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Summary: Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain. Palmitate is increased in the cerebrospinal fluid (CSF) of overweight and obese patients with amnestic mild cognitive impairment. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Palmitate induces astroglial and microglial activation in the mouse hippocampus, and its deleterious impact is mediated by microglia-derived tumor necrosis factor alpha (TNF-α) signaling. Our results establish that obesity is associated with increases in CSF palmitate. By defining a pro-inflammatory mechanism by which abnormal levels of palmitate in the brain impair memory, the results further suggest that anti-inflammatory strategies may attenuate memory impairment in obesity. : Obesity has been associated with cognitive decline. Melo et al. show that palmitate levels are increased in the CSF of overweight and obese humans. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Microglial-derived TNF-α mediates the deleterious actions of palmitate in the brain. Keywords: palmitate, memory impairment, obesity, brain inflammation, microglia, TNF-α, insulin signaling

OBJECTIVE: To study lexical semantic memory in patients with amnestic mild cognitive impairment (aMCI), mild Alzheimer's disease (AD) and normal controls. METHOD: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, and that of aMCI, on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent semantic memory tests (Boston Naming-BNT, CAMCOG Similarities item), Rey Auditory Verbal Learning Test (RAVLT), Mini-Mental Status Examination (MMSE), neuropsychological tests (counterproofs), and Cornell Scale for Depression in Dementia. Data analysis used Mann-Whitney test for intergroup comparisons and Pearson's coefficient for correlations between memory tests and counterproofs (statistical significance level was pOBJETIVO: Estudar a memória léxico-semântica no comprometimento cognitivo leve amnéstico (aCCL), doença de Alzheimer (DA) leve e controles normais. MÉTODO: Incluímos 15 pacientes com DA leve, 15 com aCCL e 15 controles normais, usando os critérios DSM-IV, NINCDS-ADRDA e CDR 1 para DA, e os do International Working Group on Mild Cognitive Impairment, e CDR 0,5 para aCCL. Todos os sujeitos passaram por testes de memória semântica (Teste de nomeação de Boston - TNB, item de Similaridades do CAMCOG), teste de aprendizado auditivo-verbal de Rey (TAAVR), Mini-Exame do Estado Mental (MEEM), testes neuropsicológicos (contraprovas) e Escala Cornell para Depressão em Demência. A análise dos dados usou o teste de Mann-Whitney para comparações entre os grupos e o coeficiente de Pearson para correlação entre testes e contraprovas (nível de significância p

Abstract Neuroanatomical correlations of naming and lexical-semantic memory are not yet fully understood. The most influential approaches share the view that semantic representations reflect the manner in which information has been acquired through perception and action, and that each brain area processes different modalities of semantic representations. Despite these anatomical differences in semantic processing, generalization across different features that have similar semantic significance is one of the main characteristics of human cognition. Methods: We evaluated the brain regions related to naming, and to the semantic generalization, of visually presented drawings of objects from the Boston Naming Test (BNT), which comprises different categories, such as animals, vegetables, tools, food, and furniture. In order to create a model of lesion method, a sample of 48 subjects presenting with a continuous decline both in cognitive functions, including naming skills, and in grey matter density (GMD) was compared to normal young adults with normal aging, amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). Semantic errors on the BNT, as well as naming performance, were correlated with whole brain GMD as measured by voxel-based morphometry (VBM). Results: The areas most strongly related to naming and to semantic errors were the medial temporal structures, thalami, superior and inferior temporal gyri, especially their anterior parts, as well as prefrontal cortices (inferior and superior frontal gyri). Conclusion: The possible role of each of these areas in the lexical-semantic networks was discussed, along with their contribution to the models of semantic memory organization.