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BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.
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Autopsia , Causas de Morte , Transtorno Depressivo Maior , Aprendizado de Máquina , Humanos , Transtorno Depressivo Maior/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos de Casos e Controles , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: To investigate epigenetic mechanisms potentially involved in the cognitive decline associated with chronic alcohol intake, we evaluated the expressions of three micro-RNAs (miR-34a, -34b, and -34c) highly expressed in the hippocampus and involved in neuronal physiology and pathology. MiR-34a participates in functioning and survival of mature neurons; miR-34b is associated with Alzheimer-like disorders; and miR-34c is implicated in the memory impairment of Alzheimer disease in rodents and humans. METHODS: A total of 69 cases were selected from the Biobank for Aging Studies and categorized according to the absence (n = 50) or presence (n = 19) of alcohol use disorder (AUD). Cases presenting with neuropathological diagnoses of dementias were excluded. Total RNA was extracted from hippocampal paraffinized slices, complementary DNA was synthesized from miRs, and RT-qPCR was performed with TaqMan® assays. RESULTS: Higher expressions of miR-34a and miR-34c, but not of miR-34b, were found in the group with AUD in comparison with the group without AUD after adjustment for potential confounders (age, sex, body mass index, presence of hypertension, diabetes mellitus, smoking, and physical inactivity). CONCLUSIONS: Hippocampal upregulation of miR-34a and miR-34c may be involved in the cognitive decline associated with chronic alcohol consumption.
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Alcoolismo/metabolismo , Disfunção Cognitiva/induzido quimicamente , Hipocampo/metabolismo , MicroRNAs/metabolismo , Idoso , Depressores do Sistema Nervoso Central/efeitos adversos , Disfunção Cognitiva/metabolismo , Epigênese Genética , Etanol/efeitos adversos , Feminino , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Cigarette smoking is a key factor in systemic inflammation and oxidative stress, and it has also been associated with the loss of muscle strength and an elevated risk of pulmonary diseases. Thus, this study aimed to analyze the effects of cigarette smoking on the diaphragm muscle structure of postmortem samples. METHODS: Immunohistochemical techniques were used for muscle remodeling (metalloproteinases 2 and 9), inflammation (cyclooxygenase-2), oxidative stress (8-hydroxy-2'-deoxyguanosine), and vascularization (vascular endothelial growth factor). Hematoxylin and eosin stain was used for histopathological analysis and Picrosirius stain was used to highlight the collagen fibers. RESULTS: Cigarette smokers had an increase of diaphragm muscle remodeling, oxidative stress, inflammation, and vascularization compared to non-smokers. CONCLUSION: Diaphragm muscle structure may be negatively affected by cigarette smoking.
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Fumar Cigarros/efeitos adversos , Diafragma/metabolismo , Diafragma/patologia , Inflamação/patologia , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Autopsia , Estudos Transversais , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Fumantes , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis. The intensity and distribution of these histopathological findings over the Cornu Ammonis (CA) subfields are important for the classification of HS and prognostication of patients with temporal lobe epilepsy (TLE). Several studies have associated the neuronal density reduction in the hippocampus with cognitive decline in patients with TLE. The current study aimed at investigating whether the expression of glial proteins in sclerotic hippocampi is associated with presurgical memory performance of patients with TLE. Before amygdalohippocampectomy, patients were submitted to memory tests. Immunohistochemical and morphometric analyses with glial fibrillary acidic protein (GFAP) for astrogliosis and human leucocyte antigen DR (HLA-DR) for microgliosis were performed in paraffin-embedded HS and control hippocampi. Sclerotic hippocampi exhibited increased gliosis in comparison with controls. In patients with TLE, the area and intensity of staining for HLA-DR were associated with worse performance in the memory tests. Glial fibrillary acidic protein was neither associated nor correlated with memory test performance. Our data suggest association between microgliosis, but not astrogliosis, with visual memory decline in patients with TLE.
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Epilepsia do Lobo Temporal/psicologia , Gliose/psicologia , Hipocampo/patologia , Transtornos da Memória/psicologia , Adulto , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/cirurgia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/complicações , Antígenos HLA-DR , Hipocampo/cirurgia , Humanos , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Procedimentos Neurocirúrgicos , Esclerose , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVE: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. METHODS: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. RESULTS: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (ß = -0.86, 95% CI = -26.50 to 24.77, p = 0.95). CONCLUSIONS: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd.
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Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Idoso , Envelhecimento/patologia , Atrofia/patologia , Autopsia , Estudos Transversais , Diabetes Mellitus/patologia , Escolaridade , Feminino , Humanos , Hipertensão/patologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tamanho do Órgão , Fatores de RiscoRESUMO
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 (neurofibrillary tangles [NFTs]). METHODS: The methods include 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 positron emission tomography scans and to monitor AD progression from presymptomatic stages.
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Doença de Alzheimer/patologia , Biomarcadores/metabolismo , Locus Cerúleo/patologia , Neurônios/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas EstereotáxicasAssuntos
Transtorno Bipolar , Biomarcadores , Encéfalo , Giro do Cíngulo , Hipocampo , Humanos , Córtex Pré-FrontalRESUMO
OBJECTIVE: To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD: A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS: Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION: Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.
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Atividades Cotidianas , Doenças do Sistema Nervoso , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Doenças do Sistema Nervoso/diagnóstico , Reprodutibilidade dos TestesRESUMO
Background: The association of moderate and severe dementia with low body mass index (BMI) is well described, but weight decline seems to also occur in individuals with preclinical neuropathologies. Considering that up to one-fifth of individuals with normal cognition meet the criteria for a dementia-related neuropathological diagnosis, autopsy studies are key to detecting preclinical neurodegenerative and cerebrovascular diseases that could be underlying weight changes. Objective: We investigated the association between dementia-related brain lesions and BMI and evaluated whether the cognitive function was a mediator of this association. Methods: In 1,170 participants, sociodemographic data, clinical history, and cognitive post-mortem evaluation were assessed with an informant. Neuropathological evaluation was performed in all cases. Linear regression models were used to investigate the association between neuropathological lesions (exposure variable) and BMI (outcome) adjusted for demographic, clinical, and cognitive variables in the whole sample, and in only those with normal cognition. Corrections for multiple comparisons were performed. In addition, a mediation analysis was performed to investigate the direct and indirect effects of cognitive abilities on the association between neuropathology and BMI. Results: Individuals with lower BMI had a higher burden of neuropathological lesions and poorer cognitive abilities. Only neurofibrillary tangles (NFT) and neuropathological comorbidity were associated with low BMI, while other neurodegenerative and cerebrovascular lesions were not. NFT were indirectly associated with BMI through cognitive abilities, and also directly, even in participants with normal cognition. Conclusions: Neurofibrillary tangles were directly associated with low BMI even in individuals with preclinical Alzheimer's disease.
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BACKGROUND: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. METHODS: Subjects were divided into three groups: never-smoker (n = 46); less than 30 pack-years of smoking (n = 12); and more than 30 pack-years of smoking (n = 30). Diaphragm samples were stained with Picrosirius red and hematoxylin and eosin stain for general structure. RESULTS: Participants with more than 30 pack-years of cigarette smoking had a significant increase in adipocytes, blood vessels and collagen deposit, as well as an increase in histopathological alterations. CONCLUSIONS: Pack-years of smoking was associated with DIAm injury. However, further clinicopathological studies are needed to confirm our findings.
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BACKGROUND: Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. OBJECTIVE: Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias in an autopsy study. METHODS: Coronary arteries were collected, and the largest luminal stenosis was measured. Sociodemographic, clinical, and cognitive information were reported by a reliable next-of-kin. The association was tested using logistic and linear regressions adjusted for sociodemographic and clinical variables. We restricted the sample to individuals that were born in 1935 or earlier and stratified the analysis by cause of death to investigate the role of selection bias. RESULTS: In 253 participants (mean ageâ=â78.0±8.5 years old, 48% male), stenosis was not associated with cognitive impairment (ORâ=â0.85, 95% CIâ=â0.69; 1.06, pâ=â0.15). In individuals who were born before 1936 in the absence of cardiovascular disease as the cause of death, greater stenosis was associated with cognitive impairment (ORâ=â4.02, 95% CIâ=â1.39; 11.6, pâ=â0.01). On the other hand, this association was not present among those born in 1935 or earlier who died of cardiovascular diseases (ORâ=â0.83, 95% CIâ=â0.60; 1.16, pâ=â0.28). CONCLUSION: We found that higher coronary stenosis was associated with cognitive impairment only in individuals born in 1935 or earlier and who had not died from cardiovascular diseases. Selection bias may be an important issue when investigating risk factors for chronic degenerative diseases in older individuals using autopsy samples.
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Aterosclerose , Doenças Cardiovasculares , Disfunção Cognitiva , Doença da Artéria Coronariana , Humanos , Masculino , Idoso de 80 Anos ou mais , Idoso , Feminino , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Doenças Cardiovasculares/complicações , Viés de Seleção , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações , Aterosclerose/complicaçõesRESUMO
Background Inflammation of the perivascular adipose tissue (PvAT) may be related to atherosclerosis; however, the association of polarized macrophages in the pericoronary PvAT with measurements of atherosclerosis components in humans has not been fully investigated. Methods and Results Coronary arteries were dissected with surrounding PvAT. We evaluated the percentage of arterial obstruction, intima-media thickness, fibrous cap thickness, plaque components, and the number of vasa vasorum. The number of proinflammatory (M1) and anti-inflammatory (M2) macrophages in the periplaque and control PvAT were evaluated using immunohistochemistry. Regression models adjusted for sociodemographic and clinical variables were used. In 319 segments from 82 individuals, we found a correlation of the M1/M2 macrophage density ratio with an increase in arterial obstruction (P=0.02) and lipid content (P=0.01), and a decrease in smooth muscle cells (P=0.02). M1 and the ratio of M1/M2 macrophages were associated with an increased risk of thrombosis (P=0.03). In plaques with thrombosis, M1 macrophages were correlated with a decrease in fibrous cap thickness (P=0.006), an increase in lipid content (P=0.008), and the number of vasa vasorum in the adventitia layer (P=0.001). M2 macrophages were correlated with increased arterial obstruction (P=0.01), calcification (P=0.02), necrosis (P=0.03) only in plaques without thrombosis, and decrease of the number of vasa vasorum in plaques with thrombosis (P=0.003). Conclusions M1 macrophages in the periplaque PvAT were associated with a higher risk of coronary thrombosis and were correlated with histological components of plaque progression and destabilization. M2 macrophages were correlated with plaque size, calcification, necrotic content, and a decrease in the number of vasa vasorum in the adventitia layer.
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Aterosclerose , Calcinose , Doença da Artéria Coronariana , Placa Aterosclerótica , Trombose , Tecido Adiposo/patologia , Aterosclerose/patologia , Calcinose/patologia , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Humanos , Lipídeos , Macrófagos/patologia , Placa Aterosclerótica/patologia , Trombose/patologiaRESUMO
OBJECTIVE: To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. METHODS: In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables. RESULTS: In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3). CONCLUSION: Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.
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Microcefalia , Adulto , Idoso , Encéfalo , Brasil/epidemiologia , Cefalometria , Cabeça/anatomia & histologia , Humanos , Masculino , Microcefalia/complicações , Microcefalia/diagnóstico , Microcefalia/epidemiologiaRESUMO
Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination. Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables. Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5-24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: ß = -1.92, 95% CI = -3.77 to -0.06, p = 0.042; severe: ß = -2.91, 95% CI = -3.97 to -1.86, p < 0.001). Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages.
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Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue. OBJECTIVE: We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules - MAP2) changes in postmortem brain samples of individuals with Lewy body pathology. METHODS: Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Aging Studies were classified into active (n=12) and non-active (n=12) groups, according to physical activity lifestyle, and paired by age, sex and Braak staging. Substantia nigra and basal ganglia were evaluated. RESULTS: Groups were not different in terms of age or gender and had similar PD neuropathological burden (p=1.00). We observed higher TH expression in the active group in the substantia nigra and the basal ganglia (p=0.04). Astrocytes was greater in the non-active subjects in the midbrain (p=0.03) and basal ganglia (p=0.0004). MAP2 levels were higher for non-active participants in the basal ganglia (p=0.003) and similar between groups in the substantia nigra (p=0.46). Neurofilament levels for non-active participants were higher in the substantia nigra (p=0.006) but not in the basal ganglia (p=0.24). CONCLUSION: Active lifestyle seems to promote positive effects on brain by maintaining dopamine synthesis and structural protein expression in the nigrostriatal system and decrease astrogliosis in subjects with the same PD neuropathology burden.
Estudos dos efeitos da atividade física relataram melhora nos sintomas e na qualidade de vida de pacientes com doença de Parkinson (DP). Além disso, alterações morfológicas do cérebro após o exercício físico foram relatadas em modelos animais da DP. No entanto, essas mudanças relacionadas ao estilo de vida não foram avaliadas em tecido cerebral post-mortem. OBJETIVO: Avaliar a expressão de astrócitos, tirosina hidroxilase (TH) e a expressão de proteínas estruturais (neurofilamentos e microtúbulos MAP2) por imuno-histoquímica, em amostras cerebrais post-mortem de indivíduos com corpos de Lewy. MÉTODOS: Amostras com estágio de Braak para DP≥III, classificação neuropatológica, fornecidas pelo biobanco de estudos do envelhecimento foram classificadas em grupos ativos (n=12) e não ativos (n=12), de acordo com o estilo de vida (atividade física), e pareados por idade, sexo e estadiamento de Braak. Analisou-se a substância negra e gânglios da base. RESULTADOS: Idade, sexo e classificação para DP foram semelhantes (p=1,00). Observou-se maior expressão de TH no grupo ativo (p=0,04). Amostras de não ativos revelaram maior expressão de astrócitos no mesencéfalo (p=0,03) e nos gânglios da base (p=0,0004); MAP2 nos gânglios da base (p=0,003); os níveis de neurofilamentos foram maiores na substância negra (p=0,006). CONCLUSÃO: O estilo de vida ativo parece promover efeitos positivos no cérebro, mantendo a síntese de dopamina e a expressão estrutural de proteínas no sistema nigrostriatal e com diminuição da ativação de astrócitos em indivíduos com a mesma classificação neuropatológica para a DP.
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Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus-brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively-from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience.
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Doença de Alzheimer/metabolismo , Córtex Entorrinal/metabolismo , Lobo Frontal/metabolismo , Neurônios/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Astrócitos/patologia , Córtex Entorrinal/patologia , Feminino , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Neurônios/patologia , Proteínas tau/metabolismoRESUMO
BACKGROUND: Depression has been associated with dementia. This study aimed to verify if ß-amyloid Alzheimer's disease-type burden was associated with lifetime major depressive disorder (MDD) and with current depressive symptoms in a large population-based autopsy study. METHODS: We included 1013 deceased subjects submitted to autopsy (mean age=74.3±11.6 years, 49% men) in a community sample. ß-amyloid burden was measured in all cases based on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for presence and density of neuritic plaques. Lifetime MDD was defined when at least one previous episode according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - DSM (SCID). Depressive symptoms and cognitive impairment were determined using the depression item of the Neuropsychiatric Inventory (D-NPI>0) and the Clinical Dementia Rating scale (CDR>0.5) respectively. RESULTS: Lifetime MDD, late life depression (LLD) and current depressive symptoms were associated with cognitive impairment (p<0.001). Additionally, neuritic plaques were associated with cognitive impairment (p<0.001). Moderate or frequent neurite plaque density was not associated with MDD, LLD or current depressive symptoms in multiple logistic models adjusted for age, gender, and cognitive impairment. LIMITATIONS: In this cross-sectional study, all neuropsychiatric and cognitive assessment were based on informant-report of deceased participants. CONCLUSIONS: Different clinical depictions of depression were associated with dementia in this large community sample of elderly individuals with multiethnic backgrounds. Notwithstanding, they were unrelated to ß-amyloid pathology in the brain areas studied. The link between depression and dementia might be complex and determined by multiple factors.
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Doença de Alzheimer , Transtorno Depressivo Maior , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides , Autopsia , Estudos Transversais , Depressão , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To analyze hypertension and its relationship with the causes of death identified by the autopsy. METHOD: Cross-sectional study analyzed 356 participants belonging to the Brazilian Aging Brain Study Group, over 50 years of age, autopsied at the Sao Paulo Autopsy Service between 2004 to 2014. A clinical interview was conducted with the informant of the deceased. Hypertension was defined by reporting the disease and/or use of antihypertensive medication, by the informant of the deceased. Descriptive analyzes and bivariate and multivariable associations were performed. RESULTS: The prevalence of hypertension was 66.2% and it was the second leading cause of death (25.6%) identified by autopsy, preceded by atherosclerosis (37.8%). The variables associated with hypertension were: female gender (OR=2.30 (1.34-3.90)); living with partner [OR=0.55 (0.32-0.92)]; Body Mass Index [OR=1.14 (1.08-1.22)] and history of diabetes [OR=2.39 (1.34-4.27)]. CONCLUSION: The prevalence of hypertension was high, and it was the second most common underlying cause of death. The gold standard for the definition of cause of death, the autopsy, shows important results, which confirmed the relevance of hypertension as a public health problem.
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Aterosclerose/epidemiologia , Causas de Morte , Hipertensão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Autopsia , Brasil/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Background Macrophages and T lymphocytes in the perivascular adipose tissue (PvAT) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human PvAT adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether PvAT inflammation was restricted to the surroundings of the atheroma plaque. Methods and Results Coronary arteries were freshly dissected with the surrounding PvAT. Atherosclerotic plaques were classified according to the internationally accepted anatomopathological criteria. Immune cells in the PvAT were detected using immunohistochemistry and then quantified. We used linear and logistic regressions with robust standard errors, adjusted for possible confounding factors. In 246 atherosclerotic plaques (205 stable and 41 unstable plaques) from 82 participants (mean age=69.0±14.4 years; 50% men), the percentage of arterial obstruction was positively correlated with the densities of CD68+ macrophages (P=0.003) and CD20+ B lymphocytes (P=0.03) in the periplaque PvAT. The number of cells was greater in the periplaque PvAT than in the distal PvAT (macrophages, P<0.001; B lymphocytes, P=0.04). In addition, the density of macrophages in the periplaque PvAT was greater in the presence of unstable plaques (P=0.03) and was also greater near unstable plaques than in the distal PvAT (P=0.001). CD3+ T lymphocytes were not associated with percentage of obstruction and stable/unstable plaque composition. Conclusions The density of CD20+ B lymphocytes and CD68+ macrophages in periplaque PvAT was increased with plaque size, and the CD68+ macrophages were greater near unstable atherosclerotic plaques than near stable lesions. This inflammation was more intense in the periplaque PvAT than in the PvAT distal to the atherosclerotic plaques.
Assuntos
Tecido Adiposo/patologia , Linfócitos B , Doença da Artéria Coronariana/patologia , Macrófagos , Placa Aterosclerótica/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Behavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation. OBJECTIVE: To compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia from those without dementia. METHODS: We included 1,565 participants (mean ageâ=â72.7±12.2 years, 48% male). BPSD and cognitive status were assessed with the NPI and the Clinical Dementia Rating (CDR). We used multivariable logistic regression models to investigate the association of BPSD with cognitive status. The area under the curve (AUC) was used to assess model discrimination, and to determine the best NPI cutoff for MCI and dementia. RESULTS: Participants were cognitively normal (CDRâ=â0; nâ=â1,062), MCI (CDRâ=â0.5; nâ=â145), or dementia (CDR≥1.0, nâ=â358). NPI symptoms were more frequent in dementia and MCI when compared to cognitively normal. Higher odds for delusions, hallucinations, disinhibition, and psychomotor alterations were found among participants with dementia and MCI than in those who were cognitively normal. The best NPI cutoff to discern participants with dementia from those cognitively normal was 11 (AUCâ=â0.755). Poor discrimination (AUCâ=â0.563) was found for the comparison of MCI and those cognitively normal. CONCLUSIONS: We found an increase in BPSD frequencies across the continuum of cognitive impairment. BPSD severity and frequency in MCI was more similar to individuals cognitively normal than with dementia. NPI scores≥to 11 in individuals with no diagnosis of dementia can support the decision for further investigation of dementia.