Cardiovascular risk in cognitively preserved elderlies is associated with glucose hypometabolism in the posterior cingulate cortex and precuneus regardless of brain atrophy and apolipoprotein gene variations.

Cardiovascular risk factors (CVRF) possibly contribute to the emergence of Alzheimer's disease (AD). Fluorodeoxyglucose-positron emission tomography (FDG-PET) has been widely used to demonstrate specific patterns of reduced cerebral metabolic rates of glucose (CMRgl) in subjects with AD and in non-demented carriers of the apolipoprotein ε4 (APOE ε4) allele, the major genetic risk factor for AD. However, functional neuroimaging studies investigating the impact of CVRF on cerebral metabolism have been scarce to date. The present FDG-PET study investigated 59 cognitively preserved elderlies divided into three groups according to their cardiovascular risk based on the Framingham 10-year risk Coronary Heart Disease Risk Profile (low-, medium-, and high-risk) to examine whether different levels of CVRF would be associated with reduced CMRgl, involving the same brain regions affected in early stages of AD. Functional imaging data were corrected for partial volume effects to avoid confounding effects due to regional brain atrophy, and all analyses included the presence of the APOE ε4 allele as a confounding covariate. Significant cerebral metabolism reductions were detected in the high-risk group when compared to the low-risk group in the left precuneus and posterior cingulate gyrus. This suggests that findings of brain hypometabolism similar to those seen in subjects with AD can be detected in association with the severity of cardiovascular risk in cognitively preserved individuals. Thus, a greater knowledge about how such factors influence brain functioning in healthy subjects over time may provide important insigths for the future development of strategies aimed at delaying or preventing the vascular-related triggering of pathologic brain changes in the AD.

Relationship between regional brain volumes and cognitive performance in the healthy aging: an MRI study using voxel-based morphometry.

The presence of cognitive impairment is a frequent complaint among elderly individuals in the general population. This study aimed to investigate the relationship between aging-related regional gray matter (rGM) volume changes and cognitive performance in healthy elderly adults. Morphometric magnetic resonance imaging (MRI) measures were acquired in a community-based sample of 170 cognitively-preserved subjects (66 to 75 years). This sample was drawn from the "São Paulo Ageing and Health" study, an epidemiological study aimed at investigating the prevalence and risk factors for Alzheimer's disease in a low income region of the city of São Paulo. All subjects underwent cognitive testing using a cross-culturally battery validated by the Research Group on Dementia 10/66 as well as the SKT (applied on the day of MRI scanning). Blood genotyping was performed to determine the frequency of the three apolipoprotein E allele variants (APOE ε2/ε3/ε4) in the sample. Voxelwise linear correlation analyses between rGM volumes and cognitive test scores were performed using voxel-based morphometry, including chronological age as covariate. There were significant direct correlations between worse overall cognitive performance and rGM reductions in the right orbitofrontal cortex and parahippocampal gyrus, and also between verbal fluency scores and bilateral parahippocampal gyral volume (p < 0.05, familywise-error corrected for multiple comparisons using small volume correction). When analyses were repeated adding the presence of the APOE ε4 allele as confounding covariate or excluding a minority of APOE ε2 carriers, all findings retained significance. These results indicate that rGM volumes are relevant biomarkers of cognitive deficits in healthy aging individuals, most notably involving temporolimbic regions and the orbitofrontal cortex.

TNF-alpha polymorphisms are associated with obsessive-compulsive disorder.

INTRODUCTION: Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases. Polymorphisms in the promoter region of the TNFA gene have been associated with RF. Given the association between OCD and RF, the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD. MATERIALS AND METHODS: Two polymorphisms were investigated: -308 G/A and -238 G/A. The allelic and genotypic frequencies of these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria for OCD and compared with the frequencies in 250 controls. RESULTS: Significant associations were observed between both polymorphisms and OCD. For -238 G/A, an association between the A allele and OCD was observed (chi(2)=12.05, p=0.0005). A significant association was also observed between the A allele of the -308 G/A polymorphism and OCD (chi(2)=7.09, p=0.007). Finally, a haplotype consisting of genotypes of these two markers was also examined. Significant association was observed for the A-A haplotype (p=0.0099 after correcting for multiple testing). DISCUSSION: There is association between the -308 G/A and -238 G/A TNFA polymorphisms and OCD in our Brazilian sample. However, these results need to be replicated in larger samples collected from different populations.

Ausência de efeito de gênero em esquizofrenia familiar: um estudo brasileiro / Lack of gender effect on familial schizophrenia: a Brazilian study

Estudos epidemiológicos em esquizofrenia estabeleceram que a idade de início para o gênero masculino precede em alguns anos aquela para o feminino. No entanto, tal efeito de gênero não vem sendo observado para os casos de esquizofrenia familiar, em que pelo menos dois membros de uma mesma família recebam o mesmo diagnóstico. Nosso estudo examina pela primeira vez esta questão em uma população brasileira. Estudamos 31 pacientes com diagnóstico de esquizofrenia pelos critérios RDC, provenientes de 13 famílias com dois ou mais afetados. Nossos resultados confirmam os da literatura internacional, não encontrando diferenças entre gênero masculino e feminino na idade de aparecimento dos sintomas. Estes resultados indicam a possibilidade da existência de influência genética na idade de início do transtorno e devem receber atenção de estudos em genética molecular.