Assessment of the quality of brain regions and neuroimaging metrics as biomarkers of Alzheimer’s disease

Alzheimer Disease (AD) is characterized by progressive cognitive decline and dementia. Earlier diagnosis and classification of different stages of the disease are currently the main challenges and can be assessed by neuroimaging. With this work we aim to evaluate the quality of brain regions and neuroimaging metrics as biomarkers of AD. Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox functionalities were used to study AD by T1weighted, Diffusion Tensor Imaging and 18FAV45 PET, with data obtained from the AD Neuroimaging Initiative database, specifically 12 healthy controls (CTRL) and 33 patients with early mild cognitive impairment (EMCI), late MCI (LMCI) and AD (11 patients/group). The metrics evaluated were gray-matter volume (GMV), cortical thickness (CThk), mean diffusivity (MD), fractional anisotropy (FA), fiber count (FiberConn), node degree (Deg), cluster coefficient (ClusC) and relative standard-uptake-values (rSUV). Receiver Operating Characteristic (ROC) curves were used to evaluate and compare the diagnostic accuracy of the most significant metrics and brain regions and expressed as area under the curve (AUC). Comparisons were performed between groups. The RH-Accumbens/Deg demonstrated the highest AUC when differentiating between CTRLEMCI (82%), whether rSUV presented it in several brain regions when distinguishing CTRL-LMCI (99%). Regarding CTRL-AD, highest AUC were found with LH-STG/FiberConn and RH-FP/FiberConn (~100%). A larger number of neuroimaging metrics related with cortical atrophy with AUC>70% was found in CTRL-AD in both hemispheres, while in earlier stages, cortical metrics showed in more confined areas of the temporal region and mainly in LH, indicating an increasing of the spread of cortical atrophy that is characteristic of disease progression. In CTRL-EMCI several brain regions and neuroimaging metrics presented AUC>70% with a worst result in later stages suggesting these indicators as biomarkers for an earlier stage of MCI, although further research is necessary.

Molecular imaging agents for detection of β-amyloid plaques in Alzheimer’s disease

The formation of amyloid structures is a neuropathological feature that characterizes several neurodegenerative disorders, such as Alzheimer´s and Parkinson´s disease. Up to now, the definitive diagnosis of these diseases can only be accomplished by immunostaining of post mortem brain tissues with dyes such Thioflavin T and congo red. Aiming at early in vivo diagnosis of Alzheimer´s disease (AD), several amyloid-avid radioprobes have been developed for b-amyloid imaging by positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of this paper is to present a perspective of the available amyloid imaging agents, special those that have been selected for clinical trials and are at the different stages of the US Food and Drugs Administration (FDA) approval.

Risk factors for metabolic bone disease in Crohn's disease patients

Background: The aim was to evaluate the presence of metabolic bone disease (MBD) in patients with Crohn’s disease (CD) and to identify potential etiologic factors. Methods: The case–control study included 99 patients with CD and 56 controls with a similar age and gender distribution. Both groups had dual-energy x-ray absorptionmetry and a nutritional evaluation. Single nucleotide polymorphisms at the IL1, TNF-a, LTa, and IL-6 genes were analyzed in patients only. Statistical analysis was performed using SPSS software. Results: The prevalence of MBD was significantly higher in patients (P ¼ 0.006). CD patients with osteoporosis were older (P < 0.005), small bowel involvement and surgical resections were more frequent (P < 0.005), they more often exhibited a penetrating or stricturing phenotype (P < 0.05), duration of disease over 15 years (P < 0.005), and body mass index (BMI) under 18.5 kg/m2 (P < 0.01) were more often found. No association was found with steroid use. Patients with a Z-score < 2.0 more frequently had chronic active disease (P < 0.05). With regard to diet, low vitamin K intake was more frequent (P ¼ 0.03) and intake of total, monounsaturated, and polyunsaturated fat was higher in patients with Z-score < 2.0 (P < 0.05). With respect to genetics, carriage of the polymorphic allele for LTa252 A/G was associated with a higher risk of osteoporosis (P ¼ 0.02). Regression analysis showed that age over 40 years, chronic active disease, and previous colonic resections were independently associated with the risk of developing MBD. Conclusions: The prevalence of MBD was significantly higher in CD patients. Besides the usual risk factors, we observed that factors related to chronic active and long-lasting disease increased the risk of MBD.

Psychosocial factors as predictors of quality of life in chronic portuguese patients

Background - Chronic illnesses are diseases of long duration and generally of slow progression. They cause significant quality of life impairment. The aim of this study was to analyse psychosocial predictors of quality of life and of subjective well-being in chronic Portuguese patients. Methods - Chronic disease patients (n = 774) were recruited from central Portuguese Hospitals. Participants completed self-reported questionnaires assessing socio-demographic, clinical, psychosocial and outcome variables: quality of life (HRQL) and subjective well-being (SWB). MANCOVA analyses were used to test psychosocial factors as determinants of HRQL and SWB. Results - After controlling for socio-demographic and clinical variables, results showed that dispositional optimism, positive affect, spirituality, social support and treatment adherence are significant predictors of HRQL and SWB. Similar predictors of quality of life, such as positive affect, treatment adherence and spirituality, were found for subgroups of disease classified by medical condition. Conclusions - The work identifies psychosocial factors associated with quality of life. The predictors for the entire group of different chronic diseases are similar to the ones found in different chronic disease subgroups: positive affect, social support, treatment adherence and spirituality. Patients with more positive affect, additional social support, an adequate treatment adherence and a feel-good spirituality, felt better with the disease conditions and consequently had a better quality of life. This study contributes to understanding and improving the processes associated with quality of life, which is relevant for health care providers and chronic diseases support.

Synthesis of optimization of [11C] Pittsburgh compound B by the captive solvent method

Mestrado em Medicina Nuclear.

Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

Factores psicossociais preditivos de ajustamento à vida de pessoas com doenças crónicas

Doenças crónicas são de longa duração, de progressão lenta e induzem alterações na vida das pessoas, que são confrontadas com um conjunto de fatores que exercem um impacto negativo na sua qualidade de vida (QdV). A QdV é um conceito envolvendo componentes essenciais da qualidade humana: físicas, psicológicas, sociais, culturais e espirituais. Após o diagnóstico e com a doença estabilizada, os doentes procuram novas formas de lidar com esta. Este estudo teve como objetivo identificar fatores psicossociais preditivos (otimismo, afeto positivo e negativo, adesão aos tratamentos, suporte social e espiritualidade) da QdV (bem-estar geral, saúde física, saúde mental) e bem-estar subjetivo (BES) em pessoas com doenças crónicas. Amostra constituída por 774 indivíduos [30% diabetes, 27,1% cancro, 17,2% diabetes, 12% epilepsia, 11,5% esclerose múltipla e 2,2% miastenia, 70,5% do sexo feminino, idade M(DP)=42,9(11,6), educação M(DP)=9,6(4,7), anos diagnóstico M(DP)=12,8(9,7), classificação da doença M(DP)=6,6 (2,8)], recrutados nos hospitais centrais portugueses. Aplicando Modelos de Equações Estruturais e ajustando para variáveis sociodemográficas e clínicas, verificou-se que, pessoas mais otimistas, mais ativas e com uma melhor adesão aos tratamentos apresentam um melhor bem-estar geral, uma melhor saúde mental e um melhor bem-estar subjetivo; uma melhor adesão aos tratamentos contribui para uma melhor saúde física; melhor suporte social reflete-se numa melhor saúde mental; pessoas com mais espiritualidade apresentam uma melhor saúde física e uma melhor saúde mental. Estas conclusões contribuem para a definição de uma terapia que pode ajudar a uma melhor adaptação dos protocolos de tratamento para atender às necessidades dos doentes.

Impacto do estigma e do bem-estar subjectivo em pessoas com doença crónica

O estudo teve como objectivo comparar o impacto do estigma e do bem-estar subjectivo em pessoas com diferentes doenças crónicas. Foram avaliados 729 doentes, recrutados em hospitais de Portugal, que após o diagnóstico retomaram a sua vida normal. Controlando para um conjunto de variáveis sócio-demográficas e clínicas, a aplicação de Modelos de Análise de Covariância Multivariada, permitiu verificar diferenças significativas apenas para a percepção do estigma entre os grupos de doenças crónicas. Pessoas com obesidade, epilepsia e esclerose múltipla referem mais estigma e pessoas com diabetes tipo1 e miastenia gravis referem menos estigma.