Executive testing predicts functional loss in subjects with white matter lesions.

In order to assess ecological validity of executive function (EF) tests and the impact of EF dysfunction on functional status in elderly subjects with moderate and severe subcortical white matter hyperintensities (WMHs), we made a correlation analysis between EF scores and two measures of Instrumental Activities of Daily Living (IADL). Trail-making test and CLOX correlated with the ability to perform IADL in subjects with severe WMH. EF tests might present low ecological validity for those with WMH below severe stage.

Expressive amusia and aphasia: the story of Maurice Ravel.

The French composer, Maurice Ravel, at the peak of his career, showed signs of a progressive disorder that affected his ability to function with verbal and musical language, as noted by the neurologist Théophile Alajouanine. The worsening of the disease led to a craniotomy, performed in 1937, which failed to reveal the cause of his illness, and he died shortly thereafter. A lack of post-mortem neuropathological evidence precluded a definitive diagnosis of the illness, which remained enigmatic. Speculations about the precise diagnosis of Ravel's neurological disease have been largely based on Alajouanine's observations, which included aphasia and amusia, mostly expressive, and ideomotor apraxia, while musical judgement, taste, and memory remained relatively intact, implying different neuroanatomical substrates. A possible subform of frontotemporal lobar degeneration complex was the diagnostic suggestion of many authors. His untimely death deprived the world of this remarkable musician, and the music that remained trapped in his mind.

O compositor francês Maurice Ravel, no ápice de sua carreira, mostrou sinais de uma desordem progressiva que afetou sua capacidade de funcionar com linguagem verbal e musical, como notado pelo neurologista Théophile Alajouanine. O agravamento de sua condição levou a uma craniotomia, efetuada em 1937, que deixou de revelar a causa de sua doença, tendo ele falecido pouco depois. A ausência de evidência neuropatológica pós-morte impediu o diagnóstico definitivo da doença, que permaneceu enigmático. Especulações sobre o diagnóstico preciso da doença neurológica de Ravel foram baseadas sobretudo nas observações de Alajouanine, que compreendiam afasia e amusia, predominantemente expressiva, e também apraxia, enquanto o julgamento, gosto e memória musicais permaneceram relativamente intactos, implicando diferentes substratos neuroanatômicos. A possibilidade de uma subforma do complexo da degenearação lobar frontotemporal foi a sugestão diagnóstica de muitos autores. A sua morte prematura privou o mundo desse notável músico e da música que permaneceu presa em sua mente.

Patterns of neuropsychiatric sub-syndromes in Brazilian and Norwegian patients with dementia.

BACKGROUND: Neuropsychiatric symptoms (NPS) affect the majority of patients who have dementia. Neuropsychiatric sub-syndromes with symptoms that occur together and have common neurobiological correlates have been identified. There are scarce data regarding the comparison of the pattern of the neuropsychiatric sub-syndromes in distinct ethnical and cultural populations. We aim at comparing the pattern of the NPS, and the factor analysis of the Neuropsychiatric Inventory (NPI-10) in two samples of outpatients with dementia living in Brazil and Norway. METHODS: This is a cross-sectional study. The sample consists of 168 Brazilian and 155 Norwegian demented patients from psychogeriatric facilities and community-based educational programs. Brazilian patients were diagnosed with Alzheimer's disease (63.7%), vascular dementia (15.5%), or mixed dementia (20.8%), whereas the diagnoses of Norwegian patients were Alzheimer's disease (97.4%) and mixed dementia (2.6%). Principal component analysis with the Varimax rotation was used for factor analysis of the NPI-10. RESULTS: Apathy (80.4 %), agitation/aggression (45.8%), and aberrant motor behavior (45.8%) were the most common symptoms in the Brazilian sample. Apathy (72.3%), dysphoria (61.9%), and anxiety (52.3%) were the most frequent symptoms in the Norwegian sample. Factor analysis of the NPI-10 revealed three syndromes for the Brazilian (Psychosis, Mood, Psychomotor) and Norwegian (Psychosis, Mood, Frontal) groups. CONCLUSIONS: The frequency of individual NPS may differ among distinct populations. However, Psychosis and Depression are common sub-syndromes in diverse ethnical and cultural patients with dementia. Our findings support the syndromic approach for the clinical assessment of the patients with dementia.

The memory engram: beginning the search.

Some of the earliest conceptual milestones in memory research with relevance to the physical means through which its preservation is made possible, namely, the 'memory trace' or 'engram', are analysed in this study. The fundamental notions were laid down by Platon and Aristoteles. While Platon regarded memory as an imprint on a 'wax block' in the immortal soul, Aristoteles considered memory a modification in the mortal soul, imprinted like a cast at birth time. The Roman orators were interested in mnemotechnics, and Cicero is credited for the term 'trace' (vestigium) used for the first time. Much later, Descartes described the (memory) 'trace' (trace), linking psychic, and physical processes. Finally, Semon posited innovative concepts and terms centralized by the 'engram' (Engramm). The search of this important question, which begun about two and a half millennia ago, continues in focus, as can be seen through the growing rate of published papers on the subject.

Alguns dos marcos conceituais iniciais na pesquisa de memória, com relevância para o meio físico, pelo qual a preservação desta é possibilitada, a saber, o 'traço de memória' ou 'engrama', são aqui analisados. As noções fundamentais foram formuladas por Platão e Aristóteles. Enquanto Platão via a memória como uma impressão em um 'bloco de cera' na alma imortal, Aristóteles considerava a memória uma modificação na alma mortal, impressa como um molde ao nascimento. Os oradores romanos tinham interesse em mnemotécnica e Cícero tem o crédito de ter usado o termo 'traço' (vestigium) pela primeira vez. Mais tarde, Descartes descreveu o 'traço' (trace) (de memória), ligando processos psíquicos e físicos. Finalmente, Semon propôs conceitos e termos inovadores centralizados pelo 'engrama' (Engramm). A busca dessa importante questão, que começou aproximadamente há dois milênios e meio, continua em foco, como pode ser visto pelo ritmo crescente de artigos publicados sobre o assunto.

Jean-Martin Charcot: the polymath.

Jean-Martin Charcot, widely regarded as a leading founder of modern neurology, made substantial contributions to the understanding and characterization of numerous medical conditions. His initial focus was on internal medicine, later expanding to include neuropathology, general neurology, and eventually emerging fields such as neuropsychology and neuropsychiatry. Furthermore, Charcot's intellectual pursuits extended beyond medicine, encompassing research in art history, medical iconography, sociology, religious studies, and the arts, solidifying his status as a polymath.

Jean-Martin Charcot, amplamente considerado como um proeminente fundador da neurologia moderna, fez contribuições substanciais para a compreensão e a caracterização de várias condições médicas. Seu foco inicial era a medicina interna, expandindo-se posteriormente para incluir a neuropatologia, a neurologia geral e, por fim, campos emergentes como a neuropsicologia e a neuropsiquiatria. Além disso, as buscas intelectuais de Charcot foram além da medicina, abrangendo pesquisas em história da arte, iconografia médica, sociologia, estudos religiosos e artes, solidificando seu status de polímata.

School attainment in childhood is an independent risk factor of dementia in late life: results from a Brazilian sample.

BACKGROUND: This study sought to assess whether lower school performance in childhood is a risk factor for dementia in old age. METHODS: Participants aged 60 years or more (n = 111) with documented proof from schools were included. Grades in three subjects - Portuguese, mathematics, and geography - were recorded and the mean final grade in all disciplines were assessed. Dementia was diagnosed using DSM-IV criteria. Sociodemographic data, school performance, and years of education were ascertained by checking documents issued by schools. Health status (hypertension and diabetes) were self reported. Regression models were used to assess the role of school performance and years of education on the risk of dementia. RESULTS: Dementia was diagnosed in 22 subjects. Higher school performance and years of education decreased the chance of dementia by 79% (OR = 0.21; CI 0.08-0.58) and 21% (OR = 0.79; CI 0.69-0.91), respectively. After adjustments for sociodemographic and clinical variables, only school performance remained statistically significant (OR = 0.06; CI 0.01-0.71). CONCLUSIONS: Education in early life should be viewed as a health issue over the life course. School attainment in certain basic disciplines may be important for cognitive reserve and prevention of dementia in the elderly.

Advancing the Genetics of Lewy Body Disorders with Disease-Modifying Treatments in Mind.

In this article, a caveat for advancing the genetics of Lewy body disorders is raised, given the nosological controversy about whether to consider dementia with Lewy bodies (DLB) and Parkinson's disease (PD) as one entity or two separate entities. Using the framework of the sufficient and component causes model of causation, as further developed into an evolution-based model of causation, it is proposed that a disease of complex etiology is defined as having a relatively high degree of sharing of the component causes (a genetic or environmental factor), that is, a low degree of heterogeneity of the sufficient causes. Based on this definition, only if the sharing of component causes within each of two diseases is similar to their combined sharing can lumping be warranted. However, it is not known whether the separate and combined sharing are similar before conducting the etiologic studies. This means that lumping DLB and PD can be counterproductive as it can decrease the ability to detect component causes despite the potential benefit of conducting studies with larger sample sizes. In turn, this is relevant to the development of disease-modifying treatments, because non-overlapping causal genetic factors may result in distinct pathogenetic pathways providing promising targets for interventions.

Echoes of William Gowers's concept of abiotrophy.

Among William Gowers's many contributions to neurology, the concept of abiotrophy ("an essential failure of vitality") has been relatively overlooked. In this article, we review the echoes of Gowers's concept in neurology, ophthalmology, and aging research. We also argue that abiotrophy is broader than both heredodegeneration and neurodegeneration. Unlike the common view that it simply means premature aging, abiotrophy currently can be understood as a progressive degenerative process of a mature specialized tissue, which is nonsynchronous with normal aging and may affect organs or systems early in life, resulting from the age-dependent effects of genetic mutations or variants, even if environmental factors may also causally contribute to the process. Although the term has largely fallen out of use, there are likely to be everlasting echoes of Gowers's concept, through which he is to be considered a source of the modern thinking about the etiology and nosology of neurological diseases.

Diagnosis of vascular cognitive impairment: recommendations of the scientific department of cognitive neurology and aging of the Brazilian Academy of Neurology.

Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care (primary, secondary and tertiary) in Brazil.

Desde a publicação das últimas recomendações para o diagnóstico e tratamento da Demência Vascular pela Academia Brasileira de Neurologia em 2011, avanços significativos ocorreram na terminologia e critérios diagnósticos. O presente manuscrito é resultado do consenso entre especialistas indicados pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia (2020-2022). O objetivo foi atualizar as recomendações práticas para a identificação, classificação e diagnóstico do Comprometimento Cognitivo Vascular (CCV). As buscas foram realizadas nas plataformas MEDLINE, Scopus, Scielo e LILACS. As recomendações buscam fornecer uma ampla revisão sobre o tema, então sintetizar as evidências para o diagnóstico do CCV não apenas para neurologistas, mas também para outros profissionais de saúde envolvidos na avaliação e nos cuidados ao paciente com CCV, considerando as diferentes realidades dos níveis de atenção à saúde (primário, secundário e terciário) no Brasil.

Marcello Malpighi: the nervous system under a microscope.

The longstanding study of gross anatomy experienced a considerable improvement with the advent of the microscope in the early 17th century. The representative personality of this new era certainly was Marcello Malpighi, seen as "founder of microscopic anatomy". He studied, with a rudimentary compound microscope, numerous tissues and organs of several classes of animals, as well as plants. He described, for the first time, the microscopic structure of the nervous system, identifying in the gray matter of its various levels minute elements he took as "glands". It should be reminded that the concept of "cell" (and "nerve cell") was unknown at his time. Many researchers followed, performing microscopic studies, but without better results, and Malpighi's view was maintained until the beginning of the 19th century, when new histological processing and staining techniques appeared, as well as improved microscopes.

DESCARTES and his project of a fantasized brain.

Interest in anatomy dates from the earliest times. Such knowledge was acquired through dissections of animals and human corpses by many researchers. The macroscopic anatomy of the varied structures of the brain were identified over the centuries, and the predominating solid substance was seen as amorphous, and devoid of any specific function, until the Renaissance. René Descartes, a personage with a brilliant and creative mind, conceived the brain, its structure and function, in a distinct manner to what was known at his time. He valued the solid matter and gave it, for the first time, a theoretical minute structure, related to a presumptive function based on the presence of the pineal gland and the animal spirits, underlying cognitive, sensory and motor activities. Such structural view was endorsed, in a given sense, by the microscopic findings of Marcello Malpighi, which begun to change the understanding of the nervous system.

O interesse pela anatomia data desde a mais remota antiguidade. Esse conhecimento foi adquirido por meio de dissecções em animais e cadáveres humanos, por muitos pesquisadores. A anatomia macroscópica de variadas estruturas do cérebro foi identificada com o passar dos séculos, e a substância sólida predominante foi vista como amorfa e destituída de qualquer função específica até o período do Renascimento. René Descartes, um personagem com uma mente brilhante e criativa, concebeu o cérebro, sua estrutura e função, de um modo distinto ao que era conhecido no seu tempo. Ele valorizou e deu à substância sólida, pela primeira vez, uma estrutura teórica formada por elementos minúsculos, relacionada a uma função presuntiva, baseada na presença da glândula pineal e dos espíritos animais, subjacentes às atividades cognitiva, sensorial e motora. Essa vista estrutural foi, de certa maneira, endossada pelos achados microscópicos de Marcello Malpighi, o que começou a modificar a compreensão do sistema nervoso.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

Education does not equally influence all the Mini Mental State Examination subscales and items: inferences from a Brazilian community sample.

OBJECTIVE: Mini-Mental State Examination cutoffs have been presented for schooling levels to screen cognitive impairment. However, items may behave differently with regards to education. The objective of this study was to examine the impact of education on MMSE subscales and items. METHOD: Community-dwelling participants aged 65 years or more (n = 990, females = 637, age = 74.1 years, range 65-108) were stratified as illiterate (n = 373), 1-8 (n = 540), 9-12 (n = 63), and more than 12 years of schooling (n = 14) and were screened with MMSE and Pfeffer Functional Activities Questionnaire. To make the Mini-Mental State Examination items comparable, each item was transformed into z scores. Multiple linear regression was used to estimate the effect of schooling on MMSE subs and items controlling for age, sex, and activities of daily life. RESULTS: Temporal and space orientation, attention/calculation, repetition, reading, writing, and drawing scores improved as education increased, but not memory registration, three step command, and naming. Reading and writing displayed the largest coefficients, whereas education exerted no influence on naming and three step command tasks. CONCLUSION: Education does not exert an important effect on naming, three step command, memory registration, and delayed recall. As memory is a key factor for diagnosing dementia, these items could be considered despite education.

Cerebral localization of higher functions: Memory-related anatomic structures.

The nature of memory and the search for its localization have been a subject of interest since Antiquity. After millennia of theoretical concepts, shifting from the heart to the brain, then from the ventricles to solid parts, the core memory-related structures finally began to be identified through modern scientifically-based methods at the diencephalic and cortical (hippocampal and neocortical) levels, mostly in the late Modern period, culminating in the current state of knowledge on the subject.

A natureza da memória e a busca de sua localização tem sido objeto de interesse desde a Antiguidade. Após milênios de conceitos teóricos, mudando do coração para o cérebro e daí dos ventrículos para as partes sólidas, as estruturas centrais relacionadas com a memória finalmente começaram a ser identificadas através de métodos modernos com base científica, nos níveis diencefálico e cortical (hipocampal e neocortical), principalmente no período Moderno tardio, aproximando-se do estado atual do conhecimento sobre o tema.

Neuropsychiatric symptoms in brain diseases - historical foundations.

Neuropsychiatric symptoms, which may appear alone or combined with cognitive and neurological manifestations, are frequent in many brain dysfunctions or lesions due to vascular, traumatic, neurodegenerative, or systemic conditions. Throughout history, many of the most prominent names have contributed to the clinical definition of the currently recognized mental symptoms and syndromes. The present paper aims at providing a comprehensive overview of the development, from ancient to modern times, of some widely known concepts and constructs about such neuropsychiatric disorders.

Os sintomas neuropsiquiátricos que podem ocorrer de modo isolado ou acompanhando manifestações cognitivas e neurológicas são ocorrências frequentes em variadas disfunções ou lesões cerebrais devidas a condições vasculares, traumáticas, neurodegenerativas ou sistêmicas. Através da história, muitos dos nomes mais proeminentes contribuíram para a definição clínica dos sintomas e síndromes mentais reconhecidos atualmente. O presente artigo visa prover uma visão abrangente sobre o desenvolvimento, desde os tempos antigos até os presentes, de alguns dos conceitos e constructos amplamente reconhecidos sobre tais transtornos neuropsiquiátricos.

Neuropsychological tests and driving in dementia: a review of the recent literature.

INTRODUCTION: Neuropsychological tests measure several aspects of cognition and are useful to evaluate elderly drivers with cognitive impairment. However, there is no consensus on a standard battery of tests that could accurately predict safe driving. OBJECTIVE: The aim of this study is to review specific neuropsychological measures that may be useful to predict driving competence of demented individuals. METHOD: To address neuropsychological tests used for dementia and the ability to drive, the authors searched for the keywords dementia, Alzheimer's, drive, driver, drivers, driving, tests, neuropsychological, and assessment, in Medline, PubMed, ISI and SciELO databases seeking articles from 2000 to 2008. RESULTS: From 131 articles, 27 met the inclusion criteria. Porteus Maze, Clock drawing, Trail B, UFOV and NAB Tests were found to be the most relevant neuropsychological measures for the evaluation of fitness to drive. CONCLUSION: Porteus Maze, Clock Drawing, Trail B, UFOV and NAB tests highlight visuospatial attention demands and/ or executive function. Those and other visuospatial and executive measures may be useful to predict driving competence of demented individuals.

Cerebral localization of higher functions: The period between Thomas Willis and Paul Broca.

The age-old debates about the localization of the mind (higher functions) took a new course when Willis located a higher nervous function (memory) in the brain parenchyma, and supposedly, in the cerebral cortex. About two centuries later, Broca, founded on solid scientific reasoning, localized a circumscribed area of the 3rd frontal circumvolution of the left hemisphere as the seat of articulate language, a higher function (speech - language domain). He (and Dax) also defined the functional asymmetry (specialization) of the hemispheres, with left dominance (for language). The period between the findings of these individuals was not quiescent, as numerous authors contributed with their theoretical and clinicopathological research toward creating a conducive scientific atmosphere for this accomplishment, and should be regarded as important. Further studies, in the decades that followed, revealed the localization of additional aspects of language and of other higher functions (cognitive domains).

Os debates milenares sobre a localização da mente (funções superiores) chegaram a um novo caminho quando Willis localizou uma função nervosa superior (memória) no parênquima cerebral, e supostamente, no córtex cerebral. Cerca de dois séculos depois, Broca, baseado em sólido pensamento científico, localizou uma área circunscrita da 3ª circunvolução frontal do hemisfério esquerdo como o sítio da linguagem articulada, uma função superior (fala - domínio da linguagem). Ele (e Dax) também definiu a assimetria funcional (especialização) dos hemisférios, com dominância esquerda (para linguagem). O período entre os achados dessas duas personalidades não ficou quiescente, considerando que numerosos autores contribuíram, com suas pesquisas teóricas e clinicopatológicas, para criar uma atmosfera científica adequada para tal realização, devendo ser vistos como importantes. Mais estudos, nas décadas seguintes, revelaram a localização de aspectos adicionais da linguagem e de outras funções superiores (domínios cognitivos).

The contribution of Alois Alzheimer and Oskar Fischer to the understanding of Pick's complex - (Historical Note) / A contribuição de Alois Alzheimer e Oskar Fischer para a compreensão do complexo de Pick - (Nota Histórica)

Arnold Pick described a series of cases with progressive aphasia, behavioural disorders, and dementia. The post-mortem examination revealed on macroscopy, beside diffuse brain atrophy, also circumscribed (lobar) atrophy of the temporal and/or frontal lobes. The histopathology was not provided. Such kind of cases were soon named after the author, being known for a time as 'Pick's disease', coming to constitute a new nosological group. A time later after the original description, Alois Alzheimer and Oskar Fischer completed microscopic examination of similar cases, where the first author found, on silver impregnation, spheric neuronal inclusions, he named 'argentophilic ball' inclusions, while the second one identified complex cortical changes he named 'spongiform cortical wasting', and additionally a type of swollen cell that was named 'ballooned neuron'. Such microscopic changes became the first histopathological markers of this group of diseases.

Arnold Pick descreveu uma série de casos apresentando, de modo progressivo, afasia, transtornos de comportamento e demência. O exame pós-morte revelou à macroscopia, além de atrofia cerebral difusa, também atrofia circunscrita (lobar) dos lobos temporais e/ou frontais. A histopatologia não foi fornecida. Tal tipo de casos foi logo denominado segundo o autor, sendo conhecido por um período como 'doença de Pick', vindo a constituir um novo grupo nosológico. Algum tempo após a discrição original, Alois Alzheimer e Oskar Fischer perfizeram exame microscópio de casos semelhantes, onde o primeiro autor encontrou inclusões neuronais esféricas à impregnação pela prata, que denominou de 'bola argirofílica', enquanto o segundo identificou alterações corticais complexas às quais denominou 'perda cortical espongiforme', além de um tipo de célula tumefeita que chamou de 'neurônio balonizado'. Tais alterações microscópicas tornaram-se os primeiros marcadores histopatológicos desse grupo de doenças.

Topiramate may modulate alcohol abuse but not other compulsive behaviors in frontotemporal dementia: case report.

Frontotemporal dementia (FTD) is an insidious presenile neurodegenerative disorder presenting with personality changes, compulsive behaviors, psychosis, apathetic, aberrant, and elated mood and behavior. No psychopharmacologic strategy has proven to be efficacious in the treatment of FTD yet. This is a case report of FTD in a 53-year-old male engineer whose alcohol abuse, but not other compulsive behaviors, responded to topiramate. Alcohol exerts reinforcing effects on cortico-mesolimbic dopamine pathways through the disinhibition of the inhibitory effects of gamma-amino-butyric acid-A neurons in the ventral tegmental area. Topiramate is a sulfamate-substituted fructopyranose derivative that may antagonize the reinforcing effects associated with the abuse liability of alcohol by modulation of cortico-mesolimbic dopamine function. On the basis of the mechanism of action of topiramate, we discuss the possible specificity of action of topiramate to control abusive drinking, but not to treat other clinical symptoms of FTD.