The human brain is often considered to be the most cognitively capable among mammalian brains and to be much larger than expected for a mammal of our body size. Although the number of neurons is generally assumed to be a determinant of computational power, and despite the widespread quotes that the human brain contains 100 billion neurons and ten times more glial cells, the absolute number of neurons and glial cells in the human brain remains unknown. Here we determine these numbers by using the isotropic fractionator and compare them with the expected values for a human-sized primate. We find that the adult male human brain contains on average 86.1 +/- 8.1 billion NeuN-positive cells ("neurons") and 84.6 +/- 9.8 billion NeuN-negative ("nonneuronal") cells. With only 19% of all neurons located in the cerebral cortex, greater cortical size (representing 82% of total brain mass) in humans compared with other primates does not reflect an increased relative number of cortical neurons. The ratios between glial cells and neurons in the human brain structures are similar to those found in other primates, and their numbers of cells match those expected for a primate of human proportions. These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that, with regard to numbers of neuronal and nonneuronal cells, the human brain is an isometrically scaled-up primate brain.

Introduction Alzheimer’s disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem’s locus coeruleus (LC) is the first area to develop neurofibrillary changes (NFT). Methods Unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages. Results As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC. Discussion The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible PET-scans and to monitor AD progression from pre-symptomatic stages.

The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

Objective: We conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia. Methods:In this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition.Results: Mean education was 3.9 6 3.5 years. The cognitive reserve theory is increasingly used to explain the clinicopathologic dissociation observed in Alzheimer disease (AD). 1 Approximately 30% of cognitively normal subjects have intermediate-to high-likelihood AD pathology at autopsy. [2][3][4][5][6][7] According to this theory, subjects with greater cognitive reserve require a more severe neuropathologic burden to reach the threshold for clinical dementia. 8 Previous clinicopathologic studies suggest that although education is not directly related to the development of neuropathologic lesions, it appears to reduce the impact of such lesions on the development of dementia, thereby increasing cognitive reserve. However, the studies supporting this hypothesis have investigated populations with relatively high levels of educational attainment, with mean formal education ranging from 9 to 18 years. [8][9][10][11][12] Little information is available regarding the effect of very few years of education on cognitive reserve. Low educational attainment is the reality for a high proportion of the elderly worldwide. According to a report from the United Nations Education, Scientific and Cultural Organization, nearly 800 million adults remained illiterate in 2009, representing about 16% of the global population. 13 Most of

RESUMOObjetivos: Identificar a prevalência de obesidade global e central através do índice de massa corpórea (IMC) e razão cintura-quadril (RCQ), e suas associações como o diabetes melito (DM), a hipertensão arterial (HA), a hipercolesterolemia, os baixos níveis de lipoproteína colesterol de alta densidade (HDL-c), a hipertrigliceridemia, nível social, a atividade física e o tabagismo em população de idosos atendida em ambulatórios. Metodologia: Foram avaliados 847 idosos ambulatoriais com 60 anos ou mais, através de um estudo transversal. Resultados: A obesidade definida pelo IMC≥ 30kg/m 2 foi identificada em 9,3% dos homens e 23,8% das mulheres (p< 0,001), sendo menor entre os idosos com 80 anos ou mais, em ambos os sexos (p< 0,05). Em homens obesos, identificou-se uma maior freqüência de DM, HDL-c baixo e hipertrigliceridemia, quando comparados aos homens com IMC< 30kg/m 2 . As mulheres obesas apresentavam uma freqüência maior apenas de HA. Os pacientes com RCQ≥ percentil 75 (RCQ> 1,01 para homens e RCQ> 0,96 para mulheres) apresentavam maiores freqüências de HA, DM, HDL-c baixo e hipertrigliceridemia no sexo masculino e HA e DM no sexo feminino. Conclusões: Os resultados revelam diferenças em relação ao sexo, com os homens apresentando menor prevalência de obesidade e maiores associações entre IMC ou RCQ com os fatores de riscos relacionados à gordura corpórea. Os dados obtidos por este estudo contribuem para ampliação do referencial antropométrico dos idosos, além de identificarem as correlações entre os indicadores antropométricos e as alterações metabólicas associadas à obesidade. ABSTRACTObjective: The goal was to define the prevalence of global and central obesity through the body mass index (BMI) and the waist-to-hip ratio (WHR). Besides, the associations between BMI and WHR were evaluated as the risk factors related to the excess of body fat and to the central pattern of distribution of fat, such as diabetes mellitus (DM), hypertension, hypercholesterolaemia, low levels of high density lipoprotein cholesterol (HDL-c), hypertriglyceridaemia, smoking, practice of physical activities, and social level. Methodology: Through a cross-sectional study, 847 outpatients 60 years old or more were evaluated. Results: Obesity was detected in 9.3% of the men and 23.8% of the women (p< 0.001), being lower among those of 80 years old or more (p< 0.05). In fat men, a higher frequency of DM, low HDL-c, and hypertriglyceridaemia were identified when compared to men with BMI< 30kg/m 2 . Fat women presented higher frequencies of hypertension only. Patients with WHR≥ percentile 75 (WHR> 1.01 for men and WHR> 0.96 for women) presented higher frequencies of hypertension, DM, low HDL-c, and hypertriglyceridaemia in the male and hypertension and DM in the female. Conclusions: The results reveal differences in relation to sex, with men presenting lower prevalence of obesity and higher associations between BMI or WHR, with risk factors related to the body fat. The data obtained contribute to the perspectivas Obesidade em Idosos...

Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation. We fit linear regressions with each count as outcomes, with Braak score and age as the predictors. In progressive Braak stages, intraneuronal active caspase-6 positivity increases both alone and overlapping with NFTs. Likewise, the proportion of NFT-bearing neurons showing autophagosomes increases. Overall, caspases may be involved in upstream cascades in AD and are associated with higher NFTs. Macroautophagy changes correlate with increasing NFT burden from early AD stages.

RESUMO -Objetivo:Investigar se a combinação de uma escala de avaliação funcional com um teste cognitivo poderia melhorar a precisão do diagnóstico de demência. Método: Foram avaliados 30 pacientes com diagnóstico de demência leve a moderada, segundo critérios da CID-10 e DSM-III-R e 46 controles idosos, divididos em grupos segundo seu nível socioeconômico e educacional (alto, médio e baixo). Nos sujeitos foi aplicado o MMSE, e em seus informantes as escalas IQCODE e B-ADL. Resultados: Pela regressão logística, o MMSE isolado classificou corretamente 86,8% dos pacientes e controles (sensibilidade 80% e especificidade 91,3%). A combinação MMSE + IQCODE classificou corretamente 92,1% dos sujeitos (sensibilidade 83,3% e especificidade de 97,8%), e a combinação MMSE + B-ADL classificou corretamente 92,1% dos sujeitos (sensibilidade 86,7% e especificidade 95,7%). Conclusão: Os resultados sugerem que a combinação de um teste cognitivo a escalas funcionais pode melhorar a detecção de casos leves ou moderados de demência, mesmo em amostras de população heterogênea com relação ao nível sócio-econômico e educacional como a brasileira.PALAVRAS-CHAVE: Demência, diagnóstico, teste cognitivo, escalas funcionais. Combined instruments on the evaluation of dementia in the elderly: preliminary results ABSTRACT -Objective:To determine if a functional scale combined with a cognitive test would improve the diagnostic accuracy of dementia. Method: Thirty patients with mild to moderate dementia, diagnosed according to ICD-10 and DSM-III-R criteria, and 46 elderly controls, divided into three groups according to their socioeconomic status and educational level (high, medium and low) were investigated. The subjects were assessed with the MMSE, and their informants were assessed with the scales IQCODE and B-ADL. Results: On the logistic regression, the MMSE isolated classified correctly 86.8% of patients and controls (80% sensitivity and 91.3% specificity). The combination MMSE + IQCODE classified correctly 92.1% of the subjects (83.3% sensitivity and 97.8% specificity), and the combination MMSE + B-ADL classified correctly 92.1% of subjects (86.7% sensitivity and 95.7% specificity). Conclusion: The results suggest that the combination of a cognitive test with a functional scale can improve the detection of mild to moderate cases of dementia even on samples of a very heterogeneous population regarding its socioeconomic status and educational level, as the Brazilian. Novas estratégias terapêuticas têm surgido no tratamento da síndrome demencial e em especial da doença de Alzheimer, retardando a progressão dessa doença e possibilitando melhora na qualidade de vida dos pacientes e seus familiares. Essas novas abordagens terapêuticas e a pesquisa de fatores de risco para demência, em estudos epidemiológicos, têm estimulado a busca de instrumentos de rastreio, que permitam identificar na prática clínica e na comunidade os casos leves dessa doença. Infelizmente, muitos dos testes neuropsicológicos usados são extensos, muito complicados, ou nece...

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas.