Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations – preliminary results

INTRODUCTION: The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimer's disease are still poorly understood. OBJECTIVE: To establish whether structural changes in grey matter volume in patients with mild Alzheimer's disease are associated with neuropsychiatric symptoms and disability METHODS: Nineteen Alzheimer's disease patients (9 females; total mean age =75.2 y old +4.7; total mean education level =8.5 y +4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation RESULTS: A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores CONCLUSIONS: The results suggest that the neuropsychiatric symptoms observed in Alzheimer's disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures

The thickness of posterior cortical areas is related to executive dysfunction in Alzheimer's disease

OBJECTIVE: To establish whether alterations of brain structures in Alzheimer's disease are associated with executive dysfunction. METHODS: Nineteen patients with Alzheimer's disease and 22 older control subjects underwent a comprehensive evaluation. The clock drawing test, digit span test, executive motor function test, Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test), and Stroop test were used to evaluate executive dysfunction. A multiparametric approach using the FreeSurfer image analysis suite provided a description of volumetric and geometric features of the gray matter structures. RESULTS: The cortical thickness maps showed a negative correlation between the Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test) and the right middle frontal gyrus; a positive correlation between the executive motor function test and the left superior parietal gyrus, left middle temporal gyrus, bilateral supramarginal gyri, right middle frontal gyrus, and right precuneus; a negative correlation between the Stroop test (part III) and the right superior parietal gyrus; and a negative correlation between the Stroop test (part III) and the right middle temporal gyrus. CONCLUSION: Executive dysfunction in Alzheimer's disease is correlated with alterations not only in the frontal areas but also within many temporal and parietal regions.Associacao Fundo de Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico ( CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Psychobiology DepartmentUniversidade Federal de São Paulo (UNIFESP) Laboratorio Interdisciplinar de Neurociencias Clinicas (LiNC) Psychiatry DepartmentFaculdade de Medicina da Universidade de São Paulo Hospital das Clinicas, Cognitive Neurology and Behavior GroupUNIFESP, Psychobiology DepartmentUNIFESP, Laboratorio Interdisciplinar de Neurociencias Clinicas (LiNC) Psychiatry Department2008/11282-9SciEL

The thickness of posterior cortical areas is related to executive dysfunction in Alzheimer's disease

OBJECTIVE: To establish whether alterations of brain structures in Alzheimer's disease are associated with executive dysfunction. METHODS: Nineteen patients with Alzheimer's disease and 22 older control subjects underwent a comprehensive evaluation. The clock drawing test, digit span test, executive motor function test, Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test), and Stroop test were used to evaluate executive dysfunction. A multiparametric approach using the FreeSurfer image analysis suite provided a description of volumetric and geometric features of the gray matter structures. RESULTS: The cortical thickness maps showed a negative correlation between the Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test) and the right middle frontal gyrus; a positive correlation between the executive motor function test and the left superior parietal gyrus, left middle temporal gyrus, bilateral supramarginal gyri, right middle frontal gyrus, and right precuneus; a negative correlation between the Stroop test (part III) and the right superior parietal gyrus; and a negative correlation between the Stroop test (part III) and the right middle temporal gyrus. CONCLUSION: Executive dysfunction in Alzheimer's disease is correlated with alterations not only in the frontal areas but also within many temporal and parietal regions

Thalamic alexia with agraphia

Alexia with agraphia is defined as an acquired impairment affecting reading and writing ability. It can be associated with aphasia, but can also occur as an isolated entity. This impairment has classically been associated with a left angular gyrus lesion In the present study, we describe a case involving a patient who developed alexia with agraphia and other cognitive deficits after a thalamic hemorrhage. In addition, we discuss potential mechanisms of this cortical dysfunction syndrome caused by subcortical injury. We examined a patient who presented with alexia with agraphia and other cognitive deficits due to a hemorrhage in the left thalamus. Neuropsychological evaluation showed attention, executive function, arithmetic and memory impairments. In addition, language tests revealed severe alexia with agraphia in the absence of aphasia. Imaging studies disclosed an old thalamic hemorrhage involving the anterior, dorsomedial and pulvinar nuclei. Tractography revealed asymmetric thalamocortical radiations in the parietal region (left <right), and single photon emission computed tomography demonstrated hypoperfusion in the left thalamus that extended to the frontal and parietal cortices. Cortical cognitive deficits, including alexia with agraphia, may occur as the result of thalamic lesions. The probable mechanism is a diaschisis phenomenon involving thalamic tract disconnections

The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks

Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

The 2022 symposium on dementia and brain aging in low‐ and middle‐income countries: Highlights on research, diagnosis, care, and impact

Two of every three persons living with dementia reside in low‐ and middle‐income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high‐income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC‐focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. Highlights: Two‐thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs

Development of the Brazilian Mini-Addenbrookes Cognitive Examination (MINI-ACE BR)

INTRODUÇÃO: A idade é o maior fator de risco para o desenvolvimento de demência e a recomendação é que os idosos sejam testados cognitivamente com o intuito de detectar comprometimento em fase inicial para o tratamento adequado. A demanda para o atendimento desses idosos é grande, chamando a atenção para a necessidade de testes rápidos, com boa acurácia e de simples aplicação para identificação de comprometimento cognitivo. OBJETIVO: Desenvolver a M-ACE versão brasileira através de dados da ACE-R como os subitens que poderiam predizer melhor o diagnóstico de comprometimento cognitivo. MÉTODOS: A M-ACE BR foi desenvolvida usando a análise da escala Mokken em 352 participantes (cognitivamente normais = 232, comprometimento cognitivo sem demência (CCSD) = 82 e demência = 38) e validada em uma amostra independente de 117 participantes (cognitivamente normais = 25, CCSD = 88 e demência = 4). RESULTADOS: A M-ACE BR possui nove itens (orientação espacial, memória anterógrada, memória retrógrada, evocação tardia, reconhecimento, fluência verbal letra P, repetição de quatro palavras, nomeação de 10 itens e compreensão/associação) com pontuação máxima de 51 pontos e duração média de sete minutos. A nota de corte < = 43/51 para CCSD apresentou sensibilidade de 59,09% e especificidade 80%. Para um teste de rastreio em que se prioriza a sensibilidade para investigação posterior mais detalhada, sugerimos o uso de corte de < = 47 (sensibilidade 85,23% e especificidade 24%) mantendo-se um bom valor preditivo positivo (79,8%). CONCLUSÕES: A M-ACE BR é um instrumento breve e adequado na detecção de comprometimento cognitivo em idosos brasileirosINTRODUCTION: Age is the most important risk factor for development of dementia and the recommendation is that the elderly be cognitively tested in order to detect impairment in the initial phase for adequate treatment. The demand for the care of these elderly people is great, drawing attention to the need for rapid tests, with good accuracy and simple application to identify cognitive impairment. OBJECTIVE: To develop the M-ACE Brazilian version using data from ACE-R deriving sub-items that could better predict the diagnosis of cognitive impairment. METHODS: The M-ACE BR was developed using Mokken scaling analysis in 352 participants (cognitively normal = 232, cognitive impairment no dementia (CIND) = 82 and dementia = 38) and validated in an independent sample of 117 participants (cognitively normal = 25, CIND = 88 and dementia = 4). RESULTS: The M-ACE BR has nine items (spatial orientation, anterograde memory, retrograde memory, delayed recall, recognition, verbal fluency letter P, repetition of four words, naming 10 items and comprehension) with a maximum score of 51 points and average duration time of seven minutes. The cutoff score < = 43/51 for CCSD had a sensitivity of 59.09% and a specificity of 80%. For a screening test in which sensitivity is prioritized for further investigation, we suggest using a cutoff of < = 47 (sensitivity 85.23% and specificity 24%), maintaining a good positive predictive value (79.8%). CONCLUSIONS: The M-ACE BR is a brief and adequate instrument for detecting cognitive impairment in elderly Brazilian

The S-TOFHLA in mild Alzheimer\'s disease and mild cognitive impairment patients as a measure of functional literacy

INTRODUÇÃO: O maior desafio no diagnóstico de perdas cognitivas na nossa população é sua heterogeneidade educacional, com um espectro que vai do analfabetismo, analfabetismo funcional até os escolarizados com diferentes graus de alfabetização mesmo com o mesmo grau de escolarização. OBJETIVOS: Comparar os resultados obtidos no S-TOFHLA entre indivíduos controles, pacientes com comprometimento cognitivo leve (CCL) e pacientes com doença de Alzheimer (DA) e correlacioná-los aos anos de escolarização formal, aos testes de Avaliação Neuropsicológica e aos escores alcançados no teste Matrizes Progressivas Coloridas de Raven e nos subtestes Vocabulário e Cubos do WAIS-III como medida de nível intelectual estimado. MÉTODOS: A amostra foi composta por 148 sujeitos, sendo 61 controles saudáveis, 42 pacientes com CCL e 45 com DA. Todos os participantes foram submetidos a avaliação neuropsicológica, S-TOFHLA e avaliação funcional. RESULTADOS: Na avaliação observou-se que nos testes: Cubos, Raven e QI Estimado foram encontradas diferenças estatísticas entre os grupos controle e CCL; controle e DA, mas não entre os grupos CCL e DA. No S-TOFHLA, observou-se diferença estatisticamente significante no item de Compreensão e Leitura e no escore total nos três grupos (controle, CCL e DA). No item Numérico, a diferença estatística ocorreu somente entre os grupos controle e DA. O S-TOFHLA correlacionou-se fortemente o QI estimado. CONCLUSÕES: O S-TOFHLA sofre influência da progressão da doença apresentando diferença entre os grupos estudados. As alterações em inteligência fluida ocorrem desde início da doença. O subteste Vocabulário permaneceu com resultados semelhantes durante os graus de comprometimento cognitivo, mostrando que memória semântica e inteligência cristalizada são preservadas.INTRODUCTION: The greatest challenge in the diagnosis of cognitive loss in our population is its educational heterogeneity, with a spectrum ranging from illiteracy, functional illiteracy and various degrees of literacy even with the same level of schooling. OBJECTIVES: To compare the results obtained in the S-TOFHLA among control subjects, patients with mild cognitive impairment (MCI) and patients with Alzheimer\'s disease (AD) and correlate those scores with years of formal schooling, Neuropsychological Assessment, and the scores achieved on Raven\'s Colored Progressive Matrices and Vocabulary and Block Design subtests of the WAIS-III as a measure of estimated intellectual level. METHODS: The sample consisted of 148 subjects, of which 61 were healthy controls, 42 had MCI and 45 had AD. All participants underwent neuropsychological assessment, S-TOFHLA and functional evaluation. RESULTS: In the neuropsychological evaluation it was observed that in the tests Block Design, Raven and IQ Estimate statistical differences were found between MCI and control groups, control and AD, but not between the MCI and AD groups. In the S-TOFHLA, there was a statistically significant difference in reading comprehension and in the total score in all three groups (control, MCI and AD). In the Numeric item, the only statistical difference occurred between control and AD. The S-TOFHLA strongly correlated with the estimated IQ. CONCLUSIONS: The S-TOFHLA is influenced by disease progression showing significant difference between groups. The changes in fluid intelligence occur since the onset of disease. The Vocabulary subtest remained with similar results in different degrees of cognitive impairment, showing that semantic memory and crystallized intelligence are preserved