Non-invasive sound wave brain stimulation with Transcranial Pulse Stimulation (TPS) improves neuropsychiatric symptoms in Alzheimer's disease.

BACKGROUND: This study explores Transcranial Pulse Stimulation (TPS) as a potential non-invasive treatment for Alzheimer's disease (AD), focusing on its impact on cognitive functions and behavioral symptoms. METHODS: In a prospective, one-arm open-label trial, ten patients with mild to moderate dementia due to AD were assessed using the Alzheimer's Disease Assessment Scale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Pfeffer Functional Activities Questionnaire, and Zarit Caregiver Burden Interview. Assessments occurred at 30- and 90-days post-treatment. The TPS protocol consisted of 10 sessions over five weeks, using the Neurolith® device to deliver 6000 focused shockwave pulses at 0.25 mJ/mm2 and a frequency of 4 Hz. RESULTS: TPS significantly reduced neuropsychiatric symptoms, with NPI scores decreasing by 23.9 points (95% CI: -39.19 to -8.61, p = 0.0042) after 30 days, and by 18.9 points (95% CI: -33.49 to -2.91, p = 0.022) after 90 days. These changes had large effect sizes (Cohen's dz = 1.43 and dz = 0.94, respectively). A decreasing trend was observed in the ADAS-Cog score (-3.6, 95% CI: -7.18 to 0.00, p = 0.05) after 90 days, indicating a potential reduction in cognitive impairment, though not statistically significant. CONCLUSION: The preliminary results indicate that TPS treatment leads to significant improvement in neuropsychiatric symptoms in AD patients, showing promise as a therapeutic approach for AD. Further research is needed to fully establish its effectiveness, especially concerning cognitive functions.

Electroconvulsive therapy for treating patients with agitation and related behavioral disorders due to dementia: a systematic review.

Behavioral disturbances are clinically relevant in patients with dementia, and pharmacological regimens to mitigate these symptoms have provided limited results. Proven to be effective in several psychiatric conditions, electroconvulsive therapy is a potentially beneficial strategy for treating severe agitation due to dementia. Objective: This review aimed to examine the publications on the efficacy, safety and tolerability of electroconvulsive therapy in treating patients with agitation due to dementia. Methods: We performed a systematic analysis on the electroconvulsive therapy to treat patients with dementia and coexisting severe agitation. Articles were classified according to the level of evidence based on methodological design. Patients received an acute course of electroconvulsive therapy, often followed by maintenance intervention. Results: We selected 19 studies (156 patients; 64.1% women; 51-98 years old), which met the inclusion criteria: one case-control study by chart analysis (level of evidence 2); one open-label study (level of evidence 3); three historical/retrospective chart analyses (level of evidence 4); and 14 case series/reports (level of evidence 5). No randomized, sham-controlled clinical trials (level of evidence 1) were identified, which represents the main methodological weakness. Some patients had postictal delirium, cardiovascular decompensation and cognitive changes, lasting for a short time. Conclusions: Overall, patients achieved significant improvement in agitation. However, the main finding of the present review was the absence of methodological design based on randomized and sham-controlled clinical trials. Despite methodological limitations and side effects requiring attention, electroconvulsive therapy was considered a safe and effective treatment of patients with severe agitation and related behavioral disorders due to dementia.

Distúrbios comportamentais são clinicamente relevantes em pacientes com demência, e regimes farmacológicos para mitigar esses sintomas têm proporcionado resultados limitados. Comprovadamente eficaz em diversas condições psiquiátricas, a eletroconvulsoterapia é uma estratégia potencialmente benéfica para o tratamento de pacientes com agitação grave na demência. Objetivos: Esta revisão examina as publicações sobre eficácia, segurança e tolerabilidade da eletroconvulsoterapia no tratamento de pacientes com agitação na demência. Métodos: Realizamos uma análise sistemática da eletroconvulsoterapia no tratamento de pacientes com demência e agitação grave. Os artigos foram classificados quanto ao nível de evidência com base no delineamento metodológico. Os pacientes receberam um curso agudo de eletroconvulsoterapia, frequentemente seguido de manutenção. Resultados: Foram selecionados 19 estudos (156 pacientes; 64,1% mulheres; 51­98 anos): um estudo caso-controle desenvolvido com base na análise de prontuários (nível de evidência 2); um estudo aberto (nível de evidência 3); três estudos de análise retrospectiva de prontuários (nível de evidência 4); e 14 séries/relatos de casos (nível de evidência 5). Não foram identificados ensaios clínicos randomizados e controlados com placebo (nível de evidência 1), fator que representa a principal fragilidade metodológica. No entanto, o principal achado da presente revisão consistiu na ausência de desenho metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Em geral, os efeitos colaterais foram transitórios e bem tolerados. Alguns pacientes apresentaram delirium pós-ictal, descompensação cardiovascular e alterações cognitivas por períodos breves. Conclusões: No geral, os pacientes obtiveram melhora significativa na agitação. No entanto, o principal achado da presente revisão foi a ausência de delineamento metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Apesar das limitações metodológicas e dos efeitos adversos, a eletroconvulsoterapia foi considerada um tratamento seguro e eficaz em pacientes com agitação grave e com outros distúrbios comportamentais clinicamente relevantes na demência.

Diagnostic Performance of an Eye-Tracking Assisted Visual Inference Language Test in the Assessment of Cognitive Decline due to Alzheimer's Disease.

BACKGROUND: The assessment of language changes associated with visual search impairment can be an important diagnostic tool in the Alzheimer's disease (AD) continuum. OBJECTIVE: Investigate the performance of an eye-tracking assisted visual inference language task in differentiating subjects with mild cognitive impairment (MCI) or AD dementia from cognitively unimpaired older adults (controls). METHODS: We assessed a group of 95 older adults (49 MCI, 18 mild dementia due to AD, and 28 controls). The subjects performed the same task under multiple experimental conditions which generate correlated responses that need to be taken into account. Thus, we performed a non-parametric repeated measures ANOVA model for verbal answers, and a linear mixed model (LMM) or its generalized version for the analysis of eye tracking variables. RESULTS: Significant differences were found in verbal answers across all diagnostic groups independently of type of inference, i.e., logic or pragmatic. Also, eye-tracking parameters were able to discriminate AD from MCI and controls. AD patients did more visits to challenge stimulus (Control-AD, -0.622, SE = 0.190, p = 0.004; MCI-AD, -0.514, SE = 0.173, p = 0.011), more visits to the correct response stimulus (Control-AD, -1.363, SE = 0.383, p = 0.002; MCI-AD, -0.946, SE = 0.349, p = 0.022), more fixations on distractors (Control-AD, -4.580, SE = 1.172, p = 0.001; MCI-AD, -2.940, SE = 1.070, p = 0.020), and a longer time to first fixation on the correct response stimulus (Control-AD, -0.622, SE = 0.190, p = 0.004; MCI-AD, -0.514, SE = 0.173, p = 0.011). CONCLUSION: The analysis of oculomotor behavior along with language assessment protocols may increase the sensitivity for detection of subtle deficits in the MCI-AD continuum, representing an important diagnostic tool.

Discourse abilities in euthymic elderly patients with bipolar disorder: a preliminary study.

Cognitive impairment has been well described in euthymic patients with bipolar disorder (BD), as well as in elderly patients. Language disturbances are less studied, and several inconsistencies are reported in the literature. Most language studies focus on verbal fluency and semantic alterations, with a lack of studies addressing discursive abilities in BD. Objective: The aim of this study was to evaluate discourse abilities in euthymic elderly individuals with BD. Methods: We studied 19 euthymic elderly patients with BD and a control group of non-BD, which performed a cognitive assessment of attention, memory, executive functions, and visual abilities. All participants produced a description from the Cookie Theft Picture in oral and written modalities that was analyzed according to micro- and macrolinguistic aspects. Generalized linear models were performed to compare intergroup linguistic performance and to determine whether any cognitive domain was associated with linguistic outcomes. Results: The BD group produced more cohesion errors in the oral and written modalities (p=0.016 and p=0.011, respectively) and fewer thematic units in the oral modality (p=0.027) than the control group. Conclusions: BD patients presented minimal changes in the descriptive discourse task. The BD group produced more cohesion errors than the control group in the oral (p=0.016) and written discourse (p=0.011); also, the BD group produced fewer thematic units than controls in the oral discourse (p=0.027).

Déficits cognitivos têm sido descritos em pacientes com transtorno bipolar (TB) em fase eutímica, bem como em idosos. Alterações linguísticas são menos estudadas, e os achados de literatura são inconsistentes. A maioria dos estudos em linguagem baseia-se em avaliações de fluência verbal e alterações semânticas, havendo escassez de trabalhos que abordem as habilidades discursivas no TB. Objetivo: Avaliar as habilidades discursivas em indivíduos idosos eutímicos com TB. Métodos: Estudamos 19 pacientes idosos eutímicos com TB e um grupo de idosos sem TB e cognitivamente saudáveis, que realizaram avaliação cognitiva da atenção, memória, funções executivas e habilidades visuoespaciais. Todos os participantes produziram uma descrição da Prancha do Roubo dos Biscoitos nas modalidades oral e escrita, que foram analisadas de acordo com aspectos micro e macrolinguísticos. Análises por meio de modelos lineares generalizados foram realizados para comparar o desempenho linguístico entre os grupos e para determinar se algum domínio cognitivo estava associado a esse desempenho. Resultados: O grupo TB produziu mais erros de coesão nas modalidades oral e escrita (p=0,016 e p=0,011, respectivamente) e menos unidades temáticas na modalidade oral (p=0,027) do que o grupo controle. Conclusão: Os pacientes com TB apresentaram alterações leves na tarefa discursiva. O grupo TB produziu maior número de erros de coesão do que o grupo controle no discurso oral (p=0,016) e escrito (p=0,011). Além disso, o grupo TB produziu menor número de unidades temáticas do que os controles na tarefa de discurso oral (p=0,027).

Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment

Objectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment.

OBJECTIVES: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. METHODS: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. RESULTS: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. CONCLUSION: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

Electroconvulsive therapy for treating patients with agitation and related behavioral disorders due to dementia: a systematic review / Eletroconvulsoterapia no tratamento de pacientes com agitação e outros distúrbios de comportamento devido à demência: uma revisão sistemática

ABSTRACT Behavioral disturbances are clinically relevant in patients with dementia, and pharmacological regimens to mitigate these symptoms have provided limited results. Proven to be effective in several psychiatric conditions, electroconvulsive therapy is a potentially beneficial strategy for treating severe agitation due to dementia. Objective: This review aimed to examine the publications on the efficacy, safety and tolerability of electroconvulsive therapy in treating patients with agitation due to dementia. Methods: We performed a systematic analysis on the electroconvulsive therapy to treat patients with dementia and coexisting severe agitation. Articles were classified according to the level of evidence based on methodological design. Patients received an acute course of electroconvulsive therapy, often followed by maintenance intervention. Results: We selected 19 studies (156 patients; 64.1% women; 51-98 years old), which met the inclusion criteria: one case-control study by chart analysis (level of evidence 2); one open-label study (level of evidence 3); three historical/retrospective chart analyses (level of evidence 4); and 14 case series/reports (level of evidence 5). No randomized, sham-controlled clinical trials (level of evidence 1) were identified, which represents the main methodological weakness. Some patients had postictal delirium, cardiovascular decompensation and cognitive changes, lasting for a short time. Conclusions: Overall, patients achieved significant improvement in agitation. However, the main finding of the present review was the absence of methodological design based on randomized and sham-controlled clinical trials. Despite methodological limitations and side effects requiring attention, electroconvulsive therapy was considered a safe and effective treatment of patients with severe agitation and related behavioral disorders due to dementia.

RESUMO Distúrbios comportamentais são clinicamente relevantes em pacientes com demência, e regimes farmacológicos para mitigar esses sintomas têm proporcionado resultados limitados. Comprovadamente eficaz em diversas condições psiquiátricas, a eletroconvulsoterapia é uma estratégia potencialmente benéfica para o tratamento de pacientes com agitação grave na demência. Objetivos: Esta revisão examina as publicações sobre eficácia, segurança e tolerabilidade da eletroconvulsoterapia no tratamento de pacientes com agitação na demência. Métodos: Realizamos uma análise sistemática da eletroconvulsoterapia no tratamento de pacientes com demência e agitação grave. Os artigos foram classificados quanto ao nível de evidência com base no delineamento metodológico. Os pacientes receberam um curso agudo de eletroconvulsoterapia, frequentemente seguido de manutenção. Resultados: Foram selecionados 19 estudos (156 pacientes; 64,1% mulheres; 51-98 anos): um estudo caso-controle desenvolvido com base na análise de prontuários (nível de evidência 2); um estudo aberto (nível de evidência 3); três estudos de análise retrospectiva de prontuários (nível de evidência 4); e 14 séries/relatos de casos (nível de evidência 5). Não foram identificados ensaios clínicos randomizados e controlados com placebo (nível de evidência 1), fator que representa a principal fragilidade metodológica. No entanto, o principal achado da presente revisão consistiu na ausência de desenho metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Em geral, os efeitos colaterais foram transitórios e bem tolerados. Alguns pacientes apresentaram delirium pós-ictal, descompensação cardiovascular e alterações cognitivas por períodos breves. Conclusões: No geral, os pacientes obtiveram melhora significativa na agitação. No entanto, o principal achado da presente revisão foi a ausência de delineamento metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Apesar das limitações metodológicas e dos efeitos adversos, a eletroconvulsoterapia foi considerada um tratamento seguro e eficaz em pacientes com agitação grave e com outros distúrbios comportamentais clinicamente relevantes na demência.

Discourse abilities in euthymic elderly patients with bipolar disorder: a preliminary study / Habilidades discursivas em pacientes idosos com transtorno afetivo bipolar: estudo preliminar

ABSTRACT Cognitive impairment has been well described in euthymic patients with bipolar disorder (BD), as well as in elderly patients. Language disturbances are less studied, and several inconsistencies are reported in the literature. Most language studies focus on verbal fluency and semantic alterations, with a lack of studies addressing discursive abilities in BD. Objective: The aim of this study was to evaluate discourse abilities in euthymic elderly individuals with BD. Methods: We studied 19 euthymic elderly patients with BD and a control group of non-BD, which performed a cognitive assessment of attention, memory, executive functions, and visual abilities. All participants produced a description from the Cookie Theft Picture in oral and written modalities that was analyzed according to micro- and macrolinguistic aspects. Generalized linear models were performed to compare intergroup linguistic performance and to determine whether any cognitive domain was associated with linguistic outcomes. Results: The BD group produced more cohesion errors in the oral and written modalities (p=0.016 and p=0.011, respectively) and fewer thematic units in the oral modality (p=0.027) than the control group. Conclusions: BD patients presented minimal changes in the descriptive discourse task. The BD group produced more cohesion errors than the control group in the oral (p=0.016) and written discourse (p=0.011); also, the BD group produced fewer thematic units than controls in the oral discourse (p=0.027).

RESUMO Déficits cognitivos têm sido descritos em pacientes com transtorno bipolar (TB) em fase eutímica, bem como em idosos. Alterações linguísticas são menos estudadas, e os achados de literatura são inconsistentes. A maioria dos estudos em linguagem baseia-se em avaliações de fluência verbal e alterações semânticas, havendo escassez de trabalhos que abordem as habilidades discursivas no TB. Objetivo: Avaliar as habilidades discursivas em indivíduos idosos eutímicos com TB. Métodos: Estudamos 19 pacientes idosos eutímicos com TB e um grupo de idosos sem TB e cognitivamente saudáveis, que realizaram avaliação cognitiva da atenção, memória, funções executivas e habilidades visuoespaciais. Todos os participantes produziram uma descrição da Prancha do Roubo dos Biscoitos nas modalidades oral e escrita, que foram analisadas de acordo com aspectos micro e macrolinguísticos. Análises por meio de modelos lineares generalizados foram realizados para comparar o desempenho linguístico entre os grupos e para determinar se algum domínio cognitivo estava associado a esse desempenho. Resultados: O grupo TB produziu mais erros de coesão nas modalidades oral e escrita (p=0,016 e p=0,011, respectivamente) e menos unidades temáticas na modalidade oral (p=0,027) do que o grupo controle. Conclusão: Os pacientes com TB apresentaram alterações leves na tarefa discursiva. O grupo TB produziu maior número de erros de coesão do que o grupo controle no discurso oral (p=0,016) e escrito (p=0,011). Além disso, o grupo TB produziu menor número de unidades temáticas do que os controles na tarefa de discurso oral (p=0,027).

Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa.

Cognitive-communication disorder following right hemisphere damage: Narrative production.

Background: Cognitive-communication disorder (CCD) results from the association of language and cognition impairment that may follow right hemisphere (RH) damage and impair the quality of life of affected persons. Objective: We studied a set of 1,625 narratives produced by a cohort of 125 individuals (50 with a single right vascular lesion in the MCA territory and 75 cognitively healthy controls) using a task of picture-based discourse production. Discourse production was analyzed in its macro-and microlinguistic aspects to characterize better the linguistic mechanisms underlying RH patients' performance. Results: The RH group produced more words and elocutions than controls, with a lower rate of informational content and a higher percentage of global coherence errors (all p-values <0.0001). Conclusion: Individuals with RH lesions showed formal lexical and syntactic aspects of discourse mostly preserved. Alterations in the macrostructure of discourse prevailed over microstructural alterations in our sample, according to most literature studies. The group of individuals with RH lesions produced narratives containing more words and utterances, with a lesser degree of lexical information and more global coherence errors.

Impact of Cognitive Demand on Eye Movement Pattern in Patients with Alzheimer's Disease.

BACKGROUND: Eye-movement behavior has been used as a reliable tool to identify cognitive and behavioral patterns in individuals with different neuropsychiatric disorders including Alzheimer's disease (AD). Most studies in the field have been dedicated to evaluating eye-movement behavior during cognitive tasks in different protocols using multiple parameters. OBJECTIVE: We aimed to evaluate the differences of eye-movement behavior in healthy subjects, subjects with mild cognitive impairment (MCI), and those with AD in a simple color task with and without cognitive demand. METHODS: 91 subjects: 18 AD, 47 MCI, and 26 healthy controls had their oculomotor parameters assessed during baseline (no cognitive demand involved) and during a simple computational color memory task using an eye-tracker. RESULTS: Baseline showed statistically different and heterogeneous results between normal cognition and MCI groups. Familiarization phase of the task could not discriminate between groups in any of the analyzed parameters. AD subjects made longer fixations and visits on distractors, and more frequent fixations and visits on the target areas than other groups during the response phase. CONCLUSION: Eye-tracking time-related parameters differentiate AD subjects from other groups under cognitive demand even in a simple color memory task.

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO Este artigo apresenta o consenso realizado pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia sobre os critérios diagnósticos da Doença de Alzheimer (DA) no Brasil. Foi realizada uma revisão da literatura e dos critérios clínicos e de pesquisa para DA, sendo propostos protocolos para o diagnóstico de DA em níveis de atenção primária, secundária e terciária. Dentro deste cenário clínico, são apresentados os critérios diagnósticos para DA típica e atípica, além de instrumentos de avaliação clínica, cognitiva e funcional; bem como propedêutica complementar com exames laboratoriais e de neuroimagem. A utilização de biomarcadores é também apresentada, tanto para o diagnóstico clínico em situações específicas quanto para pesquisa.

ABSTRACT This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Semantic processing and neurobiology in Alzheimer's disease and Mild Cognitive Impairment.

In the present theoretical review we will perform a critical surveillance of linguistic and semantic processing in Mild Cognitive Impairment and Alzheimer's disease, explicitly favouring a neurobiological prism. We conjecture that most linguistic alterations arise from semantic indiscrimination through inhibitory hypofunction. Specifically, a conjoint cluster of cholinergic dysfunction, Aß load and somatostatin-positive cell loss renders the semantic network disinhibited and overly noisy: fine discriminatory processes in temporal and medial-frontal regions cannot differentiate semantic representations from baseline unconscious activity, which leads to failures in faithful retrieval (preferentially idiosyncratic lexical-semantic links, e.g., proper names), verbal fluency anomalies, semantic interference, dampened N400 effects, and various semiological deviances.

Decision tree-based classification as a support to diagnosis in the Alzheimer's disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis

Objective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aβ1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.

Decision tree-based classification as a support to diagnosis in the Alzheimer's disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis.

OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. METHODS: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aß1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. RESULTS: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. CONCLUSION: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.

Neuropsychiatric symptoms and cerebrovascular risk in non-demented elders: cross-sectional study using the mild behavioural impairment checklist (MBI-C).

BACKGROUND: Neuropsychiatric symptoms (NPS) may represent early clinical manifestations of evolving brain diseases. Studies underpin the occurrence of NPS in the context of mild cognitive impairment (MCI) and prodromal Alzheimer's disease, where symptoms referred to as 'mild behavioural impairment' (MBI) have been shown to predict conversion to dementia and to hasten cognitive/functional decline. However, the association between NPS and cerebrovascular risk factors has been poorly investigated, despite the high prevalence of the latter among individuals with MCI. The aim of the present study was to investigate the association between MBI and cerebrovascular risk in a clinical sample of non-demented elders. METHODS: Sixty-five MCI and 15 cognitively unimpaired older adults were cross-sectionally assessed with the Mild Behavioural Impairment Checklist (MBI-C), using the cut-off score > 6.5 to define positive screening. Participants were submitted to the Hachinski Ischaemic Score (HIS) to account for cerebrovascular symptoms, vascular risk, and related comorbidities. Neuroimaging scans (magnetic resonance imaging and/or 18F-fluorodeoxyglucose-positron emission tomography) and apolipoprotein E genotype were obtained. RESULTS: Positive associations were found between total MBI-C scores and increasing number of comorbidities present (0-2 comorbidities), but not with three comorbidities. Two domains of the MBI-C-impulse dyscontrol and social inappropriateness-followed the same trend of the MBI-C total score, with higher scores with the increasing numbers of comorbidities. No significant associations were found between MBI symptoms and HIS or cerebrovascular burden in neuroimaging assessment. CONCLUSION: We found weak associations between MBI-C total score and the presence of comorbidities with cerebrovascular risk, but not with structural or functional neuroimaging abnormalities or HIS. This finding may represent that the presence of comorbidities adds limited risk to the occurrence of MBI in this sample of non-demented elders.

Impact of cognitive demand on eye movement pattern in patients with alzheimer’s disease

Background: Eye-movement behavior has been used as a reliable tool to identify cognitive and behavioral patterns in individuals with different neuropsychiatric disorders including Alzheimer’s disease (AD). Most studies in the field have been dedicated to evaluating eye-movement behavior during cognitive tasks in different protocols using multiple parameters. Objective: We aimed to evaluate the differences of eye-movement behavior in healthy subjects, subjects with mild cognitive impairment (MCI), and those with AD in a simple color task with and without cognitive demand. Methods: 91 subjects: 18 AD, 47 MCI, and 26 healthy controls had their oculomotor parameters assessed during baseline (no cognitive demand involved) and during a simple computational color memory task using an eye-tracker. Results: Baseline showed statistically different and heterogeneous results between normal cognition and MCI groups. Familiarization phase of the task could not discriminate between groups in any of the analyzed parameters. AD subjects made longer fixations and visits on distractors, and more frequent fixations and visits on the target areas than other groups during the response phase. Conclusion: Eye-tracking time-related parameters differentiate AD subjects from other groups under cognitive demand even in a simple color memory task.

Subcortical Aphasia.

PURPOSE OF REVIEW: Subcortical structures have long been thought to play a role in language processing. Increasingly spirited debates on language studies, arising from as early as the nineteenth century, grew remarkably sophisticated as the years pass. In the context of non-thalamic aphasia, a few theoretical frameworks have been laid out. The disconnection hypothesis postulates that basal ganglia insults result in aphasia due to a rupture of connectivity between Broca and Wernicke's areas. A second viewpoint conjectures that the basal ganglia would more directly partake in language processing, and a third stream proclaims that aphasia would stem from cortical deafferentation. On the other hand, thalamic aphasia is more predominantly deemed as a resultant of diaschisis. This article reviews the above topics with recent findings on deep brain stimulation, neurophysiology, and aphasiology. RECENT FINDINGS: The more recent approach conceptualizes non-thalamic aphasias as the offspring of unpredictable cortical hypoperfusion. Regarding the thalamus, there is mounting evidence now pointing to leading contributions of the pulvinar/lateral posterior nucleus and the anterior/ventral anterior thalamus to language disturbances. While the former appears to relate to lexical-semantic indiscrimination, the latter seems to bring about a severe breakdown in word selection and/or spontaneous top-down lexical-semantic operations. The characterization of subcortical aphasias and the role of the basal ganglia and thalamus in language processing continues to pose a challenge. Neuroimaging studies have pointed a path forward, and we believe that more recent methods such as tractography and connectivity studies will significantly expand our knowledge in this particular area of aphasiology.

Textual Inference Comprehension in Mild Cognitive Impairment: The Influence of Semantic Processing and Verbal Episodic Memory.

Language complaints, especially in complex tasks, may occur in mild cognitive impairment (MCI). Various language measures have been studied as cognitive predictors of MCI conversion to Alzheimer's type dementia. Understanding textual inferences is considered a high-demanding task that recruits multiple cognitive functions and, therefore, could be sensitive to detect decline in the early stages of MCI. Thus, we aimed to compare the performance of subjects with MCI to healthy elderly in a textual inference comprehension task and to determine the best predictors of performance in this ability considering one verbal episodic memory and two semantic tasks. We studied 99 individuals divided into three groups: (1) 23 individuals with amnestic mild cognitive impairment (aMCI), (2) 42 individuals with non-amnestic mild cognitive impairment (naMCI), (3), and (4) 34 cognitively healthy individuals for the control group (CG). A reduced version of The Implicit Management Test was used to assess different types of inferential reasoning in text reading. MCI patients performed poorer than healthy elderly, and there were no differences between MCI subgroups (amnestic and non-amnestic). The best predictors for inference-making were verbal memory in the aMCI and semantic tasks in the naMCI group. The results confirmed that the failure to understand textual inferences can be present in MCI and showed that different cognitive skills like semantic knowledge and verbal episodic memory are necessary for inference-making.

Semantic priming and neurobiology in schizophrenia: A theoretical review.

In this theoretical review we bridge the cognitive and neurobiological sciences to shed light on the neurocognitive foundations of the semantic priming effect in schizophrenia. We review and theoretically evaluate the neurotransmitter systems (dopaminergic, GABAergic and glutamatergic) and neurobiological underpinnings of behavioural and electrophysiological (N400) semantic priming in the pathology, and the main hypotheses on their geneses: a disinhibition of the semantic spread of activation, a disorganised semantic storage or noisy lexical-semantic associations, a psychomotor artefact, an artefact of relatedness proportions, or an inability to mobilise contextual information. We further assess the literature on the endophenotype of Formal Thought Disorder from multiple standpoints, ranging from neurophysiology to cognition: considerations are weaved on neuronal (PV basket cell, SST, VIP) and receptor deficits (DRD1, NMDA), neurotransmitter imbalances (dopamine), cortical and dopaminergic lateralisation, inter alia. In conclusion, we put forth novel postulates on the underlying causes of controlled hypopriming, automatic hyperpriming, N400 reversals (larger amplitudes for close associations), indirect versus direct hyperpriming, and the endophenotype of lexical-semantic disturbances in schizophrenia.