As intervenções cognitivas voltadas a idosos saudáveis ainda encontram-se pouco estudadas na literatura nacional, apesar de terem sido investigadas em outros países. O treino de memória oferecido a idosos com Comprometimento Cognitivo Leve (CCL) tem recebido cada vez mais atenção de pesquisadores e parece também beneficiar esta população. Não se sabe se o treino tem efeito a longo prazo e nem se os benefícios são os mesmos para idosos saudáveis e com CCL. Esta pesquisa teve como intuito avaliar o impacto do treino de memória de oito sessões oferecido a idosos controles normais (CN) e com CCL com alta escolaridade em parâmetros cognitivos. Para isso, contamos com a participação de 61 idosos acompanhados pela equipe multidisciplinar do Laboratório de Neurociências LIM 27 do Instituto de Psiquiatria da FMUSP aleatoriamente divididos em grupo experimental - GE (sendo 17 CN e 18 com CCL) e grupo controle - GC (sendo 12 CN e 14 com CCL). Estes grupos foram avaliados em quatro momentos diferentes, a saber, antes da intervenção (T0), uma semana após o término da intervenção (T1), um mês após a última avaliação (T2) e seis meses após T1 (T3). O GE recebeu treino de memória com ênfase na categorização e grifos entre T0 e T1. O GC realizou todas as avaliações no mesmo tempo de GE, mas o treino foi lhes oferecido depois de T3. Observou-se melhora em ambos os grupos GE de T0 para T1 quando comparados ao grupo GC em testes de atenção, velocidade de processamento, estratégias mnemônicas, e em testes de memória. Estes efeitos parecem se manter a curto e a longo prazo, mostrando, de maneiras diferentes, os benefícios do treino e a existência de plasticidade cognitiva em ambas as populações estudadas / The cognitive interventions aimed at elderly healthy are little studied in the national literature, despite having been investigated in other countries. The memory training offered to seniors with mild cognitive impairment (MCI) has received increasing attention from researchers and also seems to benefit this population. It is not known whether the training has long-term effect, nor whether the benefits are the same for healthy elderly and MCI. This study was aimed to evaluate the impact of eight memory training sessions offered to elderly normal controls (NC) and seniors with MCI in cognitive parameters. For this, we had the participation of 61 older people accompanied by a multidisciplinary team of the Laboratory of Neurosciences LIM 27, Institute of Psychiatry, FMUSP randomly divided into experimental group - EG (including 17 NC and 18 with MCI) and control group - CG (being 12 NC and 14 with MCI). These groups were evaluated at four different times, namely before the intervention (T0), one week after the intervention (T1), one month after the last assessment (T2) and six months after T1 (T3). EG received memory training with emphasis on categorization and underline words between T0 and T1. The CG performed all the assessments at the same time EG, but the training was offered to them after T3. Improvement was observed in both groups EG from T0 to T1 when compared to the CG on tests of attention, processing speed, mnemonic strategies, and memory tests. These effects seem to keep the short and long term, showing, in different ways, the benefits of training and the existence of cognitive plasticity in both populations studied

Introdução: Déficits de memória episódica constituem o marcador cognitivo mais frequente em pacientes com Comprometimento Cognitivo Leve (CCL).Estudos prévios mostram que déficits de memória episódica podem ser minimizados nestes pacientes por intervenções comportamentais. Entretanto, os mecanismos cerebrais envolvidos nos efeitos do treino cognitivo ainda são pouco explorados. O objetivo deste estudo foi avaliar o correlato neural por ressonância magnética funcional de um treino breve de memória em pacientes com CCL e compará-los com os achados em idosos saudáveis. Foram avaliados 18 pacientes com CCL e 19 idosos controles com a utilização de ressonância magnética funcional (RMf) em uma tarefa de codificação de listas de palavras com diferentes graus de relação semântica antes e após uma sessão de treino de estratégias de memória. Na sessão pré-treino, os participantes foram instruídos a memorizar as palavras durante a sessão de RMf sem qualquer orientação sobre o uso de estratégias de codificação. Após um treino breve no qual estratégias específicas de organização e agrupamento semântico foram exercitadas, os sujeitos foram reconduzidos ao aparelho de ressonância magnética e realizaram a sessão pós-treino, na qual foram instruídos a utilizar a estratégia treinada durante o paradigma de codificação de palavras. Os resultados dos exames de ressonância magnética funcional foram processados e analisados com o programa FSL versão 4.1. Ambos os grupos apresentaram aumento no número de palavras evocadas associado ao uso da estratégia treinada. Em ambos os grupos foi observado um aumento do sinal BOLD após o treino em regiões do córtex pré-frontal dorsolateral esquerdo e do córtex parietal bilateral. No grupo de idosos controles, entretanto, foi observada também uma redução da ativação em regiões do córtex parietal posterior esquerdo e cíngulo posterior bilateral, do córtex pré-frontal medial e cíngulo anterior direitos, do lóbulo parietal inferior e do córtex temporal superior direitos, do córtex pré-frontal dorsolateral direiro e do córtex óribito-frontal bilateral. A interação grupo x tempo foi significativa em áreas do córtex pré-frontal dorsolateral e ventromedial direitos. Estes resultado indicam que existem diferenças no recrutamento de regiões pré-frontais em resposta ao uso de estratégias de codificação em paradigmas de codificação de palavras entre pacientes com CCL e idosos cognitivamente saudáveis / The present studyinvestigated the effects of different applicationsof verbal learning strategies duringepisodicmemory encoding in patients with Mild Cognitive Impairment (MCI) (n=18) and normal controls (n=17) using functional magnetic resonance imaging (fMRI).The main goal of this study was to verify whether externally guided increases in verbal learning strategy application during episodic memory encoding modulate brain activity in memory-related networks in the same level in MCI as in controls. Participantswerescanned twice, using a word-list encoding fMRI paradigm.In the first session, self-initiated encoding strategies were used to intentionally memorize words during encoding. In the second session, participants received an explicit instruction to apply a semantic organization strategy (i.e. semantic clustering)to perform the task. The fMRI word list learning paradigm consisted of alternating blocks of encoding and resting baseline conditions. To perform the spontaneous fMRI session, participants were not instructed about the semantic organization of the words in the lists beforehand or given any practice with related lists. Therefore, any grouping by category observed in the subsequent free recall at the end of this fMRI acquisition was presumed to be self-initiated by the subject. At the end of the spontaneous session, each subject received a brief period of guidance or instructions to apply semantic strategies and organize words in terms of semantic categories during encoding, using a new set of word lists. Immediately after practicing the application of the strategy, participants were scanned again using the same type of paradigm as in the first session, except for the use of new set of word lists and the explicit instruction to apply semantic clustering.Free recall and strategic index scores were assessedafter each session. fMRI brain activation and deactivation during encoding of word lists in memory-related networks were examined across sessions. Results from the fMRI analysis revealed that after the explicit orientation to apply the verbal learning strategy, greater recruitment of frontoparietal network regions were observed in both MCI and control groups in relation to the unconstrained encoding condition. Group-differences in functional deactivations, however, were observed in the medial prefrontal (mPFC) cortex and in the right superior frontal gyrus, two critical nodes of the default mode network, related to the absence of modulation in the activity of the mPFC, along with a lack of suppression of the right superior frontal gyrus in MCI, in response to the increased use of the encoding strategy. A different association between improvement in strategy use and session-related changes in activation of the medial orbitalfrontal cortex between groups was also confirmed. That is, improvements in strategy use in controls contribute to a great extent in the amount of deactivation in OFC, whereas in patients, only a small portion of the increase in activation in this region was predicted by increases in strategy application

Introdução: o aumento da população idosa traz uma demanda significativa sobre as ciências da saúde para lidar com os problemas característicos do envelhecimento. Neste contexto, as demências são as desordens neuropsiquiátricas de maior impacto atualmente. Poucas pesquisas acerca do CCL foram dedicadas a analisar a função neuropsicológica da tomada de decisão. Esta é definida como o processo de escolher uma ação específica, dentro de um rol de alternativas possíveis, que produza o resultado mais vantajoso para o sujeito. Logo, ela possui papel clínico fundamental, pois subsidia importante espectro da funcionalidade. Objetivo: avaliar se idosos com CCL amnéstico de múltiplos domínios ou de único domínio apresentam prejuízos na tomada de decisão sob risco, quando comparados a idosos saudáveis. Métodos: foram analisados os desempenhos de 20 sujeitos (9 CCL e 11 controles) no teste de tomada de decisão Cambridge Gambling Task (CGT). Utilizou-se modelo linear geral acompanhado de análise de covariância para idade, anos de escolaridade e escore do Mini Exame do Estado Mental. Resultados: Foi verificado efeito de grupo e da idade sobre a aversão ao atraso, proporção global de aposta e assunção de risco. Conclusão: pacientes com CCL demonstraram maior impulsividade nas escolhas das apostas, além de terem apostado menos ao longo de todo o CGT. O déficit no controle da impulsividade pode ser um indicador de maior risco para conversão para demência, hipótese esta que necessita ser mais investigada. Apostas menores podem constituir estratégia compensatória em reação à impulsividade ou, ainda, ser resultado da menor confiança do paciente com CCL em suas capacidades para lidar com o teste / Introduction: The increase in elderly population brings a significant demand upon the health sciences to deal with aging-specific issues. In this context, dementia is currently the group of neuropsychiatric disorders with the greatest impact. Research on cerebral reserve shows the importance of early treatment in these syndromes, highlighting the need for comprehension about Mild Cognitive Impairment (MCI), classically defined by literature as a prodromic stage for dementia. Few existing studies on MCI aimed at investigating the neuropsychological function of decision-making, which is defined as the process of choosing a specific action among several options in order to achieve the most advantageous outcome. Therefore, this function has a fundamental clinical role, since it grants the basis for the individual functionality. Objective: investigate possible deficits in the decision-making of a sample of elderly patients diagnosed with amnestic MCI of multiple or single domain by comparing their performance with that of healthy ones. Methods: the performances of a sample 20 subjects (9 MCI and 11 controls) in the Cambridge Gambling Task (CGT) were analysed. General linear model with covariance analysis for age, years of schooling and the Mini Mental State Examination scores was used for the statistical analyses. Results: it was found that group and age effect on delay aversion, overall proportion bet, and risk taking. Conclusion: MCI patients showed higher impulsivity on bet choices and made smaller bets throughout the CGT run. The impulsivity control deficit can be an indicator of the conversion risk from MCI to dementia, hypothesis that needs further investigation. Smaller bets may be a compensatory strategy for the increased impulsivity or the result of MCI patients less confidence in their own cognitive ability to deal with the test

Obstructive sleep apnea (OSA) is a common breathing and sleeping disorder, characterized by repeated episodes of airway obstruction during sleep resulting in intermittent hypoxia (IH). From clinical reports, patients with OSA are associated with behavioral and neuropsychological deficits, including impaired spatial learning memory and cognitive deficiencies. Previous studies proposed that reactive oxygen species (ROS) and apoptosis caused by intermittent hypoxia (IH) contributed to this cognitive deficits. However, the exact mechanism is still poorly understood and not settled. / The endoplasmic reticulum (ER) is a cellular organelle in which all secretory and integral membrane proteins are folded and is also the site where proteins are post-translationally modified in ATP-dependent chaperone-mediated processes. In this study, we hypothesized that ER stress in the hippocampus is initiated in the OSA via elevated levels of ROS. Four groups of adult male mice were used, with two of them exposed to normoxia as control, and the other two exposed to IH treatment, each receiving either vehicle or tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. Eight-armed radial maze was used to investigate the performance of reference memory during the whole IH/normoxia treatment. After behavior test, long-term potentiation (LTP) was measured to investigate synaptic plasticity in hippocampus. Furthermore, ER stress-associated pro-apoptotic effectors were detected by Western blotting, and ultra-structure of rough ER and the morphology of hippocampal dendritic spines and synapses in the hippocampal CA1 area were observed. / LTP was impaired in the hippocampus after IH treatment, which was rescued by TUDCA. Furthermore, ER stress-associated pro-apoptotic effectors, CHOP and caspase-12, were up-regulated after chronic IH treatment and was abolished by co-infusion of TUDCA. Meanwhile, increased cleaved-caspase-3 after chronic IH treatment was reduced by TUDCA via increased expression of Bcl-2. On the other hand, ultrastructural analysis of rough ER in the hippocampal CA1 revealed IH-induced ER luminal swelling, and was attenuated by TUDCA. In addition, the length of synaptic active zone was significantly reduced after chronic IH treatment and was partially rescued by the application of TUDCA. Golgi staining also showed a decrease in mature dendritic spines in IH group, and reversed by TUDCA. In behavioral analysis, the number of reference memory errors significantly increased after IH treatment and rescued by TUDCA injection. Overall, the data suggest a critical role of ER stress underlying the impairment of long-term synaptic plasticity and neurocognitive deficits in chronic IH. Targeting ER stress could be a potential therapeutic strategy for neural dysfunction in OSA. / On the other hand, neuronal firing, especially robust persistent activity of neuron in hippocampus, is critical role in memory formation. Increased ROS induced by IH has been implicated in long-term potentiation of neural activity. IH could be involved in a variety of K⁺ channels which eventually leads to excitotoxicity by increased Ca2⁺-dependent glutamate release. Although the results were just shown in acute IH treatment, the chronic effect of IH on the firing frequency of hippocampus is still unknown. / Therefore, to investigate the effect of chronic IH treatment on firing activities and local field potentials of hippocampal neurons, implantation of multi-channel micro-wires electrode array into hippocampus of OSA model rat was performed to monitor spontaneous discharge. The results were shown the firing frequency of pyramidal neurons (PNs) was significantly elevated after 8 hours IH in second and third days, on the other hand, interneurons (INs) seem to be more sensitive to intermittent hypoxia since the higher firing frequency was sustained from third day to seventh day after 8 hours IH, however, at the end of 14 days IH treatment, the firing frequencies of PNs and INs are all both dramatically reduced. Meanwhile, the results in this part will enable us to understand the exact change of firing pattern and local field potential during intermittent hypoxia. The percentage of complex burst spikes was decreased after 14 days IH in PNs and the power of theta rhythms was also impaired. It suggests that the disorder of neuronal pattern and the change of local field potential are associated with cognitive impairment in OSA model. After 1 week recovery, the firing frequency of PNs was rescued again, but not for that of INs. We also found that the power of theta rhythms which had an important role in memory formation was weaker after 2 weeks IH treatment, however, the precise mechanism was still unknown. From the effect of intermittent hypoxia on spontaneous discharges and LFP of hippocampal neurons in free moving rat, it may reveal some roles of IH in cognitive impairment via disorder neuronal function in CA1 region. / 阻塞性睡眠呼吸暫停(OSA) 是一種常見的睡眠障礙疾病，這種疾病的主要特徵是在睡眠過程中反復發作的氣道阻塞，從而導致间歇性缺氧(IH)。從臨床報導中發現，OSA患者表現出行為和神經心理缺陷，包括空間學習記憶的受損和認知缺陷。通過之前的研究表明，活性氧(ROS)的增多和細胞凋亡是間歇性缺氧所引起認知功能障礙的主要機制之一，然而，其具體的機制仍不清楚。 / 作為細胞重要的細胞器，內質網是分泌蛋白和膜蛋白折疊組裝的主要場所，同時，由ATP依賴的分子伴侶所介導的蛋白質翻譯後修飾這一過程也主要在內置網中完成。在本課題中，我們假設在OSA模型的海馬組織中，內質網應激的啟動是由於缺氧引起的與活性氧(ROS)的升高。在本課題中，我們使用了四組成年雄性小鼠，其中兩組作為正常對照組，分別接受生理鹽水和牛磺去氧膽酸（一種常用的內質網抑制劑）的腹腔注射，另外兩組接受缺氧處理，同時也分別接受照生理鹽水和牛磺去氧膽酸注射。八臂放射迷宮被用來研究參考記憶的表現。行為學結束之後，長時程增強(LTP)用來測定海馬的突觸可塑性。用免疫印跡的方法檢測內質網應激的相關凋亡蛋白的表達情況，並且觀察海馬CA1區域中，內質網超微結構和海馬樹突棘數目及突觸形態的變化。 / 從實驗結果中，LTP在缺氧後減弱，而TUDCA能夠部分恢復由於缺氧所導致的LTP的降低。除此之外，內質網應激相關的促凋亡蛋白(CHOP和caspase-12)在缺氧組中表達升高，但是在TUDCA組中有所減低，同時，我們還發現，TUDCA也能夠減低缺氧組中cleaved-caspase-3的表達，而這一作用，可能與提高Bcl-2蛋白的表達（一個可標記的抗凋亡蛋白）有關。在間歇性缺氧組的海馬CA1區域中，粗面內質網出現管腔的腫脹，這一超微結構的變化表明在內質網出現官腔中有的許多未折疊蛋白聚集，並通過TUDCA的注射能夠降解未折疊蛋白來緩解這一現象的發生。同時，在IH處理後，突觸超微結構也發生了形態上的變化。突觸活性區的長度在IH處理組中顯著減少，但是在TUDCA組中有一定程度的恢復。高爾基染色顯示，成熟樹突棘（海馬突觸可塑性的結構基礎）的數目在間歇性缺氧組中有所下降，而在TUDCA治療後，成熟樹突棘的數目有所上升。我們發現參考記憶錯誤次數在缺氧後都有明顯的升高，而在注射TUDCA後，參考記憶錯誤次數都有所降低。總之，這些結果證明，內質網應激在間歇性缺氧的所引起的長時程突觸可塑性減弱和神經認知功能的損傷起到關鍵的作用，而抑制內質網應激對OSA中的出現神經功能紊亂起到一定的預防和治療效果。 / 而另一方面，神經元的放電，特別是海馬中神經元穩定持久的放電形式，對記憶的形成起到關鍵的作用。間歇性缺氧所引起的ROS的升高對於長時程增強的神經活動存在一定的關係，因為，通過以往的研究發現，間歇性缺氧可以通過多種鉀離子通道的啟動，最終由於鈣離子依賴的谷氨酸釋放的增多从而導致興奮性毒性的神經遞質的釋放。而這些結果只在急性缺氧模型中發現，慢性的間歇性缺氧對海馬的放電頻率的影響仍是未知之數。 / 因此，為了探討長時程的間歇性缺氧對海馬神經元的放電頻率和局部場電位的影響，多管道微絲電極陣列植入OSA大鼠的海馬中來監控自發放電的影響。結果表明，錐體細胞的放電頻率在第二天和第三天的8小時的間歇性低氧後明顯的升高了。另一方面，我們觀察到中間神經元似乎對間歇性缺氧更敏感，因為，從第三天到第七天缺氧8小時後，神經元的放電頻率都明顯的增高。但是在間歇性缺氧14天后，錐體細胞和中間神經元的放電頻率都所有顯著性的減少。同時，這一部分結果準確表明了海馬神經元的放電模式和局部場電位在間歇性缺氧的模型的是如何變化的。我們發現錐體細胞所具有的複合簇狀放電的比例減少，同時，theta波(與記憶的形成有關)的能量也有所減低。而這種神經元活動和局部的場電位的異常變化可能與OSA模型中出現的總認知功能障礙有關。在恢復一周後，錐體細胞的放電頻率有所增加，基本上可以恢復到缺氧前的狀態，但是中間神經元的頻率卻沒有多大的改變, 但是，其具體機制仍不清楚。從間歇性缺氧對大鼠海馬神經元自發放電和場電位影響的結果，它揭示了間歇性缺氧通過擾亂海馬CA1區域神經元的功能從而導致認知功能損傷。 / Xu, Linhao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 167-199). / Abstracts also in Chinese. / Title from PDF title page (viewed on 03, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Objetivo: Avaliar a atrofia do corpo caloso (CC) em pacientes com doença de Alzheimer (DA) e comprometimento cognitivo leve (CCL) e quantificar quais regiões dessa estrutura são mais acometidas nessa doença como uso de técnicas quantitativas de ressonância magnética. Metodologia: O estudo contou com a participação de 75 indivíduos sendo 22 controles normais (CN), 30 com CCL e 23 com DA. O volume total do corpo caloso e suas 3 diferentes sub regiões foram delimitadas em cortes sagitais de imagem de ressonância magnética. Os volumes obtidos foram corrigidos para a variação de volume intracraniano. As mascaras foram co-registradas a mapas de relaxometria e transferência de magnetização para analise quantitativa. Resultados: Encontramos atrofia e redução dos valores de relaxometria e transferência de magnetização nos pacientes do grupo DA. As tres sub regiões do corpo caloso apresentaram redução de volume na doença sendo que a atrofia foi maior nas regiões anteriores. Não encontramos diferença significativa nos parâmetros estudados entre CCL e CN. Conclusões: Embora o corpo caloso esteja envolvido no processo de desconexão cortical presente na doença de Alzheimer seu envolvimento não é precoce. / Objective: To evaluate the atrophy of the corpus callosum (CC) in patients with Alzheimer disease (AD) and mild cognitive impairment (CCL) and quantify which regions of this structure are most affected in this disease as using quantitative MRI techniques. Methodology: The study counted on the participation of 75 individuals being 22 normal controls (CN), 30 with CCL and 23 with AI). The total volume of the corpus callosum and its v 3 different sub regions were delimited in sagittal sections of magnetic resonance imaging. The volumes obtained were corrected for intracranial volume variation. The masks were recorded with maps of relaxometry and transfer of magnetization for quantitative analysis. Results: We found atrophy and reduced values of relaxometry and magnetization transfer in patients in the AD group. The three sub regions of the corpus callosum showed volume reduction in the disease, with atrophy being greater in the anterior region. We found no significant difference in the parameters studied between CCL and CN fit .Conclusions: Although the corpus callosum is involved in the process of cortical detachment present in Alzheimer\'s disease, its involvement is late.

Introdução: o aumento da população idosa traz uma demanda significativa sobre as ciências da saúde para lidar com os problemas característicos do envelhecimento. Neste contexto, as demências são as desordens neuropsiquiátricas de maior impacto atualmente. Poucas pesquisas acerca do CCL foram dedicadas a analisar a função neuropsicológica da tomada de decisão. Esta é definida como o processo de escolher uma ação específica, dentro de um rol de alternativas possíveis, que produza o resultado mais vantajoso para o sujeito. Logo, ela possui papel clínico fundamental, pois subsidia importante espectro da funcionalidade. Objetivo: avaliar se idosos com CCL amnéstico de múltiplos domínios ou de único domínio apresentam prejuízos na tomada de decisão sob risco, quando comparados a idosos saudáveis. Métodos: foram analisados os desempenhos de 20 sujeitos (9 CCL e 11 controles) no teste de tomada de decisão Cambridge Gambling Task (CGT). Utilizou-se modelo linear geral acompanhado de análise de covariância para idade, anos de escolaridade e escore do Mini Exame do Estado Mental. Resultados: Foi verificado efeito de grupo e da idade sobre a aversão ao atraso, proporção global de aposta e assunção de risco. Conclusão: pacientes com CCL demonstraram maior impulsividade nas escolhas das apostas, além de terem apostado menos ao longo de todo o CGT. O déficit no controle da impulsividade pode ser um indicador de maior risco para conversão para demência, hipótese esta que necessita ser mais investigada. Apostas menores podem constituir estratégia compensatória em reação à impulsividade ou, ainda, ser resultado da menor confiança do paciente com CCL em suas capacidades para lidar com o teste / Introduction: The increase in elderly population brings a significant demand upon the health sciences to deal with aging-specific issues. In this context, dementia is currently the group of neuropsychiatric disorders with the greatest impact. Research on cerebral reserve shows the importance of early treatment in these syndromes, highlighting the need for comprehension about Mild Cognitive Impairment (MCI), classically defined by literature as a prodromic stage for dementia. Few existing studies on MCI aimed at investigating the neuropsychological function of decision-making, which is defined as the process of choosing a specific action among several options in order to achieve the most advantageous outcome. Therefore, this function has a fundamental clinical role, since it grants the basis for the individual functionality. Objective: investigate possible deficits in the decision-making of a sample of elderly patients diagnosed with amnestic MCI of multiple or single domain by comparing their performance with that of healthy ones. Methods: the performances of a sample 20 subjects (9 MCI and 11 controls) in the Cambridge Gambling Task (CGT) were analysed. General linear model with covariance analysis for age, years of schooling and the Mini Mental State Examination scores was used for the statistical analyses. Results: it was found that group and age effect on delay aversion, overall proportion bet, and risk taking. Conclusion: MCI patients showed higher impulsivity on bet choices and made smaller bets throughout the CGT run. The impulsivity control deficit can be an indicator of the conversion risk from MCI to dementia, hypothesis that needs further investigation. Smaller bets may be a compensatory strategy for the increased impulsivity or the result of MCI patients less confidence in their own cognitive ability to deal with the test

As intervenções cognitivas voltadas a idosos saudáveis ainda encontram-se pouco estudadas na literatura nacional, apesar de terem sido investigadas em outros países. O treino de memória oferecido a idosos com Comprometimento Cognitivo Leve (CCL) tem recebido cada vez mais atenção de pesquisadores e parece também beneficiar esta população. Não se sabe se o treino tem efeito a longo prazo e nem se os benefícios são os mesmos para idosos saudáveis e com CCL. Esta pesquisa teve como intuito avaliar o impacto do treino de memória de oito sessões oferecido a idosos controles normais (CN) e com CCL com alta escolaridade em parâmetros cognitivos. Para isso, contamos com a participação de 61 idosos acompanhados pela equipe multidisciplinar do Laboratório de Neurociências LIM 27 do Instituto de Psiquiatria da FMUSP aleatoriamente divididos em grupo experimental - GE (sendo 17 CN e 18 com CCL) e grupo controle - GC (sendo 12 CN e 14 com CCL). Estes grupos foram avaliados em quatro momentos diferentes, a saber, antes da intervenção (T0), uma semana após o término da intervenção (T1), um mês após a última avaliação (T2) e seis meses após T1 (T3). O GE recebeu treino de memória com ênfase na categorização e grifos entre T0 e T1. O GC realizou todas as avaliações no mesmo tempo de GE, mas o treino foi lhes oferecido depois de T3. Observou-se melhora em ambos os grupos GE de T0 para T1 quando comparados ao grupo GC em testes de atenção, velocidade de processamento, estratégias mnemônicas, e em testes de memória. Estes efeitos parecem se manter a curto e a longo prazo, mostrando, de maneiras diferentes, os benefícios do treino e a existência de plasticidade cognitiva em ambas as populações estudadas / The cognitive interventions aimed at elderly healthy are little studied in the national literature, despite having been investigated in other countries. The memory training offered to seniors with mild cognitive impairment (MCI) has received increasing attention from researchers and also seems to benefit this population. It is not known whether the training has long-term effect, nor whether the benefits are the same for healthy elderly and MCI. This study was aimed to evaluate the impact of eight memory training sessions offered to elderly normal controls (NC) and seniors with MCI in cognitive parameters. For this, we had the participation of 61 older people accompanied by a multidisciplinary team of the Laboratory of Neurosciences LIM 27, Institute of Psychiatry, FMUSP randomly divided into experimental group - EG (including 17 NC and 18 with MCI) and control group - CG (being 12 NC and 14 with MCI). These groups were evaluated at four different times, namely before the intervention (T0), one week after the intervention (T1), one month after the last assessment (T2) and six months after T1 (T3). EG received memory training with emphasis on categorization and underline words between T0 and T1. The CG performed all the assessments at the same time EG, but the training was offered to them after T3. Improvement was observed in both groups EG from T0 to T1 when compared to the CG on tests of attention, processing speed, mnemonic strategies, and memory tests. These effects seem to keep the short and long term, showing, in different ways, the benefits of training and the existence of cognitive plasticity in both populations studied

abstract: Alzheimer’s disease (AD) is characterized by the degeneration of cholinergic basal forebrain (CBF) neurons in the nucleus basalis of Meynert (nbM), which provides the majority of cholinergic input to the cortical mantle and together form the basocortical cholinergic system. Histone deacetylase (HDAC) dysregulation in the temporal lobe has been associated with neuronal degeneration during AD progression. However, whether HDAC alterations play a role in cortical and cortically-projecting cholinergic nbM neuronal degeneration during AD onset is unknown. In an effort to characterize alterations in the basocortical epigenome semi-quantitative western blotting and immunohistochemistry were utilized to evaluate HDAC and sirtuin (SIRT) levels in individuals that died with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD (mAD), or severe AD (sAD). In the frontal cortex, immunoblots revealed significant increases in HDAC1 and HDAC3 in MCI and mAD, followed by a decrease in sAD. Cortical HDAC2 levels remained stable across clinical groups. HDAC4 was significantly increased in prodromal and mild AD compared to aged cognitively normal controls. HDAC6 significantly increased during disease progression, while SIRT1 decreased in MCI, mAD, and sAD compared to controls. Basal forebrain levels of HDAC1, 3, 4, 6 and SIRT1 were stable across disease progression, while HDAC2 levels were significantly decreased in sAD. Quantitative immunohistochemistry was used to identify HDAC2 protein levels in individual cholinergic nbM nuclei immunoreactive for the early phosphorylated tau marker AT8, the late-stage apoptotic tau marker TauC3, and Thioflavin-S, a marker of mature neurofibrillary tangles (NFTs). HDAC2 nuclear immunoreactivity was reduced in individual cholinergic nbM neurons across disease stages, and was exacerbated in tangle-bearing cholinergic nbM neurons. HDAC2 nuclear reactivity correlated with multiple cognitive domains and with NFT formation. These findings identify global HDAC and SIRT alterations in the cortex while HDAC2 dysregulation contributes to cholinergic nbM neuronal dysfunction and NFT pathology during the progression of AD. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2018

Executive function describes high-level cognitive-abilities including planning, decision-making, set switching and response inhibition. Impairments of the executive functions in disease states may be subtle but can greatly reduce the quality of life and independence. The overarching theme of this project was to investigate the network of brain regions that are needed to support executive function. This was undertaken using a two-fold approach: one, to apply network analysis to resting state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) data in order to describe how differences in morphometry and connectivity correlate to executive function differences of individuals with Mild Cognitive Impairment (MCI), and two, to describe the brain networks involved in one form of executive function, decision-making under uncertain conditions, in young, healthy individuals. Impaired decision-making can dramatically impact day-to-day functioning and understanding the underlying network of regions that support this task can provide a target for future intervention studies. Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were used in the studies of MCI. Individuals were grouped by their executive abilities. A regions-of-interest approach was used to parcel and label various brain regions and a network of connections was constructed out of these regions. Differences between the networks were then compared between the MCI subjects with good and poor executive functions. Those with high executive abilities showed decreased functional network connectivity and increased structural network connectivity. The second arm of these studies was based an original decision-making paradigm that was used to compare of networks involved in decision-making at times of uncertainty in healthy young individuals using both electroencephalography (EEG) and task-based functional magnetic resonance imaging (fMRI). Overall we found greater network connectivity in the uncertain condition of the task than in the certain condition. This suggests that with increased uncertainty comes increased organized connectivity. Taken together, the results of this study re-iterate the notion that cognition depends upon the efficient communication between a network of brain regions rather than on isolated regions. They also highlight the importance of having a well-defined network of nodes and connections for optimal executive functioning.

Mild cognitive impairment (MCI) has long been associated with depression; however, few studies have addressed the presence of (prolonged) intrapersonal grief or its contribution to emotional distress in MCI. This may be a result of both an over-reliance on interpersonal models of grief (i.e. bereavement) and a systematic undervaluing of MCI individuals’ perspectives. Thus, this study took a qualitative approach, using interpretive description, to understand the first-hand experience of persons with MCI, with the intent of 1) determining whether grief occurs for this group and, if so, 2) comparing this experience to well-defined grief constructs. Six themes were identified: Uncertainty and ambiguity, losses of self and role, disenfranchisement and disconnection, primacy of MCI, emotional distress, and coping. A relationship between themes was found, such that uncertainty and ambiguity, losses of self and role, and disenfranchisement and disconnection comprised the core dimensions of the MCI experience, with losses of self and role serving a central and binding role between the other two. These core dimensions then contributed individually and collectively to the primacy of the MCI experience and emotional distress, which in turn exhibited a reciprocal relationship with coping. The overall experience of MCI reflects features of several grief reactions to nonfinite loss, most notably chronic sorrow and disenfranchised grief. Implications for practice and further investigation are discussed. / Graduate