Cognitive dysfunction is a core characteristic of schizophrenia, which can often persist when other symptoms, particularly positive symptoms, may be improved with drug treatment. The non-competitive NMDA receptor antagonist, phencyclidine (PCP), is a psychomotor stimulant drug that has been shown to induce symptoms characteristic of schizophrenia in humans and animals. The aim of these studies was to use the sub-chronic PCP model in rats to investigate cognitive dysfunction in behavioural tests which have been highlighted as relevance by the MATRICS initiative (MATRICS.ucla.edu). The main tests used were attentional set-shifting, operant reversal learning, and novel object recognition tasks. The pharmacology of antipsychotics was studied in the reversal learning task using receptor selective compounds. Following this, experiments were carried out using in vitro electrophysiology and in vivo microdialysis in an attempt to investigate the mechanisms underpinning the PCP-induced cognitive deficits. The attentional set-shifting task is a test of executive function, the extra-dimensional shift (EDS) phase relates to the ability to shift attention to a different stimulus dimension; this is impaired in patients with schizophrenia. The studies presented in chapter 2 showed that sub-chronic PCP administration impaired attentional set-shifting performance selectively in the EDS phase, a deficit which was significantly attenuated by sub-chronic administration of clozapine and risperidone, but not haloperidol. The effect of PCP was also shown to be more robust in female rats compared to males. A deficit in set-shifting ability was also observed in isolation reared rats. However, the deficits produced by PCP were more robust than the deficit produced by isolation rearing. The reversal learning task is another test of executive function. Chapter 3 reported that sub-chronic PCP administration impairs reversal learning ability in an operant task, as demonstrated by reduced percent correct responding in the reversal phase of the reversal learning task. It was found that a D1 agonist (SKF-38398), a 5-HT1A partial agonist (buspirone), a 5-HT2C antagonist (SB-243213A) and an agonist and positive allosteric modulator of the alpha 7 nACh receptor (PNU-282987 and PheTQS respectively) are able to reverse the sub-chronic PCP-induced deficit in reversal learning. Although many antipsychotics have affinity for muscarinic M1 and histamine H1 receptors, selective agents at these receptors were not able to improve the PCP-induced deficit. In chapter 4, the atypical antipsychotics, clozapine and risperidone, when given alone to naïve rats had no effect on reversal learning. Haloperidol when given to naïve rats impaired performance at the highest dose. Sub-chronic PCP was again found to impair reversal learning performance. Investigative experiments revealed that the 2 min time-out could be important as a cue. Following a double reversal, olanzapine-treated rats lost the ability to switch between the rules, whereas clozapine and risperidone-treated rats could perform the double reversal. Experiments with the extended (15 min) reversal phase could allow the investigation of the time-course effects of antipsychotics or selective compounds. The studies presented in chapter 5 found a reduction in gamma oscillations in the CA3 region of the hippocampus, following sub-chronic PCP treatment (2-5 weeks post treatment) that was paralleled by a deficit in parvalbumin immunoreactive (IR) cell density, at a similar time point (2 weeks post treatment). In contrast, a time-dependent increase in gamma oscillations was observed (6-8 weeks post treatment), at which point parvalbumin IR cell density was unchanged (8 weeks post treatment). Gamma oscillations were unchanged in the prefrontal cortex (PFC) following the PCP treatment regime. Locomotor activity tests were also carried out to ensure that the sub-chronic PCP treatment was successful. In-vivo microdialysis revealed that vehicle-treated rats show an increase in dopamine in the PFC which is selective for the retention trial of the novel object recognition task. PCP-treated rats were unable to distinguish between the novel and familiar objects and the increase in dopamine observed in vehicle rats was absent. As a control experiment it was also shown that sub-chronic PCP did not induce anxiety-like symptoms in the elevated plus maze and open field tests. These studies suggest that sub-chronic PCP induces cognitive deficits in behavioural tasks, and these deficits may be due to GABAergic mediated processes in the hippocampus and dopaminergic dysfunction in the PFC. These behavioural and neurochemical results are concurrent to findings observed in schizophrenia.

No description available.

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.

The National Comprehensive Cancer Network identified occupational therapy as a first line of intervention for the treatment of cancer-related cognitive dysfunction (CRCD) (National Comprehensive Cancer Network [NCCN], 2016). Thus, occupational therapists have an opportunity to develop interventions that facilitate participation in meaningful occupations for survivors of cancer living with CRCD. In this article, we argue for occupational therapists to create occupation- and evidence-based, client-centered interventions for survivors of cancer with CRCD that address the multidimensional presentation of CRCD. One survivor’s story illustrates the affect of CRCD on occupational performance and the features to consider when developing interventions to meet the unique needs of survivors of cancer with CRCD. We recommend that interventions can be provided through self-paced home programming, community settings, or delivered through modes such as tele-rehabilitation to reach the growing population of survivors of cancer.

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-04-11T21:48:45Z No. of bitstreams: 1 2012 - Patr?cia de Pinho e Souza Souza.pdf: 538207 bytes, checksum: 8ed2985bb737e29762d7f0ad26645bba (MD5) / Made available in DSpace on 2017-04-11T21:48:45Z (GMT). No. of bitstreams: 1 2012 - Patr?cia de Pinho e Souza Souza.pdf: 538207 bytes, checksum: 8ed2985bb737e29762d7f0ad26645bba (MD5) Previous issue date: 2012-07-25 / CAPES / With increased life expectancy of cats, age-related problems also begin to increase, including increased behavior problems. Among the behavioral problems in cats can cite feline cognitive dysfunction (DCF), a disease very similar to Alzheimer's in humans. The semalhan?as go beyond behavior such as disorientation, social interaction / environmental disorder of sleep and wakefulness, hygiene and change the activity. The semelhana?as are also in the neuropathological changes. Nowadays the diagnosis of HD is made after excluding all differential diagnoses, which may cause the same behavioral changes. These diagnoses are made by clinical examination, laboratory tests, CT, MRI and others, but the final diagnosis can only be closed by a biopsy of brain tissue, which allows virtually no owner. Therefore, despite a growing number of elderly cats with behavioral problems, the DCF is underdiagnosed, because the vast majority of owners do not report these changes to the veterinarian, because I think it is old age and has no how to improve the living condition of the patient. So this work would bring a simple questionnaire easy to understand for the owner, which contains questions about changes in your pet's behavior that only those who live with him could answer, so we can do a levantameto Brazilian reality regarding DCF, also know what age we see an increase in behavioral changes, changes which are more common if we have correlation with gender, age, residence, has ascesso the street, whether it is full or catrados. In this case 129 cats participated in the survey are grouped into 3 major groups animals aged 7 to 11 years, between 11 and 14 years and above 15 years. And these groups were further divided into animals without alteration suggestive of DCF with 21.7% of the cats of all ages, animals with 1 to 3 changes consistent with DCF being 31% of feline animals with 3-6 changes consistent with DCF 34.9% of cats and animals with over 7 changes being compatible with DCF 12.4% of the animals. Where we can most frequent signs sleep much during the day, fights with other animals, sad when alone, looking at nothing. It was quite evident that the older the cat is more chance of it developing this disease and be more severe. And that race, sex, residence, or if he was neutered whole had no relationship with DCF. / Com o aumento da expectativa de vida dos felinos, problemas relacionados ? idade tamb?m come?am a aumentar, inclusive o aumento de problemas comportamentais. Entre os problemas comportamentais nos gatos podemos citar a disfun??o cognitiva felina (DCF), doen?a muito semelhante ao Mal de Alzheimer em humanos. As semalhan?as v?o al?m do comportamento como: desorienta??o, intera??o s?cio/ambiental, dist?rbio de sono e vig?lia, higiene e altera??o da atividade. As semelhana?as tamb?m est?o nas altera??es neuropatol?gicas. Hoje em dia o diagnostico da DCF ? feito depois de excluir todos os diagn?sticos diferenciais, que possa causar as mesmas altera??es comportamentais. Esses diagn?sticos s?o feitos atrav?s de exames cl?nicos, laboratoriais, tomografia, resson?ncia magn?tica entre outros; mas o diagn?stico final s? pode ser fechado por uma bi?psia de tecido cerebral, o que praticamente nenhum propriet?rio permite fazer. Por isso, apesar de haver um n?mero cada vez maior de gatos idosos com problemas comportamentais, a DCF ? subdiagnosticada, at? porque a grande maioria dos propriet?rios n?o relata essas mudan?as para o m?dico veterin?rio, por achar que se trata de velhice e que n?o tem como melhorar a condi??o de vida do paciente. Ent?o este trabalho quis trazer um question?rio simples de f?cil entendimento para o propriet?rio, que cont?m perguntas sobre altera??es de comportamento do seu animal que somente quem convive com ele poderia responder, para que possamos fazer um levantameto da realidade brasileira com rela??o DCF, saber tamb?m com que idade vemos um aumento das altera??es comportamentais, quais altera??es s?o mais comuns, se temos correla??o com sexo, idade, moradia, se tem ascesso a rua, se ? catrados ou inteiro. Neste caso 129 gatos participaram da pesquisa sendo agrupados em 3 grandes grupos os animais com idades entre 7 a 11 anos, entre 11 a 14 anos e acima de 15 anos. E esses grupos ainda foram divididos em animais sem altera??o sugestiva de DCF com 21,7% dos felinos de todas as idades, animais com 1 a 3 altera??es compat?veis com DCF sendo 31% dos felinos, animais com 3 a 6 altera??es compat?veis com DCF com 34,9% dos gatos e animais com mais de 7 altera??es compat?veis com DCF sendo 12,4% dos animais. Onde temos como sinais mais frequentes dormir muito durante o dia, briga com outros animais, triste quando sozinho, olha para o nada. Ficou bem evidente que quanto mais idoso for o felino maior a chance dele desenvolver da doen?a e desta ser mais grave. E que ra?a, sexo, moradia, se ele era castrado ou inteiro n?o tiveram rela??o com a DCF.

Introduction Approximately 1-2% of the adult population in developed countries suffer from heart failure (HF), with the prevalence rising to more than 10% among patients 80 years of age or older. The HF syndrome is associated with elevated mortality and morbidity, and decreased quality of life. Cognitive dysfunction has been reported in patients suffering from a variety of cardiovascular disorders. However, few studies have systematically assessed cognitive performance in HF patients, its prevalence and other factors influencing cognition in HF patients. Further, it is of great interest to understand the relationship between self-care in HF and cognition. It may be important to screen for cognitive dysfunction as it may influence HF patients’ ability to perform self-care, e.g. make lifestyle changes, adhere to medical treatment and monitor, evaluate and treat symptoms of deterioration. Aim The overall aim of this thesis was to explore cognitive function in elderly patients with chronic heart failure with focus on prevalence, risk factors, sleep and self-care. Design and method This thesis is based on four quantitative studies. The data from study I and II were collected in a prospective longitudinal design, including Swedish same-sex twin pairs born in 1913 or earlier in Sweden. The study was conducted 1991-2002 and a total of 702 individuals aged 80 and older were included. Study III and IV had a cross- sectional design and included stable HF patients, median 72 years of age, living in the community in the south of Sweden. Data were collected between 2009 and 2012. Study III included a total of 137 patients and Study IV included 142 patients. Results Study I found that  octogenarians with HF had significantly poorer spatial performance and episodic memory, and that the episodic memory declined more over time compared to a non-HF population of the same ages. Study II showed that octogenarians with HF had a significantly higher prevalence of vascular dementia, 16% vs. 6%, and all types of dementia, 40% vs. 30%, than those not diagnosed with HF. Factors related to dementia in individuals with HF were depression, hypertension and increased levels of homocysteine. Diabetes was associated with an increased risk for vascular dementia. In study III we found that  HF patients with sleep disordered breathing (SDB) (apnoea-hypopnoea index >15) had significantly higher saturation time < 90%, more difficulties maintaining sleep and lower levels of daytime sleepiness compared to those in the non-SDB group. Cognitive function did not differ between the SDB and the non-SDB-group. Only insomnia was associated with a decreased global cognititive function measured with the Mini Mental State Examination instrument. Finally, in study IV, the relationship between self-care and different dimensions of cognitive function was explored. Psycho- and visuomotor function (speed and attention) was the only dimension of cognitive function associated with self-care. Conclusion Octogenarians suffering from HF have a decreased performance in spatial and episodic memory and they also have a higher risk for developing dementia. Cognitive dysfunction as well as higher prevalence of dementia can contribute to decreased adherence to prescribed therapy and self-care management, and lead to other socio-behavioural problems.   Self-care was found to be associated with psychomotor speed. This may influence sustained attention negatively and the ability to carry out more than one task at the same time. This may lead to decreased attention for receiving and understanding information on self-care. / Thesis

Cognitive dysfunction is a core characteristic of schizophrenia, which can often persist when other symptoms, particularly positive symptoms, may be improved with drug treatment. The non-competitive NMDA receptor antagonist, phencyclidine (PCP), is a psychomotor stimulant drug that has been shown to induce symptoms characteristic of schizophrenia in humans and animals. The aim of these studies was to use the sub-chronic PCP model in rats to investigate cognitive dysfunction in behavioural tests which have been highlighted as relevance by the MATRICS initiative (MATRICS.ucla.edu). The main tests used were attentional set-shifting, operant reversal learning, and novel object recognition tasks. The pharmacology of antipsychotics was studied in the reversal learning task using receptor selective compounds. Following this, experiments were carried out using in vitro electrophysiology and in vivo microdialysis in an attempt to investigate the mechanisms underpinning the PCP-induced cognitive deficits. The attentional set-shifting task is a test of executive function, the extra-dimensional shift (EDS) phase relates to the ability to shift attention to a different stimulus dimension; this is impaired in patients with schizophrenia. The studies presented in chapter 2 showed that sub-chronic PCP administration impaired attentional set-shifting performance selectively in the EDS phase, a deficit which was significantly attenuated by sub-chronic administration of clozapine and risperidone, but not haloperidol. The effect of PCP was also shown to be more robust in female rats compared to males. A deficit in set-shifting ability was also observed in isolation reared rats. However, the deficits produced by PCP were more robust than the deficit produced by isolation rearing. The reversal learning task is another test of executive function. Chapter 3 reported that sub-chronic PCP administration impairs reversal learning ability in an operant task, as demonstrated by reduced percent correct responding in the reversal phase of the reversal learning task. It was found that a D1 agonist (SKF-38398), a 5-HT1A partial agonist (buspirone), a 5-HT2C antagonist (SB-243213A) and an agonist and positive allosteric modulator of the alpha 7 nACh receptor (PNU-282987 and PheTQS respectively) are able to reverse the sub-chronic PCP-induced deficit in reversal learning. Although many antipsychotics have affinity for muscarinic M1 and histamine H1 receptors, selective agents at these receptors were not able to improve the PCP-induced deficit. In chapter 4, the atypical antipsychotics, clozapine and risperidone, when given alone to naïve rats had no effect on reversal learning. Haloperidol when given to naïve rats impaired performance at the highest dose. Sub-chronic PCP was again found to impair reversal learning performance. Investigative experiments revealed that the 2 min time-out could be important as a cue. Following a double reversal, olanzapine-treated rats lost the ability to switch between the rules, whereas clozapine and risperidone-treated rats could perform the double reversal. Experiments with the extended (15 min) reversal phase could allow the investigation of the time-course effects of antipsychotics or selective compounds. The studies presented in chapter 5 found a reduction in gamma oscillations in the CA3 region of the hippocampus, following sub-chronic PCP treatment (2-5 weeks post treatment) that was paralleled by a deficit in parvalbumin immunoreactive (IR) cell density, at a similar time point (2 weeks post treatment). In contrast, a time-dependent increase in gamma oscillations was observed (6-8 weeks post treatment), at which point parvalbumin IR cell density was unchanged (8 weeks post treatment). Gamma oscillations were unchanged in the prefrontal cortex (PFC) following the PCP treatment regime. Locomotor activity tests were also carried out to ensure that the sub-chronic PCP treatment was successful. In-vivo microdialysis revealed that vehicle-treated rats show an increase in dopamine in the PFC which is selective for the retention trial of the novel object recognition task. PCP-treated rats were unable to distinguish between the novel and familiar objects and the increase in dopamine observed in vehicle rats was absent. As a control experiment it was also shown that sub-chronic PCP did not induce anxiety-like symptoms in the elevated plus maze and open field tests. These studies suggest that sub-chronic PCP induces cognitive deficits in behavioural tasks, and these deficits may be due to GABAergic mediated processes in the hippocampus and dopaminergic dysfunction in the PFC. These behavioural and neurochemical results are concurrent to findings observed in schizophrenia.

Išsėtinė sklerozė (IS) – demielinizuojanti uždegiminė neurologinė liga, kylanti dažniausiai jauniems žmonėms. Svarbi ne tik IS fizinė negalia, bet ne mažiau svarbi ir kognityvinė negalia, kuri reiškiasi kognityvinių funkcijų sutrikimu (KFS). Nors KFS simptomai gali būti labai įvairūs, dažniausiai nukenčia išmokimas, atmintis, dėmesys, informacijos apdorojimo greitis, vizualiniai konstrukciniai gebėjimai ir valdomosios funkcijos. Darbo tikslas buvo įvertinti demografinių ir klinikinių ligos rodiklių bei pakitimų magnetinio rezonanso tomografijos tyrime įtaką išsėtine skleroze sergančių ligonių kognityvinėms funkcijoms (KF). Ištyrėme 120 IS sergančių ligonių ir 40 sveikų asmenų. Įvertinome fizinę negalią, subjektyvius nusiskundimus atmintimi ir nuovargiu, objektyvų nuovargį, depresiją ir nerimą. Kognityvinių funkcijų vertinimui buvo atlikta vienuolikos kognityvinių testų rinkinys. Galvos smegenų magnetinio rezonanso tomografijos (MRT) tyrimuose įvertintas demielinizacijos židinių skaičius, tiesiniai atrofijos matmenys ir jų santykiai. Sergančių IS KF buvo blogesnės nei sveikų asmenų, priklausė nuo ligos eigos, objektyvi depresija blogino KF rezultatus. IS subjektyvūs skundai atmintimi ir nuovargiu neturėjo ryšio su KF. IS sergančiųjų KFS ir galvos smegenų atrofija buvo labiau išreikšti sergant antrinės progresuojančios (AP) negu recidyvuojančios remituojančios (RR) eigos IS. MRT židinių skaičiaus įtaka KF testų rezultatams labiau atsispindėjo IS pradžioje. Sergančiuosius RR ir... [toliau žr. visą tekstą] / Multiple sclerosis (MS) is a chronic demyelinating inflammatory neurological disease in young adults. Cognitive dysfunction (CD) contributes significantly to patient’s disability status. Although almost all kind of CD can be observed in MS, the typical profile is the impairment of information processing speed, memory, attention and often executive skills. The aim of the study was to investigate the influence of different demographic and clinical markers of the disease and changes in MRI tomography on cognitive functions in MS patients. The study involved 120 patients with MS and 40 healthy controls. Neurological examination, complaints of memory and fatigue, objective depression, anxiety and objective fatigue were evaluated. Cognitive functions (CF) were tested using battery of 11 cognitive tests. Brain MRI was performed to evaluate focal demyelinised lesions and to calculate regional linear markers of brain atrophy. The impairment of CF was much more expressed in MS patients as compared to controls. CF were negatively affected by objective depression and disease course. Subjective memory complaints and subjective fatigue in MS patients did not correlate with CF however they did correlate with objective fatigue. Self reported memory impairment worsened with the progression of disease. CD and brain atrophy reflected by MRI linear parameters were more expressed in secondary progressive (SP) MS as compared to relapsing remitting (RR) MS. Number of demyelinated lesions were... [to full text]

Išsėtinė sklerozė (IS) – demielinizuojanti uždegiminė neurologinė liga, kylanti dažniausiai jauniems žmonėms. Svarbi ne tik IS fizinė negalia, bet ne mažiau svarbi ir kognityvinė negalia, kuri reiškiasi kognityvinių funkcijų sutrikimu (KFS). Nors KFS simptomai gali būti labai įvairūs, dažniausiai nukenčia išmokimas, atmintis, dėmesys, informacijos apdorojimo greitis, vizualiniai konstrukciniai gebėjimai ir valdomosios funkcijos. Darbo tikslas buvo įvertinti demografinių ir klinikinių ligos rodiklių bei pakitimų magnetinio rezonanso tomografijos tyrime įtaką išsėtine skleroze sergančių ligonių kognityvinėms funkcijoms (KF). Ištyrėme 120 IS sergančių ligonių ir 40 sveikų asmenų. Įvertinome fizinę negalią, subjektyvius nusiskundimus atmintimi ir nuovargiu, objektyvų nuovargį, depresiją ir nerimą. Kognityvinių funkcijų vertinimui buvo atlikta vienuolikos kognityvinių testų rinkinys. Galvos smegenų magnetinio rezonanso tomografijos (MRT) tyrimuose įvertintas demielinizacijos židinių skaičius, tiesiniai atrofijos matmenys ir jų santykiai. Sergančių IS KF buvo blogesnės nei sveikų asmenų, priklausė nuo ligos eigos, objektyvi depresija blogino KF rezultatus. IS subjektyvūs skundai atmintimi ir nuovargiu neturėjo ryšio su KF. IS sergančiųjų KFS ir galvos smegenų atrofija buvo labiau išreikšti sergant antrinės progresuojančios (AP) negu recidyvuojančios remituojančios (RR) eigos IS. MRT židinių skaičiaus įtaka KF testų rezultatams labiau atsispindėjo IS pradžioje. Sergančiuosius RR ir... [toliau žr. visą tekstą] / Multiple sclerosis (MS) is a chronic demyelinating inflammatory neurological disease in young adults. Cognitive dysfunction (CD) contributes significantly to patient’s disability status. Although almost all kind of CD can be observed in MS, the typical profile is the impairment of information processing speed, memory, attention and often executive skills. The aim of the study was to investigate the influence of different demographic and clinical markers of the disease and changes in MRI tomography on cognitive functions in MS patients. The study involved 120 patients with MS and 40 healthy controls. Neurological examination, complaints of memory and fatigue, objective depression, anxiety and objective fatigue were evaluated. Cognitive functions (CF) were tested using battery of 11 cognitive tests. Brain MRI was performed to evaluate focal demyelinised lesions and to calculate regional linear markers of brain atrophy. The impairment of CF was much more expressed in MS patients as compared to controls. CF were negatively affected by objective depression and disease course. Subjective memory complaints and subjective fatigue in MS patients did not correlate with CF however they did correlate with objective fatigue. Self reported memory impairment worsened with the progression of disease. CD and brain atrophy reflected by MRI linear parameters were more expressed in secondary progressive (SP) MS as compared to relapsing remitting (RR) MS. Number of demyelinated lesions were... [to full text]

The aim of this thesis was to develop a questionnaire for cognitive functioning, which could possibly be used as a screening instrument for early signs of dementia in the future. The introduction discusses the often made distinction between subjective and objective measures. A background to the four articles is provided, focussing on findings of weak relationships between self-report- and laboratory measures of memory/cognition. Studies I and II provided results and conclusions that guided instrument development and validation in Studies III and IV. All studies were based on data from participants in the Betula Prospective Cohort Study. Study I investigated predictors of scores on an established self-report instrument for memory failures (PRMQ). Candidate predictors were memory performance on laboratory tests, age, depressive symptoms, and personality traits. There was no relation to age, and test performance did not predict self-reported memory, but depressive symptoms and personality did. Given the finding of a lack of a relation to age, and a bulk of research articles claiming that memory complaints are common in the elderly or increase with age, Study II used a global rating of problems with memory, and reports of perceived causes. In contrast to Study I, problems ratings were related to age, such that increasing age meant higher severity of problems. Furthermore, perceived causes of memory problems differed across age. The elderly reported aging while the young reported stress and multitasking as primary causes. With these results as a background, the purpose of Study III was to develop a new instrument (the Cognitive Dysfunction Questionnaire - CDQ) with the explicit aim that scores should be related to laboratory test performance. A global construct of cognitive functioning with an emphasis on memory systems was adopted, and an item pool was generated. Based on exploratory principal components analysis and correlations with criterion measures (laboratory test performance), twenty items in six domains were selected. Preliminary psychometric evidence showed that the CDQ was reliable, and related to age and objective measures, but not to depressive symptoms. In Study IV, twenty additional items were constructed, and the CDQ was responded to by participants in independent samples. Confirmatory factor analysis was used to test the factor structure derived from Study III, and refinement was undertaken by collapse of two domains and exclusion of items. The final factor structure was cross-validated. Competing models and measurement invariance across age and sex was tested. Psychometric properties were investigated for the final 20-item version.