Cerebrospinal fluid irisin and lipoxin A4 are reduced in elderly Brazilian individuals with depression: Insight into shared mechanisms between depression and dementia.

INTRODUCTION: Depression is frequent among older adults and is a risk factor for dementia. Identifying molecular links between depression and dementia is necessary to shed light on shared disease mechanisms. Reduced brain-derived neurotrophic factor (BDNF) and neuroinflammation are implicated in the pathophysiology of depression and dementia. The exercise-induced hormone, irisin, increases BDNF and improves cognition in animal models of Alzheimer's disease. Lipoxin A4 is a lipid mediator with anti-inflammatory activity. However, the roles of irisin and lipoxin A4 in depression remain to be determined. METHODS: In the present study, blood and CSF were collected from 61 elderly subjects, including individuals with and without cognitive impairment. Screening for symptoms of depression was performed using the 15-item Geriatric Depression Scale (GDS-15). RESULTS: CSF irisin and lipoxin A4 were positively correlated and reduced, along with a trend of BDNF reduction, in elderly individuals with depression, similar to previous observations in patients with dementia. DISCUSSION: Our findings provide novel insight into shared molecular signatures connecting depression and dementia.

Age-linked suppression of lipoxin A4 associates with cognitive deficits in mice and humans.

Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system. We demonstrate that genetic suppression of 5-lipoxygenase (5-LOX), the enzyme mediating LXA4 synthesis, promotes learning impairment in mice. Conversely, administration of exogenous LXA4 attenuated cytokine production and memory loss induced by inflammation in mice. We further show that cerebrospinal fluid LXA4 is reduced in patients with dementia and positively associated with cognitive performance, brain-derived neurotrophic factor (BDNF), and AD-linked amyloid-ß. Our findings suggest that reduced LXA4 levels may lead to vulnerability to age-related cognitive disorders and that promoting LXA4 signaling may comprise an effective strategy to prevent early cognitive decline in AD.

Mild Cognitive Impairment or Attention-Deficit/Hyperactivity Disorder in Older Adults? A Cross Sectional Study.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental condition, which may be associated with life-enduring cognitive dysfunction. It has been hypothesized that age-related cognitive decline may overlap with preexisting deficits in older ADHD patients, leading to increased problems to manage everyday-life activities. This phenomenon may mimic neurodegenerative disorders, in particular Mild Cognitive Impairment (MCI). This cross-sectional study aims to assess cognitive and behavioral differences between older subjects with ADHD and MCI. Methods: A total of 107 older participants (41 controls; 40 MCI and 26 ADHD; mean age = 67.60 ± 7.50 years; mean schooling = 15.14 ± 2.77 years; 65.4% females) underwent clinical, cognitive, and behavioral assessments by a multidisciplinary team at the Memory Clinic, D'Or Institute for Research and Education, Rio de Janeiro, Brazil. Mean scores in neuropsychological tasks and behavioral scales were compared across groups. Results: Participants with ADHD showed poorer performances than controls in episodic memory and executive function with large effect-sizes. Performances were comparable between MCI and ADHD for all domains. Discussion: MCI and ADHD in older individuals are dissociated clinical entities with overlapping cognitive profiles. Clinicians ought to be aware of these converging phenotypes to avoid misdiagnosis.

Cerebrospinal Fluid Neurotransmitters, Cytokines, and Chemokines in Alzheimer's and Lewy Body Diseases.

BACKGROUND: Alzheimer's disease (AD) and Lewy body disease (LBD) are complex neurodegenerative disorders that have been associated with brain inflammation and impaired neurotransmission. OBJECTIVE: We aimed to determine concentrations of multiple cytokines, chemokines, and neurotransmitters previously associated with brain inflammation and synapse function in cerebrospinal fluid (CSF) from AD and LBD patients. METHODS: We examined a panel of 50 analytes comprising neurotransmitters, cytokines, chemokines, and hormones in CSF in a cohort of patients diagnosed with mild cognitive impairment (MCI), AD, LBD, or non-demented controls (NDC). RESULTS: Among neurotransmitters, noradrenaline (NA) was increased in AD CSF, while homovanillic acid (HVA), a dopamine metabolite, was reduced in both AD and LBD CSF relative to NDC. Six cytokines/chemokines out of 30 investigated were reliably detected in CSF. CSF vascular endothelial growth factor (VEGF) was significantly reduced in LBD patients relative to NDC. CONCLUSIONS: CSF alterations in NA, HVA, and VEGF in AD and LBD may reflect pathogenic features of these disorders and provide tools for improved diagnosis. Future studies are warranted to replicate current findings in larger, multicenter cohorts.

Anosognosia for memory in dementia with Lewy bodies compared with Alzheimer's disease.

OBJECTIVES: Anosognosia is the inability to recognize one's own symptoms. Although dementia with Lewy bodies (DLB) is the second most common degenerative dementia, there is little evidence of memory deficit awareness in this condition. The objectives of this research were to compare anosognosia between individuals with DLB and dementia due to Alzheimer's disease (AD) and to evaluate whether medial temporal atrophy, a marker of AD pathology, could help to explain different rates of anosognosia in DLB and dementia due to AD. METHODS/DESIGN: This is a cross-sectional study that took place at the Memory Clinic of D'Or Institute for Research and Education (IDOR). Twenty individuals with DLB and 20 with dementia due to AD were included in this study. We assessed anosognosia for memory using an index derived from subjective memory complaints (using the Memory Complaint Questionnaire) and from the performance in memory neuropsychological testing (Rey Auditory Verbal Learning Test). Thirty-one participants also underwent brain Magnetic Resonance Imaging to evaluate hippocampal atrophy with a visual scale (MTA-score [medial temporal atrophy score]). RESULTS: There was no significant difference between groups regarding age, years of education, sex or time of disease. Individuals with DLB had a higher index of anosognosia than dementia due to AD (2.92 and 1.87; p = 0.024), meaning worse awareness of memory deficits. MTA-score was slightly higher in dementia due to AD than in DLB, albeit without statistical significance. CONCLUSION: Our study was the first to demonstrate that anosognosia for memory is worse in DLB than in dementia due to AD. This finding supports the hypothesis that anosognosia in DLB is a heterogeneous phenomenon.

Cerebrospinal fluid irisin correlates with amyloid-ß, BDNF, and cognition in Alzheimer's disease.

INTRODUCTION: Irisin is a novel hormone originally identified for its role as a regulator of peripheral metabolism and recently found to protect synapses and rescue memory in mouse models of Alzheimer's disease (AD). However, whether and how cerebrospinal fluid (CSF) irisin varies in relation to canonical AD biomarkers and cognition in humans remains unknown. METHODS: We determined CSF levels of irisin and brain-derived neurotrophic factor (BDNF) and examined their correlations with CSF amyloid beta (Aß)42, total tau, and Mini-Mental State Exam (MMSE) scores in a cohort comprising AD patients (n = 14) and non-demented controls (NDC; n = 25). RESULTS: CSF irisin correlated positively with BDNF, Aß42, and MMSE scores, but not with CSF total tau. DISCUSSION: Results indicate that CSF irisin and BDNF are directly correlated with Aß pathology and cognition in AD.

Dementia screening in Brazil: a systematic review of normative data for the mini-mental state examination.

The Mini-Mental State Examination (MMSE) is the most widely used instrument for the screening of older adults with suspected cognitive impairment; the MMSE has been translated and validated in numerous languages and countries. The cultural and sociodemographic characteristics of the sample can influence performance on the test; therefore, applying the MMSE in different populations usually requires adjustments of those variables. From this perspective, the present study aims to review the normative data for the MMSE in the Brazilian older population, including those adaptations to the original test. Database searches were performed in Medline, Web of Knowledge, Scielo and Pepsic for articles assessing healthy elderly Brazilian samples using the MMSE. Heterogeneity across and within the studies was analyzed. Of a total of 1,085 retrieved articles, 14 were included. Significant differences across studies were identified for the characteristics of the samples, the presence of alterations to the MMSE subtests and the presentation of the results. The risk of biases was relevant for all the studies. Considering the large methodological heterogeneity among studies, the generalization of the available normative data for the MMSE may not be appropriate for the general elderly Brazilian population.

Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.

BACKGROUND: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied. OBJECTIVES: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum. RESULTS: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aß1-42 ratio in CSF. CONCLUSIONS: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF. METHODS: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.

Inter-method and anatomical correlates of episodic memory tests in the Alzheimer's Disease spectrum.

BACKGROUND: Episodic memory impairments have been described as initial clinical findings in the Alzheimer's Disease (AD) spectrum, which could be associated with the presence of early hippocampal dysfunction. However, correlates between performances in neuropsychological tests and hippocampal volumes in AD were inconclusive in the literature. Divergent methods to assess episodic memory have been depicted as a major source of heterogeneity across studies. METHODS: We examined correlates among performances in three different delayed-recall tasks (Rey-Auditory Verbal-Learning Test-RAVLT, Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale) and fully-automated volumetric measurements of the hippocampus (estimated using Neuroquant®) of 83 older subjects (47 controls, 27 Mild Cognitive Impairment individuals and 9 participants with Dementia due to AD). RESULTS: Inter-method correlations of episodic memory performances were at most moderate. Scores in the RAVLT predicted up to 48% of variance in HOC (Hippocampal Occupancy Score) among subjects in the AD spectrum. DISCUSSION: Tests using different stimuli (verbal or visual) and presenting distinct designs (word list, story or figure learning) may assess divergent aspects in episodic memory, with heterogeneous anatomical correlates. CONCLUSIONS: Different episodic memory tests might not assess the same construct and should not be used interchangeably. Scores in RAVLT may correlate with the presence of neurodegeneration in AD.

The Von Restorff effect in the Brazilian version of the Rey Auditory Verbal Learning Test in an elderly population.

The Von Restorff (isolation) effect refers to a stimulus that is more likely to be remembered amongst other stimuli in memory tasks. It has been demonstrated with different age ranges and methodologies. OBJECTIVE: To investigate: a) the presence of the isolation effect in elders tested with the new Brazilian Portuguese version of the Rey Auditory Verbal Learning Task (RAVLT) in which a word with potential emotional weight (mother) was introduced; b) whether isolation effects persist in memory disorders of different degrees of severity (Mild Cognitive Impairment [MCI]; Alzheimer's Dementia [AD]). METHODS: The RAVLT was administered to 287 consecutive volunteers. Individuals underwent medical and neuropsychological evaluation and were further sub-grouped into normal controls (n=114), MCI (n=87) and AD (n=86) patients. One-way analysis of variance (ANOVA) and Chi-squared tests were performed. Post-hoc Tukey analysis was conducted to assess significance of group differences. RESULTS: There were significant group effects on the learning curve. A W-shape - instead of the classical U-shape - was found for the serial position curve in all groups. CONCLUSION: The new Brazilian version of the RAVLT exhibited the Von Restorff effect, where this phenomenon was evident not only in older adults but also patients with MCI and AD, providing further psychometric measures for inter-group analyses.

Efeito de von Restorff (efeito de isolamento) refere-se ao estímulo que é mais facilmente lembrado em relação a outros em tarefas de memória. Tal efeito foi demonstrado em diferentes faixas etárias com diferentes metodologias. OBJETIVO: Investigar: a) presença do efeito de isolamento numa população idosa avaliada com a nova versão brasileira do Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT), em que uma palavra com potencial carga emocional ('mãe') foi introduzida; b) se o efeito de isolamento persiste em distúrbios de memória de diferentes gravidades (Comprometimento Cognitivo Leve [MCI]; Demência de Alzheimer [AD]). MÉTODOS: RAVLT foi aplicado em 287 voluntários. Indivíduos participaram de avaliações médica e neuropsicológica e foram posteriormente agrupados em controles normais (n=114), MCI (n=87) e DA (n=86). Análises de variância e testes de Chi-quadrado foram realizados. Análises post-hoc foram conduzidas para avaliar diferenças de características entre os grupos. RESULTADOS: Observaram-se efeitos significativos de grupo na curva de aprendizagem. Todos os grupos apresentaram curva de posição serial em formato W - invés do clássico formato em U. CONCLUSÃO: A nova versão brasileira do RAVLT evidenciou um efeito de von Restorff. Tal fenômeno foi visto não apenas em idosos, mas também em pacientes com MCI e AD, fornecendo medidas psicométricas adicionais para análises de diferenças intergrupais.

The Von Restorff effect in the Brazilian version of the Rey Auditory Verbal Learning Test in an elderly population / Efeito de Von Restorff na versão brasileira do Teste de Aprendizagem Auditivo-Verbal de Rey em idosos

ABSTRACT. The Von Restorff (isolation) effect refers to a stimulus that is more likely to be remembered amongst other stimuli in memory tasks. It has been demonstrated with different age ranges and methodologies. Objective: To investigate: a) the presence of the isolation effect in elders tested with the new Brazilian Portuguese version of the Rey Auditory Verbal Learning Task (RAVLT) in which a word with potential emotional weight (mother) was introduced; b) whether isolation effects persist in memory disorders of different degrees of severity (Mild Cognitive Impairment [MCI]; Alzheimer's Dementia [AD]). Methods: The RAVLT was administered to 287 consecutive volunteers. Individuals underwent medical and neuropsychological evaluation and were further sub-grouped into normal controls (n=114), MCI (n=87) and AD (n=86) patients. One-way analysis of variance (ANOVA) and Chi-squared tests were performed. Post-hoc Tukey analysis was conducted to assess significance of group differences. Results: There were significant group effects on the learning curve. A W-shape - instead of the classical U-shape - was found for the serial position curve in all groups. Conclusion: The new Brazilian version of the RAVLT exhibited the Von Restorff effect, where this phenomenon was evident not only in older adults but also patients with MCI and AD, providing further psychometric measures for inter-group analyses.

RESUMO. Efeito de von Restorff (efeito de isolamento) refere-se ao estímulo que é mais facilmente lembrado em relação a outros em tarefas de memória. Tal efeito foi demonstrado em diferentes faixas etárias com diferentes metodologias. Objetivo: Investigar: a) presença do efeito de isolamento numa população idosa avaliada com a nova versão brasileira do Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT), em que uma palavra com potencial carga emocional ('mãe') foi introduzida; b) se o efeito de isolamento persiste em distúrbios de memória de diferentes gravidades (Comprometimento Cognitivo Leve [MCI]; Demência de Alzheimer [AD]). Métodos: RAVLT foi aplicado em 287 voluntários. Indivíduos participaram de avaliações médica e neuropsicológica e foram posteriormente agrupados em controles normais (n=114), MCI (n=87) e DA (n=86). Análises de variância e testes de Chi-quadrado foram realizados. Análises post-hoc foram conduzidas para avaliar diferenças de características entre os grupos. Resultados: Observaram-se efeitos significativos de grupo na curva de aprendizagem. Todos os grupos apresentaram curva de posição serial em formato W - invés do clássico formato em U. Conclusão: A nova versão brasileira do RAVLT evidenciou um efeito de von Restorff. Tal fenômeno foi visto não apenas em idosos, mas também em pacientes com MCI e AD, fornecendo medidas psicométricas adicionais para análises de diferenças intergrupais.

Dementia screening in Brazil: a systematic review of normative data for the mini-mental state examination

The Mini-Mental State Examination (MMSE) is the most widely used instrument for the screening of older adults with suspected cognitive impairment; the MMSE has been translated and validated in numerous languages and countries. The cultural and sociodemographic characteristics of the sample can influence performance on the test; therefore, applying the MMSE in different populations usually requires adjustments of those variables. From this perspective, the present study aims to review the normative data for the MMSE in the Brazilian older population, including those adaptations to the original test. Database searches were performed in Medline, Web of Knowledge, Scielo and Pepsic for articles assessing healthy elderly Brazilian samples using the MMSE. Heterogeneity across and within the studies was analyzed. Of a total of 1,085 retrieved articles, 14 were included. Significant differences across studies were identified for the characteristics of the samples, the presence of alterations to the MMSE subtests and the presentation of the results. The risk of biases was relevant for all the studies. Considering the large methodological heterogeneity among studies, the generalization of the available normative data for the MMSE may not be appropriate for the general elderly Brazilian population.

Metabolic Syndrome and cognitive decline in the elderly: A systematic review.

BACKGROUND: Metabolic Syndrome (MetS) refers to a cluster of metabolic disturbances which is associated with increased risk for vascular and degenerative conditions in general population. Although the relationship between vascular risk factors and dementia is undisputable, additional hazard for cognitive decline in older population with concurrent metabolic disorders still waits to be demonstrated. The present review aims to analyze data on MetS and risk for cognitive decline in elderly persons. METHODS: Database searches were performed in Medline, ISI and PsycINFO for articles assessing cognitive performances of older subjects with MetS. RESULTS: Of a total of 505 studies, 25 were selected for the review. Risk of selection biases was identified in all the studies. Although all articles followed recognized diagnostic recommendations for MetS, minor criteria modifications were detected in most of them. Hyperglycemia was consistently associated with impaired cognitive performances in older individuals, but the role of MetS for cognitive decline and for the onset of dementia showed heterogeneous results. DISCUSSION: Current available data in the literature concerning the impact of MetS on the cognition of older population is inconclusive and based on inconsistent evidence. Differential effects of individual MetS components and factors associated with the age of the sample may have accounted for divergent findings among articles, but larger and higher quality studies in this field are still needed.

Deficits in narrative discourse elicited by visual stimuli are already present in patients with mild cognitive impairment.

Language batteries used to assess the skills of elderly individuals, such as naming and semantic verbal fluency, present some limitations in differentiating healthy controls from patients with amnestic mild cognitive impairment (a-MCI). Deficits in narrative discourse occur early in dementia caused by Alzheimer's disease (AD), and the narrative discourse abilities of a-MCI patients are poorly documented. The present study sought to propose and evaluate parameters for investigating narrative discourse in these populations. After a pilot study of 30 healthy subjects who served as a preliminary investigation of macro- and micro-linguistic aspects, 77 individuals (patients with AD and a-MCI and a control group) were evaluated. The experimental task required the participants to narrate a story based on a sequence of actions visually presented. The Control and AD groups differed in all parameters except narrative time and the total number of words recalled. The a-MCI group displayed mild discursive difficulties that were characterized as an intermediate stage between the Control and AD groups' performances. The a-MCI and Control groups differed from the AD group with respect to global coherence, discourse type and referential cohesion. The a-MCI and AD groups were similar to one another but differed from the Control group with respect to the type of words recalled, the repetition of words in the same sentence, the narrative structure and the inclusion of irrelevant propositions in the narrative. The narrative parameter that best distinguished the three groups was the speech effectiveness index. The proposed task was able to reveal differences between healthy controls and groups with cognitive decline. According to our findings, patients with a-MCI already present narrative deficits that are characterized by mild discursive difficulties that are less severe than those found in patients with AD.

A preceptoria na rede básica da Secretaria Municipal de Saúde do Rio de Janeiro: opinião dos profissionais de Saúde / Student supervision in primary care clinics in the Rio de Janeiro City Health Department: opinions by healthcare professionals

A formação de profissionais de saúde com as competências para prestação de cuidados básicos deve ser iniciada na graduação. Entretanto, o treinamento na rede básica de saúde (RBS) ainda encontra barreiras nas esferas docente, discente e nas unidades das Secretarias Municipais de Saúde (SMS). Considerando a relevância do papel dos preceptores na formação dos estudantes da área da saúde, avaliamos a opinião dos profissionais de saúde da RBS da SMS do Rio de Janeiro sobre a atividade de preceptoria. Um questionário foi respondido por 351 profissionais de saúde de 13 das 67 unidades da RBS. Destes, 77 por cento consideram que a preceptoria faz parte das atribuições do profissional e 61 por cento gostariam de assumir esta tarefa. Várias dificuldades foram apontadas, incluindo problemas estruturais e de recursos humanos. Os resultados responsabilizam, de alguma forma, as instituições de ensino superior (IES) e o Estado pela pouca valorização e estímulo às ações de preceptoria, na medida em que apontam a necessidade de rever as condições de trabalho e de ensino na RBS. Destacam-se a melhoria dos salários e da infraestrutura e a oportunidade de capacitação profissional, o que implica parcerias efetivas entre as IES e as SMS.

Training of health professionals with the necessary skills in primary care should begin during undergraduate medical education. However, training in the primary care network still faces obstacles among faculty, students, and the primary care clinics operated by municipal health departments. Considering the relevant role of supervisors in training students in health-related fields, we investigated the opinions of healthcare professionals in the primary care network in Rio de Janeiro concerning their student supervision activities. A total of 351 health professionals from 13 of the 67 primary care clinics answered a questionnaire. Of these, 77 percent felt that student supervision is part of their responsibilities, and 61 percent said they would like to play this role. Various difficulties were identified, including structural and human resources problems. According to the findings, medical schools and the government are responsible for the under-valuing of student supervision, emphasizing the need to review the working and teaching conditions in the primary care network. The results also highlight improvements in wages and infrastructure and the opportunity for professional advancement, requiring effective partnerships between medical schools and the Municipal Health Department.