ABSTRACT
Frontotemporal dementia (FTD) affects behavior, language, and personality. This study aims to explore functional connectivity changes in three FTD variants: behavioral (bvFTD), semantic (svPPA), and nonfluent variant (nfvPPA). Seventy-six patients diagnosed with FTD by international criteria and thirty-two controls were investigated. Functional connectivity from resting functional magnetic resonance imaging (fMRI) was estimated for the whole brain. Two types of analysis were done: network basic statistic and topological measures by graph theory. Several hubs in the limbic system and basal ganglia were compromised in the behavioral variant apart from frontal networks. Nonfluent variants showed a major disconnection with respect to the behavioral variant in operculum and parietal inferior. The global efficiency had lower coefficients in nonfluent variants than behavioral variants and controls. Our results support an extensive disconnection among frontal, limbic, basal ganglia, and parietal hubs.
Subject(s)
Aphasia, Primary Progressive/physiopathology , Connectome/methods , Frontotemporal Dementia/physiopathology , Nerve Net/physiopathology , Aged , Aphasia, Primary Progressive/diagnostic imaging , Female , Frontotemporal Dementia/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/diagnostic imaging , Primary Progressive Nonfluent Aphasia/diagnostic imaging , Primary Progressive Nonfluent Aphasia/physiopathologyABSTRACT
AIM: To evaluate the performance of patients with Alzheimer's disease (AD) in the mild-moderate stage in a verbal material abstraction task that involves interpreting the implicit meaning of proverbs and sayings. SUBJECTS AND METHODS: A qualitative-quantitative analysis was carried out of the performance of 30 patients with AD and 30 controls, paired by age, gender and level of education. RESULTS: Patients had significantly greater difficulties than the controls when it came to interpreting proverbs. A high correlation was found between subjects' years of schooling and the overall score on the proverb interpretation test. Results suggest that the processes that may be predominantly affected in patients with AD are the investigation of the conditions of the problem, together with selecting an alternative and formulating a cognitive plan to resolve the task. CONCLUSIONS: The results help to further our knowledge of the characteristics of performance of patients with AD in a test involving the interpretation of the implicit meaning of proverbs and also provide information about the processes that may be predominantly affected. Further research is needed, however, on this subject area in order to obtain more conclusive explanations.
Subject(s)
Alzheimer Disease , Comprehension , Language Tests , Psycholinguistics , Aged , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Educational Status , Female , Humans , Male , Neuropsychological Tests , Psychomotor Performance/physiology , Semantics , Verbal BehaviorABSTRACT
Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset < or = 65 years). No APP missense mutations were identified. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in five AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations.
Subject(s)
Alzheimer Disease/genetics , Proteins/genetics , Age of Onset , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Amino Acid Sequence , Amino Acid Substitution , Amyloid beta-Protein Precursor/genetics , Base Sequence , Colombia/epidemiology , DNA/chemistry , DNA/genetics , DNA Mutational Analysis , Female , Gene Frequency , Humans , Male , Membrane Proteins/genetics , Middle Aged , Mutation , Point Mutation , Polymorphism, Restriction Fragment Length , Polymorphism, Single-Stranded Conformational , Presenilin-1 , Presenilin-2ABSTRACT
La doble disociación entre el sistema semántico y el fonológico se evidencia en la presentación de dos casos con degeneración focal bilateral de los lóbulos temporales. Uno, con pérdida progresiva y selectiva de los aspectos fonológicos, con una profunda agnosia auditiva verbal y no-verbal y parafasias fonológicas en la denominación, con conservación de la semántica; el otro, con una pérdida progresiva pero selectiva de los aspectos semánticos del lenguaje, con conservación del nivel fonológico, evidente en la excelente discriminación de los sonidos del lenguaje, buena repetición y escritura fonológica, pero ausencia de comprensión de los significados de las palabras, caras o figuras, y producción exclusiva de parafasias semánticas en pruebas de denominación.El primer caso (AV), es de un paciente evaluado a los 52 años, con un deterioro progresivo de 10 años de evolución, caracterizado por pérdida de la capacidad para comprender el lenguaje, percibiéndolo como un lenguaje extranjero. Este paciente presenta dificultades de identificación fonológica, de discriminación de sonidos, de repetición y desintegración fonológica en la denominación y en la escritura. El segundo caso (OV), es de una mujer de 60 años, evaluada por un deterioro progresivo de las capacidades de denominación, de 7 años de evolución. El perfil global es el de una paciente que, en su lenguaje, conserva los niveles fonológicos y sintácticos, pero tiene un compromiso significativo de la memoria semántica. En ambos pacientes, el examen neurológico es normal, excepto por los hallazgos en la esfera mental; no tienen antecedentes patológicos familiares y hay ausencia de enfermedad cardiovascular. Ambos presentan depresión, reactiva a la conciencia del deterioro. La paciente con alteración de la semántica conserva intactas sus habilidades atencionales, práxicas y de pensamiento; en el TAC cerebral se evidencia atrofia temporal bilateral de predominio izquierdo. Contrariamente, con la evolución de la enfermedad, el paciente con alteración de la fonología, ha venido presentando un déficit cognoscitivo global; el TAC cerebral se observa atrofia bitemporal de predominio derecho. Con la presentación de estos dos casos, se presenta evidencia de la fragmentación de los niveles semánticos y fonológicos del lenguaje y se realiza una diferenciación clínica entre afasia primaria progresiva, demencia semántica, enfermedad de Pick y enfermedad de Alzheimer