Meia-Idade , Presenilina-2/genética , Presenilina-1/genética , Linhagem , Idade de Início , Precursor de Proteína beta-Amiloide/genética , Idoso de 80 Anos ou maisRESUMO
Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease of the central nervous system, characterized by the presence of auto-antibodies directed against aquaporin-4 (AQP4) expressed on astrocyte end-feet. Despite NMOSD does not primarily belong to the spectrum of paraneoplastic neurological syndromes, rare cases of association with neoplasia have been outlined. Here, we report the association of NMOSD with ovarian teratoma in 3 cases. Pathological analysis of teratomas revealed glial component strongly expressing AQP4 and closely localized to immune infiltrates. Our series highlight the rare association of teratoma with NMOSD and the possible paraneoplastic mechanism.
Assuntos
Neuromielite Óptica/complicações , Neuromielite Óptica/patologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Teratoma/complicações , Teratoma/patologia , Adolescente , Adulto , Aquaporina 4/metabolismo , Feminino , Humanos , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/metabolismo , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Teratoma/diagnóstico , Teratoma/metabolismo , Adulto JovemRESUMO
BACKGROUND: Knowledge of functional evolution in dementia is crucial for the patients and their families as well as the clinician. OBJECTIVE: This review identifies scales and outcomes used to describe the natural history of functional decline and describes the natural history of functional decline in a representative clinical population sample of published studies of patients with Alzheimer's disease (AD). METHODS: A search of three relevant databases was conducted and limited to articles published in English and French between 1998 to March 2012, using the keywords "Dementia", "Activities of Daily Living", "Instrumental Activities of Daily Living", "Functional Impairment", "Prognosis", and "Disease Progression". RESULTS: The search strategy displayed 683 articles, 20 of which were found to be related to the functional evolution of AD. In these studies, different scales were used to describe the evolution of the functional decline, except for the decline of instrumental activities, for which the Lawton scale was used in all studies. Thus, it is difficult to represent the evolution of the functional decline from a clinical point of view. CONCLUSION: Relatively little data are available to estimate the functional evolution of AD. A consensus with broadened thought is required to know if the progression of the incapacities in these scales is additive or hierarchical.