Visto que o estresse oxidativo está intimamente relacionado com a progressão da demência, este se apresenta como um possível alvo terapêutico a fim de preservar as funções cognitivas. No mesmo sentido, estudos mostram o papel antioxidante do selênio, mineral que atua por meio das selenoproteínas, com destaque para a família de enzimas antioxidantes glutationa peroxidase (GPx) e a selenoproteína responsável pelo transporte de selênio, a selenoproteína P (SePP). Entretanto, diferentes genótipos dos genes que codificam essas selenoproteínas podem refletir em diferentes respostas diante de intervenções alimentares. Assim, este trabalho teve como objetivo verificar os efeitos da suplementação com castanha-do-brasil sobre o estresse oxidativo em pacientes com comprometimento cognitivo leve (CCL) e verificar sua relação com os polimorfismos rs1050450 (Pro198Leu) no gene da GPx1, rs3877899 e rs7579 no gene da selenoproteína P. Participaram do estudo 31 indivíduos com CCL, voluntários, de ambos os sexos, frequentadores do Ambulatório de Memória do Idoso do Serviço de Geriatria da Faculdade de Medicina da Universidade de São Paulo, com idade igual ou superior a 60 anos, que foram distribuídos aleatoriamente entre os grupos Castanha e Controle. O grupo Castanha recebeu uma unidade de castanha-do-brasil por dia durante seis meses. Foram avaliados os seguintes marcadores: determinação de selênio no plasma e nos eritrócitos, atividade da GPx eritrocitária, avaliação dos níveis de oxygen radical absorbance capacity (ORAC) e de malondialdeído (MDA) plasmáticos, perfil lipídico sérico e expressão gênica de GPx1 e SePP. Além disso, os participantes foram submetidos à avaliação cognitiva e genotipados quanto aos polimorfismos rs1050450, rs3877899 e rs7579. Cada unidade de castanha-do-brasil forneceu 288,75µg de selênio. Dentre os 31 participantes selecionados, apenas 20 concluíram o estudo, e observou-se que, antes da intervenção, os grupos de estudo não apresentavam diferença quanto aos níveis de selênio no plasma e no eritrócito, bem como na atividade da GPx e nos níveis plasmáticos de ORAC e de MDA. Porém, após a suplementação, verificou-se aumento significativo no selênio plasmático (290,6±74,6) e eritrocitário (574,6±181,4) e na atividade da GPx (59,55±20,79) no grupo Castanha, diferente do grupo Controle (47,48±11,7 no plasma; 33,5±16,1 no eritrócito; 42,54±13,05 atividade da GPx). Em relação ao MDA, verificou-se que ambos os grupos apresentaram aumento após a intervenção, porém não significativo. No caso do ORAC, não se verificou alteração entre os grupos após os seis meses. O escore CERAD, que avalia desempenho cognitivo, não foi diferente entre os grupos após o tratamento, entretanto as mudanças observadas na fluência verbal e na praxia construtiva ao longo do acompanhamento foram mais favoráveis no grupo Castanha. A frequência dos genótipos de referência foram 40% para Pro198Leu, 55% para rs7579 e 60% para rs3877899. Não foram identificadas diferenças entre os níveis de selênio, de atividade da GPx, de MDA e de ORAC entre os genótipos, porém em análise multivariada verificou-se que o alelo variante do Pro198Leu se relacionou com aumento de 0,613 dp na concentração de selênio no plasma no baseline. A influência dos polimorfismos na resposta à intervenção com castanha-do-brasil foi avaliada nos 11 participantes do grupo Castanha, e observou-se que os genótipos não influenciaram na resposta quanto os níveis de selênio plasmático e eritrocitário, bem como de MDA. Entretanto, quanto à atividade da GPx, embora todos os genótipos tenham apresentado aumento após a intervenção, isso não foi significativo para o genótipo dominante do rs7579 e para o variante do rs3877899. A expressão de GPx1 e de SePP também foi diferente entre os genótipos: indivíduos com alelo variante do Pro198Leu apresentaram redução da expressão da GPx1, enquanto carreadores do genótipo homozigoto dominante tiveram aumento. Também percebeu-se que a expressão da SePP foi reduzida em todos os genótipos, entretanto essa mudança foi mais relevante para os genótipos variantes do Pro198Leu e rs7579 e para o genótipo GG do rs3877899. A partir desses resultados, concluiu-se que o consumo de apenas uma castanha-do-brasil diariamente, durante seis meses, é suficiente para recuperar o estado nutricional relativo ao selênio, e isso parece ter efeitos positivos sobre a cognição em idosos com CCL. Além disso, observou-se que o polimorfismo Pro198Leu no gene da GPx1 parece influenciar o estado nutricional quanto ao selênio, bem como a expressão de GPx, enquanto que os polimorfismos rs7579 e rs3877899 parecem não influenciar, de maneira significativa, o metabolismo de selênio frente ao consumo de castanha-do-brasil. / Since oxidative stress is closely related to progression of dementia, the antioxidant system may be a potential therapeutic target to preserve cognitive function. In this way, studies show the antioxidant role of selenium, which plays as selenoproteins especially glutathione peroxidase (GPx) family and selenoprotein P (SePP). However, different genotypes of selenoprotein genes may result in different response to dietary intake. Therefore, this work aimed to verify the effects of Brazil nuts intake on oxidative stress and the role of the polymorphisms rs1050450 (Pro198Leu) in GPx1 gene and rs7579 and rs3877899 in SePP gene in mild cognitive impairment (MCI) patients. Study subjects comprised 31 voluntary patients with MCI who attended the Memory and Aging Unit of the Geriatrics Division, University of São Paulo Medical School (Brazil). They were randomly assigned to ingestion of Brazil nuts or to the control group. Brazil nuts group received one nut daily during six months. The following parameters were analysed: selenium concentration in plasma and erythrocyte, GPx activity in erythrocyte, plasmatic levels of oxygen radical absorbance capacity (ORAC) and of malondialdedyde (MDA), serum lipid profile. Besides, we evaluated cognitive performance and the patients were genotyped to rs1050450, rs3877899 e rs7579 polymorphisms. Each Brazil nut provided 288.75µg of selenium. Among 31 enrolled participants, only 20 finished the study. No differences regarding selenium levels, GPx activity, ORAC and MDA levels were observed at baseline between groups. However, after treatment, we observed significant increase in selenium in plasma (290.6±74.6) and in erythrocyte (574.6±181.4) and in GPx activity (59.55±20.79) in treated group, unlike control group (47.48±11.70 selenium in plasma; 33.5±16.1 selenium in erythrocyte; 42.54±13.05 GPx activity). Although not significant, MDA level increased after 6 months in both groups and ORAC levels were not different across time. CERAD total score was not different across time between groups, however changes in verbal fluency and constructional praxis subtests across time were significantly more favorable on the supplemented group when compared with control group. The frequency of dominant genotypes for Pro198Leu, rs7579 and rs3877899 were 40%, 55% and 60%, respectively. We did not observe differences regarding to selenium ORAC and MDA levels and GPx activity among genotypes, however after linear regression analysis the presence of variant allele of Pro198Leu was associated with an increase of 0.613 SD in selenium plasma level at baseline. The effect of polymorphisms in response to Brazil nut intake was analysed in Brazil nut group, and we observed that sele nium and MDA levels were not affected by polymorphisms. However although GPx activity increased in all genotype groups, this was not significant in dominant genotype of rs7579 and variant genotypes of rs3877899. GPx1 and SePP expression was also different among groups across time: variant allele of Pro198Leu presented decreased expression of GPx1 while dominant homozygous presented increase of expression. We also observed that SePP expression was reduced in all genotypes, but his was more important in variant genotypes of Pro198Leu and rs7579 and in GG genotype of rs3877899. From these results, we can conclude that consumption of only one Brazil nut is enough to restore selenium status, and this may be positive effects on cognition performance. Furthermore we observed that Pro198Leu polymorphism may influence selenium nutritional status and GPx activity whereas rs7579 and rs3877899 polymorphisms did not have an effect on selenium metabolism after Brazil nut intake.

Since neuroinflammation is present in patients with mild cognitive impairment (MCI) andAlzheimer's disease (AD) and since cholinesterase inhibitors increases the level ofacetylcholine, the aim was to investigate whether inflammatory markers of cholinoceptive cellsare affected in these patients. Near a biological hallmark of AD, amyloid plaque, activatedastrocytes and microglia can be found and higher levels of proinflammatory cytokines, i.e. IL-1β. To study the inflammatory response, proteins GFAP and S100B are used as CSF glialmarkers. IL-1β can bind to the membrane-bound IL-1 receptor or soluble sIL-1β-RII. When IL-1β binds to the soluble receptor instead of the membrane-bound receptor, no intracellular signalpropagation occur, thereby sIL-1βRII exerts an antagonistic effect and diminishedinflammatory responses. Thus a reduction in ratio of IL-1β to sIL-1RII levels may be indicativeof anti-inflammatory response. Available data on CSF GFAP, S100B, IL-1β and sIL-1β-RIIlevels in AD patients and MCI patients was used. MCI group were longitudinally followedafter start of treatment with a cholinesterase inhibitor (ChEI). AD group had data from baselineand after short-term treatment with a ChEI. The statistics application StatView was used toanalyse data. The activity of the cholinesterase enzymes, BuChE and AChE showed significantinhibition in the CSF of the MCI patients compared to baseline CSF GFAP level wassignificantly lower in MCI than AD patients at baseline. The levels of both GFAP and S100Bwere increased with time in MCI patients to comparable levels in the AD patients, indicative ofastroglial activation in MCI patients. However, the ratio of IL-1β to sIL-1RII showed alongitudinal reduction in the MCI patients after the treatment with the ChEIso that this ratiowas significantly higher in AD than in MCI patients. Thus despite the activation of astroglialcells in the treated MCI patients the proinflammatory effect of IL-1β was prevented byinduction of sIL-1βRII levels indicative of an anti-inflammatory outcome of treatment. Thisstudy suggests that proper activation of astroglial cells may have beneficial effect on ADpathogenesis, and conversion of MCI to AD. It also suggests that cholinesterase inhibitors may have an anti-inflammatory effect.

Objective: The nature of disaster research makes it difficult to adequately measure the impact that significant events have on a population. Large, representative samples are required, ideally with comparable data collected before the event. When Christchurch, New Zealand, was struck by multiple, devastating earthquakes, there presented an opportunity to investigate the effects of dose-related quakes (none, one, two or three over a 9-month period) on the cognition of Canterbury’s elderly population through the New Zealand Brain Research Institute’s (NZBRI’s) cognitive screening study. The related effects of having a concomitant medical condition, sex, age and estimated- full scale IQ (Est-FSIQ) on cognition were also investigated. Method: 609 participants were tested on various neuropsychological tests and a self-rated dementia scale in a one hour interview at the NZBRI. Four groups were established, based on the number of major earthquakes experienced at the time of testing: “EQ-dose: None” (N = 51) had experienced no quakes; “EQ-dose: One” (N = 193) had experienced the initial quake in September 2010; “EQ-dose: Two” (N = 82) also experienced the most devastating February 2011 quake; and “EQ-dose: Three” (N = 265) also the June 2011 quake at testing. Results: Two neuropsychological variables of Trail A and the AD8 were impacted by an EQ-dose effect, while having a medical condition was associated with poorer function on the MoCA, Rey Copy and Recall, Trail A, and AD8. Having a major medical condition led to worse performance on the Rey Copy and Recall following the major February earthquake. Males performed significantly better on Trail A and Rey Planning, while females better on the MoCA. Older participants (>73) had significantly lower scores on the MoCA than younger participants (<74), while those with a higher Est-FSIQ (>111) had better scores on the MoCA and Rey Recall than participants with a lower Est-FSIQ. Finally, predicted variable analysis (based on calculated, sample-specific Z-scores) failed to find a significant earthquake effect when variables of age, sex and Est-FSIQ were controlled for, while there was a significant effect of medical condition on each measure. Conclusion: The current thesis provides evidence suggesting resilience amongst Canterbury’s elderly population in the face of the sequence of significant quakes that struck the region over a year from September 2010. By contrast, having a major medical condition was a ‘more significant life event’ in terms of impact on cognition in this group.

Darbo tikslas: įvertinti ankstyva Parkinsono liga (PL) be demencijos sergančių asmenų pažinimo funkcijas naudojant Kembridžo kompiuterinės neuropsichologinio ištyrimo sistemos testų rinkinį, palyginti rezultatus su kontrolinės grupės asmenų duomenimis bei nustatyti kognityvinių rodiklių ryšius su biologiniais žymenimis ir klinikiniais nekognityviniais PL simptomais. Darbo uždaviniai: ištirti ankstyva PL sergančių asmenų dėmesio, atminties, regos erdvinę ir vykdomąsias funkcijas, naudojant kompiuterizuotų testų rinkinį CANTAB eclipse 3.0.0, ir palyginti juos su kontrolinių asmenų duomenimis; nustatyti pacientų kognityvinių funkcijų ryšį su UPLVS skale įvertintu ligos sunkumu, transkranijinės sonografijos (TKS) metodu nustatytu juodosios medžiagos (JM) echogeniškumu, presinapsinio dopamine transporterio koncentracija dryžuotame kūne, nustatyta radionuklidinės kompiuterinės tomografijos (RKT) su I¹²³-FP-CIT būdu, miego, nuovargio bei demografiniais veiksniais, gyvenimo kokybės rodikliais, PL gydyti skiriamų vaistų vartojimu; išanalizuoti kompiuterizuotais testais įvertintų kognityvinių funkcijų diagnostinę vertę sergant ankstyva PL. Metodai. Tyrimas atliktas Vilniaus universiteto ligoninės Santariškių klinikų Neurologijos centre. Atrinkta 115 pacientų, sergančių ankstyva kliniškai tikėtina PL, kurie atitiko įtraukimo kriterijus bei nebuvo neįtraukimo kriterijų, ir 42 pagal amžių, lytį, mokymosi trukmę atrinkti kontroliniai tiriamieji, kurie nesirgo PL ar kitomis... [toliau žr. visą tekstą] / The aim of the study: to evaluate the cognitive functions of patients with early-stage Parkinson‘s disease (PD) without dementia using Cambridge Neuropsychological Test Automated Battery (CANTAB Eclipse 3.0.0), to compare the obtained results with the data of control subjects, to determine the associations of the variables of cognitive testing with biological markers and clinical non-cognitive symptoms of PD. Objectives: to examine attention, memory, visuospatial and executive functions of patients with early-stage PD without dementia using CANTAB Eclipse 3.0.0 and to compare the obtained results with the data of control subjects; to investigate the relationship between the cognitive functions of patients with early-stage PD and the severity of disease measured by UPDRS score, the echogenic properties of brainstem nigral substance (SN) examined by transcranial sonography (TCS), the striatal binding of presinaptic dopamine transporter determined by single-photon emission computed tomography (SPECT) with I¹²³-FP-CIT, sleep, fatigue, demographic factors and quality of life scores, the usage of medications for early-stage PD; to analize the diagnostic characteristics of particular computerised tests for evaluation of cognitive function in patients with early-stage PD. Methods. The study was performed at the Department of Neurology of Vilnius University Hospital Santariškių Klinikos. 115 patients diagnosed with clinically probable early-stage PD who met inclusion criteria and... [to full text]

The aim of the study: to evaluate the cognitive functions of patients with early-stage Parkinson‘s disease (PD) without dementia using Cambridge Neuropsychological Test Automated Battery (CANTAB Eclipse 3.0.0), to compare the obtained results with the data of control subjects, to determine the associations of the variables of cognitive testing with biological markers and clinical non-cognitive symptoms of PD. Objectives: to examine attention, memory, visuospatial and executive functions of patients with early-stage PD without dementia using CANTAB Eclipse 3.0.0 and to compare the obtained results with the data of control subjects; to investigate the relationship between the cognitive functions of patients with early-stage PD and the severity of disease measured by UPDRS score, the echogenic properties of brainstem nigral substance (SN) examined by transcranial sonography (TCS), the striatal binding of presinaptic dopamine transporter determined by single-photon emission computed tomography (SPECT) with I¹²³-FP-CIT, sleep, fatigue, demographic factors and quality of life scores, the usage of medications for early-stage PD; to analize the diagnostic characteristics of particular computerised tests for evaluation of cognitive function in patients with early-stage PD. Methods. The study was performed at the Department of Neurology of Vilnius University Hospital Santariškių Klinikos. 115 patients diagnosed with clinically probable early-stage PD who met inclusion criteria and... [to full text] / Darbo tikslas: įvertinti ankstyva Parkinsono liga (PL) be demencijos sergančių asmenų pažinimo funkcijas naudojant Kembridžo kompiuterinės neuropsichologinio ištyrimo sistemos testų rinkinį, palyginti rezultatus su kontrolinės grupės asmenų duomenimis bei nustatyti kognityvinių rodiklių ryšius su biologiniais žymenimis ir klinikiniais nekognityviniais PL simptomais. Darbo uždaviniai: ištirti ankstyva PL sergančių asmenų dėmesio, atminties, regos erdvinę ir vykdomąsias funkcijas, naudojant kompiuterizuotų testų rinkinį CANTAB eclipse 3.0.0, ir palyginti juos su kontrolinių asmenų duomenimis; nustatyti pacientų kognityvinių funkcijų ryšį su UPLVS skale įvertintu ligos sunkumu, transkranijinės sonografijos (TKS) metodu nustatytu juodosios medžiagos (JM) echogeniškumu, presinapsinio dopamine transporterio koncentracija dryžuotame kūne, nustatyta radionuklidinės kompiuterinės tomografijos (RKT) su I¹²³-FP-CIT būdu, miego, nuovargio bei demografiniais veiksniais, gyvenimo kokybės rodikliais, PL gydyti skiriamų vaistų vartojimu; išanalizuoti kompiuterizuotais testais įvertintų kognityvinių funkcijų diagnostinę vertę sergant ankstyva PL. Metodai. Tyrimas atliktas Vilniaus universiteto ligoninės Santariškių klinikų Neurologijos centre. Atrinkta 115 pacientų, sergančių ankstyva kliniškai tikėtina PL, kurie atitiko įtraukimo kriterijus bei nebuvo neįtraukimo kriterijų, ir 42 pagal amžių, lytį, mokymosi trukmę atrinkti kontroliniai tiriamieji, kurie nesirgo PL ar kitomis... [toliau žr. visą tekstą]

Introduction: Idiopathic Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that is characterised by motor symptoms. However, there is increasing awareness that a range of neuropsychiatric and cognitive problems also accompanys PD. The objective of this thesis was to examine the profile of neuropsychiatric and cognitive problems for patients with PD without dementia. Parkinson's disease patients who could be identified at the time of this study were invited to participate. Each patient was individually matched to a healthy control in terms of age, premorbid intelligence, and years of education. Results: Neuropsychiatric symptoms were common for this patient group, over 40% self reported symptoms consistent with depression, 40% with physical fatigue, 38% with mental fatigue, 38% with apathy and 32% with sleep problems. More than 77% of patients with PD reported symptoms associated with at least one problem and over 46% with 3 or more problems. Increased symptoms consistent with depression and anxiety and the presence of hallucinations also predicted poorer quality of life after controlling for motor symptoms. However, the of level agreement between patient report and that of a person who know them well was low: 40.9% for apathy, 28% for hallucinations, 39% for depression, 25% for sleep problems and only 7.7% agreement for the presence of anxiety. To obtain an accurate profile of cognitive impairments patients were assessed on measures of higher order language ability and a broad range of commonly used cognitive tests. Overall, PD patients were impaired on aspects of higher-order language. However, results indicated that these deficits were not a primary effect of PD, but could be explained in terms of deficits in speed of information processing associated with the disease. Compared to healthy controls, PD patients also showed deficits on measures of executive function, working memory, problem solving, and visuospatial skills. However, they were unimpaired on measures of planning, attention and memory/learning. Deficits in problem solving were only evident for tasks with a high visuospatial content and were no longer significant when visuospatial skills were controlled for. Further investigation indicated that planning in PD patients was not impaired in general and was dependent on the sensitivity of tests used. To further examine cognitive deficits, patients were divided into groups according to their cognitive performance. Three sub-groups of patients were identified that formed a continuum of cognitive impairment from none/mild to severe. Compared to controls, one subgroup showed no or minimal impairment (PD-NCI), a second group showed a more variable pattern of severe and mild impairments (PD-UCI), and a third group had evidence of severe impairment across most of the cognitive domains tested. This latter group was labelled PD-Mild Cognitive Impairment (PD-MCI). The PD-UCI and PD-MCI groups were also significantly different from their controls with respect to their ability to carry out functional activities of everyday living. The PD-MCI group had evidence of global cognitive decline, possibly reflecting a stage of pre-clinical dementia. The severity of cognitive deficits was not associated with other clinical and demographic characteristics such as motor impairments, age or disease duration. These results were confirmed when patients were retested one year later. Conclusions: Comorbid neuropsychiatric and cognitive problems are common for patients with PD prior to any overt signs of dementia. However, PD patients are heterogeneous with regard to their presentation and different subgroups of patients are identifiable based on cognitive performance. This information has both theoretical and clinical relevance.

Demencija yra vienas iš dažniausiai sutinkamų psichikos sutrikimų vyresniame amžiuje. Pastebėta, kad dalis vyresnio amžiaus pacientų, kuriems vėliau išsivysto demencija, dažniau nei bendraamžiai skundžiasi pažinimo sutrikimais, tačiau kasdieninė veikla yra nesutrikusi. Ši būklė buvo pavadinta lengvu kognityviniu sutrikimu (LKS). Neurosonografiniai tyrimai pateikia daug naudingos informacijos apie funkcinius galvos ir kaklo kraujagyslių parametrus. Tyrimo tikslas buvo nustatyti neurosonografinių galvos ir kaklo arterijų parametrų vertę prognozuojant demenciją lengvu kognityviniu sutrikimu sergantiems pacientams. Tyrimo uždaviniai: 1) ištirti LKS turinčių pacientų demografines ir klinikines charakteristikas ir įvertinti jų ir progresavimo į demenciją ryšį; 2) ištirti LKS turinčių pacientų ekstrakranijinės kraujotakos parametrus ir įvertinti jų ir progresavimo į demenciją ryšį; 3) ištirti LKS turinčių pacientų intrakranijinės kraujotakos parametrus ir įvertinti jų ir pogresavimo į demenciją ryšį; 4) ištirti LKS turinčių pacientų miego arterijų sienelių parametrus ir įvertinti jų ir pogresavimo į demenciją ryšį; 5) ištirti LKS turinčių pacientų miego arterijų aterosklerozinius požymius ir įvertinti jų ir pogresavimo į demenciją ryšį; 6) įvertinti bendrą tiriamųjų demografinių ir klinikinių charakteristikų bei neurosonografinių parametrų diagnostinę reikšmę prognozuojant progresavimą iš lengvo kognityvinio sutrikimo į demenciją. / Dementia is one of the most commonly occurring mental disorders in older age. It was noticed that some of the elderly patients who later develop dementia, more often than contemporaries complained of cognitive impairment, but daily activities were not affected. This condition was called mild cognitive impairment (MCI). Neurosonographic studies provide a lot of useful information about the functional head and neck vascular parameters. The aim of our study was to provide more information about the significance of the extra- and intracranial arterial blood flow and carotid arterial wall parameters for prediction of dementia for patients with MCI. Objectives of the study is 1) to investigate the demographic and clinical characteristics of MCI patients and to assess their relation with progression to dementia; 2) to investigate blood flow parameters of the extracranial arteries and to assess their relation with progression to dementia; 3) to investigate blood flow parameters of the intracranial arteries and to assess their relation with progression to dementia; 4) to investigate the intima-media thickness and stiffness of carotid arteries walls and to assess their relation with progression to dementia, 5) to investigate the atherosclerotic changes and to assess their relation with progression to dementia; 6) to assess the value of demographic and clinical characteristics and neurosonographic parameters for prediction of dementia.

Introdução: Perda de memória é um dos sintomas mais comuns em pacientes nos estágios iniciais da doença de Alzheimer; esses déficits são um reflexo do envolvimento da formação do hipocampo. O BDNF tem sido relacionado com a plasticidade do hipocampo. Neste sentido, as combinações de biomarcadores, como, por exemplo, a volumetria do hipocampo, pode apresentar um maior valor preditivo para diferenciar doença de Alzheimer do envelhecimento normal em pacientes com comprometimento cognitivo leve. Objetivo: A presente tese de doutorado teve como objetivo avaliar os níveis séricos do BDNF e o volume do hipocampo em pacientes com demência devido à doença de Alzheimer, Comprometimento Cognitivo Leve (CCL) e idosos saudáveis. Métodos: Para realização do estudo foram selecionados 10 idosos saudáveis, 10 CCL e 13 pacientes com demência devido à doença de Alzheimer pelos critérios NIA-AA. Todos participantes foram submetidos a uma avaliação cognitiva. Para as análises do BDNF, foi utilizado método de ELISA e para as análises de volumetria do hipocampo as imagens foram obtidas por meio de equipamento de ressonância de 1.5T e os volumes obtidos por meio do programa NeuroQuant®. Resultados: Idosos saudáveis apresentaram níveis séricos mais elevados de BDNF do que os CCL e pacientes com demência. O grupo de pacientes com demência apresentou menor volume total do hipocampo do que os idosos saudáveis e os CCL. Não houve correlação significativa do BDNF sérico com volume do hipocampo. Conclusão: Considerando nossos resultados em conjunto (baixos níveis de BDNF nos grupos CCL e demência devido à DA e menor volume do hipocampo na demência devido à AD), podemos supor que a diminuição dos níveis de BDNF ocorre antes da lesão neuronal expressa pela redução do hipocampo. / Introduction: Memory impairment is the most common symptom in patients in the early stages of Alzheimer's disease; this deficit is a reflection of the involvement of the hippocampal formation. BDNF has been linked to the hippocampal plasticity. Combinations of biomarkers, such as the hippocampal volumetry may have higher predictive value for differentiating Alzheimer's disease from normal aging in patients with mild cognitive impairment. Objective: The objective of present thesis was to evaluate serum levels of BDNF and hippocampal volume in patients with Mild Cognitive Impairment (MCI) and dementia due to Alzheimer's disease, and healthy elderly participants. Method: Ten healthy elderly subjects, 10 MCI and 13 patients with dementia due to Alzheimer's Disease (NIA-AA criteria) were selected for the study. All participants were assessed cognitively. The ELISA method was used for BDNF analysis, and the analysis of hippocampal volumetric images were acquired with 1.5T magnetic resonance equipment and volumes obtained with NeuroQuant® program. Results: Healthy elderly had higher BDNF serum levels than MCI and dementia due to AD patients. The group of dementia patients had lower total hippocampal volume than MCI and healthy elderly participants. No significant correlation between serum BDNF and hippocampal volume was observed. Conclusion: Taking our results together (lower BDNF levels in MCI and dementia due to AD and smaller hippocampal volume in dementia due to AD) we can hypothesize that the decrease of BDNF may start before the establishment of neuronal injury expressed by the hippocampal reduction.

Esta dissertação consiste em dois estudos que têm por objetivo investigar a existência de disfunções executivas no envelhecimento. Estudos recentes sugerem a existência de disfunções executivas no Declínio Cognitivo Leve (DCL). O objetivo do Estudo 1 foi verificar a presença de disfunções executivas em pacientes com DCL. Os instrumentos utilizados foram o Teste Wisconsin de Classificação de Cartas (WCST) e a Iowa Gambling Test (IGT). Foram estudados dez pacientes com e 27 sem DCL. Os dados foram analisados através do teste t de Student para amostras independentes e da análise de variância (ANOVA) para medidas repetidas. Os resultados não evidenciaram diferença significativa entre os grupos nos índices de resposta do WCST e no número de cartas retiradas de cada baralho no IGT. O estudo da evolução do desempenho no IGT revelou diferença qualitativa entre os grupos. Idosos sem DCL aprendem ao longo da tarefa, enquanto idosos com DCL não o fazem, sugerindo uma interferência dos sistemas de memória na tomada de decisão. O Iowa Gambling Test tem sido um instrumento utilizado na avaliação da tomada de decisão. O objetivo do Estudo 2 foi investigar se alterações nos procedimentos de aplicação do instrumento interferem no desempenho durante a execução do teste. Foi realizado um estudo transversal comparando dois grupos de idosos saudáveis em duas variações do instrumento. O grupo I contou com 27 participantes, que executaram a tarefa sem pista de reforço visual. O grupo II foi composto por 17 participantes, submetidos à tarefa com pista. Os dados foram analisados através dos testes t de Student para amostras independentes e ANOVA para medidas repetidas. Houve diferença estatisticamente significativa entre os dois grupos na execução do teste em relação à aversão ao risco (F=2,466; p=0,05; df=2). Os resultados indicam que uma pista de reforço visual possibilita maior alocação de recursos atencionais e de memória de trabalho, permitindo que os idosos tomem decisões menos arriscadas. / This dissertation is formed by two works that aim to investigate executive dysfunction on ageing. Recent studies suggest the existence of executive dysfunctions in Mild Cognitive Impairment (MCI). The aim of the first study was to verify the presence of executive dysfunctions in patients with MCI. The instruments used were the Wisconsin Card Sorting Test (WCST) and the Iowa Gambling Test (IGT). Ten patients with and 27 without MCI were assessed. The data were analyzed through Student t test for independent samples and analysis of variance (ANOVA) for repeated measures. The results did not show significant difference between groups in the answer rates of WCST and in the number of cards withdrawn from each pack of cards in the IGT. The study of the performance evolution in the IGT revealed a qualitative difference between the groups. Elderly without MCI learn along the task, while elderly with MCI did not, suggesting an interference of memory systems in decision making. The Iowa Gambling Test has been an instrument used in the assessment of decision making. The aim of the second study was to investigate if changes in the application procedures of the instrument interfere in the performance through the test execution. A cross sectional study was carried out comparing two groups of healthy elderly in two variations of the instrument. The group I included 27 participants, which executed the task without clue of visual reinforcement. The group II was composed by 17 participants, submitted to the task with clue. The data were analyzed through the Student t test for independent samples and ANOVA for repeated measures. It was found statistically significant difference between the two groups in the execution of the test in relation to risk aversion (F=2,466; p=0,05; df=2). The results indicate that a clue of visual reinforcement permits greater allocation of attention resources and of working memory, allowing elderly to make least risky decisions.

Purpose: The systematic review summarised the research investigating Acceptance and Commitment Therapy (ACT) with older adults. The empirical study explored psychosocial adjustment patterns to a diagnosis of mild cognitive impairment, a condition characterised by memory or thinking problems. Method: The review included 14 studies identified through database searches using predefined eligibility criteria. The empirical study employed a cross-sectional design. Thirty-five participants completed a short cognitive assessment and a series of questionnaires measuring perceptions of MCI, cognitive fusion (i.e. how caught up someone is with their thoughts), anxiety, depression and quality of life. Results: The review found initial evidence to suggest that ACT is an acceptable and effective intervention for reducing distress in older adults. The empirical study found that threatening perceptions of MCI were more strongly related to psychosocial adjustment outcomes than objective level of cognitive impairment. The study also found evidence to suggest that cognitive fusion is associated with adjustment outcomes in an MCI population. Conclusions: The systematic review highlights the limited, but promising evidence-base for the application of ACT with older adults. The review emphasises the need for further research with improved methodological rigor. Findings from the empirical study need to be replicated with a larger sample, however the results indicate that psychological interventions such like ACT could have utility for MCI patients with adjustment difficulties.