Cerebrovascular disease is one of the leading causes of death among persons aged 50 and above and when a stroke does not result in death, it can cause residual cognitive, motor and behavioural disabilities. Emotional effects of brain injury range from reduced quality of life to various neuropsychiatric disturbances and are of great interest in the South African context and throughout the world as they pose a major obstacle to the rehabilitation process. This study explored the relationship between emotion processing, neuropsychiatric symptoms and quality of life specifically, how they operate following a cerebrovascular accident. In order to achieve this, an adult population of high functioning stroke survivors completed the emotion processing scale (EPS), Minnesota Multiphasic Personality Inventory (MMPI-2) and comprehensive quality of life inventory (ComQOL-A5) and a factor analysis provided statistical evidence suggestive of intercorrelations among the variables. The results lent support to this theoretical relationship and determined the structure of this relationship as follows: The satisfaction with quality of life after a stroke that relates to traditional masculine or feminine roles, when not fulfilled, related to neuropsychiatric symptoms of general maladjustment i.e. schizophrenia and psychopathic deviate. The second factor encompassed symptoms of general anxiety both internally and externally directed: Internally directed anxiety included symptoms of hypochondriasis and hysterical conversion, while externally directed anxiety included neuropsychiatric symptoms of paranoia. The third factor was associated with mood modulation in that elevated mood connected to neuropsychiatric symptoms of hypomania and depressed mood connected to symptoms of depression and social introversion. Finally, emotion processing and psychasthenia made up the last principal component, namely emotion modulation. This meant that avoidance of emotional iv content, suppression of emotion, unprocessed emotion etc. related to neuropsychiatric symptoms of obsessions or compulsions. High functioning stroke survivors’ behaviours were thus characterised by general maladjustment, anxiety, and symptoms related to mood and emotion modulation. This study underlies the importance of diagnosing, treating and monitoring stroke survivors’ emotional alterations and suggests the usefulness of its application in clinical settings to evaluate the effectiveness of treatments or more general interventions to improve the neuropsychiatric sequelae and quality of life of stroke survivors. Improved understanding of these constructs from the stroke survivor’s perspective has obvious impact for the therapeutic interventions inherent in stroke rehabilitation and as such, contributes towards the fields of neuropsychology, neuropsychotherapy and the social sciences.

To date, the most common pharmacological treatments for dementia are cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists (antidementia medications), which are associated with a delay in the progression of the cognitive and functional symptoms. Studies of the effects of antidementia medications on neuropsychological symptoms (NPS) show varying results. Presence of NPS can also affect the amount of time caregivers spend with persons with dementia, which can affect informal costs of the condition. This project used extant data from the longitudinal, population-based Cache County Study on Memory and Aging (CCSMA) and the Dementia Progression Study (DPS), which included permanent residents aged ≥ 65 of Cache County, Utah. Linear mixed models were used to assess the association between antidementia medications with informal costs and NPS. The first study examined whether antidementia medications were associated with a decrease in informal costs. Use of antidementia medications was not significantly associated with informal costs (expβ = .79, p = .090). When restricting the sample to only the participants who were of mild dementia severity at baseline, antidementia medications were associated with a 28% decrease in informal costs (expβ = .72, p = .039). The second study evaluated whether antidementia medications were associated with a decrease in NPS. Results indicated that use of antidementia medications was associated with a 28% increase in NPS (expβ = 1.28, p < .001). However, this association was no longer significant with the inclusion of covariates, in particular, the use of psychotropic medications. Use of any psychotropic medication was significantly associated with a 30% increase in Neuropsychiatric Inventory (NPI) score. Overall, the use of antidementia medications may not significantly reduce informal costs or NPS. The use of antidementia medications may reflect patterns of use that are prompted by severity of dementia and NPS.

Yes / Current policy emphasises the importance of 'living well' with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1-0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder amongst older adults. Features of this disease include accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles (NFT), neuroinflammation, and neurodegeneration. These result in a progressive decline in memory and executive function in patients. Anxiety-related behaviours are disparaging comorbidities of AD, but how they arise in patients remains elusive. Protein-tyrosine phosphatase 1B (PTP1B) has been associated with Aβ pathology and with anxiety in separate paradigms, but whether PTP1B is involved in anxiety-related behaviours in AD mouse models is unknown. The objective of this project was to compare anxiety-related behaviours between the hAPP-J20 (Aβ pathology) and PS19 (Tau pathology) mouse models of AD and determine whether PTP1B is involved in these behaviours. Another major objective of this project was to investigate the role of PTP1B in tau pathology in the PS19 mouse model in anxiety-related brain regions, since this has not been previously examined. Using key anxiety-testing paradigms such as the elevated plus maze (EPM) and the open field test (OF), an age-based dimorphism in the onset of an inappropriately lowered anxiety response in the J20 and PS19 mouse models was identified. Furthermore, it was shown that this abnormal anti-anxiety baseline phenotype could be normalized with selective PTP1B inhibition by the drug trodusquemine and by genetic neuronal ablation. Finally, in PS19 mice at 8 months of age, it was shown that PTP1B blockade has the therapeutic effect of relieving neurotoxic phospho-tau burden and neuroinflammation. Together, these findings suggest that unleashed PTP1B may serve as a potential therapeutic target, with a possible role in AD-associated anxiety-related behaviours and AD pathology.

No description available.

Correlations between neuropsychiatric symptoms and beta-amyloid (Aβ) burden in specific brain regions in living Alzheimer’s disease (AD) patients remain to be elucidated. Ten mild AD patients underwent MR and [11C]SB-13 PET imaging. Neuropsychiatric symptoms were quantified with the Neuropsychiatric Inventory (NPI). NPI-depression/dysphoria, -apathy, -agitation/aggression, -anxiety, and -appetite/eating disorders scores were hypothesized to correlate with Aβ burden in particular brain regions. Pearson’s correlation coefficient revealed that depression/dysphoria scores positively correlated (p<0.05) with standardized uptake values (SUVs) from left medial temporal lobe (r=0.67), and agitation/aggression correlated with SUVs from bilateral anterior cingulate (right, r=0.71; left, r=0.78), temporal (right, r=0.71; left, r=0.75), parietal (right, r=0.77; left, r=0.81), and dorsolateral prefrontal cortex (right, r=0.74; left, r=0.73). However, NPI scores did not significantly correlate with better estimates of Aβ burden that use the cerebellum as reference region. Overall, our results confirm the lack of association between Aβ burden and neuropsychiatric symptoms reported in autopsy studies.

Correlations between neuropsychiatric symptoms and beta-amyloid (Aβ) burden in specific brain regions in living Alzheimer’s disease (AD) patients remain to be elucidated. Ten mild AD patients underwent MR and [11C]SB-13 PET imaging. Neuropsychiatric symptoms were quantified with the Neuropsychiatric Inventory (NPI). NPI-depression/dysphoria, -apathy, -agitation/aggression, -anxiety, and -appetite/eating disorders scores were hypothesized to correlate with Aβ burden in particular brain regions. Pearson’s correlation coefficient revealed that depression/dysphoria scores positively correlated (p<0.05) with standardized uptake values (SUVs) from left medial temporal lobe (r=0.67), and agitation/aggression correlated with SUVs from bilateral anterior cingulate (right, r=0.71; left, r=0.78), temporal (right, r=0.71; left, r=0.75), parietal (right, r=0.77; left, r=0.81), and dorsolateral prefrontal cortex (right, r=0.74; left, r=0.73). However, NPI scores did not significantly correlate with better estimates of Aβ burden that use the cerebellum as reference region. Overall, our results confirm the lack of association between Aβ burden and neuropsychiatric symptoms reported in autopsy studies.

Le tube digestif héberge une communauté microbienne complexe, le microbiote intestinal, dont les capacités métaboliques sont plus riches et diversifiées que celles codées par le génome de l'hôte. L'implication du microbiote intestinal dans divers aspects de la physiologie de l'hôte, comme le métabolisme nutritionnel et l'immunité, est depuis longtemps étudiée. En revanche, l'action potentielle du microbiote sur le développement et le fonctionnement du cerveau constitue une nouvelle piste de recherche, encore peu explorée. Dans ce contexte, nous avons réalisé une première étude générale de l'action du microbiote intestinal sur le cerveau en comparant les fonctions sensori-motrices, le comportement de type anxieux, l'état d'activation de l'axe hypothalamo-hypophyso-surrénalien et le profil cérébral des monoamines de rats F344 axéniques et conventionnels. Les résultats révèlent que, chez cette lignée particulièrement sensible au stress, l'absence de microbiote intestinal exacerbe le comportement de type anxieux et la réponse hormonale au stress, et atténue le métabolisme dopaminergique cérébral. Afin d'étudier par quel moyen le microbiote peut agir sur le cerveau, une seconde étude a été menée, ciblant un métabolite bactérien spécifique, l’indole, dont certains dérivés oxydés par le foie sont connus pour avoir des propriétés neuroactives. L'indole est un métabolite naturel du microbiote intestinal, dont la surproduction pourrait survenir lors d'une dysbiose du microbiote. Deux cas de surproduction ont été modélisés : chronique et aiguë. Dans les deux cas, des modifications importantes du comportement de l'hôte ont été observées. En situation de surproduction chronique, l'indole favorise des comportements de type anxieux et dépressif, tandis qu'une surproduction aiguë a un effet sédatif marqué. D'un point de vue mécanistique, nous confirmons que l’indole peut agir sur le système nerveux central par la voie sanguine impliquant les dérivés oxydés et montrons pour la première fois qu'il peut aussi agir en activant les noyaux cérébraux du nerf vague. / The gastro-intestinal tract hosts a complex microbial community, the gut microbiota, whose collective genome coding capacity vastly exceeds that of the host genome. The involvement of the gut microbiota in various aspects of the host physiology, such as the nutritional metabolism and the immunity, has long been studied. In contrast, the possible action of the gut microbiota on brain development and functioning is a new line of research, still poorly explored. In this context, we performed a first general study of the effect of gut microbiota on the brain by comparing the sensory-motor functions, the anxiety-like behaviour, the activation of the hypothalamic-pituitary-adrenal axis and the brain monoamine profile in germ-free and conventional F344 rats. The results show that, in this particularly stress-sensitive strain, absence of gut microbiota exacerbates the anxiety-like behaviour and neuroendocrine response to stress, and reduces brain dopamine metabolism. To investigate the means by which the microbiota can affect the brain, a second study was conducted, targeting a specific bacterial metabolite, indole, whose oxidative derivatives, produced by the liver, are known to have neuroactive properties. Indole is a natural metabolite of the gut microbiota, whoseoverproduction could occur during a microbiota dysbiosis. Two conditions of overproduction, namely chronic and acute, were modelled. In both cases, significant changes in the behaviour of the host were observed. In chronic overproduction, indole promotes anxiety- and depressive-like behaviours, while acute overproduction has a marked sedative effect. From a mechanistic point of view, we confirm that indole can act on the central nervous system through its oxidized derivatives and show for the first time that it can also act by activating the brain nuclei of the vagus nerve.

Background: Data regarding both drug-related and non-drug-related costs in patients with Parkinson's disease (PD) are scarce, mainly due to the difficulties in data acquisition in experimental designs. Likewise, the reported impact of drug costs on total direct costs varies across different studies. In addition, the influence of comorbidities on both treatment costs and health-related quality of life has not been adequately evaluated. Methods: A sample of office-based neurologists (n = 315) in Germany was asked to examine up to five consecutive patients with PD (n = 1449) on a specified day during the study period. Patients of all ages were eligible and their evaluation was performed using standardized questionnaires. Results: PD-specific therapy costs increased with the stage of the disease, early onset of the disease and disease duration. The major costs were due to PD-related therapy, whereas other medications only resulted in minor costs. Disease stage mainly influenced direct therapy costs, with an observed increase of total daily costs from €7.3 to €11.3/day. In addition, disease onset at age < 65 years resulted in total daily costs of €11.2 compared to late onset of disease (> 75 years) with daily therapy costs of €5.3. In this patient group neuropsychiatric comorbidities such as dementia and depression were only insufficiently treated. In addition, these comorbidities severely affected health-related quality of life. Conclusion: Therapy costs were influenced by disease stage, disease onset as well as present comorbidities. Furthermore, comorbidities such as depression and dementia were diagnosed but were not adequately treated.

The aim of this study was to investigate the relationship between noncognitive symptoms and premorbid temperament in a group with Alzheimer’s disease. The relationship between premorbid temperament and noncognitive symptoms can be used to understand symptom susceptibility and risk, caregiver burdens, as well as providing insights into the neuroanatomical substrates of temperament and noncognitive behaviour. Sixty-three primary caregivers of Alzheimer’s patients fulfilled the eligibility criteria for this study. Information regarding the noncognitive symptoms and premorbid temperament was procured from the primary caregivers. In fifty-one cases, a secondary caregiver also provided information about the premorbid temperament of the Alzheimer’s patient. The latter was obtained to enhance the reliability of retrospective data. The Behaviour Rating Scale for Dementia, the Formal Characteristics of Behaviour-Temperament Inventory, and the Blessed Dementia scale were used to elicit data on noncognitive symptomatology, premorbid temperament, and current cognitive status, respectively. ii Noncognitive symptoms were grouped into two clusters namely neuropsychiatric and neurobehavioural disturbances. The neuropsychiatric cluster included mood and psychotic symptoms and the neurobehavioural cluster included vegetative and overall behavioural dysregulatory symptoms. Results showed that there is a wide spectrum of noncognitive symptom manifestation in patients’ profiles and that the neurobehavioural dysregulatory symptoms are more common than the neuropsychiatric symptoms in this Alzheimer’s cohort. With regard to symptom manifestation and cognitive status, a Pearson product moment correlational analysis showed that a lower level of cognitive functioning is significantly associated with aggressive episodes and a higher level of cognitive functioning with manifestations of depressive symptoms. In terms of interrater concordance on premorbid temperament ratings, intraclass correlations were significant for five of the six temperament domains, thus indicating a reliable estimate of premorbid disposition. Canonical correlational analysis yielded two significant variates. The first variate indicated that Alzheimer’s disease patients with a proclivity for aggressive behaviours and general behavioural deregulation but lower depressive profiles, were premorbidly more emotionally reactive, had low sensory thresholds (high sensitivity), and greater cognitive deficit. The second variate showed that patients with Alzheimer’s disease who tended to manifest with depressive and dysregulatory behaviour appear to have been premorbidly perseverative in temperament with a low sensory threshold (high sensitivity) and the tendency to maintain and attain a low level of activity (stimulation). Taken together, the significant variates revealed a dimensional relationship between depressive symptoms, aggressive symptoms, and behavioural dysregulation; and sensory sensitivity, emotional reactivity, perseverance, and activity, with cognitive status serving as a moderating variable. In conclusion, the study indicated a dimensional relationship between specific premorbid temperament traits and noncognitive symptoms, thereby highlighting the possible predictive influence of premorbid temperament on noncognitive manifestations in Alzheimer’s disease patients. / Thesis (PhD (Psychology))--University of Pretoria, 2005. / Psychology / unrestricted