High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population

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 (São 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 (

Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum

The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer’s disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([11C]PIB) assessing amyloid beta (Aβ) aggregation (A) and 18fluorine-fluorodeoxyglucose ([18F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum

Patterns of cortical atrophy and cognitive decline associated with healthy aging: a structural magnetic resonance imaging study

Diversos estudos de ressonância magnética (RM) em idosos saudáveis tem avaliado a relação entre envelhecimento, diminuições volumétricas de substância cinzenta (SC) e desempenho cognitivo, usando desenhos de corte transversal e testes de correlação. No entanto, poucos estudos de volumetria baseada em voxel (VBM) tem relatado a diminuição de SC em idosos saudáveis com medições repetidas de RM nos mesmos indivíduos, e nenhum desses estudos longitudinais investigaram a relação entre as mudanças de SC e desempenho cognitivo ao longo do tempo. Além disso, não está claro em achados longitudinais qual a extensão da influência do APOE?4 sobre as reduções de SC em idosos saudáveis. Foram inicialmente avaliados 187 sujeitos idosos (acima de 65 anos) da comunidade, e após 3 anos, uma subamostra de 55 sujeitos realizaram um segundo exame de RM estrutural em equipamento de 1,5 Tesla, bem como reavaliação cognitiva com instrumentos padronizados e validados transculturalmente. Todos os sujeitos foram genotipados para determinar a presença/ausência do alelo APOEe4, bem como a avaliação clínica do grau do risco cardiovascular de acordo com escores de Framingham (FRS). Usando a técnica de VBM, testamos as hipóteses de que: a progressão da perda do desempenho cognitivo está associada a diminuições volumétricas de SC ao longo de 3 anos, envolvendo a região hipocampal e os neocórtices temporal e frontal; e perdas cognitivas associadas à diminuição progressiva de SC cerebral serão maiores em indivíduos com alto risco cardiovascular e em portadores de alelo da APOEe4. Foram encontradas reduções globais e regionais de SC no tálamo direito e giro parahipocampal esquerdo (p < 0,05, family-wise error corrigido para comparações múltiplas por todo o cérebro). Estes resultados não foram afetados pela influência da APOEe4. Foi detectada uma tendência (p=0,093) na correlação entre o grau de declínio cognitivo e redução volumétrica no tálamo direito. Este resultado se manteve quando um coeficiente parcial de correlação foi calculado levando em conta as variações nos escores FRS. Independentemente da APOEe4, as análises longitudinais de VBM mostraram que a região do hipocampo e tálamo são áreas críticas onde a redução de SC e maior que a redução volumétrica global em idosos saudáveis. Os resultados da associação entre a redução de SC no tálamo e a mudança no desempenho cognitivo ao longo do tempo, apoia o recente reconhecimento do papel do tálamo no declínio cognitivo sutil associado ao envelhecimento saudávelA number of magnetic resonance imaging (MRI) studies have investigated the relationship between aging, reduced gray matter (GM) volumes in the brain and cognitive performance, using cross-sectional designs and correlation tests. However, very few VBM studies have documented GM decrements in healthy elderlies with repeated MRI measurements obtained in the same subjects, and none of these longitudinal studies investigated the relationship between GM deficits and changes in cognitive performance over time. Also, it is unclear the extent to which the APOE e4 allele influences on longitudinal findings of GM reductions in healthy elderlies. Were initially evaluated 187 elderly subjects (over 65 years); after 3 years, a sub-sample of 55 individuals underwent a second MRI examination in a 1.5 Tesla equipment, and a cognitive re-evaluation using a structured, transculturally validated neuropsychological battery. All subjects also underwent genotyping for ascertainment of the presence of the APOEe4 allele, as well as clinical assessment of cardiovascular risk according with Framingham scores (FRS). Using voxel-based morphometry (VBM), we will test the following hypotheses: the progression of cognitive decline will be associated with volumetric reductions of GM over three years, involving the hippocampal region and the temporal and frontal neocortices; cognitive decline associated with progressive GM volume reductions will be greater in individuals with higher cardiovascular risk and carriers of the APOE?4 allele. We found global GM reductions as well as regional GM decrements that were significant in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE e4. A trend correlation (p=0.093) was detected between the degree of cognitive decline over time and right thalamic volume shrinkage. This finding retained statistical significance when a partial coefficient of correlation was calculated taking into account variations in FRS scores. Irrespective of APOEe4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is significantly greater than the degree of global brain volume reduction in healthy elders. The trend towards an association between thalamic GM decrement and cognitive performance change over time supports the recently recognized role of the thalamus in the subtle cognitive decline associated with healthy human agin

Brain abnormalities associated with the presence of cognitive impairment in elderly: an MRI study using voxel-based morphometry

Introdução: Em estudos de ressonância magnética (RM) estrutural e tomografia por emissão de pósitrons (positron emission tomography; PET), métodos de análise voxel-a-voxel permitem comparações entre grupos do volume de substância cinzenta ou do metabolismo de glicose de forma automatizada, em todo o cérebro. Em estudos com portadores de transtornos cognitivos como a Demência de Alzheimer (DA) comparados a controles saudáveis, tais métodos mostram alterações não só em regiões cerebrais classicamente envolvidas na DA (como hipocampo), mas também em áreas não investigadas anteriormente. Mesmo na ausência de demência, sujeitos idosos apresentam freqüentemente alterações cognitivas, sobretudo em associação com fatores de risco cardiovascular, tais como hipertensão arterial sistêmica. Metodologia: Foi realizado numa amostra de 265 idosos na faixa etária entre 66 e 75 anos exames de RM. A amostra foi dividida em dois grupos, o primeiro com perda cognitiva compatível com diagnóstico prejuízo cognitivo (caracterizado pelo desempenho de 1.5 desvio padrão abaixo da média do grupo) e o segundo grupo sem perda cognitiva. A presença de alterações cerebrais associadas à presença de déficit cognitivos entre os grupos foi investigada utilizando uma metodologia automatizada de avaliação voxel-a-voxel através do SPM. Resultados: Identificamos 5 sujeitos com prejuízo cognitivo numa amostra populacional de 244 indivíduos. A presença de prejuízo cognitivo foi associada à presença de lesão silenciosa (p=0,001), idade (p=0,002), e a presença de diabetes (p=0,026). Prejuízos no desempenho cognitivo total foram associados à redução de SC envolvendo o hipocampo e giro parahipocampal à direita (p=0,049 e p=0,036, respectivamente). Prejuízos no desempenho em tarefas de memória foram associados à redução de SC envolvendo regiões de hipocampo, giro parahipocampal e amídala à esquerda (p=0,026, p=0,031, e p=0,007, respectivamente). Prejuízos em tarefas de atenção foram associados à redução de SC envolvendo hipocampo e giro parahipocampal à esquerda (p=0,019 e p=0,013, respectivamente). Finalmente, prejuízos no desempenho cognitivo em tarefas fluência verbal foram associados à redução de SC envolvendo córtex temporal medial à direita (p=0,041). Conclusão: A presença de prejuízo cognitivo foi observada numa pequena porcentagem da população geral quando avaliada através da comparação com o desempenho no próprio grupo. Estudo de volumetria cerebral, após exclusão dos sujeitos com lesão silenciosa, observou que o desempenho cognitivo de idosos da comunidade apresentou relação direta com o volume cerebral de regiões límbicas, importantes para a cognição e memória.Introduction: In studies with structural magnetic resonance imagery (MRI) and positron emission tomography (PET), methods of analysis voxel-by-voxel allow comparisons among groups of gray matter volume or glucose metabolisms in an automatized fashion all around the brain. In studies with cognitive disorder carriers, such as Alzheimer\'s Disease (AD) compared to healthy controls, such methods show alterations not only in the brain regions classically involved in AD (such as hippocampus), but also in areas not previously investigated. Even in the absence of dementia, elderly people often present cognitive changes, mainly in association with cardiovascular risk factors, such as systemic arterial hypertension. Methodology: We performed MRI in a sample of 265 elderly people in the age range between 66 to 75 years old. The sample was divided in two groups: the first one with cognitive loss compatible to cognitive impairment diagnosis (characterized by the performance of 1.5 standard deviation below the group average) and the second group without cognitive loss. The presence of brain alterations associated to the presence of cognitive deficits between the groups was investigated using an automatized methodology of voxel-to-voxel evaluation through statistical parametric mapping (SPM). Results: It was identified 5 subjects with cognitive impairment in a population sample of 244 individuals. The presence of cognitive impairment was associated to the presence of silent lesion (p=0.001), age (p=0.002), and the presence of diabetes (p=0.026). Impairments in the overall cognitive performance were associated to the reduction of the gray matter (GM) involving the hippocampus and parahippocampal gyrus to the right (p=0.049 and p=0.036, respectively). Impairments in the performance of memory tasks were associated to the reduction of GM involving the hippocampus, parahippocampal gyrus and amygdala regions to the left (p=0.026, p=0.031, and p=0.007, respectively). Impairments in attention tasks were associated to the reduction of GM involving the hippocampus and the parahippocampal gyrus to the left (p=0.019 and p=0.013, respectively). Finally, impairments in the cognitive performance of verbal fluency tasks were associated to the reduction of GM involving the medial temporal cortex to the right (p=0.041). Conclusion: The presence of cognitive impairment was observed in a small percentage of the general population when evaluated through the comparison of the performance in the group itself. The study of brain morphometry after the exclusion of subjects with silent lesion observed that the cognitive performance of the elderly people from the community presented direct relationship with the brain volume of the limbic regions, important for the cognition and memory

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

Objective: To review functional neuroimaging studies about the relationship between cardiovascular risk factors (CVRFs), Alzheimer's disease (AD), and mild cognitive impairment (MCI). Methods: We performed a comprehensive literature search to identify articles in the neuroimaging field addressing CVRF in AD and MCI. We included studies that used positron emission tomography (PET), single photon emission computerized tomography (SPECT), or functional magnetic resonance imaging (fMRI). Results: CVRFs have been considered risk factors for cognitive decline, MCI, and AD. Patterns of AD-like changes in brain function have been found in association with several CVRFs (both regarding individual risk factors and also composite CVRF measures). In vivo assessment of AD-related pathology with amyloid imaging techniques provided further evidence linking CVRFs and AD, but there is still limited information resulting from this new technology. Conclusion: There is a large body of evidence from functional neuroimaging studies supporting the hypothesis that CVRFs may play a causal role in the pathophysiology of AD. A major limitation of most studies is their cross-sectional design; future longitudinal studies using multiple imaging modalities are expected to better document changes in CVRF-related brain function patterns and provide a clearer picture of the complex relationship between aging, CVRFs, and AD

High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population

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 (São 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

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 "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 &lt; 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.CAPES (Brazil)CAPES-BrazilWellcome Trust, UK [GR066133MA]Wellcome Trust, UKFAPESP (Brazil)FAPESP, Brazil [2004/15336-5]CNPQ-BrazilCNPq (Brazil

Grey and white matter volumes either in treatment-naïve or hormone-treated transgender women: a voxel-based morphometry study

Abstract Many previous magnetic resonance imaging (MRI) studies have documented sex differences in brain morphology, but the patterns of sexual brain differences in transgender women – male sex assigned at birth – with a diagnosis of gender dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI data for the following four (n = 80) groups: treatment-naïve TW (TNTW), TW treated with cross-sex hormones for at least one year (TTW), cisgender men, and cisgender women (cisgender individuals as controls). Differences in whole-brain and regional white matter volume and grey matter volume (GMV) were assessed using voxel-based morphometry. We found lower global brain volumes and regional GMVs in a large portion of the posterior-superior frontal cortex in the cisgender women group than in the TTW and cisgender men groups. Additionally, both transgender groups exhibited lower bilateral insular GMVs than the cisgender women group. Our results highlight differences in the insula in both transgender groups; such differences may be characteristic of TW. Furthermore, these alterations in the insula could be related to the neural network of body perception and reflect the distress that accompanies gender dysphoria

Topography of 11C-Pittsburgh compound B uptake in Alzheimer’s disease: a voxel-based investigation of cortical and white matter regions

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer’s disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD