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COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62-62.23 vs. Mild 3.91 pg/mL CI 1.5-10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4-4.4 vs. Non-Pronounced 2.0, CI 1.4-2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89-123.31 vs Non-Pronounced 6.22, CI 2.9-13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases., Competing Interests: none., (© 2024 The Authors.)

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., (© 2022 the Alzheimer's Association.)

Background: maladaptive changes in the autonomic nervous system (ANS) have been observed in short and long-term phases of COVID-19 infection. Identifying effective treatments to modulate autonomic imbalance could be a strategy for preventing and reducing disease severity and induced complications., Objective: to investigate the efficacy, safety, and feasibility of a single session of bihemispheric prefrontal tDCS on indicators of cardiac autonomic regulation and mood of COVID-19 inpatients., Methods: patients were randomized to receive a single 30-min session of bihemispheric active tDCS over the dorsolateral prefrontal cortex (2 mA; n = 20) or sham (n = 20). Changes in time [post-pre intervention] in heart rate variability (HRV), mood, heart rate, respiratory rate, and oxygen saturation were compared between groups. Additionally, clinical worsening indicators and the occurrence of falls and skin injuries were evaluated. The Brunoni Adverse Effects Questionary was employed after the intervention., Results: there was a large effect size (Hedges' g = 0.7) of intervention on HRV frequency parameters, suggesting alterations in cardiac autonomic regulation. An increment in oxygen saturation was observed in the active group but not in the sham after the intervention (P = 0.045). There were no group differences regarding mood, incidence and intensity of adverse effects, no occurrence of skin lesions, falls, or clinical worsening., Conclusions: a single prefrontal tDCS session is safe and feasible to modulate indicators of cardiac autonomic regulation in acute COVID-19 inpatients. Further research comprising a thorough assessment of autonomic function and inflammatory biomarkers is required to verify its potential to manage autonomic dysfunctions, mitigate inflammatory responses and enhance clinical outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen and Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação no conselho consultivo dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo do laboratório Biogen. Participação como palestrante em simpósios promovidos pelo laboratório Biogen; RN: Participação no conselho consultivo do laboratório Biogen; BJAPB, JISN, GSA, FKS, CKS, FTM, NAFF, FACV, SMDB, EE, MLFC: There is no conflict of interest to declare.

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-β. 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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mendonca, Sudo, Santiago-Bravo, Oliveira, Assuncao, Rodrigues, Soares, Calil, Bernardes, Erthal, Drummond, Tovar-Moll and Mattos.)

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., (© 2021 John Wiley & Sons Ltd.)

Previous research investigating language in attention-deficit hyperactivity disorder (ADHD) has demonstrated several deficits in many aspects. However, no previous study employed quantitative methodology providing objective measures that could be compared among different studies with diverse samples. To fill this gap, we used network analysis to investigate how ADHD symptomatology impacts narrative discourse, a complex linguistic task considered to be an ecological measure of language. Fifty-eight adults (34 females and 24 males) with a mean age of 26 years old and a mean of 17 years of educational level were administered the Adult Self-Rating Scale for ADHD symptomatology. They also completed the State-Trait Anxiety Inventory, the Beck Depression Inventory and the Urgency, Premeditation, Perseverance, Sensation Seeking Behavior Scale. Intelligence quotient was calculated. Individuals were asked to tell a story based on a wordless picture book. Speech was recorded and transcribed as an input to SpeechGraphs software. Parameters were total number of words (TNW), number of loops of one node (L1), repeated edges (RE), largest strongly connected component (LSC) and average shortest path (ASP). Verbosity was controlled. Statistical analysis was corrected for multiples comparisons and partial correlations were performed for confounding variables. After controlling for anxiety, depression, IQ, and impulsiveness ADHD symptomatology was positively correlated with L1 and negatively correlated with LSC. TNW was positively correlated with ADHD symptoms. In a subdomain analysis, both inattention and hyperactivity-impulsivity were negatively correlated with LSC. Only hyperactivity-impulsivity positively correlated with TNW and L1. Results indicated a correlation between ADHD symptoms and lower connectedness in narrative discourse (as indicated by higher L1 and lower LSC), as well as higher total number of words (TNW). Our results suggest that the higher the number of ADHD symptoms, the less connectivity among words, and a higher number of words in narrative discourse., Competing Interests: The authors have declared that no competing interests exist.

Background: Anosognosia, i.e. lack of awareness of one's own symptoms, is a very common finding in patients with dementia and is related to neuropsychiatric symptoms and worse prognosis. Although dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia, literature on anosognosia in this disease is scarce., Objectives: This paper aimed to review the current evidence on anosognosia in patients with DLB, including its prevalence in comparison with other neurological conditions, its severity and anatomical correlations., Methods: Database searches were performed in PubMed, Web of Knowledge and PsycINFO for articles assessing anosognosia in DLB. A total of 243 studies were retrieved, but only six were included in the review., Results: Potential risk of selection, comparison or outcome biases were detected in relation to all the studies selected. Most of the studies used self-report memory questionnaires to assess cognitive complaints and compared their results to scores from informant-based instruments or to participants' cognitive performance in neuropsychological tasks. Subjects with DLB had worse awareness regarding memory than healthy older controls, but the results concerning differences in anosognosia between DLB and Alzheimer's disease (AD) patients were inconsistent across studies. Presence of AD pathology and neuroimaging biomarkers appeared to increase the prevalence of anosognosia in individuals with DLB., Conclusion: Anosognosia is a common manifestation of DLB, but it is not clear how its prevalence and severity compare with AD. Co-existence of AD pathology seems to play a role in memory deficit awareness in DLB.

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.

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., Competing Interests: Disclosure: The authors report no conflicts of interest.

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 (Aβ) 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, Aβ 42 , and MMSE scores, but not with CSF total tau., Discussion: Results indicate that CSF irisin and BDNF are directly correlated with Aβ pathology and cognition in AD., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

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.

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/Aβ1-42 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.

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., Competing Interests: The authors have declared that no competing interests exist.

Neuropsychiatric symptoms (NPS) in dementia are prevalent, under-recognized and little studied regarding their pathophysiological aspects. The pathophysiological mechanism, as well as the possible role of vascular lesions in the genesis of these symptoms, are still matters of debate., Objective: to describe and compare the prevalence and severity of NPS in subjects with Alzheimer's disease (AD) and vascular dementia (VaD)., Methods: a cross-sectional study involving 82 outpatients, divided into two groups (AD × VaD), was conducted. Patients were submitted to the Cambridge Cognitive Test (CAMCOG), the Clock Drawing Test (CLOX 1 and 2), the Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating (CDR) scale. Neuroimaging was scored using the de Leon and Fazekas scales., Results: 90.8% of the patients had at least one neuropsychiatric symptom. There were statistical differences on the CLOX test and in the apathy symptoms between AD and VaD groups. Apathy and disinhibition proved more prevalent in patients with higher vascular load., Conclusion: apathy and impaired executive function may reflect vascular damage in subcortical circuits in dementia patients., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts. Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) ( n = 16)], late-onset bipolar disorder [(LOD)( n = 14)] and healthy controls ( n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups. Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups. Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.

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.

The last decade has witnessed substantial progress in acquiring diagnostic biomarkers for the diagnostic workup of cerebrovascular disease (CVD). Advanced neuroimaging methods not only provide a strategic contribution for the differential diagnosis of vascular dementia (VaD) and vascular cognitive impairment (VCI), but also help elucidate the pathophysiological mechanisms ultimately leading to small vessel disease (SVD) throughout its course., Objective: In this review, the novel imaging methods, both structural and metabolic, were summarized and their impact on the diagnostic workup of age-related CVD was analysed. Methods: An electronic search between January 2010 and 2017 was carried out on PubMed/MEDLINE, Institute for Scientific Information Web of Knowledge and EMBASE., Results: The use of full functional multimodality in simultaneous Magnetic Resonance (MR)/Positron emission tomography (PET) may potentially improve the clinical characterization of VCI-VaD; for structural imaging, MRI at 3.0 T enables higher-resolution scanning with greater imaging matrices, thinner slices and more detail on the anatomical structure of vascular lesions., Conclusion: Although the importance of most of these techniques in the clinical setting has yet to be recognized, there is great expectancy in achieving earlier and more refined therapeutic interventions for the effective management of VCI-VaD., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder., Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach., Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models., Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls., Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control., Competing Interests: Disclosure: The authors report no conflicts of interest.

Objectives: Financial capacity (FC) refers to a set of cognitively mediated abilities related to one's competency to manage propriety and income. Identifying intact from impaired FC in older persons with dementia is a growing concern in geriatric practice, but the best methods to assess this function still need to be determined. This study aims to review data on FC in dementia and on instruments used to assess this domain of capacity., Methods: Database search was performed in Medline, ISI Web of Knowledge, LILACS and PsycINFO. Studies that objectively assessed FC in dementia of any etiology were included., Results: Of a total of 125 articles, 10 were included. Mild Alzheimer's Disease (AD) was associated with impaired complex FC abilities, namely checkbook management, bank statement management and financial judgment, but simple FC skills were preserved. Moderate AD was associated with impairment in all domains of FC. The Financial Capacity Instrument (FCI) was applied in most of the selected studies and correlated with neuropsychological and neuroimaging variables., Conclusions: Early dementia is associated with partially preserved FC. More validation studies using objective and evidence-based FC assessment tools, such as the FCI, are still needed.

Background: Behavioral and psychological symptoms of dementia (BPSD) associated with Alzheimer's Disease (AD) have been linked to structural and functional alterations in fronto-temporal circuits and cortical abnormalities. However, little is known on how specific volumetric and functional brain changes may be associated with the frequency, severity and pattern of BPSD., Methods: A systematic review of the literature regarding neuroimaging and BPSD changes in AD was performed through Pubmed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2015. Eligible references (n=40) included clinical studies in which structural or functional neuroimaging assessment was performed in AD subjects presenting BPSD features., Results: BPSD symptoms, particularly apathy and psychosis have been associated in most of studies with either volume reductions or decreased metabolism in the prefrontal cortex (orbital and dorsolateral portions), anterior cingulate, insula and temporal lobes (middle portion). WM lacunes associated with AD progression have been associated with depressive symptoms., Conclusion: The sum of evidence highlights the importance of BPSD-related imaging findings for the understanding of the non-cognitive symptom spectrum in AD. Results suggest that structural and functional changes in fronto-limbic areas may lead to emotional deregulation and symptom unawareness. As these findings may be present early on the AD clinical course, they may have a relevance for the development of imaging markers that could be used in diagnosis, disease monitoring and prediction of therapeutic response.

Background: Staging vascular cognitive impairment (VCI) might be useful for sample selection in clinical trials and for guiding clinical decision-making. Clinical dementia rating (CDR) has been applied for staging cognitive impairments of different etiologies, but it may underestimate severity of non-Alzheimer's disease cognitive deficits., Methods: Out of a total of 147 elderly subjects, 23 (mean age: 72.95 ± 7.51 years; 56% female; mean schooling: 9.52 ± 5.11 years) fulfilled clinical and neuroimaging criteria for VCI. Correlations among cognitive and functional status and scores in CDR and its subsums (CDR Sum of Boxes - CDR-SoB - and CDR Functional Subsum - CDR-FUNC) were performed., Results: Both CDR-SoB and CDR-FUNC correlated with global cognitive performance, functional status, CLOX 2, working memory and abstraction tests. CDR global score only correlated with functional status., Discussion: CDR-FUNC, as well as CDR-SoB, appear to be better indexes of severity in VCI than CDR global score.

The Brazilian Civil Code, which came into force in 2002, established a functional criterion for guardianship proceedings and introduced the concept of "limited guardianship," applied to cases in which incapacity to exercise civil rights is partial. With population aging and the growth in the number of older people with cognitive impairments, such as Alzheimer's disease (AD), the need to invoke legal remedies against elder abuse increased; however, difficulties in assessing capacity still lead to a majority of decisions in favor of plenary guardianship. The present article compiled data on capacity in AD subjects. The varying degrees of decision-making impairment at different stages of AD might be compatible with limited guardianship in milder cases of the disease.

The recognition of Cerebrovascular Disease (CVD) at earlier clinical stages may favor the control of vascular risk factors and prevention of dementia. However, operational criteria for symptomatic phases at non-dementia stages are often difficult, as the current criteria normally require the evidence of extensive subcortical disease., Objective: To identify the neuroimaging profile of Vascular Mild Cognitive Impairment (VaMCI), the impact of those aspects over cognition and the neuropsychological tests that distinguished VaMCI from other groups., Methods: Searches were performed in Scopus, ISI and PsycINFO, using the following key terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular cognitive impairment not demented" OR "subcortical mild cognitive impairment"., Results: Of 249 papers, 20 studies were selected. Ten of those included only patients with severe White Matter Hyperintensities (WMH), whereas 10 others admitted subjects with moderate-to-severe WMH. Both groups showed poor performances in Executive Function (EF) tasks in comparison to normal controls and other diagnostic groups. Among EF tests, those assessing "complex" EF abilities consistently distinguished VaMCI from other groups, regardless of the severity of WMH. VaMCI subjects with severe or moderate-to-severe WMH showed cognitive deficits in comparison with other groups. "Complex" EF tests were the most useful in differentiating those patients from the other groups., Conclusion: The occurrence of VaMCI may be associated with the presence of CVD at moderate levels; the detection of vascular damage at earlier stages may allow the adoption of therapeutic actions with significant effect-sizes., Competing Interests: Disclosure: The authors report no conflits of interest

Neuropsychiatric symptoms or Behavioral and Psychological Symptoms of Dementia (BPSD) are common and invariably appear at some point during the course of the disease, mediated both by cerebrovascular disease and neurodegenerative processes. Few studies have compared the profiles of BPSD in Vascular Cognitive Impairment (VCI) of different subtypes (subcortical or cortical) and clinical stages (Vascular Cognitive Impairment No Dementia [VaCIND] and Vascular Dementia [VaD])., Objective: To review the BPSD associated with different subtypes and stages of VCI using the Neuropsychiatric Inventory (NPI)., Methods: Medline, Scielo and Lilacs databases were searched for the period January 2000 to December 2014, with the key words: "BPSD AND Vascular Dementia, "NPI AND Vascular Dementia" and "NPI AND VCI. Qualitative analysis was performed on studies evaluating BPSD in VCI, using the Neuropsychiatric Inventory (NPI)., Results: A total of 82 studies were retrieved of which 13 were eligible and thus included. Among the articles selected, 4 compared BPSD in Subcortical Vascular Dementia (SVaD) versus Cortical-Subcortical Vascular Dementia (CSVaD), 3 involved comparisons between SVaD and VaCIND, 1 study analyzed differences between CSVaD and VaCIND, while 5 studies assessed BPSD in CSVaD. Subcortical and Cortical-Subcortical VaD were associated predominantly with Apathy and Depression. VaCIND may present fewer behavioral symptoms than VaD., Conclusion: The profile of BPSD differs for different stages of VCI. Determining the most prevalent BPSD in VCI subtypes might be helpful for improving early diagnosis and management of these symptoms., Competing Interests: Disclosure: The authors report no conflits of interest.

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.

Clinical manifestations of major depressive disorder (MDD) have been linked to structural and functional alterations in fronto-limbic circuits and white matter microstructural abnormalities. However, little is known about how brain pathological changes in volume and microstructure are related to illness progression throughout aging, including course deterioration and treatment response. A comprehensive review of the literature regarding midlife- and late-onset MDD was performed through PubMed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2014. Eligible references included prospective studies in which structural neuroimaging assessments were performed in MDD samples. The course of MDD may be associated with brain aging modifications, including hippocampal, amigdalar and frontal volume reductions. White matter changes associated with MDD progression have been reported in the corpus callosum, frontal and temporal regions and may be associated with poorer response to treatment. The data suggest that both cortical and subcortical alterations may interact along the progression of MDD. Further knowledge brought by neuroimaging studies, through the integration of multimodal techniques, may help to improve the accuracy of diagnosis, disease monitoring and treatment response in MDD.

Unlabelled: Vascular mild cognitive impairment (VaMCI) represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction., Methods: Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years) were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15) were compared to normal controls (NC, n=11) and correlated with Fazekas scale., Results: VaMCI performed significantly worse than NC in Trail-Making Test (TMT) B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG) final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors), difference TMT B-A and CAMCOG total score., Conclusion: Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.

Strategic regions correspond to associative, limbic and paralimbic structures and related circuits, that underpin cognitive/behavioral functions. Strokes in these eloquent sites produce pictures of vascular dementia with syndromic features due to specific site lesion and/or interruption of their interconnections. This study aims at analysing subcortical strategic strokes that express similar cognitive/behavioral elements, by sharing common pathways. Patients (n=6) who attended in specialized ambulatory, were submitted to neuropsychological and neuroimaging assessments through MRI (GE Signa Horizon 1.5T) and brain SPECT (Millennium MG, ECD [TC-99m]). Stroke locations and respective main symptoms were: 1. anteromedian thalamus [L]: anterograde and retrograde amnesia (ARA), expression aphasia (EA), executive dysfunction (ED), apathy, and depression; 2. anterior thalamus [R]: ARA, inattention, apathy, and aggressiveness; 3. dorsomedian thalamus [L]: inattention, ED, anosognosia, and aggressiveness; 4. central paramedian thalamus [R]: EA, visual perception deficits (VPD), ED, infantility, and personality disorder; 5. caudate nucleus (ventral-head) [L]: VPD, ED, delirium, visual hallucinations, and personality disorder; and 6. anterior capsule [L]: VPD, ED, apathy, and depression. Vascular strategic syndromes connote the predominantly impaired cognitive/behavioral symptom of each site. Temporal and frontal disconnection symptoms were produced by disrupted MTT/hippocampal and IML/amygdala circuits expressing amnesic syndrome associated with heterogeneous dysexecutive syndrome, in all the cases, by disrupting frontal-basal ganglia-thalamus-cortical net, in three different levels of their pathway., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Neuropsychiatric symptoms are common in patients with cognitive impairments, mediated by both neurodegenerative processes and cerebrovascular disease. Previous studies have reported that Behavioral and Psychological Symptoms of Dementia (BPSD) might correlate with severity of cognitive decline. Thus far, the impact of the association between white-matter hyperintensities (WHM) and hippocampal atrophy (HA) on the incidence of these symptoms has been less studied., Objective: This cross-sectional study aimed to describe the clinical profile of a sample with large extensions of WMH, examining the association between different degrees of HA and cognitive, functional, and behavioral status., Methods: Fifty outpatients (mean age: 76.86±8.70 years; 58% female; mean schooling: 7.44±4.69 years) with large extensions of WMH (modified-Fazekas scale=3) on MRI and different degrees of hippocampal atrophy (according to de Leon Score) underwent cognitive, functional, and behavioral assessments., Results: Patients with mild-moderate to severe HA had worse performance on the Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia Rating and Pfeffer's Functional Activities Questionnaire, compared to the group with none or questionable HA. Appetite/Eating Behavior was the only cluster of neuropsychiatric symptoms associated with presence of HA in Vascular Cognitive Impairment patients., Discussion: Although HA may exhibit distinct impact on cognitive performance and functional status, it appears to have little effect on behavioral symptoms in patients with high severity WMH., Competing Interests: Disclosure: The authors report no conflicts of interest.

Objective: Non-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI) may represent preclinical Vascular Dementia (VaD). The aim of this study was to summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and to assess its patterns of progression to dementia., Methods: Searches were made in the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms "mild cognitive impairment" and "executive function". Altogether, 944 articles were retrieved., Results: VaMCI cases had poorer performances on fronto-executive tasks, a higher prevalence of stroke, presence of periventricular and profound white matter hyperintensities on MRI images, as well as more extrapyramidal signs and behavioral symptoms. Executive dysfunction might be associated with disconnection of fronto-parietal-subcortical circuits. Progression to dementia was associated with baseline deficits in executive function, in simple sustained attention and language, and large periventricular WMH., Discussion: VaMCI develops with impairment in non-memory domains and subcortical white matter changes on MRI images, which are consistent with clinical and neuroimaging findings in VaD., Competing Interests: Disclosure: The authors report no conflicts of interest.

Cerebrovascular disease (CVD) is often present in old age and may be associated with microstructural pathology of white matter (WM) and cognitive dysfunction. The current review investigated the relationship between CVD, cognitive status and WM integrity as assessed by diffusion tensor imaging (DTI)., Methods: DTI studies were searched on ISI and Pubmed databases from 2002 to 2012., Results: Studies evidenced DTI changes in WM as associated with vascular disease and provide increasing support for DTI as a valuable method for early detection of CVD., Conclusion: DTI parameters can serve as important biomarkers in monitoring vascular disease progression and treatment response and may represent a surrogate marker of WM tract integrity., Competing Interests: Disclosure: The authors report no conflicts of interest.

Unlabelled: Caring for a demented family member has been associated with burden. Studies concerning health self-perception of family caregivers are still scarce., Objective: To investigate caregivers perceived health and to look into relationships with patients and caregivers' sociodemographic and clinical data., Method: Dyads of dementia outpatients and family caregivers (n=137) were assessed with Mini Mental State Examination, Functional Activities Questionnaire, Neuropsychiatric Inventory and Clinical Dementia Rating. Caregivers answered Sociodemographic Questionnaire, Beck Depression and Anxiety Inventories, Zarit Burden Interview and Maslach Burnout Inventory., Results: Caregivers poor perceived health was associated with emotional exhaustion, burden, depression and anxiety. Logistic regression analyses revealed caregivers' age, anxiety and physical problem as the main predictors of health self-perception., Conclusion: Aged family caregivers with anxiety who also report physical problem characterize a group at risk for poor self-perceived health. Evaluation of health self-perception may be useful for designing interventions to improve anxiety and physical health.

Objective: Cerebrovascular disease (CVD) is associated with cognitive deficits. This cross-sectional study examines differences among healthy elderly controls and patients with vascular mild cognitive impairment (VaMCI) and vascular dementia (VaD) in performances on CAMCOG subscales., Method: Elderly individuals (n=61) were divided into 3 groups, according to cognitive and neuroimaging status: 16 controls, 20 VaMCI and 25 VaD. VaMCI and VaD individuals scored over 4 points on the Hachinski Ischemic Scale., Results: Significant differences in total CAMCOG scores were observed across the three groups (p<0.001). VaD subjects performed worse than those with VaMCI in most CAMCOG subscales (p<0.001). All subscales showed differences between controls and VaD (p<0.001). Performance on abstract thinking showed difference between VaMCI and controls (p<0.001)., Conclusion: CAMCOG discriminated controls from VaMCI and VaD. Assessment of abstract thinking may be useful as a screening item for diagnosis of VaMCI.

Background: Vascular white matter lesions (WML) represent one of the main neuroimage findings in individuals older than 65 years and its clinical significance is still partially understood., Objective: To describe and analyze the clinical profile of a high severity sample with WML focusing on the frontal executive control., Method: Outpatients (n=20) with high severity WML evaluated with magnetic resonance imaging were selected using the Fazekas scale., Results: Most patients (n=17; 85%) presented an altered Trail Making Test ratio (section B/section A); on verbal fluency, 15 individuals (75%) performed below the cutoff score. Apathy (5.9 +/- 4.65) and depression (3.05+/-3.67) were frequent as assessed by the Neuropsychiatric Inventory. The impairment in functional activities strongly correlated with apathy (r=0.814, p<0.001) and verbal fluency (r=0.744, p<0.001)., Conclusion: Executive dysfunction, apathy, and ratio depression were the main characteristics found. Extension of WML may have distinct impact on the clinical picture, but further studies with methodological adjustments are necessary to provide more definitive conclusions.

Objective: To study the integrity of the white matter in Binswanger's disease (BD) patients with quantitative fractional anisotropy (DTI-FA)., Method: Controls (12) and patients with BD (12) were included. Scans performed with MR (GE Signa Horizon/1.5T). Fazekas's score=6 with white matter hyperintensities extension >75% assessed on FLAIR scans. Standard parameters for DTI-FA were used. ROIs placed in symmetrical regions on two axial planes, data pooled in anterior (frontal) and posterior (temporo-parieto-occipital) regions. Analysis with Functool. Statistics for anterior and posterior regions comparison., Results: DTI-FA showed reduction of anisotropy, reflecting axonal damage and demyelination of fibers, more prominent in anterior in relation to posterior region, in BD patients in comparison to controls., Conclusion: Loss of integrity of fiber tracts reflects interruption of neural networks that subserve cognitive, behavioral, and motor integration. The more severely affected frontal region is related to executive dysfunction, a characteristic feature of Binswanger's disease.

To study the integrity of the corpus callosum in Binswanger's disease (BD) patients using quantitative fractional anisotropy (DTI-FA)., Methods: Controls (12) and patients with BD (12) were included. MR [GE Signa Horizon-1.5T] scans were performed. BD patients presented Fazekas's score=6 and leukoaraiosis extension =75%, as assessed on FLAIR sequence. Standard parameters for DTI-FA acquisition were used. Functool was employed for post-processing, and ROIs placed on the genu and splenium of the corpus callosum on one axial plane at the basal ganglia level. Statistics [ANOVA] for genu and splenium comparison were analyzed., Results: DTI-FA showed reduction of anisotropy in both regions of the corpus callosum, more prominently in anterior (genu) than posterior (splenium) in BD patients versus controls., Conclusion: The reduction of anisotropy reflects loss of integrity of fibers of the studied regions of the corpus callosum. This finding indicates an interruption of the most important inter-hemispheric commissure, and component of neural networks that underlies cognitive, behavioral, motor and sensory integration. The affected genu and splenium, together with damage to other fiber systems that connect the prefrontal and parietal-occipital regions, may manifest clinically as dysfunction of high-level integrative regions linked to the domains of executive and sensory functions, respectively, that can occur in Binswanger's disease.