Leptin in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid-ß protein (Aß) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function.

Cognitive impairment and magnetic resonance imaging correlations in Wilson's disease.

OBJECTIVES: To evaluate the cognitive performance of a group of patients with Wilson's disease (WD) and to correlate the cognitive findings with changes in magnetic resonance imaging (MRI). METHODS: All patients with WD consecutively attended in a Movement Disorders Clinic between September 2006 and October 2007 were invited to participate in the study, together with a group of matched healthy controls. Patients and controls were submitted to comprehensive neuropsychological assessment. MRI was performed in all patients, and abnormalities (high-intensity signal, low-intensity signal and atrophy) were semi-quantitatively rated. Performance of patients and controls in each cognitive test was compared, and correlations between cognitive scores and MRI changes were investigated within the patients' group. RESULTS: Twenty patients with WD (11 men) and 20 controls (nine men) were evaluated. Mean age in the WD and control groups was 30.05 ± 7.25 and 32.15 ± 5.37 years, respectively. Mean schooling years were 11.15 ± 3.73 among WD cases and 10.08 ± 2.62 among controls. Patients with WD performed significantly worse than controls in the Mini-Mental State Examination, Dementia Rating Scale, phonemic verbal fluency (FAS), verb generation, digit span forward, Stroop test, Frontal Assessment Battery and in the Brief Cognitive Screening Battery. A significant correlation emerged between global cognitive impairment and MRI scale (r = 0.535), being higher for high-intensity signal plus atrophy (r = 0.718). CONCLUSION: Patients with WD presented cognitive impairment, especially in executive functions, with good correlation between cognitive abnormalities and MRI changes.

Spectrum of cognitive impairment in neurocysticercosis: differences according to disease phase.

OBJECTIVES: Cognitive decline related to neurocysticercosis (NC) remains poorly characterized and underdiagnosed. In a cross-sectional study with a prospective phase, we evaluated cognitive decline in patients with strictly calcified form (C-NC), the epidemiologically largest subgroup of NC, and investigated whether there is a spectrum of cognitive abnormalities in the disease. METHODS: Forty treatment-naive patients with C-NC aged 37.6 ± 11.3 years and fulfilling criteria for definitive C-NC were submitted to a comprehensive cognitive and functional evaluation and were compared with 40 patients with active NC (A-NC) and 40 healthy controls (HC) matched for age and education. Patients with dementia were reassessed after 24 months. RESULTS: Patients with C-NC presented 9.4 ± 3.1 altered test scores out of the 30 from the cognitive battery when compared to HC. No patient with C-NC had dementia and 10 patients (25%) presented cognitive impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients with A-NC with dementia previously still presented cystic lesions with scolex on MRI and still had dementia. One patient died and the remaining patient no longer fulfilled criteria for either dementia or CIND, presenting exclusively calcified lesions on neuroimaging. CONCLUSIONS: Independently of its phase, NC leads to a spectrum of cognitive abnormalities, ranging from impairment in a single domain, to CIND and, occasionally, to dementia. These findings are more conspicuous during active vesicular phase and less prominent in calcified stages.

Cross-cultural adaptation of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to Brazilian Portuguese / Adaptação transcultural da escala de distonia cervical de Toronto (TWSTRS) para o português

Cervical dystonia (CD) is a prevalent and incapacitating movement disorder which needs a thorough clinical evaluation of every patient to better tailor treatment strategies. In Brazil, there are no validated CD scales that measure the burden of dystonia. The aim of our study was to translate and adapt the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to Brazilian Portuguese. After translation and back-translation according to international methods, a pre-test was carried out with 30 patients. Patients under 8 years of formal schooling had severe difficulty in understanding the whole scale. The scale went through a remodeling process, without loss of its conceptual and semantic properties. The new scale was tested in 15 patients, with good understanding scores. We are now in the process of validation of the adapted scale.

Distonia cervical (DC) é um transtorno de movimento prevalente e incapacitante, sendo uma avaliação global e consistente de cada paciente necessária para a melhor intervenção diagnóstica e terapêutica. No Brasil, não há escalas validadas para avaliar o impacto da DC. O objetivo deste trabalho foi traduzir e adaptar uma escala mundialmente conhecida e usada, a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) para o português. Após a tradução e retro-tradução da escala segundo as normas e critérios internacionais, realizamos o pré-teste com 30 pacientes, sendo que o completo entendimento da escala ficou prejudicado nos pacientes com escolaridade abaixo de 8 anos. Tornou-se necessária a re-adaptação da escala, com modificação de alguns elementos, tentando manter-se sua integridade conceitual e semântica. Após pré-teste adicional com 15 pacientes, verificou-se que a escala foi completamente entendida por praticamente todos os pacientes. A validação da escala está em andamento.

The assessment and management of pain in the demented and non-demented elderly patient / Avaliação e manejo da dor em pacientes idosos com e sem demência

Persistent pain is a frequent health problem in the elderly. Its prevalence ranges from 45 percent to 80 percent. Chronic diseases, such as depression, cardiovascular disease, cancer and osteoporosis have a higher prevalence in aged individuals and increase the risk of developing chronic pain. The presence of pain is known to be associated with sleep disorders in these patients, as well as functional impairment, decreased sociability and greater use of the health system, with consequent increase in costs. Alzheimer's disease patients seem to have a normal pain discriminative capacity and they may probably have weaker emotional and affective experience of pain when compared to other types of dementia. Many patients have language deficits and thus cannot properly describe its characteristics. In more advanced cases, it becomes even difficult to determine whether pain is present or not. Therefore, the evaluation of these patients should be performed in a systematic way. There are three ways to measure the presence of pain: by direct questioning (self-report), by direct behavioral observation and by interviews with caregivers or informants. In recent years, many pain scales and questionnaires have been published and validated specifically for the elderly population. Some are specific to patients with cognitive decline, allowing pain evaluation to be conducted in a structured and reproducible way. The next step is to determine the type of painful syndrome and discuss the bases of the pharmacological management, the use of multiple medications and the presence of comorbidities demand the use of smaller doses and impose contra-indications against some drug classes. A multiprofessional approach is the rule in the management of these patients.

Dor persistente é um problema de saúde frequente no idoso e sua prevalência varia de 45 a 80 por cento. Doenças crônicas, como depressão, distúrbios cardiovasculares, câncer e osteoporose tem alta prevalência em indivíduos idosos e aumentam o risco de desenvolver dor crônica. Nestes indivíduos, a presença de dor está associada a distúrbios do sono, prejuízo funcional, diminuição da sociabilidade e maior procura dos serviços de saúde, com o consequente aumento dos custos de saúde. Pacientes com Alzheimer têm uma capacidade discriminativa dolorosa normal e uma experiência afetiva e emocional da dor mais atenuada quando comparados com outros tipos de demência. Muitos pacientes têm déficits de linguagem e não podem descrever adequadamente as características de sua dor. Em casos avançados, torna-se difícil determinar se a dor está realmente presente ou não. Desta forma, a avaliação destes doentes deve ser realizada de forma sistemática. Há três formas de se avaliar a dor: questionários diretos, observação direta do comportamento ou entrevistas diretas com os cuidadores ou informantes. Nos últimos anos muitas escalas e questionários para dor foram publicados e validados especificamente para a população idosa. Alguns são específicos para pacientes com declínio cognitivo, permitindo que a evolução da dor possa ser conduzida de uma forma estruturada e reprodutível. O passo seguinte é se determinar o tipo de síndrome dolorosa e se discutir as bases do manejo farmacológico. O uso de múltiplas medicações e a presença de comorbidades exige o uso de pequenas doses e impõem contra-indicações para algumas classes de drogas. A abordagem multidisciplinar é a regra no seguimento a longo prazo destes doentes.

Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study.

OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.

Chronic stress is associated with high cortisol levels and emotional coping mechanisms in amnestic mild cognitive impairment.

BACKGROUND/AIMS: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI). METHODS: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale. RESULTS: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023). CONCLUSION: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory defi- cit awareness constitutes an additional potential factor involved in high stress severity.

Beyond neuropathy in hereditary sensory and autonomic neuropathy type V: cognitive evaluation.

BACKGROUND AND PURPOSE: Hereditary sensory and autonomic neuropathy (HSAN) type V is a very rare disorder. It is characterized by the absence of thermal and mechanical pain perception caused by decreased number of small diameter neurons in peripheral nerves. Recent genetic studies have pointed out the aetiological role of nerve growth factor beta, which is also involved in the development of the autonomic nervous system and cholinergic pathways in the brain. HSAN type V is usually reported not to cause mental retardation or cognitive decline. However, a structured assessment of the cognitive profile of these patients has never been made. METHODS AND RESULTS: We performed a throughout evaluation of four HSAN type V patients and compared their performance with 37 normal individuals. Our patients showed no cognitive deficits, not even mild ones. DISCUSSION AND CONCLUSIONS: Although newer mutations on this and related disorders are continuously described, their clinical characterization has been restricted to the peripheral aspects of these conditions. A broader characterization of this rare disorder may contribute to better understand the mechanisms of the nociceptive and cognitive aspects of pain.

Patterns of cerebral activation during lexical and phonological reading in Portuguese

According to the concepts of cognitive neuropsychology, there are two principal routes of reading processing: a lexical route, in which global reading of words occurs and a phonological route, responsible for the conversion of the graphemes into their respective phonemes. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the patterns of cerebral activation in lexical and phonological reading by 13 healthy women with a formal educational level greater than 11 years. Participants were submitted to a silent reading task containing three types of stimuli: real words (irregular and foreign words), nonwords and illegitimate graphic stimuli. An increased number of activated voxels were identified by fMRI in the word reading (lexical processing) than in the nonword reading (phonological processing) task. In word reading, activation was greater than for nonwords in the following areas: superior, middle and inferior frontal gyri, and bilateral superior temporal gyrus, right cerebellum and the left precentral gyrus, as indicated by fMRI. In the reading of nonwords, the activation was predominant in the right cerebellum and in the left superior temporal gyrus. The results of the present study suggest the existence of differences in the patterns of cerebral activation during lexical and phonological reading, with greater involvement of the right hemisphere in reading words than nonwords.

Patterns of cerebral activation during lexical and phonological reading in Portuguese.

According to the concepts of cognitive neuropsychology, there are two principal routes of reading processing: a lexical route, in which global reading of words occurs and a phonological route, responsible for the conversion of the graphemes into their respective phonemes. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the patterns of cerebral activation in lexical and phonological reading by 13 healthy women with a formal educational level greater than 11 years. Participants were submitted to a silent reading task containing three types of stimuli: real words (irregular and foreign words), nonwords and illegitimate graphic stimuli. An increased number of activated voxels were identified by fMRI in the word reading (lexical processing) than in the nonword reading (phonological processing) task. In word reading, activation was greater than for nonwords in the following areas: superior, middle and inferior frontal gyri, and bilateral superior temporal gyrus, right cerebellum and the left precentral gyrus, as indicated by fMRI. In the reading of nonwords, the activation was predominant in the right cerebellum and in the left superior temporal gyrus. The results of the present study suggest the existence of differences in the patterns of cerebral activation during lexical and phonological reading, with greater involvement of the right hemisphere in reading words than nonwords.

Spelling tasks and Alzheimer's disease staging.

Reading, writing and oral spelling were evaluated in 30 normal elderly individuals and 28 patients with probable Alzheimer's disease (AD). Significant differences between control and AD groups were found in all tasks. Oral spelling was the most impaired function in AD and the only one which differentiated mild and moderate dementia cases. This task is very sensitive to the disease's effects on working memory and may be included in batteries aimed at staging AD.

Incidence of dementia in a community-dwelling Brazilian population.

The authors report the incidence of dementia in a community-dwelling Brazilian population. In 1997, 1656 individuals aged 65 years or more, the majority being of very low educational level, were screened at their homes in Catanduva, Brazil, and dementia was diagnosed in 118 cases. The remaining 1538 individuals were rescreened 3.25 years later applying a health questionnaire, the Mini-Mental State Examination (MMSE) and the Pfeffer Functional Activities Questionnaire (PFAQ). According to PFAQ and MMSE scores, selected subjects were submitted to clinical, neurologic, and cognitive evaluations. The subjects diagnosed with dementia underwent laboratory tests and brain computed tomography. A total of 1119 individuals were rescreened and 50 incident cases of dementia (28 with Alzheimer disease [AD]) were identified. The incidence rate of dementia was 13.8 and of AD was 7.7 per 1000 person-years for individuals aged 65 years or older. The incidence rates of dementia almost doubled with every 5 years of age. There was no difference according to gender, but women had a higher incidence of dementia, predominantly AD, in very old age. There was a trend for higher incidence of dementia in illiterates (p = 0.07), but multivariate analysis disclosed significant association only between age and higher incidence of dementia. The incidence rates of dementia in this Brazilian community are comparable to those reported in Western and Asian studies.

Primary progressive aphasia: analisys of 16 cases.

Primary progressive aphasia (PPA) is an intriguing syndrome, showing some peculiar aspects that differentiate it from classical aphasic pictures caused by focal cerebral lesions or dementia. The slow and progressive deterioration of language occurring in these cases provides an interesting model to better understand the mechanisms involved in the linguistic process. We describe clinical and neuroimaging aspects found in 16 cases of PPA. Our patients underwent language and neuropsychological evaluation, magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT). We observed a clear distinction in oral expression patterns; patients were classified as fluent and nonfluent. Anomia was the earliest and most evident symptom in both groups. Neuroimaging pointed to SPECT as a valuable instrument in guiding the differential diagnosis, as well as in making useful clinical and anatomical correlations. This report and a comparison to literature are an attempt to contribute to a better understanding of PPA.

Involuntary hand levitation associated with parietal damage: another alien hand syndrome.

The alien hand syndrome (AHS) usually consists of an autonomous motor activity perceived as an involuntary and purposeful movement, with a feeling of foreignness of the involved limb, commonly associated with a failure to recognise ownership of the limb in the absence of visual clues. It has been described in association to lesions of the frontal lobes and corpus callosum. However, parietal damage can promote an involuntary, but purposeless, hand levitation, which, sometimes, resembles AHS. In the present study, four patients (cortico-basal ganglionic degeneration - n=2; Alzheimer's disease - n=1 and parietal stroke - n=1) who developed alien hand motor behaviour and whose CT, MRI and/or SPECT have disclosed a major contralateral parietal damage or dysfunction are described. These results reinforce the idea that parietal lobe lesions may also play a role in some patients with purposeless involuntary limb levitation, which is different from the classic forms of AHS.

Elderly Japanese emigrants to Brazil before World War II: II. Prevalence of senile dementia.

BACKGROUND: We previously showed the prevalence of dementia in the town of Tajiri (Miyagi Prefecture, Japan), and found it to be 8.0%. The first population-based study on dementia in Brazil (Catanduva) disclosed the prevalence as being 7.1%. To evaluate the effects of environment on development of dementia, elderly Japanese immigrants living in Brazil were examined. Brazil is the country with the largest number of Japanese immigrants. METHODS: All immigrants aged 65 years and over from Miyagi Prefecture, living in the four cities of the São Paulo Metropolitan area were targeted (n = 192). We were able to examine 166 subjects (86.5%). The diagnosis of dementia was based on the DSM-IV with the severity assessed by the CDR (clinical dementia rating) scales. The cognitive ability screening instrument (CASI) was used for neuropsychological assessment. RESULTS: Thirteen subjects were diagnosed with dementia, CDR 1-3, the prevalence being 7.8%. Older subjects suffered more from dementia, and, paradoxically, the more highly educated subjects also suffered more. All the CASI items, except for long-term memory and visual construction, significantly deteriorated in the CDR 0.5 group compared with the CDR 0 group. COMMENTS: The prevalence of dementia was not thought to be affected by environmental factors. A paradoxically higher rate of dementia in the more educated subjects was probably due to the historical problems of the immigrants. Intact CASI item long-term memory in the CDR 0.5 group indicated that suspected dementia patients could maintain this function. This is the first epidemiological study on dementia in elderly Japanese immigrants in Brazil.

Elderly Japanese emigrants to Brazil before World War II: I. Clinical profiles based on specific historical background.

OBJECTIVE: To research the demographic and clinical profiles of elderly Japanese emigrants, who arrived in Brazil before World War II, in order to give them appropriate psychogeriatric care. DESIGN: Elderly Japanese immigrants aged 65 years and over, belonging to the Miyagi Association in the São Paulo Metropolitan Area, were targeted. They emigrated from Miyagi Prefecture to Brazil and are now living in the area. We were able to interview 166 respondents. All data were gathered using standardized interview methods covering (a) free interview about the immigration history, (b) demographics, and (c) physical status. RESULTS: Through the free interview, we found their immigration histories, which affected their clinical profiles. The mean age and educational level were 77.5 years and 6.3 years, respectively. Sixty per cent of them immigrated when they were younger than 14. Ninety-four per cent of them still keep Japanese nationality. Fifty-seven per cent of them usually use Japanese, while 10% of them use Portuguese. Although their emigration histories were hard, 76% of them perceived their health as being excellent or relatively good. The percentages of subjects with histories of disease were hypertension, 52.5%; cardiac disease, 20.8%; diabetes mellitus, 24.2%; and hyperlipidemia, 25.0%, which were affected by the Brazilian environment. CONCLUSION: The elderly Japanese who emigrated to Brazil before World War II have a unique historical and demographic background. Their clinical profiles cannot be fully understood without knowing their histories. They definitely need high quality international psychogeriatric care.

[Clinical characterization of vascular dementia: retrospective evaluation of an outpatient sample]. / Caracterização clínica da demência vascular: avaliação retrospectiva de uma amostra de pacientes ambulatoriais.

OBJECTIVE: to analyze the clinical features and associated morbidity in a group of patients with vascular dementia (VD). METHODS: we retrospectively evaluated 25 patients with diagnosis of VD, based on the State of California Alzheimers Disease Diagnostic and Treatment Centers (ADDTC) criteria. Clinical and neuroimaging data and laboratory test results were obtained for the characterization of the sample. RESULTS: the mean age was 68.7 +/- 14.6 years (64.0% men), with mean educational level of 5.2 +/- 4.4 years. Sudden onset of symptoms was observed in 48.0% of patients and stepwise deteriorating and fluctuating courses being observed in 4.0% and 16% respectively. Focal neurologic deficits were the first symptom in 48.0%, with focal deficits being observed in 80% on examination. The main morbidity were: hypertension (92.0%); hypercholesterolemia (64.0%); coronary heart disease (40.0%); smoking (40.0%); hypertriglyceridemia (36.0%); diabetes mellitus (32.0%); Chagas' disease (8.0%). CONCLUSIONS: we observed strong association between VD and hypertension and hypercholesterolemia. The observation of two patients presenting Chagas' disease suggests that this endemic condition may be considered a possible regional risk factor.

Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17.

OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD), the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 +/- 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.