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A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis
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Marques, Julia Hatagami

; Talib, Leda Leme

; Hortêncio, Lucas

; Andrade, Julio Cesar

; Alves, Tania Maria

; Serpa, Mauricio Henriques

; Yamamoto, Guilherme Lopes

; van de Bilt, Martinus Theodorus

; Rössler, Wulf

; Gattaz, Wagner Farid

; Loch, Alexandre Andrade

Brazilian Journal of Psychiatry

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2023, Volume 45 N. 3 Pages 268 - 273

Abstract: En | Text: En | PDF: En

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

https://doi.org/10.47626/1516-4446-2023-3044

Decision tree-based classification as a support to diagnosis in the Alzheimer’s disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis
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Costa, Alana

; Pais, Marcos

; Loureiro, Júlia

; Stella, Florindo

; Radanovic, Márcia

; Gattaz, Wagner

; Forlenza, Orestes

; Talib, Leda

Brazilian Journal of Psychiatry

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aug 2022, Volume 44 N. 4 Pages 370 - 377

Abstract: En | Text: En | PDF: En

Objective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer’s disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aβ1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.

https://doi.org/10.47626/1516-4446-2021-2277

Translation and validation of the Structured Interview for Prodromal Syndromes (SIPS) to Portuguese
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Diniz, Gabriel N.

; Santos, Pedro A.M.F.

; Andrade, Julio C.

; Alves, Tania M.

; Hortêncio, Lucas

; van de Bilt, Martinus T.

; Rössler, Wulf

; Gattaz, Wagner F.

; Loch, Alexandre A.

Brazilian Journal of Psychiatry

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oct 2021, Volume 43 N. 5 Pages 560 - 562

Abstract: En | Text: En | PDF: En

https://doi.org/10.1590/1516-4446-2021-2056 43 downloads

Influence of migration on the thought process of individuals at ultra-high risk for psychosis
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Nogueira, Arthur S.

; Andrade, Julio C.

; Serpa, Mauricio H.

; Alves, Tania M.

; Freitas, Elder L.

; Hortêncio, Lucas

; van de Bilt, Martinus T.

; Rössler, Wulf

; Gattaz, Wagner F.

; Loch, Alexandre A.

Brazilian Journal of Psychiatry

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jun 2021, Volume 43 N. 3 Pages 285 - 288

Abstract: En | Text: En | PDF: En

Objective: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. Methods: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student’s t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. Results: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. Conclusions: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

https://doi.org/10.1590/1516-4446-2019-0685 127 downloads

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain
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Borrione, Lucas

; Bellini, Helena

; Razza, Lais Boralli

; Avila, Ana G.

; Baeken, Chris

; Brem, Anna-Katharine

; Busatto, Geraldo

; Carvalho, Andre F.

; Chekroud, Adam

; Daskalakis, Zafiris J.

; Deng, Zhi-De

; Downar, Jonathan

; Gattaz, Wagner

; Loo, Colleen

; Lotufo, Paulo A.

; Martin, Maria da Graça M.

; McClintock, Shawn M.

; O’Shea, Jacinta

; Padberg, Frank

; Passos, Ives C.

; Salum, Giovanni A.

; Vanderhasselt, Marie-Anne

; Fraguas, Renerio

; Benseñor, Isabela

; Valiengo, Leandro

; Brunoni, Andre R.

Brazilian Journal of Psychiatry

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aug 2020, Volume 42 N. 4 Pages 403 - 419

Abstract: En | Text: En | PDF: En

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more “precision-oriented” practice.

https://doi.org/10.1590/1516-4446-2019-0741 1546 downloads

Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial
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Brunoni, Andre R.

; Carracedo, Angel

; Amigo, Olalla M.

; Pellicer, Ana L.

; Talib, Leda

; Carvalho, Andre F.

; Lotufo, Paulo A.

; Benseñor, Isabela M.

; Gattaz, Wagner

; Cappi, Carolina

Brazilian Journal of Psychiatry

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apr 2020, Volume 42 N. 2 Pages 128 - 135

Abstract: En | Text: En | PDF: En

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.

https://doi.org/10.1590/1516-4446-2019-0620 1172 downloads

Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer’s disease patients
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JOAQUIM, HELENA P. G.

; COSTA, ALANA C.

; FORLENZA, ORESTES V.

; GATTAZ, WAGNER F.

; TALIB, LEDA L.

Archives of Clinical Psychiatry (São Paulo)

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oct 2019, Volume 46 N. 5 Pages 120 - 124

Abstract: En | Text: En | PDF: En

Abstract Background Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer’s disease (AD). Objective The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods Plasmatic polyamines were quantified using the AbsoluteIDQ® p180 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.

https://doi.org/10.1590/0101-60830000000209 768 downloads

Schizophrenia TreAtment with electRic Transcranial Stimulation (STARTS): design, rationale and objectives of a randomized, double-blinded, sham-controlled trial
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Valiengo, Leandro

; Gordon, Pedro Caldana

; de Carvalho, Juliana Barbosa

; Rios, Rosa Maria

; Koebe, Stephanie

; Serpa, Mauricio Henrique

; van de Bilt, Martinus

; Lacerda, Acioly

; Elkis, Helio

; Gattaz, Wagner Farid

; Brunoni, André Russowsky

Trends in Psychiatry and Psychotherapy

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jun 2019, Volume 41 N. 2 Pages 104 - 111

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

Resumo Introdução A esquizofrenia é um transtorno mental grave. Embora alguns medicamentos antipsicóticos tenham demonstrado eficácia no tratamento de sintomas positivos, não há tratamento amplamente reconhecido para sintomas negativos, o que pode causar sofrimento e prejuízo significativos para pacientes com esquizofrenia. Aqui descrevemos a fundamentação teórica e o design do estudo STARTS (Schizophrenia TreAtment with electRic Transcranial Stimulation), um ensaio clínico destinado a testar a eficácia de um tratamento não farmacológico conhecido como estimulação transcraniana por corrente contínua (ETCC) para tratar os sintomas negativos da esquizofrenia. Métodos O estudo STARTS foi concebido como um ensaio clínico randomizado, controlado por simulação, duplo-cego, avaliando a ETCC para o tratamento dos sintomas negativos da esquizofrenia. Cem pacientes serão incluídos e submetidos a 10 sessões de ETCC sobre o córtex pré-frontal dorsolateral esquerdo (estimulação anódica) e a junção temporoparietal esquerda (estimulação catodal) durante 5 dias consecutivos. Os participantes serão avaliados através de testes clínicos e neuropsicológicos antes e após a intervenção. O desfecho primário é a mudança na pontuação da subescala negativa da Escala da Síndrome Positiva e Negativa (Positive and Negative Syndrome Scale [PANSS]) ao longo do tempo e entre os grupos. Marcadores biológicos, incluindo neurotrofinas e interleucinas do sangue, polimorfismos genéticos e excitabilidade cortical motora, também serão avaliados. Resultados Os resultados clínicos fornecerão informações sobre a ETCC como um tratamento para os sintomas negativos da esquizofrenia, e a investigação dos biomarcadores contribuirá para uma melhor compreensão dos mecanismos de ação da ETCC. Conclusão Nossos resultados podem trazer uma nova técnica terapêutica para o tratamento dos sintomas negativos da esquizofrenia. Registro do ensaio clínico: ClinicalTrials.gov, NCT02535676.

Abstract Introduction Schizophrenia is a severe mental disorder. While some antipsychotic medications have demonstrated efficacy in treating positive symptoms, there is no widely recognized treatment for negative symptoms, which can cause significant distress and impairment for patients with schizophrenia. Here we describe the rationale and design of the STARTS study (Schizophrenia TreAtment with electRic Transcranial Stimulation), a clinical trial aimed to test the efficacy of a non-pharmacological treatment known as transcranial direct current stimulation (tDCS) for treating the negative symptoms of schizophrenia Methods The STARTS study is designed as a randomized, sham-controlled, double-blinded trial evaluating tDCS for the treatment of the negative symptoms of schizophrenia. One-hundred patients will be enrolled and submitted to 10 tDCS sessions over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporoparietal junction (cathodal stimulation) over 5 consecutive days. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in the Positive and Negative Syndrome Scale (PANSS) negative subscale score over time and across groups. Biological markers, including blood neurotrophins and interleukins, genetic polymorphisms, and motor cortical excitability, will also be assessed. Results The clinical results will provide insights about tDCS as a treatment for the negative symptoms of schizophrenia, and the biomarker investigation will contribute towards an improved understanding of the tDCS mechanisms of action. Conclusion Our results could introduce a novel therapeutic technique for the negative symptoms of schizophrenia. Clinical trial registration: ClinicalTrials.gov, NCT02535676 .

https://doi.org/10.1590/2237-6089-2018-0047 1787 downloads

A new editorial board for new challenges
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Gattaz, Wagner F.

; Crippa, José A. S.

Archives of Clinical Psychiatry (São Paulo)

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jun 2017, Volume 44 N. 3 Pages 55 - 55

Abstract: En | Text: En | PDF: En

https://doi.org/10.1590/0101-60830000000119 507 downloads

10.

Benefits of psychodynamic group therapy on depression, burden and quality of life of family caregivers to Alzheimer’s disease patients
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Kamkhagi, Dorli

; Costa, Ana Carolina Oliveira

; Kusminsky, Sandra

; Supino, Deborah

; Diniz, Breno Satler

; Gattaz, Wagner Farid

; Forlenza, Orestes Vicente

Archives of Clinical Psychiatry (São Paulo)

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dec 2015, Volume 42 N. 6 Pages 157 - 160

Abstract: En | Text: En | PDF: En

Abstract Background Family members providing continuous care to demented patients suffer from severe burden that impairs quality of life and often evolves to depression. Objective This study aims to evaluate the effect of psychodynamic group psychotherapy (PGT) compared to body awareness therapy (BAT) on caregiver burden, depressive symptoms, and quality of life among family caregivers to Alzheimer disease (AD) patients. Methods Thirty-seven healthy family caregivers were randomly allocated to receive PGT (n = 20) or BAT (n = 17). Interventions were administered in the format of 14 weekly group sessions. Outcome measures were: modification of scores on Zarit Burden Scale, Beck Depression Inventory and WHO-QoL Scale. Results Participants in the PGT group displayed significant reduction on burden (p = 0.01) and depression scores (p = 0.005), and improved quality of life (p = 0.002), whereas those in the BAT group showed improvements in burden of care (p = 0.001) and quality of life (p = 0.01), but not on depressive symptoms (p = 0.13). Discussion Psychodynamic psychotherapy was associated with amelioration of depressive symptoms, but overall benefits on burden of care and quality of life were similar irrespective of the type of intervention, i.e., psychologically-oriented or not. We hypothesize that these interventions can be complementary to improve depression and burden of care among family caregivers of AD patients.

https://doi.org/10.1590/0101-60830000000067 4478 downloads

11.

Multidisciplinary rehabilitation program: effects of a multimodal intervention for patients with Alzheimer’s disease and cognitive impairment without dementia
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Santos, Glenda Dias

; Nunes, Paula Villela

; Stella, Florindo

; Brum, Paula Schimidt

; Yassuda, Monica Sanches

; Ueno, Linda Massako

; Gattaz, Wagner Farid

; Forlenza, Orestes Vicente

Archives of Clinical Psychiatry (São Paulo)

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dec 2015, Volume 42 N. 6 Pages 153 - 156

Abstract: En | Text: En | PDF: En

Abstract Background Non-pharmalogical interventions represent an important complement to standard pharmalogical treatment in dementia. Objective This study aims to evaluate the effects of a multidisciplinary rehabilitation program on cognitive ability, quality of life and depression symptoms in patients with Alzheimer’s disease (AD) and cognitive impairment without dementia (CIND). Methods Ninety-seven older adults were recruited to the present study. Of these, 70 patients had mild AD and were allocated into experimental (n = 54) or control (n = 16) groups. Two additional active comparison groups were constituted with patients with moderate AD (n = 13) or with CIND (n = 14) who also received the intervention. The multidisciplinary rehabilitation program lasted for 12 weeks and was composed by sessions of memory training, recreational activities, verbal expression and writing, physical therapy and physical training, delivered in two weekly 6-hour sessions. Results As compared to controls, mild AD patients who received the intervention had improvements in cognition (p = 0.021) and quality of life (p = 0.003), along with a reduction in depressive symptoms (p < 0.001). As compared to baseline, CIND patients displayed at the end of the intervention improvements in cognition (p = 0.005) and depressive symptoms (p = 0.011). No such benefits were found among patients with moderate AD.Discussion: This multidisciplinary rehabilitation program was beneficial for patients with mild AD and CIND. However, patients with moderate dementia did not benefit from the intervention.

https://doi.org/10.1590/0101-60830000000066 81826 downloads

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Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission
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Loch, Alexandre A.

; van de Bilt, Martinus T.

; Bio, Danielle S.

; Prado, Carolina M. do

; Sousa, Rafael T. de

; Valiengo, Leandro L.

; Moreno, Ricardo A.

; Zanetti, Marcus V.

; Gattaz, Wagner F.

Brazilian Journal of Psychiatry

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sep 2015, Volume 37 N. 3 Pages 235 - 241

Abstract: En | Text: En | PDF: En

Objective: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly. Methods: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. Results: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001). Conclusion: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

https://doi.org/10.1590/1516-4446-2014-1553 2214 downloads

13.

A randomized clinical trial of home-based telepsychiatric outpatient care via videoconferencing: design, methodology, and implementation
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Hungerbuehler, Ines

; Leite, Rodrigo Fonseca Martins

; Bilt, Martinus Theodorus Van de

; Gattaz, Wagner Farid

Archives of Clinical Psychiatry (São Paulo)

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jun 2015, Volume 42 N. 3 Pages 76 - 78

Abstract: En | Text: En | PDF: En

Background Healthcare providers are continuously challenged to find innovative, cost-effective alternatives and to scale up existent services to meet the growing demand upon mental health care delivery. Due to continuous advances in technologies, telepsychiatry has become an effective tool for psychiatric care. In 2012, the Institute of Psychiatry of the University of São Paulo Medical School started a randomized clinical trial of home-based telepsychiatric outpatient care via videoconferencing. Objective The objective of this article is to describe the design, methodology and implementation of a pilot project, which aimed to verify the applicability and efficiency of psychiatric attendance via Internet-based videoconferencing in a resource-constrained environment. Methods The project consisted of a 12 months follow-up study with a randomized clinical trial, which compared various quality indicators between home-based telepsychiatric aftercare via videoconferencing and face-to-face aftercare. Results The final sample comprised 107 outpatients (53 in the telepsychiatry group and 54 in the control group). Among 1,227 realized consultations, 489 were held by videoconferencing. Satisfaction with the aftercare by videoconferencing and the medication delivery was high among patients. Attending psychiatrists were satisfied with the assistance by videoconferencing. Discussion The experiences during this pilot project have overall been very positive and psychiatric outpatient care by videoconferencing seems viable to treat patients even in a resource-constrained environment.

https://doi.org/10.1590/0101-60830000000052 1906 downloads

14.

Mild cognitive impairment (part 2): biological markers for diagnosis and prediction of dementia in Alzheimer's disease
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Forlenza, Orestes V.

; Diniz, Breno S.

; Teixeira, Antonio L.

; Stella, Florindo

; Gattaz, Wagner

Brazilian Journal of Psychiatry

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sep 2013, Volume 35 N. 3 Pages 284 - 294

Abstract: En | Text: En | PDF: En

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.

https://doi.org/10.1590/1516-4446-2012-3505 6135 downloads

15.

Mild cognitive impairment (part 1): clinical characteristics and predictors of dementia
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Forlenza, Orestes V.

; Diniz, Breno S.

; Stella, Florindo

; Teixeira, Antonio L.

; Gattaz, Wagner F.

Brazilian Journal of Psychiatry

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jun 2013, Volume 35 N. 2 Pages 178 - 185

Abstract: En | Text: En | PDF: En

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.

https://doi.org/10.1590/1516-4446-2012-3503 13642 downloads

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