RESUMO

BACKGROUND: Age is the most important risk factor for develop dementia, and the recommendation is that older adults are cognitively tested to detect impairment in the initial stage for adequate treatment. The demand for the care of these older adults is great, drawing attention to the need for rapid tests, with good accuracy and simple application to identify cognitive impairment. OBJECTIVE: To develop and validate the Brazilian Mini-Addenbrooke Cognitive Examination (M-ACE BR) as a short screening test for cognitive impairment in older adults. METHODS: The M-ACE BR was developed using the Mokken scaling analysis in 352 participants (cognitively unimpaired [CU] = 232, cognitive impairment no dementia [CIND] = 82; and dementia = 38) and validated in an independent sample of 117 participants (CU = 25; CIND = 88; and dementia = 4). RESULTS: The Mokken scaling analysis derived 9 items (spatial orientation, anterograde memory, retrograde memory, delayed recall, recognition [name and address], letter verbal fluency, repetition of 4 words, naming of 10 items, and comprehension) with a maximum score of 51 points and an average duration time of 7 minutes. The cut-off score ≤ 43/51 for CIND 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%). CONCLUSION: The M-ACE BR is a brief and adequate instrument to detect cognitive impairment in older Brazilian adults. However, screening for CIND and for different educational levels should be further explored.

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ANTECEDENTES: A idade é o fator de risco mais importante para o desenvolvimento de demência, e a recomendação é que os idosos sejam testados cognitivamente para detectar comprometimento na fase inicial para o tratamento adequado. A demanda pelo atendimento desses idosos é grande, chamando atenção para a necessidade de testes rápidos, com boa acurácia e de simples aplicação para identificar o comprometimento cognitivo. OBJETIVO: Desenvolver e validar a versão brasileira do Mini-Addenbrooke's Cognitive Examination (M-ACE BR) como um teste rápido para rastreio de comprometimento cognitivo em idosos. MéTODOS: A M-ACE BR foi desenvolvida usando análise da escala de Mokken em 352 participantes (cognitivamente saudáveis [CS] = 232, comprometimento cognitivo sem demência [CCSD] = 82; e demência = 38) e validado em uma amostra independente de 117 participantes (CS = 25; CCSD = 88; e demência = 4). RESULTADOS: A análise de escala de Mokken derivou 9 itens (orientação espacial, memória anterógrada, memória retrógrada, evocação tardia, reconhecimento [nome e endereço], fluência verbal de letras, repetição de 4 palavras, nomeação de 10 itens e compreensão) com pontuação máxima de 51 pontos e tempo médio de duração de 7 minutos. O escore de corte ≤ 43/51 para CCSD teve sensibilidade de 59,09% e especificidade de 80%. Para um teste de rastreio, em que a sensibilidade é priorizada para investigação posterior, sugerimos utilizar um ponto de corte ≤ 47 (sensibilidade 85,23% e especificidade 24%), mantendo um bom valor preditivo positivo (79,8%). CONCLUSãO: A M-ACE BR é um instrumento breve e adequado para detectar comprometimento cognitivo em idosos brasileiros. No entanto, o rastreio para a identificação de CCSD e para diferentes níveis de escolaridade deve ser melhor explorado.

Assuntos

Disfunção Cognitiva , Sensibilidade e Especificidade , Humanos , Idoso , Brasil , Feminino , Masculino , Disfunção Cognitiva/diagnóstico , Reprodutibilidade dos Testes , Idoso de 80 Anos ou mais , Testes de Estado Mental e Demência , Demência/diagnóstico , Testes Neuropsicológicos/normas , Pessoa de Meia-Idade , Traduções , Programas de Rastreamento/métodos

RESUMO

Importance: Race differences in dementia prevalence and incidence have previously been reported, with higher dementia burden in Black decedents. However, previous neuropathological studies were conducted mostly in convenience samples with White participants; conducting clinicopathological studies across populations is crucial for understanding the underlying dementia causes in individuals from different racial backgrounds. Objective: To compare the frequencies of neuropathological lesions and cognitive abilities between Black and White Brazilian adults in an autopsy study. Design, Setting, and Participants: This cross-sectional study used samples from the Biobank for Aging Studies, a population-based autopsy study conducted in Sao Paulo, Brazil. Participants were older adults whose family members consented to the brain donations; Asian participants and those with missing data were excluded. Samples were collected from 2004 to 2023. Neuropathologists were masked to cognitive outcomes. Exposure: Race as reported by the deceased's family member. Main Outcomes and Measures: The frequencies of neurodegenerative and cerebrovascular lesions were evaluated in 13 selected cerebral areas. Cognitive and functional abilities were examined with the Clinical Dementia Rating Scale. Results: The mean (SD) age of the 1815 participants was 74.0 (12.5) years, 903 (50%) were women, 617 (34%) were Black, and 637 (35%) had cognitive impairment. Small vessel disease (SVD) and siderocalcinosis were more frequent in Black compared with White participants (SVD: odds ratio [OR], 1.74; 95% CI, 1.29-2.35; P < .001; siderocalcinosis: OR, 1.70; 95% CI, 1.23-2.34; P = .001), while neuritic plaques were more frequent in White compared with Black participants (OR, 0.61; 95% CI, 0.44-0.83; P = .002). Likewise, Alzheimer disease neuropathological diagnosis was more frequent in White participants than Black participants (198 [39%] vs 77 [33%]), while vascular dementia was more common among Black participants than White participants (76 [32%] vs 121 [24%]). Race was not associated with cognitive abilities, nor did it modify the association between neuropathology and cognition. Conclusions and Relevance: In this cross-sectional study of Brazilian older adults, Alzheimer disease pathology was more frequent in White participants while vascular pathology was more frequent in Black participants. Further neuropathological studies in diverse samples are needed to understand race disparities in dementia burden.

Assuntos

População Branca , Humanos , Brasil/epidemiologia , Feminino , Masculino , Idoso , Estudos Transversais , População Branca/estatística & dados numéricos , População Branca/psicologia , Idoso de 80 Anos ou mais , Cognição , Demência/epidemiologia , Demência/etnologia , Encéfalo/patologia , Autopsia , População Negra/estatística & dados numéricos , População Negra/psicologia

RESUMO

Background: The Addenbrooke's Cognitive Examination-Revised (ACE-R) is an accessible cognitive tool that supports the early detection of mild cognitive impairment (MCI), Alzheimer's disease (AD), and behavioral variant frontotemporal dementia (bvFTD). Objective: To investigate the diagnostic efficacy of the ACE-R in MCI, AD, and bvFTD through the identification of novel coefficients for differentiation between these diseases. Methods: We assessed 387 individuals: 102 mild AD, 37 mild bvFTD, 87 with amnestic MCI patients, and 161 cognitively unimpaired controls. The Mokken scaling technique facilitated the extraction out of the 26 ACE-R items that exhibited a common latent trait, thereby generating the Mokken scales for the AD group and the MCI group. Subsequently, we performed logistic regression, integrating each Mokken scales with sociodemographic factors, to differentiate between AD and bvFTD, as well as between AD or MCI and control groups. Ultimately, the Receiver Operating Characteristic curve analysis was employed to assess the efficacy of the coefficient's discrimination. Results: The AD-specific Mokken scale (AD-MokACE-R) versus bvFTD exhibited an Area Under the Curve (AUC) of 0.922 (88% sensitivity and specificity). The AD-MokACE-R versus controls achieved an AUC of 0.968 (93% sensitivity, 94% specificity). The MCI-specific scale (MCI-MokACE-R) versus controls demonstrated an AUC of 0.859 (78% sensitivity, 79% specificity). Conclusions: The ACE-R's capacity is enhanced through statistical methods and demographic integration, allowing for accurate differentiation between AD and bvFTD, as well as between MCI and controls. This new method not only reinforces its clinical value in early diagnosis but also surpasses traditional approaches noted in prior studies.

Assuntos

Doença de Alzheimer , Disfunção Cognitiva , Demência Frontotemporal , Testes Neuropsicológicos , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Feminino , Masculino , Disfunção Cognitiva/diagnóstico , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/psicologia , Idoso , Testes Neuropsicológicos/estatística & dados numéricos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Sensibilidade e Especificidade

RESUMO

The second part of this review is an attempt to explain why only Homo sapiens developed language. It should be remarked that this review is based on the opinion of a clinical neurologist and does not intend to go beyond an overview of this complex topic. The progressive development of language was probably due to the expansion of the prefrontal cortex (PFC) and its networks. PFC is the largest area of the human cerebral cortex and is much more expanded in humans than in other primates. To achieve language, several other functions should have been attained, including abstraction, reasoning, expanded working memory, and executive functions. All these functions are strongly related to PFC and language had a profound retroactive impact on them all. Language and culture produce anatomic and physiological modifications in the brain. Learning to read is presented as an example of how culture modifies the brain.

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A segunda parte desta revisão é uma tentativa de explicar por que apenas o Homo sapiens desenvolveu a linguagem. Ressalta-se que esta revisão é baseada na opinião de um neurologista clínico e não pretende ir além de uma visão geral deste tema complexo. O desenvolvimento progressivo da linguagem provavelmente se deveu à expansão do córtex pré-frontal (PFC) e de suas conexões. O PFC é a maior área do córtex cerebral humano e é muito maior em seres humanos do que em outros primatas. Para adquirir a linguagem, diversas outras funções precisavam ter sido alcançadas, incluindo abstração, raciocínio, expansão da memória de trabalho e funções executivas. Todas essas funções estão fortemente relacionadas com o PFC e a linguagem teve um profundo impacto retroativo em todas elas. A linguagem e a cultura produzem modificações anatômicas e fisiológicas no cérebro. Aprender a ler é apresentado como um exemplo de como a cultura modifica o cérebro.

RESUMO

This review is based on a conference presented in June 2023. Its main objective is to explain the cognitive differences between humans and non-human primates (NHPs) focusing on characteristics of their brains. It is based on the opinion of a clinical neurologist and does not intend to go beyond an overview of this complex topic. As language is the main characteristic differentiating humans from NHPs, this review is targeted at their brain networks related to language. NHPs have rudimentary forms of language, including primitive lexical/semantic signs. Humans have a much broader lexical/semantic repertory, but syntax is the most important characteristic, which is probably unique to Homo sapiens. Angular gyrus, Broca's area, temporopolar areas, and arcuate fascicle, are much more developed in humans. These differences may explain why NHPs did not develop a similar language to ours. Language had a profound influence on all other higher nervous activities.

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Esta revisão baseia-se numa conferência apresentada em junho de 2023. O seu principal objetivo é explicar as diferenças cognitivas entre humanos e primatas não humanos (PNH) com base nas características dos seus cérebros. Baseia se na opinião de um neurologista clínico e não pretende ir além de uma visão geral deste tema complexo. Como a linguagem é a principal característica que diferencia os humanos dos PNH, esta revisão concentra-se nas redes cerebrais relacionadas à linguagem. Os PNH têm formas rudimentares de linguagem, incluindo sinais lexicais/semânticos primitivos. Os humanos têm um repertório léxico/semântico muito mais amplo, mas a sintaxe é a característica mais importante e única do Homo sapiens. O giro angular, a área de Broca, as áreas temporopolares e o fascículo arqueado são muito mais desenvolvidos em humanos. Essas diferenças podem explicar por que os PNH não desenvolveram uma linguagem semelhante à nossa. A linguagem teve influência profunda em todas as outras atividades nervosas superiores.

RESUMO

The absence of a natural animal model is one of the main challenges in Alzheimer's disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread ß-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of ß-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer's disease.

Assuntos

Doença de Alzheimer , Cebinae , Humanos , Animais , Camundongos , Idoso , Doença de Alzheimer/patologia , Cebus , Haplorrinos , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Placa Amiloide/patologia , Proteínas tau/metabolismo

RESUMO

ABSTRACT. This review is based on a conference presented in June 2023. Its main objective is to explain the cognitive differences between humans and non-human primates (NHPs) focusing on characteristics of their brains. It is based on the opinion of a clinical neurologist and does not intend to go beyond an overview of this complex topic. As language is the main characteristic differentiating humans from NHPs, this review is targeted at their brain networks related to language. NHPs have rudimentary forms of language, including primitive lexical/semantic signs. Humans have a much broader lexical/semantic repertory, but syntax is the most important characteristic, which is probably unique to Homo sapiens. Angular gyrus, Broca's area, temporopolar areas, and arcuate fascicle, are much more developed in humans. These differences may explain why NHPs did not develop a similar language to ours. Language had a profound influence on all other higher nervous activities.

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RESUMO Esta revisão baseia-se numa conferência apresentada em junho de 2023. O seu principal objetivo é explicar as diferenças cognitivas entre humanos e primatas não humanos (PNH) com base nas características dos seus cérebros. Baseia se na opinião de um neurologista clínico e não pretende ir além de uma visão geral deste tema complexo. Como a linguagem é a principal característica que diferencia os humanos dos PNH, esta revisão concentra-se nas redes cerebrais relacionadas à linguagem. Os PNH têm formas rudimentares de linguagem, incluindo sinais lexicais/semânticos primitivos. Os humanos têm um repertório léxico/semântico muito mais amplo, mas a sintaxe é a característica mais importante e única do Homo sapiens. O giro angular, a área de Broca, as áreas temporopolares e o fascículo arqueado são muito mais desenvolvidos em humanos. Essas diferenças podem explicar por que os PNH não desenvolveram uma linguagem semelhante à nossa. A linguagem teve influência profunda em todas as outras atividades nervosas superiores.

RESUMO

Abstract Background Age is the most important risk factor for develop dementia, and the recommendation is that older adults are cognitively tested to detect impairment in the initial stage for adequate treatment. The demand for the care of these older adults is great, drawing attention to the need for rapid tests, with good accuracy and simple application to identify cognitive impairment. Objective To develop and validate the Brazilian Mini-Addenbrooke Cognitive Examination (M-ACE BR) as a short screening test for cognitive impairment in older adults. Methods The M-ACE BR was developed using the Mokken scaling analysis in 352 participants (cognitively unimpaired [CU] = 232, cognitive impairment no dementia [CIND] = 82; and dementia = 38) and validated in an independent sample of 117 participants (CU = 25; CIND = 88; and dementia = 4). Results The Mokken scaling analysis derived 9 items (spatial orientation, anterograde memory, retrograde memory, delayed recall, recognition [name and address], letter verbal fluency, repetition of 4 words, naming of 10 items, and comprehension) with a maximum score of 51 points and an average duration time of 7 minutes. The cut-off score ≤ 43/51 for CIND 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%). Conclusion The M-ACE BR is a brief and adequate instrument to detect cognitive impairment in older Brazilian adults. However, screening for CIND and for different educational levels should be further explored.

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Resumo Antecedentes A idade é o fator de risco mais importante para o desenvolvimento de demência, e a recomendação é que os idosos sejam testados cognitivamente para detectar comprometimento na fase inicial para o tratamento adequado. A demanda pelo atendimento desses idosos é grande, chamando atenção para a necessidade de testes rápidos, com boa acurácia e de simples aplicação para identificar o comprometimento cognitivo. Objetivo Desenvolver e validar a versão brasileira do Mini-Addenbrooke's Cognitive Examination (M-ACE BR) como um teste rápido para rastreio de comprometimento cognitivo em idosos. Métodos A M-ACE BR foi desenvolvida usando análise da escala de Mokken em 352 participantes (cognitivamente saudáveis [CS] = 232, comprometimento cognitivo sem demência [CCSD] = 82; e demência = 38) e validado em uma amostra independente de 117 participantes (CS = 25; CCSD = 88; e demência = 4). Resultados A análise de escala de Mokken derivou 9 itens (orientação espacial, memória anterógrada, memória retrógrada, evocação tardia, reconhecimento [nome e endereço], fluência verbal de letras, repetição de 4 palavras, nomeação de 10 itens e compreensão) com pontuação máxima de 51 pontos e tempo médio de duração de 7 minutos. O escore de corte ≤ 43/51 para CCSD teve sensibilidade de 59,09% e especificidade de 80%. Para um teste de rastreio, em que a sensibilidade é priorizada para investigação posterior, sugerimos utilizar um ponto de corte ≤ 47 (sensibilidade 85,23% e especificidade 24%), mantendo um bom valor preditivo positivo (79,8%). Conclusão A M-ACE BR é um instrumento breve e adequado para detectar comprometimento cognitivo em idosos brasileiros. No entanto, o rastreio para a identificação de CCSD e para diferentes níveis de escolaridade deve ser melhor explorado.

RESUMO

BACKGROUND: Corticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category "probable 4R-tauopathy" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD). OBJECTIVES: To investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns. METHODS: Thirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18 F]fluorodeoxyglucose and [11 C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group. RESULTS: Eleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata. CONCLUSIONS: The 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.

Assuntos

Degeneração Corticobasal , Tauopatias , Humanos , Fluordesoxiglucose F18/metabolismo , Tauopatias/metabolismo , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Atrofia/metabolismo

RESUMO

Introduction: Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. Methods: Participants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. Results: Patients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). Conclusion: RAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

RESUMO

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Assuntos

Doença de Alzheimer , Arteriosclerose , Angiopatia Amiloide Cerebral , Doença por Corpos de Lewy , Acidente Vascular Cerebral Lacunar , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Doença de Alzheimer/patologia , Apolipoproteína E4/genética , Apolipoproteínas E/metabolismo , Arteriosclerose/genética , Autopsia , Angiopatia Amiloide Cerebral/genética , Cognição , Proteínas de Ligação a DNA/genética , Genótipo , Doença por Corpos de Lewy/genética , Acidente Vascular Cerebral Lacunar/genética

RESUMO

Abstract Background Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases. Objective To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD. Methods A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021. Results The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD. Conclusion The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.

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Resumo Antecedentes A doença de Alzheimer (DA) foi descrita em 1907 e, desde então, deixou de ser relativamente rara para se tornar uma das doenças mais prevalentes. Objetivo Descrever a evolução das noções sobre demências e DA e investigar as razões do aumento do interesse científico pela DA. Métodos Foi realizada uma análise histórica dos conhecimentos sobre demência, o local da atividade mental, as relações entre doenças cerebrais e a atividade mental, e sobre os avanços na pesquisa sobre a DA, desde a sua descoberta até a publicação da hipótese da cascata amiloide em 1992. Foi realizada uma busca na Biblioteca Nacional de Medicina dos Estados Unidos da América (PubMed) por artigos científicos que incluíssem os termos demência ou DA nos 50 anos, de 1972 a 2021. Resultados A pesquisa científica sobre DA aumentou de 615 artigos com o termo doença de Alzheimer na primeira década (1972-1981), para 100.028 artigos na última década (2012-2021): um aumento de 162,6 vezes enquanto as publicações com o termo demência aumentaram 28,6 vezes no mesmo período. Nas décadas de 1960 e 1970, chegou-se a um consenso de que a DA é responsável pela maioria dos casos de demência, anteriormente conhecida como demência senil. Na década de 1980, o peptídeo beta-amiloide foi identificado no núcleo da placa senil, a proteína tau hiperfosforilada foi encontrada em emaranhados neurofibrilares e uma mutação foi descoberta em uma forma hereditária de DA. Conclusão A expansão do conceito de DA para incluir a demência senil e as descobertas ocorridas na década de 1980 ampliaram enormemente a pesquisa em DA.

RESUMO

BACKGROUND: Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases. OBJECTIVE: To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD. METHODS: A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021. RESULTS: The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD. CONCLUSION: The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.

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ANTECEDENTES: A doença de Alzheimer (DA) foi descrita em 1907 e, desde então, deixou de ser relativamente rara para se tornar uma das doenças mais prevalentes. OBJETIVO: Descrever a evolução das noções sobre demências e DA e investigar as razões do aumento do interesse científico pela DA. MéTODOS: Foi realizada uma análise histórica dos conhecimentos sobre demência, o local da atividade mental, as relações entre doenças cerebrais e a atividade mental, e sobre os avanços na pesquisa sobre a DA, desde a sua descoberta até a publicação da hipótese da cascata amiloide em 1992. Foi realizada uma busca na Biblioteca Nacional de Medicina dos Estados Unidos da América (PubMed) por artigos científicos que incluíssem os termos demência ou DA nos 50 anos, de 1972 a 2021. RESULTADOS: A pesquisa científica sobre DA aumentou de 615 artigos com o termo doença de Alzheimer na primeira década (1972-1981), para 100.028 artigos na última década (2012-2021): um aumento de 162,6 vezes enquanto as publicações com o termo demência aumentaram 28,6 vezes no mesmo período. Nas décadas de 1960 e 1970, chegou-se a um consenso de que a DA é responsável pela maioria dos casos de demência, anteriormente conhecida como demência senil. Na década de 1980, o peptídeo beta-amiloide foi identificado no núcleo da placa senil, a proteína tau hiperfosforilada foi encontrada em emaranhados neurofibrilares e uma mutação foi descoberta em uma forma hereditária de DA. CONCLUSãO: A expansão do conceito de DA para incluir a demência senil e as descobertas ocorridas na década de 1980 ampliaram enormemente a pesquisa em DA.

Assuntos

Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Emaranhados Neurofibrilares/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo

RESUMO

Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population. Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimer's disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.

RESUMO

BACKGROUND: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are important causes of dementia with challenging differential diagnoses in many cases. Addenbrooke's Cognitive Examination-Revised (ACE-R) is a cognitive battery that may be useful to differentiate the two disorders. OBJECTIVE: The objectibe of this study is to investigate the value of the ACE-R combined with sociodemographic factors in the differential diagnosis between AD and bvFTD. METHODS: The ACE-R was administered to 102 patients with mild dementia due to probable AD, 37 with mild bvFTD, and 135 controls. Performances of patients and controls were analyzed by logistic regression and by ROC curves to refine the diagnostic accuracy of the ACE-R in AD and bvFTD. RESULTS: The ACE-R subscores Attention and Orientation, Fluency, and Memory, in combination with schooling differentiated AD from controls with an area under the ROC curve (AUC) of 0.936 (86% sensitivity and 87% specificity). The ACE-R subscores Attention and Orientation, Fluency, and Language, in combination with sex (male), age, and schooling, discriminated bvFTD from controls with an AUC of 0.908 (81% sensitivity and 95% specificity). In the differentiation between AD and bvFTD, the ACE-R subscores Attention and Orientation, Fluency, and Language, together with age, displayed an AUC of 0.865 (78% sensitivity and 85% specificity). CONCLUSION: The combination of ACE-R scores with sociodemographic data allowed good differentiation between AD and bvFTD in the study sample.

RESUMO

Alzheimer's disease (AD) represents a substantial burden to patients, their caregivers, health systems, and society in Latin America and the Caribbean (LAC). This impact is exacerbated by limited access to diagnosis, specialized care, and therapies for AD within and among nations. The region has varied geographic, ethnic, cultural, and economic conditions, which create unique challenges to AD diagnosis and management. To address these issues, the Americas Health Foundation convened a panel of eight neurologists, geriatricians, and psychiatrists from Argentina, Brazil, Colombia, Ecuador, Guatemala, Mexico, and Peru who are experts in AD for a three-day virtual meeting to discuss best practices for AD diagnosis and treatment in LAC and create a manuscript offering recommendations to address identified barriers. In LAC, several barriers hamper diagnosing and treating people with dementia. These barriers include access to healthcare, fragmented healthcare systems, limited research funding, unstandardized diagnosis and treatment, genetic heterogeneity, and varying social determinants of health. Additional training for physicians and other healthcare workers at the primary care level, region-specific or adequately adapted cognitive tests, increased public healthcare insurance coverage of testing and treatment, and dedicated search strategies to detect populations with gene variants associated with AD are among the recommendations to improve the landscape of AD.

RESUMO

BACKGROUND: Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care. OBJECTIVE: The aim of this study was to investigate the current practices and the local limits on the diagnosis and management of FTD in Brazil. METHODS: We elaborated an online survey, composed of 29 questions and divided in four parts, comprising questions about existing health facilities, clinical practices related to FTD, and suggestions to increment the national research on FTD. The invitation to participate was sent by email to all neurologists affiliated to the Brazilian Academy of Neurology (n = 3658), and to all physicians who attended the XII Meeting of Researchers on Alzheimer's disease, in 2019 (n = 187). The invitation was also diffused through social media. RESULTS: 256 Brazilian physicians answered the questionnaire. The three most relevant disorders for the differential diagnosis of FTD were Alzheimer's disease (AD) (n = 211), bipolar disorder (n = 117) and dementia with Lewy bodies (n = 92). Most respondents (125/256) reported the difficulty in performing genetic testing as the main limit in the diagnostic of FTD. 93% and 63% of participants considered that the assessment of social cognition and AD CSF biomarkers are useful for the diagnosis of FTD, respectively. CONCLUSIONS: The present study may provide valuable insights for the medical education and clinical training of physicians, and to foster future research on FTD in Brazil.

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ANTECEDENTES: A demência frontotemporal (DFT) é causa frequente de demência pré-senil e representa um desafio em termos de diagnóstico e de manejo clínico. É essencial avaliar as dificuldades existentes na propedêutica e nos cuidados médicos. OBJETIVO: Investigar as práticas médicas e as dificuldades para diagnóstico e manejo da DFT no Brasil. MéTODOS: Elaborou-se um questionário online, composto de 29 questões, divididas em quatro partes, com perguntas sobre infraestrutura existente, práticas clínicas relacionadas à DFT e sugestões para desenvolver a pesquisa nacional na área. O convite para participação foi enviado por e-mail a todos neurologistas afiliados à Academia Brasileira de Neurologia (n = 3658), e aos médicos que participaram da XII Reunião de Pesquisadores de Doença de Alzheimer, em 2019 (n = 187). O convite também foi divulgado através de mídias sociais. RESULTADOS: 256 médicos brasileiros responderam o questionário. Os três principais diagnósticos diferenciais de DFT foram doença de Alzheimer (n = 211), transtorno bipolar (n = 117) e demência com corpos de Lewy (n = 92). A maior parte dos respondedores (125/256) apontou a dificuldade em realizar testagem genética como o maior limite no diagnóstico de DFT. 93% e 63% dos respondedores indicaram que a avaliação de cognição social e o uso de biomarcadores liquóricos de doença de Alzheimer são úteis no diagnóstico de DFT, respectivamente. CONCLUSõES: Estes resultados devem ser considerados na educação e treinamento médicos, e no desenvolvimento da pesquisa brasileira em DFT.

Assuntos

Doença de Alzheimer , Demência Frontotemporal , Humanos , Demência Frontotemporal/diagnóstico , Doença de Alzheimer/diagnóstico , Brasil , Diagnóstico Diferencial , Biomarcadores

RESUMO

Abstract Background Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care. Objective The aim of this study was to investigate the current practices and the local limits on the diagnosis and management of FTD in Brazil. Methods We elaborated an online survey, composed of 29 questions and divided in four parts, comprising questions about existing health facilities, clinical practices related to FTD, and suggestions to increment the national research on FTD. The invitation to participate was sent by email to all neurologists affiliated to the Brazilian Academy of Neurology (n = 3658), and to all physicians who attended the XII Meeting of Researchers on Alzheimer's disease, in 2019 (n = 187). The invitation was also diffused through social media. Results 256 Brazilian physicians answered the questionnaire. The three most relevant disorders for the differential diagnosis of FTD were Alzheimer's disease (AD) (n = 211), bipolar disorder (n = 117) and dementia with Lewy bodies (n = 92). Most respondents (125/256) reported the difficulty in performing genetic testing as the main limit in the diagnostic of FTD. 93% and 63% of participants considered that the assessment of social cognition and AD CSF biomarkers are useful for the diagnosis of FTD, respectively. Conclusions The present study may provide valuable insights for the medical education and clinical training of physicians, and to foster future research on FTD in Brazil.

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Resumo Antecedentes A demência frontotemporal (DFT) é causa frequente de demência pré-senil e representa um desafio em termos de diagnóstico e de manejo clínico. É essencial avaliar as dificuldades existentes na propedêutica e nos cuidados médicos. Objetivo Investigar as práticas médicas e as dificuldades para diagnóstico e manejo da DFT no Brasil. Métodos Elaborou-se um questionário online, composto de 29 questões, divididas em quatro partes, com perguntas sobre infraestrutura existente, práticas clínicas relacionadas à DFT e sugestões para desenvolver a pesquisa nacional na área. O convite para participação foi enviado por e-mail a todos neurologistas afiliados à Academia Brasileira de Neurologia (n = 3658), e aos médicos que participaram da XII Reunião de Pesquisadores de Doença de Alzheimer, em 2019 (n = 187). O convite também foi divulgado através de mídias sociais. Resultados 256 médicos brasileiros responderam o questionário. Os três principais diagnósticos diferenciais de DFT foram doença de Alzheimer (n = 211), transtorno bipolar (n = 117) e demência com corpos de Lewy (n = 92). A maior parte dos respondedores (125/256) apontou a dificuldade em realizar testagem genética como o maior limite no diagnóstico de DFT. 93% e 63% dos respondedores indicaram que a avaliação de cognição social e o uso de biomarcadores liquóricos de doença de Alzheimer são úteis no diagnóstico de DFT, respectivamente. Conclusões Estes resultados devem ser considerados na educação e treinamento médicos, e no desenvolvimento da pesquisa brasileira em DFT.

RESUMO

Subjective cognitive decline is defined as a self-perceived cognitive decline but with normal performance in neuropsychological assessments. Objective: To verify the evolution of patients diagnosed with subjective cognitive decline compared to the cognitively normal group without any concern. Methods: This is a follow-up study based on data analysis from the Tremembé epidemiologic study, in Brazil. The 211 individuals classified as cognitively normal and 174 diagnosed as having subjective cognitive decline at baseline were invited to participate. Results: After a median follow-up time of five years, 108 subjective cognitive decline participants (62.0%) were reassessed. Of these, 58 (53.7%) kept this diagnosis, whereas 14 individuals (12.9%) progressed to mild cognitive impairment and 5 (4.6%) to dementia. In the cognitively normal group, 107 (50.7%) were reassessed, of which 51 (47.7%) were still classified likewise, 6 (5.6%) evolved to mild cognitive impairment and 9 (8.4%) to dementia. The presence of cognitive decline had a significant association with increasing age and depression symptoms. Considering the total number of baseline participants in each group: the subjective cognitive decline group showed higher percentage of mild cognitive impairment (p=0.022) and no difference was found in progression to dementia (p=0.468) between the groups after follow-up assessment. Conclusion: Most subjective cognitive decline participants at baseline kept their cognitive complaint at follow-up and this group progressed more to mild cognitive impairment than the other group. No difference in the progression to dementia was found, despite the higher incidence of dementia in the cognitively normal group.

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O declínio cognitivo subjetivo (DCS) é definido como autopercepção de declínio cognitivo, mas com desempenho normal nas avaliações neuropsicológicas. Objetivo: O objetivo foi verificar a evolução dos pacientes diagnosticados com DCS em relação ao grupo cognitiva mente normal (CN), sem qualquer queixa. Métodos: Trata-se de um estudo de seguimento baseado na análise de dados do estudo epidemiológico de Tremembé, Brasil. Os 211 indivíduos classificados como CN e os 174 diagnosticados como DCS na fase inicial do estudo foram convidados a participar. Resultados: Após o tempo médio de seguimento de cinco anos, 108 participantes da DCS (62,0%) foram reavaliados. Deles, 58 (53,7%) mantiveram o diagnóstico de DCS, enquanto 14 (12,9%) evoluíram para comprometimento cognitivo leve (CCL) e cinco (4,6%) para demência. No grupo CN, 107 (50,7%) foram reavaliados, dos quais 51 (47,7%) ainda foram classificados como CN, seis (5,6%) evoluíram para CCL e nove (8,4%) para demência. A presença de declínio cognitivo teve associação significativa com o aumento da idade e com sintomas de depressão. Considerando-se o número total de participantes da fase inicial do estudo de cada grupo: o grupo DCS apresentou maior percentual de CCL (p=0,022) e não houve diferença na progressão para demência (p=0,468) entre ambos os grupos após a avaliação de seguimento. Conclusão: A maioria dos participantes DCS da fase inicial do estudo manteve sua queixa cognitiva no seguimento, e esse grupo progrediu mais para CCL. Não foi encontrada diferença na progressão para demência, apesar da maior incidência de demência no grupo CN.