Search

IntroductionPost-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.MethodsIn this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6–12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment.ResultsSRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1β serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Abstract The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1–4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04–2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50–3.33], P

Background: There is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer’s disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. Methods: Cortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2 mM, 0.2 mM and 0.02 mM) for seven days. Amyloid toxicity was induced 24 h before the end of lithium treatment. Results: Lithium resulted in 120% (2 mM), 180% (0.2 mM) and 140% (0.02 mM) increments in telomere length as compared to untreated controls. Incubation with Aβ1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls. Conclusions: Lithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with Aβ fibrils.

ObjectiveTo analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19.MethodsWe assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers.ResultsConcerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p

Abstract Introduction Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and causing increased burden and morbidity. Clinical presentations are pleomorphic and clinical management often requires combinations of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse psychotropic drug events emphasize the need for novel therapeutic options. Objectives To review the evidence supporting use of medical cannabinoids for treatment of neuropsychiatric symptoms (NPS) of dementia. Methods We conducted a systematic review of the medical literature to examine scientific publications reporting use of medical cannabinoids for treatment of NPS. Medical Subject Headings (MeSH) were used to search for relevant publications and only papers reporting original clinical information were included. A secondary search was performed within selected publications to capture relevant citations that were not retrieved by the systematic review. The papers selected were categorized according to the level of evidence generated by the studies in relation to this clinical application, i.e. (1) controlled clinical trials; (2) open-label or observational studies; and (3) case reports. Results Fifteen publications with original clinical data were retrieved: five controlled clinical trials, three open-label/observational studies, and seven case reports. Most studies indicated that use of medical cannabinoids engendered favorable outcomes for treatment of NPS related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior, sleep disorder, and sexual disinhibition. Conclusion Medical cannabinoids constitute a promising pharmacological approach to treatment of NPS with preliminary evidence of benefit in at least moderate to severe dementia. Controlled trials with longitudinal designs and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration, and concentrations of active compounds (e.g., cannabidiol [CBD]/ Δ9-tetrahydrocannabinol [THC] ratio) in commercial preparations of medical cannabinoids.

The prevalence of Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is expected to more than double by 2050. Studies on the pathophysiology of AD have been changing our understanding of this disorder and setting a new scenario for drug development and other therapies. Concepts like the “amyloid cascade” and the “continuum of AD,” discussed in this article, are now well established. From updated classifications and recommendations to advances in biomarkers of AD, we aim to critically assess the literature on AD, addressing new definitions and challenges that emerged from recent studies on the subject. Updates on the status of major clinical trials are also given, and future perspectives are discussed.

OBJECTIVE: In 2020, the COVID-19 pandemic brought a work and stress overload to healthcare workers, increasing their vulnerability to mental health impairments. In response, the authors created the COMVC-19 program. The program offered preventive actions and mental health treatment for the 22,000 workers of The Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). This paper aims to describe its implementation and share what we have learned from this experience. METHODS: Workers were able to easily access the program through a 24/7 hotline. Additionally, a mobile phone app that screened for signs and symptoms of emotional distress and offered psychoeducation and/or referral to treatment was made available. Data from both these sources as well as any subsequent psychiatric evaluations were collected. RESULTS: The first 20 weeks of our project revealed that most participants were female, and part of the nursing staff working directly with COVID-19 patients. The most frequently reported symptoms were: anxiety, depression and sleep disturbances. The most common diagnoses were Adjustment, Anxiety, and Mood disorders. CONCLUSIONS: Implementing a mental health program in a multimodal intervention was feasible in a major quaternary public hospital. Our data also suggests that preventive actions should primarily be aimed at anxiety and depression symptoms, with a particular focus on the nursing staff.

Neuronal-glial interactions are critical for brain homeostasis, and disruption of this process may lead to excessive glial activation and inadequate pro-inflammatory responses. Abnormalities in neuronal-glial interactions have been reported in the pathophysiology of Alzheimer’s disease (AD), where lithium has been shown to exert neuroprotective effects, including the up-regulation of cytoprotective proteins. In the present study, we characterize by Gene Ontology (GO) the signaling pathways related to neuronal-glial interactions in response to lithium in a triple-transgenic mouse model of AD (3×-TgAD). Mice were treated for 8 months with lithium carbonate (Li) supplemented to chow, using two dose ranges to yield subtherapeutic working concentrations (Li1, 1.0 g/kg; and Li2, 2.0 g/kg of chow), or with standard chow (Li0). The hippocampi were removed and analyzed by proteomics. A neuronal-glial interaction network was created by a systematic literature search, and the selected genes were submitted to STRING, a functional network to analyze protein interactions. Proteomics data and neuronal-glial interactomes were compared by GO using ClueGo (Cytoscape plugin) with p ≤ 0.05. The proportional effects of neuron-glia interactions were determined on three GO domains: (i) biological process; (ii) cellular component; and (iii) molecular function. The gene ontology of this enriched network of genes was further stratified according to lithium treatments, with statistically significant effects observed in the Li2 group (as compared to controls) for the GO domains biological process and cellular component. In the former, there was an even distribution of the interactions occurring at the following functions: “positive regulation of protein localization to membrane,” “regulation of protein localization to cell periphery,” “oligodendrocyte differentiation,” and “regulation of protein localization to plasma membrane.” In cellular component, interactions were also balanced for “myelin sheath” and “rough endoplasmic reticulum.” We conclude that neuronal-glial interactions are implicated in the neuroprotective response mediated by lithium in the hippocampus of AD-transgenic mice. The effect of lithium on homeostatic pathways mediated by the interaction between neurons and glial cells are implicated in membrane permeability, protein synthesis and DNA repair, which may be relevant for the survival of nerve cells amidst AD pathology.

Introduction: There is a growing awareness about the noxious effects of the 2019 Coronavirus Disease (COVID-19) pandemic on the mental health of the elderly. However, there is limited information from clinically driven research. The objectives of the present study were to examine the magnitude of psychiatric symptoms and to determine their association with caregiver distress, in a cross-section of community-dwelling older adults and a subsample of aging adults with Down syndrome (DS) attending a psychogeriatric service in São Paulo, Brazil.Method: Telephone-based interviews and electronically filled self-assessment questionnaires were used to collect information from patients and caregivers, addressing their impressions and concerns about the pandemic and related effects on the patient's emotional state and behavior. Clinical information was obtained from hospital charts, medical records, and psychometric tests administered through telephone interviews [Hospital Anxiety and Depression Scale (HADS) and Neuropsychiatric Inventory Questionnaire (NPI-Q)].Results: We included 100 consecutive participants, comprising 71 older adults with psychogeriatric/neurocognitive disorders and 29 aging adults with DS. Higher HADS and NPI-Q scores were significantly associated with caregiver distress (p < 0.05) in both groups. Correlation analyses indicated strong, positive associations between caregiver burden and scores in HADS anxiety (HADS-A) and HADS depression (HADS-D) scales in the subsamples of euploid and DS subjects. Higher NPI-Q scores in the former group were also correlated with caregiver distress, with stronger associations for neuropsychiatric symptoms. Similar findings were observed among DS subjects. ANOVA tests indicated significant associations between NPI-Q scores and caregiver distress among dementia patients, as well as with HADS scores. Similar results were found after multiple linear regressions; as such, among the elderly subsample, higher scores in HADS-A (p = 0.002) and HADS-D (p = 0.001) predict a significant impact on caregiver burden (p < 0.00001, R2 0.46); taking into consideration caregiver burden as a dependent variable and NPI-Q total score as an independent variable, we obtained significant strong prediction values for either DS (p < 0.00001, R2 0.95) or elderly adults (p < 0.00001, R2 0.88).Conclusion: During the COVID-19 pandemic, patients with neurocognitive disorders present with clinically relevant neuropsychiatric symptoms, with significant impact on caregiver distress. Apathy, aberrant motor behavior, sleep disorders, and psychoses were the main psychopathological domains, which had determined caregiver burden worsening.

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer’s disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Objective: There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. Methods: A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD) stable on pharmacotherapy. The experimental group (EG) was assigned to 20 weekly art therapy sessions (90 min/session). The control group (CG) was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and cognitive measures. Results: Logistic regression analysis adjusted for age revealed that women in EG (n=31) had significant improvement in GDS (p = 0.007), BDI (p = 0.025), and BAI (p = 0.032) scores as compared with controls (n=25). No difference was found in the cognitive measures. Conclusion: Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. Clinical trial registration: RBR-2YXY7Z

Objective: To present a critical review of publications reporting on the rationale and clinical implications of the use of biomarkers for the early diagnosis of Alzheimer's disease (AD). Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012, and based on the following terms: mild cognitive impairment, Alzheimer's disease OR dementia, biomarkers. We retrieved 1,130 articles, of which 175 were reviews. Overall, 955 original articles were eligible. Results: The following points were considered relevant for the present review: a) rationale for biomarkers research in AD and mild cognitive impairment (MCI); b) usefulness of distinct biomarkers for the diagnosis and prediction of AD; c) the role of multimodality biomarkers for the diagnosis and prediction of AD; d) the role of biomarkers in clinical trials of patients with AD and MCI; and e) current limitations to the widespread use of biomarkers in research and clinical settings. Conclusion: Different biomarkers are useful for the early diagnosis and prediction of AD in at-risk subjects. Nonetheless, important methodological limitations need to be overcome for widespread use of biomarkers in research and clinical settings.

Objective: To critically review and evaluate existing knowledge on the conceptual limits and clinical usefulness of the diagnosis of mild cognitive impairment (MCI) and the neuropsychological assessment and short- and long-term prognosis thereof. Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012. Based on the search terms mild cognitive impairment or MCI and epidemiology or diagnosis, we retrieved 1,698 articles, of which 248 were critically eligible (cross-sectional and longitudinal studies); the abstracts of the remaining 1,450 articles were also reviewed. Results: A critical review on the MCI construct is provided, including conceptual and diagnostic aspects; epidemiological relevance; clinical assessment; prognosis; and outcome. The distinct definitions of cognitive impairment, MCI included, yield clinically heterogeneous groups of individuals. Those who will eventually progress to dementia may present with symptoms consistent with the definition of MCI; conversely, individuals with MCI may remain stable or return to normal cognitive function. Conclusion: On clinical grounds, the cross-sectional diagnosis of MCI has limited prognostic relevance. The characterization of persistent and/or progressive cognitive deficits over time is a better approach for identification of cases at the pre-dementia stages, particularly if these cognitive abnormalities are consistent with the natural history of incipient Alzheimer's disease.

In this study, we investigated the associations between single-nucleotide polymorphisms in GAB2 (rs2373115), GSK3B (rs6438552) and SORL1 (rs641120) and Alzheimer's disease (AD), both alone and in combination with the APOE*4 allele.

OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment.

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.OBJETIVO: A identificação de preditores da conversão para a doença de Alzheimer em pacientes com comprometimento cognitivo leve é relevante para o manejo clínico e para decidir sobre a prescrição de drogas antidemência. MÉTODO: Estudo longitudinal em coorte de indivíduos idosos com comprometimento cognitivo leve amnéstico e controles saudáveis; estimativa do risco da progressão para doença de Alzheimer nos dois grupos; determinação das variáveis preditivas desse desfecho. RESULTADOS: Pacientes com comprometimento cognitivo leve amnéstico apresentaram maior risco de desenvolver doença de Alzheimer ao longo do seguimento (odds ratio = 4,5, CI95% [1,3-13,6], p = 0,012). Na avaliação inicial, idade mais avançada, escores mais baixos nos testes cognitivos e do alelo APOE*4 foram preditores da conversão do comprometimento cognitivo leve amnéstico para doença de Alzheimer. Em uma subamostra de pacientes com comprometimento cognitivo leve amnéstico, aqueles que progrediram para doença de Alzheimer tinham concentrações liquóricas mais baixas do peptídeo beta-amilóide (Aβ42, p = 0,020) e mais altas da proteína TAU total (p = 0,030) e TAU fosforilada (p = 0,010) do que os pacientes que não progrediram para doença de Alzheimer. DISCUSSÃO: Este é o primeiro estudo brasileiro com biomarcadores liquóricos a relatar preditores da conversão comprometimento cognitivo leve-doença de Alzheimer. Nossos dados biológicos (aumento de TAU total e fosfo-TAU; redução de Aβ42), e podem auxiliar na identificação dos pacientes com comprometimento cognitivo leve com maior risco de evolução para demência.

OBJECTIVE: To determine the accuracy of the Mini-Mental State Examination combined with the Verbal Fluency Test and Clock Drawing Test for the identification of patients with mild cognitive impairment and Alzheimer's disease (AD). METHOD: These tests were used to evaluate cognitive function in 247 older adults. Subjects were divided into three groups according to their cognitive state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired controls (n=83), based on clinical and neuropsychological data. The diagnostic accuracy of each test for discriminating between these diagnostic groups (mild cognitive impairment or AD vs. controls) was examined with the aid of Receiver Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of the combination of tests on diagnostic accuracy. RESULTS: Although they were accurate enough for the identification of Alzheimer's disease, neither test alone proved adequate for the correct separation of patients with mild cognitive impairment from healthy subjects. Combining these tests did not improve diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in the identification of patients with mild cognitive impairment or Alzheimer's disease. CONCLUSIONS: The present data do not warrant the combined use of the Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test as a sufficient diagnostic schedule in screening for mild cognitive impairment. The present data do not support the notion that the combination of test scores is better that the use of Mini-Mental State Examination scores alone in the screening for Alzheimer's disease.

As presentes recomendações e sugestões para o "Tratamento da Doença de Alzheimer" foram elaboradas por grupo de trabalho constituído por participantes da IV Reunião de Pesquisadores em Doença de Alzheimer e Desordens Relacionadas, patrocinada pelo Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia. Compreendem tópicos sobre o tratamento farmacológico e não farmacológico do comprometimento cognitivo e declínio funcional, assim como dos sintomas de comportamento e psicológicos dessa doença demenciante. São utilizados diversos níveis de evidências e de recomendações e sugestões para os diversos fármacos propostos, assim como para o tratamento não farmacológico, baseado em ampla revisão bibliográfica, nacional e internacional.The present recommendations and suggestions on "Treatment of Alzheimer’s Disease" were elaborated by a work group constituted by participants of the IV Meeting of Researchers on Alzheimer’s Disease and Related Disorders, sponsored by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. They comprise topics on pharmacological and non-pharmacological treatment of cognitive impairment and functional decline, as well as of behavioral and psychological symptoms of this dementing disease. Several levels of evidence and of recommendations and suggestions are used for the various proposed drugs, as well as for non-pharmacological treatment, underpinned by a wide national and international bibliographical review.

Abstract Quality of life is seldom explored in evaluations of therapeutic interventions in Alzheimer's disease. Objective: To verify whether participation in a cognitive and functional rehabilitation program improves quality of life (QOL) among Alzheimer's disease (AD) patients. Methods: 19 AD patients participated in this study, 12 of whom attended 24 multi-professional intervention sessions - the experimental group - whereas the remaining 7 comprised the control group. The following tools were used to assess changes: a) Mini-Mental State Examination (MMSE); b) Geriatric Depression Scale (GDS); c) Quality of Life in AD evaluation scale (QOL-AD); d) Open question on QOL. Results: Participation had no positive impact on quantitative clinical variables (MMSE, GDS, QOL-AD). The answers to the open question, examined using the Collective Subject Discourse (CSD) method, suggested that QOL improved after the intervention. Conclusion: Combining pharmacological treatment with psychosocial intervention may prove to be an effective strategy to enhance the QOL of AD patients.

ABSTRACT. Cognitive impairment includes mild cognitive decline and dementia, such as Alzheimer's disease (AD) and cerebrovascular-related pathologies. Objective: To investigate the profile of AD-related CSF biomarkers in a sample of cognitively impaired and unimpaired older adults with concomitant subcortical cerebrovascular burden. Methods: Seventy-eight older adults attending an outpatient psychogeriatric clinic were enrolled. Diagnoses were based on clinical, neuropsychological, laboratory, and neuroimaging data. Participants were classified into: cognitively normal (controls, n = 30), mild cognitive impairment (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF analyses for determination of amyloid-beta (Aβ1-42), total tau (t-tau), phosphorylated tau (p-tau) and Aβ1-42/p-tau ratio according to the Luminex method. MRI was performed in all individuals, and was scored independently by two experts according to Fazekas scale. Statistical analyses were conducted with the aid of general linear model procedures, and the Chi-squared test. Results: T-tau levels were significantly associated with subcortical lesion pattern when Fazekas was considered as a group factor. CSF biomarkers were not associated with MCI, AD, or controls when considered separately. There was a tendency for reduction in CSF Aβ1-42 together with increasing Fazekas scores, but without statistical significance. Comparisons of Aβ1-42 and t-tau with each clinical group or with each neuroimaging pattern did not reach statistical differences. Likewise, Fazekas scores had no impact on CAMCOG scores. Conclusion: We found a significant association between t-tau levels and subcortical lesions when all Fazekas classifications were considered as a single group; comparisons of Fazekas subgroups and CSF biomarkers did not reach significance.

Abstract This consensus prepared by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology is aimed at recommending new criteria for the diagnosis of dementia and Alzheimer's disease (AD) in Brazil. A revision was performed of the proposals of clinical and of research criteria suggested by other institutions and international consensuses. The new proposal for the diagnosis of dementia does not necessarily require memory impairment if the cognitive or behavioral compromise affects at least two of the following domains: memory, executive function, speech, visual-spatial ability and change in personality. For the purpose of diagnosis, AD is divided into three phases: dementia, mild cognitive impairment and pre-clinical phase, where the latter only applies to clinical research. In the dementia picture, other initial forms were accepted which do not involve amnesia and require a neuroimaging examination. Cerebrospinal fluid biomarkers are recommended for study, but can be utilized as optional instruments, when deemed appropriate by the clinician.

Objective: To review the most common mental health strategies aimed at alleviating and/or preventing mental health problems in individuals during the coronavirus disease 2019 (COVID-19) and other coronavirus pandemics. Methods: We conducted a systematic review of the literature assessing three databases (PubMed, SCOPUS, and PsycINFO). A meta-analysis was performed with data from randomized controlled trials (RCTs). For non-RCT studies, a critical description of recommendations was performed. Results: From a total of 2,825 articles, 125 were included. Of those, three RCTs were included in the meta-analysis. The meta-analysis revealed that the interventions promoted better overall mental health outcomes as compared to control groups (standardized mean difference [SMD] = 0.87 [95%CI 0.33-1.41], p < 0.001, I2 = 69.2%), but did not specifically improve anxiety (SMD = 0.98 [95%CI -0.17 to 2.13], p > 0.05; I2 = 36.8%). Concerning the systematic review, we found a large body of scientific literature proposing recommendations involving psychological/psychiatric interventions, self-care, education, governmental programs, and the use of technology and media. Conclusions: We found a large body of expert recommendations that may help health practitioners, institutional and governmental leaders, and the general population cope with mental health issues during a pandemic or a crisis period. However, most articles had a low level of evidence, stressing the need for more studies with better design (especially RCTs) investigating potential mental health interventions during COVID-19. PROSPERO registration: CRD42020190212.

Objective: The relationship between biomarkers of amyloid-beta aggregation (Aβ1-42) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses. Methods: We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer’s disease (AD), and 26 with other dementias (OD). Results: MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). Aβ1-42 and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The Aβ1-42/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001). Conclusion: CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.