JAQUELINE HATSUKO TAMASHIRO DURAN
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
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- 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(2013) TAMASHIRO-DURAN, Jaqueline Hatsuko; SQUARZONI, Paula; DURAN, Fabio Luis de Souza; CURIATI, Pedro Kallas; VALLADA, Homero Pinto; BUCHPIGUEL, Carlos Alberto; LOTUFO, Paulo Andrade; WAJNGARTEN, Mauricio; MENEZES, Paulo Rossi; SCAZUFCA, Marcia; ALVES, Tania Correa de Toledo Ferraz; BUSATTO, Geraldo FilhoCardiovascular 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 epsilon 4 (APOE epsilon 4) 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 epsilon 4 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.
- Prefrontal-Parietal White Matter Volumes in Healthy Elderlies Are Decreased in Proportion to the Degree of Cardiovascular Risk and Related to Inhibitory Control Deficits(2017) SANTOS, Pedro P.; SILVEIRA, Paula S. Da; SOUZA-DURAN, Fabio L.; TAMASHIRO-DURAN, Jaqueline H.; SCAZUFCA, Marcia; MENEZES, Paulo R.; LEITE, Claudia Da Costa; LOTUFO, Paulo A.; VALLADA, Homero; WAJNGARTEN, Mauricio; ALVES, Tania C. De Toledo Ferraz; RZEZAK, Patricia; BUSATTO, Geraldo F.Cardiovascular risk (CVR) factors may be associated with poor cognitive functioning in elderlies and impairments in brain structure. Using MRI and voxel-based morphometry (VBM), we assessed regional white matter (WM) volumes in a population-based sample of individuals aged 65-75 years (n = 156), subdivided in three CVR subgroups using the Framingham Risk Score. Cognition was assessed using the Short Cognitive Performance Test. In high-risk subjects, we detected significantly reduced WM volume in the right juxtacortical dorsolateral prefrontal region compared to both low and intermediate CVR subgroups. Findings remained significant after accounting for the presence of the APOE epsilon 4 allele. Inhibitory control performance was negatively related to right prefrontal WM volume, proportionally to the degree of CVR. Significantly reduced deep parietal WM was also detected bilaterally in the high CVR subgroup. This is the first large study documenting the topography of CVR-related WM brain volume deficits. The significant association regarding poor response inhibition indicates that prefrontal WM deficits related to CVR are clinically meaningful, since inhibitory control is known to rely on prefrontal integrity.
- Framingham coronary heart disease risk score can be predicted from structural brain images in elderly subjects(2014) RONDINA, Jane Maryam; SQUARZONI, Paula; SOUZA-DURAN, Fabio Luis; TAMASHIRO-DURAN, Jaqueline Hatsuko; SCAZUFCA, Marcia; MENEZES, Paulo Rossi; VALLADA, Homero; LOTUFO, Paulo A.; ALVES, Tania Correade Toledo Ferraz; FILHO, Geraldo BusattoRecent literature has presented evidence that cardiovascular risk factors (CVRF) play an important role on cognitive performance in elderly individuals, both those who are asymptomatic and those who suffer from symptoms of neurodegenerative disorders. Findings from studies applying neuroimaging methods have increasingly reinforced such notion. Studies addressing the impact of CVRF on brain anatomy changes have gained increasing importance, as recent papers have reported gray matter loss predominantly in regions traditionally affected in Alzheimer's disease (AD) and vascular dementia in the presence of a high degree of cardiovascular risk. In the present paper, we explore the association between CVRF and brain changes using pattern recognition techniques applied to structural MRI and the Framingham score (a composite measure of cardiovascular risk largely used in epidemiological studies) in a sample of healthy elderly individuals. We aim to answer the following questions: is it possible to decode (i.e., to learn information regarding cardiovascular risk from structural brain images) enabling individual predictions? Among clinical measures comprising the Framingham score, are there particular risk factors that stand as more predictable from patterns of brain changes? Our main findings are threefold: (i) we verified that structural changes in spatially distributed patterns in the brain enable statistically significant prediction of Framingham scores. This result is still significant when controlling for the presence of the APOE 4 allele (an important genetic risk factor for both AD and cardiovascular disease). (ii) When considering each risk factor singly, we found different levels of correlation between real and predicted factors; however, single factors were not significantly predictable from brain images when considering APOE4 allele presence as covariate. (iii) We found important gender differences, and the possible causes of that finding are discussed.
- Age-Related Metabolic Profiles in Cognitively Healthy Elders: Results from a Voxel-Based [F-18]Fluorodeoxyglucose-Positron-Emission Tomography Study with Partial Volume Effects Correction(2011) CURIATI, P. K.; TAMASHIRO-DURAN, J. H.; DURAN, F. L. S.; BUCHPIGUEL, C. A.; SQUARZONI, P.; ROMANO, D. C.; VALLADA, H.; MENEZES, P. R.; SCAZUFCA, M.; BUSATTO, G. F.; ALVES, T. C. T. F.BACKGROUND AND PURPOSE: Functional brain variability has been scarcely investigated in cognitively healthy elderly subjects, and it is currently debated whether previous findings of regional metabolic variability are artifacts associated with brain atrophy. The primary purpose of this study was to test whether there is regional cerebral age-related hypometabolism specifically in later stages of life. MATERIALS AND METHODS: MR imaging and FDG-PET data were acquired from 55 cognitively healthy elderly subjects, and voxel-based linear correlations between age and GM volume or regional cerebral metabolism were conducted by using SPM5 in images with and without correction for PVE. To investigate sex-specific differences in the pattern of brain aging, we repeated the above voxelwise calculations after dividing our sample by sex. RESULTS: Our analysis revealed 2 large clusters of age-related metabolic decrease in the overall sample, 1 in the left orbitofrontal cortex and the other in the right temporolimbic region, encompassing the hippocampus, the parahippocampal gyrus, and the amygdala. The division of our sample by sex revealed significant sex-specific age-related metabolic decrease in the left temporolimbic region of men and in the left dorsolateral frontal cortex of women. When we applied atrophy correction to our PET data, none of the above-mentioned correlations remained significant. CONCLUSIONS: Our findings suggest that age-related functional brain variability in cognitively healthy elderly individuals is largely secondary to the degree of regional brain atrophy, and the findings provide support to the notion that appropriate PVE correction is a key tool in neuroimaging investigations.
- Relationship Between Regional Brain Volumes and Cognitive Performance in the Healthy Aging: An MRI Study Using Voxel-Based Morphometry(2012) SQUARZONI, Paula; TAMASHIRO-DURAN, Jaqueline; DURAN, Fabio Luis Souza; SANTOS, Luciana Cristina; VALLADA, Homero Pinto; MENEZES, Paulo Rossi; SCAZUFCA, Marcia; BUSATTO FILHO, Geraldo; ALVES, Tania Correa Toledo de FerrazThe 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 ""Sao 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 Sao 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 epsilon 2/epsilon 3/epsilon 4) 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 epsilon 4 allele as confounding covariate or excluding a minority of APOE epsilon 2 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.
- Subtle Gray Matter Changes in Temporo-Parietal Cortex Associated with Cardiovascular Risk Factors(2011) DE TOLEDO FERRAZ ALVES, Tania Correa; SCAZUFCA, Marcia; SQUARZONI, Paula; DE SOUZA DURAN, Fabio Luiz; TAMASHIRO-DURAN, Jaqueline Hatsuko; VALLADA, Homero P.; ANDREI, Anna; WAJNGARTEN, Mauricio; MENEZES, Paulo R.; BUSATTO, Geraldo F.Vascular risk factors may play an important role in the pathophysiology of Alzheimer's disease (AD). While there is consistent evidence of gray matter (GM) abnormalities in earlier stages of AD, the presence of more subtle GM changes associated with vascular risk factors in the absence of clinically significant vascular events has been scarcely investigated. This study aimed to examine GM changes in elderly subjects with cardiovascular risk factors. We predicted that the presence of cardiovascular risk would be associated with GM abnormalities involving the temporal-parietal cortices and limbic structures. We recruited 248 dementia-free subjects, age range 66-75 years, from the population-based "Sao Paulo Ageing and Health Study", classified in accordance to their Framingham Coronary Heart Disease Risk (FCHDR) score to undergo an MRI scan. We performed an overall analysis of covariance, controlled to total GM and APOE4 status, to investigate the presence of regional GM abnormalities in association with FCHDR subgroups (high-risk, medium-risk, and low-risk), and followed by post hoc t-test. We also applied a co-relational design in order to investigate the presence of linear progression of the GM vulnerability in association with cardiovascular risk factor. Voxel-based morphometry showed that the presence of cardiovascular risk factors were associated with regional GM loss involving the temporal cortices bilaterally. Those results retained statistical significance after including APOE4 as a covariate of interest. We also observed that there was a negative correlation between FCHDR scores and rGM distribution in the parietal cortex. Subclinical cerebrovascular abnormalities involving GM loss may provide an important link between cardiovascular risk factors and AD.
- Relationship between Brain Age-Related Reduction in Gray Matter and Educational Attainment(2015) RZEZAK, Patricia; SQUARZONI, Paula; DURAN, Fabio L.; ALVES, Tania de Toledo Ferraz; TAMASHIRO-DURAN, Jaqueline; BOTTINO, Cassio M.; RIBEIZ, Salma; LOTUFO, Paulo A.; MENEZES, Paulo R.; SCAZUFCA, Marcia; BUSATTO, Geraldo F.Inter-subject variability in age-related brain changes may relate to educational attainment, as suggested by cognitive reserve theories. This voxel-based morphometry study investigated the impact of very low educational level on the relationship between regional gray matter (rGM) volumes and age in healthy elders. Magnetic resonance imaging data were acquired in elders with low educational attainment (less than 4 years) (n = 122) and high educational level (n = 66), pulling together individuals examined using either of three MRI scanners/acquisition protocols. Voxelwise group comparisons showed no rGM differences (p<0.05, family-wise error corrected for multiple comparisons). When within-group voxel-wise patterns of linear correlation were compared between high and low education groups, there was one cluster of greater rGM loss with aging in low versus high education elders in the left anterior cingulate cortex (p<0.05, FWE-corrected), as well as a trend in the left dorsomedial prefrontal cortex (p<0.10). These results provide preliminary indication that education might exert subtle protective effects against age-related brain changes in healthy subjects. The anterior cingulate cortex, critical to inhibitory control processes, may be particularly sensitive to such effects, possibly given its involvement in cognitive stimulating activities at school or later throughout life.
- High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population(2017) SQUARZONI, Paula; TAMASHIRO-DURAN, Jaqueline H.; DURAN, Fabio L. S.; LEITE, Claudia C.; WAJNGARTEN, Mauricio; SCAZUFCA, Marcia; MENEZES, Paulo R.; LOTUFO, Paulo A.; ALVES, Tania C. T. F.; BUSATTO, Geraldo F.OBJECTIVE: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (Sao Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. METHODS: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n= 185; 21 with no formal education). RESULTS: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (p<0.002). CONCLUSIONS: Silent brain infarcts were present at a substantially high frequency in our elderly sample from an economically disadvantaged urban region and were significantly more prevalent in subjects with lower levels of education. Covert cerebrovascular disease significantly contributes to cognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.