Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of ß-amyloid deposition and neurodegeneration.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum.

The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([11C]PIB) assessing amyloid beta (Aß) aggregation (A) and 18fluorine-fluorodeoxyglucose ([18F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.

Effect of medication withdrawal on pain in Parkinson's disease patients - an observational study based on a sample of patients without antiparkinsonian medications.

OBJECTIVES: To assess the effect of withdrawal of the antiparkinsonian drug regimen administration on patients with PD and its relation to pain. METHODS: The sample included 22 men and 12 women who were candidates for neurosurgery to control motor signs and symptoms treated with L-dopa as a drug, alone or in combination with others (Cholinergic Antagonists; Dopamine Agents). All of them were examined at two different moments, with and without medication, and analyzed for painful symptoms. The Hoehn and Yahr scale was used for functional staging of the disease. Pain intensity was assessed by using the numerical verbal scale. RESULTS: The mean pain intensity among those on medication {2.17±0.39 (SE)} was significantly lower than in the abstinence group {4.2±0.59 (SE), p=0.006, Wilcoxon}, which corresponded to the increase in the total functional staging score from 93 to 111, respectively. CONCLUSION: The interruption of the administration of specific medications in patients with Parkinson's disease caused, or increased the intensity of, painful discomfort correlated with the intensity of functional impairment. This effect was also observed in women, but it was statistically relevant only for men. The results suggest that pain may be a "red flag" that points to the need for a therapeutic drug review when its presence or worsening is detected.

Frontotemporal Dementia and Late-Onset Bipolar Disorder: The Many Directions of a Busy Road.

It is a common pathway for patients with the behavioral variant of frontotemporal dementia (bvFTD) to be first misdiagnosed with a primary psychiatric disorder, a considerable proportion of them being diagnosed with bipolar disorder (BD). Conversely, not rarely patients presenting in late life with a first episode of mania or atypically severe depression are initially considered to have dementia before the diagnosis of late-onset BD is reached. Beyond some shared features that make these conditions particularly prone to confusion, especially in the elderly, the relationship between bvFTD and BD is far from simple. Patients with BD often have cognitive complaints as part of their psychiatric disorder but are at an increased risk of developing dementia, including FTD. Likewise, apathy and disinhibition, common features of depression and mania, respectively, are among the core features of the bvFTD syndrome, not to mention that depression may coexist with dementia. In this article, we take advantage of the current knowledge on the neurobiology of these two nosologic entities to review their historical and conceptual interplay, highlighting the clinical, genetic and neuroimaging features that may be shared by both disorders or unique to each of them.

Loss of functional capacity in elderly individuals with Alzheimer disease.

BACKGROUND: The functional capacity of elderly individuals with Alzheimer disease (AD) progressively declines. OBJECTIVE: To verify the influence of sociodemographic, clinical, staging, mobility, and postural and cognitive balance data on the impairment of the functional capacity of elderly individuals with AD. METHODS: This observational, analytical, cross-sectional study was performed at the Physiotherapy Department of the Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. The study consisted of forty elderly individuals aged ≥60 years old with mild or moderate AD, who could ambulate independently. The instruments used included a questionnaire to assess sociodemographic and anthropometric data; the Mini-Mental Health State Examination (MMSE); the Clinical Dementia Rating (CDR); a clock drawing test (CDT); a verbal fluency test (VFT); the Timed Up and Go Test (TUG); and the Clinical Test of Sensory Organization and Balance (CTSIB). Simple descriptive analyses, Mann-Whitney test, Spearman's correlation test, linear regression modeling, and prediction equation (p<0.05, 95% confidence interval [95%CI]) were performed. RESULTS: Fifteen linear regression models were generated, with the final model chosen for analysis. The variables assumed in that model were CDR, MMSE score, and condition 3 of the CTSIB, which explained 60.1% of the outcome. CONCLUSIONS: Impairment of functional capacity in elderly individuals with AD was influenced by disease progression, which was due to cognitive deficits and deficits in postural balance, which are related to the inaccuracy of the somatosensory system in performing sensory integration.

INTRODUÇÃO: A capacidade funcional de idosos com doença de Alzheimer (DA) sofrerá prejuízo progressivo. OBJETIVO: O presente estudo visou verificar a influências de dados sociodemográficos, clínicos, de estadiamento, mobilidade, equilíbrio postural e cognitivos no prejuízo da capacidade funcional de idosos com DA. MÉTODOS: Trata-se de um estudo observacional, analítico e transversal, realizado no Departamento de Fisioterapia da Universidade Federal do Rio Grande do Norte, em Natal, Rio Grande do Norte, Brasil. O estudo contou com a participação de 40 idosos com idade igual ou superior a 60 anos com DA leve ou moderada, com deambulação independente. Os instrumentos utilizados incluíram um questionário para avaliação de dados sociodemográficos e antropométricos; o Mini-Exame de Estado de Saúde Mental (MEEM); a Avaliação Clínica da Demência (CDR); o Teste do desenho do Relógio (TDR); o Teste de Fluência Verbal (TFV); o Timed Up and Go Test (TUG); e o Clinical Test of Sensory Organization and Balance (CTSIB). Foram realizadas análises descritivas simples, teste de Mann-Whitney, teste de correlação de Spearman, modelo de regressão linear e equação de predição (p<0,05 e intervalo de 95% [IC95%]). RESULTADOS: Foram gerados quinze modelos de regressão linear e foi escolhido o último para a análise. As variáveis assumidas nesse modelo citado foram: CDR, MEEM e condição três do CTSIB, que explicam 60,1% do desfecho. CONCLUSÕES: Pode-se concluir que o prejuízo da capacidade funcional de idosos com DA é influenciado pelo avançar da doença, pelos déficits cognitivo e de equilíbrio postural, sendo esse mais relacionado à imprecisão do sistema somatossensorial em realizar a integração sensorial.

Evaluation of whole-body MRI with diffusion-weighted sequences in the staging of pediatric cancer patients.

BACKGROUND: The purpose of this study was to determine whether whole-body MRI (WBMRI) with diffusion-weighted sequences, which is free of ionizing radiation, can perform as well as traditional methods when used alone for staging or follow-up of pediatric cancer patients. METHODS: After obtaining approval from our institutional research ethics committee and appropriate informed consent, we performed 34 examinations in 32 pediatric patients. The examinations were anonymized and analyzed by two radiologists with at least 10 years' experience. RESULTS: The sensitivity and specificity findings, respectively, were as follows: 100% and 100% for primary tumor; 100% and 86% for bone metastasis; 33% and 100% for lung metastasis; 85% and 100% for lymph node metastasis; and 100% and 62% for global investigation of primary or secondary neoplasias. We observed excellent interobserver agreement for WBMRI and excellent agreement with standard staging examination results. CONCLUSIONS: Our results suggest that pediatric patients can be safely imaged with WBMRI, although not as the only tool but in association with low-dose chest CT (for subcentimeter pulmonary nodules). However, additional exams with ionizing radiation may be necessary for patients who tested positive to correctly quantify and locate the lesions.

Relationship Between PET-Assessed Amyloid Burden and Visual and Verbal Episodic Memory Performance in Elderly Subjects.

BACKGROUND: Studies of elderly subjects using biomarkers that are proxies for Alzheimer's disease (AD) pathology have the potential to document meaningful relationships between cognitive performance and biomarker changes along the AD continuum. OBJECTIVE: To document cognitive performance differences across distinct AD stages using a categorization based on the presence of PET-assessed amyloid-ß (Aß) burden and neurodegeneration. METHODS: Patients with mild dementia compatible with AD (n = 38) or amnestic mild cognitive impairment (aMCI; n = 43) and a cognitively unimpaired group (n = 27) underwent PET with Pittsburgh compound-B (PiB) assessing Aß aggregation (A+) and [18F]FDG-PET assessing neurodegeneration ((N)+). Cognitive performance was assessed with verbal and visual episodic memory tests and the Mini-Mental State Examination. RESULTS: The A+(N)+ subgroup (n = 32) showed decreased (p < 0.001) cognitive test scores compared to both A+(N)-(n = 18) and A-(N)-(n = 49) subjects, who presented highly similar mean cognitive scores. Despite its modest size (n = 9), the A-(N)+ subgroup showed lower (p < 0.043) verbal memory scores relative to A-(N)-subjects, and trend lower (p = 0.096) scores relative to A+(N)-subjects. Continuous Aß measures (standard uptake value ratios of PiB uptake) were correlated most significantly with visual memory scores both in the overall sample and when analyses were restricted to dementia or (N)+ subjects, but not in non-dementia or (N)-groups. CONCLUSION: These results demonstrate that significant Aß-cognition relationships are highly salient at disease stages involving neurodegeneration. The fact that findings relating Aß burden to memory performance were detected only at (N)+ stages, together with the similarity of test scores between A+(N)-and A-(N)-subjects, reinforce the view that Aß-cognition relationships during early AD stages may remain undetectable unless substantially large samples are evaluated.

Effect of medication withdrawal on pain in Parkinson's disease patients - an observational study based on a sample of patients without antiparkinsonian medications

SUMMARY OBJECTIVES: To assess the effect of withdrawal of the antiparkinsonian drug regimen administration on patients with PD and its relation to pain. METHODS: The sample included 22 men and 12 women who were candidates for neurosurgery to control motor signs and symptoms treated with L-dopa as a drug, alone or in combination with others (Cholinergic Antagonists; Dopamine Agents). All of them were examined at two different moments, with and without medication, and analyzed for painful symptoms. The Hoehn and Yahr scale was used for functional staging of the disease. Pain intensity was assessed by using the numerical verbal scale. RESULTS: The mean pain intensity among those on medication {2.17±0.39 (SE)} was significantly lower than in the abstinence group {4.2±0.59 (SE), p=0.006, Wilcoxon}, which corresponded to the increase in the total functional staging score from 93 to 111, respectively. CONCLUSION: The interruption of the administration of specific medications in patients with Parkinson's disease caused, or increased the intensity of, painful discomfort correlated with the intensity of functional impairment. This effect was also observed in women, but it was statistically relevant only for men. The results suggest that pain may be a "red flag" that points to the need for a therapeutic drug review when its presence or worsening is detected.

In vivo evidence for neuroplasticity in older adults.

Neuroplasticity can be conceptualized as an intrinsic property of the brain that enables modification of function and structure in response to environmental demands. Neuroplastic strengthening of synapses is believed to serve as a critical mechanism underlying learning, memory, and other cognitive functions. Ex vivo work investigating neuroplasticity has been done on hippocampal slices using high frequency stimulation. However, in vivo neuroplasticity in humans has been difficult to demonstrate. Recently, a long-term potentiation-like phenomenon, a form of neuroplastic change, was identified in young adults by differences in visual evoked potentials (VEPs) that were measured before and after tetanic visual stimulation (TVS). The current study investigated whether neuroplastic changes in the visual pathway can persist in older adults. Seventeen healthy subjects, 65 years and older, were recruited from the community. Subjects had a mean age of 77.4 years, mean education of 17 years, mean MMSE of 29.1, and demonstrated normal performance on neuropsychological tests. 1Hz checkerboard stimulation, presented randomly to the right or left visual hemi-field, was followed by 2min of 9Hz stimulation (TVS) to one hemi-field. After 2min of rest, 1Hz stimulation was repeated. Temporospatial principal component analysis was used to identify the N1b component of the VEPs, at lateral occipital locations, in response to 1Hz stimulation pre- and post-TVS. Results showed that the amplitude of factors representing the early and late N1b component was substantially larger after tetanic stimulation. These findings indicate that high frequency visual stimulation can enhance the N1b in cognitively high functioning old adults, suggesting that neuroplastic changes in visual pathways can continue into late life. Future studies are needed to determine the extent to which this marker of neuroplasticity is sustained over a longer period of time, and is influenced by age, cognitive status, and neurodegenerative disease.

Reversible dementia due to neurocysticercosis: Improvement of the racemose type with antihistamines.

Infection of the human central nervous system (CNS) by the larvae of Taenia solium, termed neurocysticercosis (NCC), is endemic in most developing countries, where it is a major cause of acquired seizures and other neurological morbidity, including neuropsychiatric symptoms. However, despite its frequent manifestation, some findings, such as cognitive impairment and dementia, remain poorly understood. Less commonly, NCC may affect the ventricular system and subarachnoid spaces and this form is known as extraparenchymal neurocysticercosis. A particular presentation of the subarachnoid form is called racemose cysticercosis, which has a progressive pattern, frequently leads to hydrocephalus and can be life-threatening. Here we review a case of the racemose variety of cysticercosis, complicated by hydrocephalus and reversible dementia, with remission of symptoms after derivation and that remained stable with use of dexchlorpheniramine. We discuss the challenges in diagnosis, imaging findings, treatment and follow-up of this disease.

A infecção do sistema nervoso central (SNC) pela larva da Taenia solium, intitulada neurocisticercose (NCC) é endêmica na maior parte dos países "em desenvolvimento", onde é a principal causa de convulsão adquirida, além de outras morbidades neurológicas, entre elas, sintomas neuropsiquiátricos. No entanto, apesar de manifestações neuropsiquiátricas serem frequentes, alguns achados, tais como comprometimento cognitivo e demência, continuam a ser mal compreendidos. Menos frequentemente, NCC pode afetar o sistema ventricular e espaços subaracnóideos e esta forma é conhecida como NCC extraparenquimatosa. Uma apresentação particular subaracnóidea, chamada cisticercose racemosa, é encontrada mais raramente, evolui de forma progressiva, associada a hidrocefalia e pode levar a morte. Neste artigo revisamos um caso da variedade racemosa de NCC, complicada com hidrocefalia e demência reversível que evoluiu com remissão dos sintomas após derivação ventricular e permaneceu estável com uso de dexclorfeniramina. Discutimos os desafios no diagnóstico, achados de imagem, tratamento e acompanhamento desta forma de doença.