Neuroimaging in Alzheimer's disease: current role in clinical practice and potential future applications

Alzheimer's disease is the most common cause of dementia and its prevalence is expected to increase in the coming years. Therefore, accurate diagnosis is crucial for patients, clinicians and researchers. Neuroimaging techniques have provided invaluable information about Alzheimer's disease and, owing to recent advances, these methods will have an increasingly important role in research and clinical practice. The purpose of this article is to review recent neuroimaging studies of Alzheimer's disease that provide relevant information to clinical practice, including a new modality: in vivo amyloid imaging. Magnetic resonance imaging, single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography are currently available for clinical use. Patients with suspected Alzheimer's disease are commonly investigated with magnetic resonance imaging because it provides detailed images of brain structure and allows the identification of supportive features for the diagnosis. Neurofunctional techniques such as single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography can also be used to complement the diagnostic investigation in cases of uncertainty. Amyloid imaging is a non-invasive technique that uses positron emission tomography technology to investigate the accumulation of the β-amyloid peptide in the brain, which is a hallmark of Alzheimer's disease. This is a promising test but currently its use is restricted to very few specialized research centers in the world. Technological innovations will probably increase its availability and reliability, which are the necessary steps to achieve robust clinical applicability. Thus, in the future it is likely that amyloid imaging techniques will be used in the clinical evaluation of patients with Alzheimer's disease

Learning and memory and its relationship with the lateralization of epileptic focus in subjects with temporal lobe epilepsy

Background : In medial temporal lobe epilepsy (MTLE), previous studies addressing the hemispheric laterality of epileptogenic focus and its relationship with learning and memory processes have reported controversial findings. Objective : To compare the performance of MTLE patients according to the location of the epileptogenic focus on the left (MTLEL) or right temporal lobe (MTLER) on tasks of episodic learning and memory for verbal and visual content. Methods : One hundred patients with MTLEL and one hundred patients with MTLER were tested with the following tasks: the Rey Auditory Verbal Learning Test (RAVLT) and the Logical Memory-WMS-R to evaluate verbal learning and memory; and the Rey Visual Design Learning Test (RVDLT) and the Visual Reproduction-WMS-R to evaluate visual learning and memory. Results : The MTLEL sample showed significantly worse performance on the RAVLT (p < 0.005) and on the Logical Memory tests (p < 0.01) than MTLER subjects. However, there were no significant between-group differences in regard to the visual memory tests. Discussion : Our findings suggest that verbal learning and memory abilities are dependent on the structural and functional integrity of the left temporal lobe, while visual abilities are less dependent on the right temporal lobe.Contexto : Estudos anteriores abordando a lateralidade hemisférica de foco epiléptico na epilepsia do lobo temporal mesial (ELTM) e sua relação com os processos de aprendizagem e memória têm relatado resultados controversos. Objetivo : Comparar o desempenho de pacientes com ELTM de acordo com a localização do foco epiléptico à esquerda (ELTME) ou à direita (ELTMD) em tarefas de aprendizagem e memória episódica para conteúdo verbal e visual. Métodos: Cem pacientes com ELTME e cem pacientes com ELTMD foram avaliados com os seguintes testes: Teste de Aprendizagem Auditiva Verbal de Rey (RAVLT) e Memória Lógica – WMS-R para avaliar aprendizagem e memória verbal e o Teste de Aprendizagem Visual para Desenhos de Rey (RVDLT) e Reprodução Visual – WMS-R para avaliar a aprendizagem e memória visual. Resultados : A amostra com ELTME mostrou desempenho significativamente pior no RAVLT (p < 0,005) e na Memória Lógica (p < 0,01) em comparação aos indivíduos ELTMD. No entanto, não houve diferenças significativas entre os grupos no que diz respeito aos testes de aprendizagem e memória visual. Conclusão : Nossos resultados sugerem que a aprendizagem e a memória verbais são dependentes da integridade estrutural e funcional do lobo temporal esquerdo, enquanto as capacidades de aprendizagem e memória visual são menos dependentes do lobo temporal direito

Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system

PURPOSE: To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. METHODS: We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. RESULTS: There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (pOBJETIVO: Avaliar a viabilidade de emprego do programa Statistical Parametric Mapping (SPM) para investigar de forma automatizada, voxel-a-voxel, a presença de déficits de fluxo sanguíneo cerebral regional (FSCr) em pacientes com doença de Alzheimer (DA) comparados a sujeitos-controle pareados para idade, usando imagens de SPECT adquiridas com um equipamento convencional de detector único. MÉTODOS: Foi utilizado um banco de imagens adquiridas após injeção de 99mTc-HMPAO em 19 pacientes com diagnóstico provável de DA e 15 voluntários idosos saudáveis, usando um equipamento de SPECT Orbiter-Siemens de detector único. Empregando o programa SPM, as imagens foram transformadas espacialmente, suavizadas (12mm FWHM), e comparadas estatisticamente voxel-a-voxel entre os dois grupos, usando o teste de T. RESULTADOS: Foram identificadas reduções significativas de FSCr nos pacientes com DA comparados aos controles em regiões previstas a priori como afetadas por esta forma de demência, quais sejam os neocórtices temporal e parietal em hemisfério esquerdo e o cíngulo posterior direito (p<0,05, corrigido para comparações múltiplas). DISCUSSÃO: A localização dos focos de redução de FSCr em pacientes com DA no nosso estudo é, de forma geral, consistente com os achados de déficits cerebrais detectados em estudos anteriores de neuroimagem funcional na DA realizados com equipamentos de resolução espacial mais alta. Isto sugere o potencial de utilidade do programa SPM para a análise de dados de SPECT adquiridos com equipamentos de detector único, apesar da sensibilidade e resolução espacial limitadas de tais aparelhos

Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system

PURPOSE: To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. METHODS: We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. RESULTS: There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (pOBJETIVO: Avaliar a viabilidade de emprego do programa Statistical Parametric Mapping (SPM) para investigar de forma automatizada, voxel-a-voxel, a presença de déficits de fluxo sanguíneo cerebral regional (FSCr) em pacientes com doença de Alzheimer (DA) comparados a sujeitos-controle pareados para idade, usando imagens de SPECT adquiridas com um equipamento convencional de detector único. MÉTODOS: Foi utilizado um banco de imagens adquiridas após injeção de 99mTc-HMPAO em 19 pacientes com diagnóstico provável de DA e 15 voluntários idosos saudáveis, usando um equipamento de SPECT Orbiter-Siemens de detector único. Empregando o programa SPM, as imagens foram transformadas espacialmente, suavizadas (12mm FWHM), e comparadas estatisticamente voxel-a-voxel entre os dois grupos, usando o teste de T. RESULTADOS: Foram identificadas reduções significativas de FSCr nos pacientes com DA comparados aos controles em regiões previstas a priori como afetadas por esta forma de demência, quais sejam os neocórtices temporal e parietal em hemisfério esquerdo e o cíngulo posterior direito (

Neuroanatomical pattern classification in a population-based sample of first-episode schizophrenia

AbstractRecent neuroanatomical pattern classification studies have attempted to individually classify cases with psychotic disorders using morphometric MRI data in an automated fashion. However, this approach has not been tested in population-based samples, in which variable patterns of comorbidity and disease course are typically found. We aimed to evaluate the diagnostic accuracy (DA) of the above technique to discriminate between incident cases of first-episode schizophrenia identified in a circumscribed geographical region over a limited period of time, in comparison with next-door healthy controls. Sixty-two cases of first-episode schizophrenia or schizophreniform disorder and 62 age, gender and educationally-matched controls underwent 1.5T MRI scanning at baseline, and were naturalistically followed-up over 1year. T1-weighted images were used to train a high-dimensional multivariate classifier, and to generate both spatial maps of the discriminative morphological patterns between groups and ROC curves. The spatial map discriminating first-episode schizophrenia patients from healthy controls revealed a complex pattern of regional volumetric abnormalities in the former group, affecting fronto-temporal-occipital gray and white matter regions bilaterally, including the inferior fronto-occipital fasciculus, as well as the third and lateral ventricles. However, an overall modest DA (73.4%) was observed for the individual discrimination between first-episode schizophrenia patients and controls, and the classifier failed to predict 1-year prognosis (remitting versus non-remitting course) of first-episode schizophrenia (DA=58.3%). In conclusion, using a “real world” sample recruited with epidemiological methods, the application of a neuroanatomical pattern classifier afforded only modest DA to classify first-episode schizophrenia subjects and next-door healthy controls, and poor discriminative power to predict the 1-year prognosis of first-episode schizophrenia

Controle cognitivo associado à indução de irritabilidade: um estudo de RMf usando recordações autobiográficas

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.OBJETIVO: Apesar da relevância de emoções de irritabilidade para o tratamento, prognóstico e classificação dos transtornos psiquiátricos, as bases neurobiológicas deste tipo de estado emocional foram raramente investigadas até hoje. Este estudo avaliou os circuitos cerebrais subjacentes à irritabilidade induzida por scripts pessoais em voluntários saudáveis (n = 11) usando ressonância magnética funcional. MÉTODO: Mudanças no sinal dependente do nível de oxigenação sanguínea (blood-oxygen level dependent signal) foram registradas durante a apresentação por via auditiva de scripts pessoais de irritabilidade em contraste com scripts de felicidade ou de conteúdo emocional neutro. Escores em escalas de autoavaliação emocional e medidas de condutância da pele também foram obtidos. A aquisição de imagens foi realizada em aparelho de ressonância magnética de 1,5 T. Os mapas de ativação cerebral foram construídos a partir das imagens individuais, e as diferenças entre as condições experimentais foram investigadas utilizando testes não-paramétricos baseados em permutações. RESULTADOS: Em comparação com scripts neutros, a apresentação de scripts de irritabilidade levou a aumentos de sinal dependente do nível de oxigenação sanguínea na porção subgenual do giro do cíngulo anterior esquerdo e nas porções medial, ântero-lateral e póstero-lateral do córtex pré-frontal dorsal (cluster-wise p-valor < 0,05). Enquanto o envolvimento do cíngulo anterior subgenual e do córtex pré-frontal dorsal antero-lateral surgiu apenas em associação com o estado de irritabilidade, aumentos do sinal dependente do nível de oxigenação sanguínea nas porções dorso-medial e dorsal póstero-lateral do córtex pré-frontal também estiveram presentes durante indução de felicidade. CONCLUSÃO: Indução de irritabilidade está associada a mudanças de atividade funcional num conjunto restrito de regiões cerebrais previamente implicadas na mediação de estados emocionais. Mudanças na atividade de porções do giro do cíngulo e pré-frontais podem estar relacionadas a esforço de controle cognitivo associado à expressão de emoções de irritabilidade

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 (

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil.

OBJECTIVE: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. METHODS: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. RESULTS: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. CONCLUSION: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil.

OBJECTIVE: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. METHODS: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. RESULTS: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. CONCLUSION: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research