Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of ß-amyloid deposition and neurodegeneration.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

18F-FDG PET/CT Osteometabolic Activity in Metastatic Parathyroid Carcinoma.

Parathyroid cancer is an uncommon type of malignancy, which is frequently associated with poor prognosis. Clinical manifestations are caused by elevated serum calcium and parathyroid hormone (PTH). Diagnostic imaging studies as neck ultrasonography, technetium Tc Tc-sestamibi whole body scintigraphy, CT, and MR are already established tools for this malignancy. Nevertheless, the role of F-FDG PET/CT remains unknown in this scenario, with few published studies in literature. Hence, in this article, we aimed to report an illustrative case of increased skeletal FDG uptake associated with high calcium and PTH levels.

Effects of Duodenal-Jejunal Bypass Liner (EndoBarrier®) on Gastric Emptying in Obese and Type 2 Diabetic Patients.

INTRODUCTION: The duodenal-jejunal bypass liner (DJBL) is a promising technique for treating obesity and type 2 diabetes mellitus (T2DM). However, despite promising results, its mechanism of action has not been elucidated. It is thought to promote changes in gastric emptying owing to the neuro-endocrine axis. OBJECTIVE: The aim of this paper was to study DJBL-induced changes in gastric emptying and the relationship of those changes with weight loss and T2DM. METHODS: Twenty-five patients with obesity and T2DM met inclusion criteria. Scintigraphic gastric emptying testing was performed prior to implantation, 16 weeks after implantation, and 4 weeks after removal. The average gastric retention was compared between tests, to examine the relationship between gastric emptying and those who lost more than 10 % of total body weight. Similarly, we compared average gastric retention between those who achieved a glycated hemoglobin target lower than 7 %. RESULTS: Average gastric retention was greater after DJBL implantation compared with the baseline (first hour, 74 ± 16.3 %, p = 0.001; second hour, 45 ± 25 %, p < 0.001; fourth hour, 15.8 ± 15 %, p < 0.001). There was no difference between the baseline and 4 weeks after device removal (fourth hour, p = 0.057). Gastric retention was similar between patients who achieved T2DM control and those who did not (p = 0.73). Additionally, no difference was seen between patients who lost more than 10 % of body weight and those who did not (p = 0.275). CONCLUSIONS: DJBL delays gastric emptying but is reversible after withdrawal. The changes in gastric emptying have no relationship to weight loss and T2DM control.

Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment.

BACKGROUND: Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). OBJECTIVE: To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. METHODS: Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with 18F-fluorodeoxyglucose ([18F]FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2max (mL/Kg/min). [18F]FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. RESULTS: Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p <  0.001) and VO2max scores (M difference: 1.8 (2.0) mL/kg/min, p <  0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho =-0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r =-0.51, p = 0.001). CONCLUSION: AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.

Long-term lithium treatment reduces glucose metabolism in the cerebellum and hippocampus of nondemented older adults: an [¹8F]FDG-PET study.

Lithium modulates several intracellular pathways related to neuroplasticity and resilience against neuronal injury. These properties have been consistently reported in experimental models, and involve the up-regulation of neurotrophic response and autophagy, and down-regulation of apoptosis, oxidative stress, and inflammation. Clinical and epidemiological studies in bipolar disorder show that acute treatment with lithium increases plasma concentrations of brain-derived neurotrophic factor, and long-term treatment lowers the risk of dementia. Neuroimaging studies indicate that lithium use is further associated with increased cortical thickness and larger hippocampal volumes. The objective of the present study was to evaluate whether these neurobiological properties of lithium reflect in increased regional brain glucose metabolism, as shown by [(18)F]FDG-PET. Participants (n = 19) were nondemented older adults recruited at the end point of a controlled trial addressing clinical and biological effects of lithium in a sample of patients with amnestic mild cognitive impairment. Twelve patients who had received low-dose lithium carbonate for 4 years were compared to seven matched controls. Chronic lithium treatment was not associated with any significant increase in brain glucose metabolism in the studied areas. Conversely, we found a significant reduction in glucose uptake in several clusters of the cerebellum and in both hippocampi. These findings were not associated with any clinical evidence of toxicity. The clinical implications of the present findings need to be clarified by future controlled studies, particularly in the light of the potential use of lithium as a disease-modifying treatment approach for certain neurodegenerative disorders, namely, Alzheimer's disease and amyotrophic lateral sclerosis.

Paraneoplastic limbic encephalitis with prominent neuropsychiatric apathy.

The spectrum of paraneoplastic neurologic syndromes has increased with the description of encephalitis associated with antibodies against cell surface and synaptic proteins. Subacute cognitive impairment, movement disorders, late onset epilepsy and neuropsychiatric syndromes were recently linked to paraneoplastic encephalitis. Despite that, probably some syndromes and antibodies are yet to be reported. Herein we reported the clinical and neuroimaging pictures of a patient with late onset medial temporal lobe epilepsy, subtle cognitive impairment, psychosis and severe apathy diagnosed with antibody-negative paraneoplastic encephalitis due to colonic adenocarcinoma. The apathy markedly improved after removal of the tumor, without concomitant immunotherapy (steroids, intravenous immunoglobulins, immunosuppressants, plasmapheresis, etc.). Our report highlights the importance of a full clinical and neurologic investigation in cases of atypical neuropsychiatric presentations, particularly in the elderly and with the concomitance of epilepsy and cognitive decline. Even chronic presentations must be considered. Neuroimaging is an important tool to demonstrate structural and functional brain dysfunction in these cases. Colonic adenocarcinoma should be searched for in cases in which a typical tumor related to paraneoplastic neurologic syndromes is not found.

Análise de alterações volumétricas e metabólicas cerebrais nos diferentes subtipos de comprometimento cognitivo leve / Volumetric, metabolic and CSF biomarkers profile in different subtypes of MCI

Introducão: o comprometimento cognitivo leve (CCL) é reconhecido como um estágio transicional sintomático entre o envelhecimento normal e a demência, particularmente a doença de Alzheimer (DA). Apresenta como subtipos principais o amnéstico (CCLa), com comprometimento de memória, e o não amnéstico (CCLna), que apresenta perda de outras funções, principalmente executivas, de atenção, de linguagem e visuoespaciais. Aparentemente o CCLna tem menor taxa de conversão para demências ao longo do tempo que o subtipo amnéstico, particularmente para a DA. Dessa forma, o CCLna poderia apresentar um perfil de biomarcadores diferente do CCLa no momento do diagnóstico. Estudos na literatura investigando o padrão de biomarcadores no CCLna como grupo independente são raros, alguns destes indicando perfil menos relacionado à DA no CCLna que o visto no CCLa. Segundo nosso conhecimento, não há estudos investigando concomitantemente volume e metabolismo cerebrais, além de biomarcadores no LCR de uma mesma amostra de CCLna, em comparação com CCLa e um grupo de idosos cognitivamente normais. Objetivo: investigar as alterações de volume e metabolismo cerebral em grupos de indivíduos com os subtipos amnéstico e não amnésico de CCL, comparativamente a voluntários idosos sem comprometimento cognitivo, com o intuito de avaliar se há concordância entre estas alterações. Avaliou-se ainda possíveis associações entre os perfis dos estudos de imagem com padrões classicamente descritos na para CCL em risco de evolução para DA, investigando ainda a existência de correlações entre destes achados com o dos diferentes biomarcadores no LCR e com dados clínicos. Métodos: cento e quatorze voluntários foram incluídos em três diferentes grupos: gCCLna (N = 38), gCCLa (N = 46) e GC (N = 30). Após entrevista clínica, exame neurológico e classificação por uma bateria de testes neuropsicológicos, estes foram submetidos a exames de RM cerebral (para excluir outras causas de comprometimento cognitivo e...

Introduction: Mild cognitive impairment (MCI) is presumably a transitional stage between normal aging and dementia, particularly Alzheimer's disease (AD). Non-amnestic subtypes (naMCI) present with executive, attention, visuospatial and language dysfunctions. They have a lower conversion rate to dementia compared to amnestic subtypes (aMCI). Investigations regarding biomarker profiles of naMCI as an independent group are scarce. To our knowledge there is no study investigating the brain volumetric and metabolic features, as well as the profile of cerebrospinal fluid (CSF) biomarkers of naMCI patients as a single group in comparison to aMCI and cognitively normal elderly patients (control group - CG). Objective: to investigate the brain volumetric and metabolic changes in individuals presenting amnestic and non-amnestic MCI subtypes in comparison to elderly volunteers without cognitive impairment, aiming to verify if there are agreements between these changes. Possible associations between the imaging profile of these groups and classical patterns of high risk for developing AD were also evaluated, as well as possible correlations between imaging biomarkers, CSF biomarkers and clinical data. Methods: a hundred and fourteen (114) patients were included in three different groups: naMCIg (N = 38), aMCIg (N = 46) and CG (N = 30). Patients underwent brain MRI (in order to exclude other causes of the cognitive impairment but also for VBM analysis) and [18F]FDG-PET. A subsample (naMCIg = 33, aMCIg = 38) also underwent a lumbar puncture in order to assess the profile of amyloid-ß peptide, tau and phosphorylated tau protein levels in the CSF. Results: There was no difference in CSF biomarkers, education years, age, gender and cardiovascular risk factors between the naMCI and aMCI groups, except for a higher prevalence of dyslipidemia in aMCI. The amnestic MCI group had lower rBGM in relation to control group in the precuneus, posterior cingulate and...

Efeito da cicatrização induzida no desenvolvimento do tumor de Walker 256 no estômago de ratos / Wound healing effects on the development of gastric cancer induced by Walker 256 tumor in rats

Introdução: A influência da cicatrização de feridas cutâneas a distância no crescimento de neoplasias tem-se mostrado evidente em diversos modelos experimentais de câncer induzidos quimicamente. Em 1998, Oliveira e coloestabeleceram um modelo experimental de inoculação de tumor de Walker 256 no estômago de ratos, tendo estabelecido o mesmo como um modelo para estudo de câncer gástrico experimental. Objetivo: Estudar o efeito da cicatrização de ferida cutânea no crescimento do Tumor de Walker implantado no estômago de ratos. Método: Foramutilizados 14 Rattus Norvegicus albinus,linhagem Wistar; machos, distribuídos, aleatoriamente, em 2 grupos: grupo ferida tumor (GFT) e grupo tumor (GT), sendo então as células tumor ais administradas por gavagem no estômago dos animais (IrJi células em lml) em homogeneizado, no dia O. Na segunda etapa do experimento, uma feridacutânea foi realizada, no 110 dia, no dorso de animais do GFT. Ao 210 dia, os órgãos foram retirados para comparação do crescimento neoplásico. Resultados: Nos animais em que ocorreu implante tumoral, a neoplasia invadiu até a serosa do estômago de 100por cento em todos animais de ambos os grupos, apresentando o mesmo número ( 100 por cento) para o acometimento macroscópico dos estômagos, atingindo toda a extensão do órgão. Conclusão: Ao final do estudo, não houve diferença entre os grupos, ocorrendo crescimento acentuado do tumor em ambos