Includes bibliographical references. / AIMS: To examine the relationship between prospective memory, cognitive function and Diffusion tensor imaging (DTI)/ White matter integrity of human immunodeficiency virus (HIV) positive individuals in the Western Cape. We hypothesize that: 1. Individuals infected with HIV will exhibit significantly poorer microstructural integrity of the white matter than HIV negative individuals, as determined by in vivo diffusion tensor imaging. We expect that values of fractional anisotropy (FA) - a measure of directional water diffusion- in the frontal white matter will be significantly lower among HIV patients compared to controls 2. Lower FA measured in the frontal white matter will correlate significantly with impaired performance on tests of prospective memory

Background: Methamphetamine (MA) abuse is a global health concern due to widespread use and harmful effects, which includes neurotoxicity. This study aimed to describe neurocognitive deficits associated with MA dependence in young adults and to explore whether these deficits correlate with white matter (WM) microstructural abnormalities using diffusion tensor imaging (DTI). Methods: Twenty-one MA dependent individuals recently enrolled in an outpatient rehabilitation program and nineteen healthy controls participated in the study. Each participant completed a neuropsychological evaluation and underwent diffusion tensor imaging within one week of testing. Average whole-brain fractional anisotropy (FA) and mean diffusion (MD) measures derived from DTI data were compared between groups. Group differences in performance within specific neurocognitive domains and in a composite global neurocognitive score (GNS) were tested using non-parametric univariate statistics and within a linear regression framework, adjusting for age and gender. Correlation analyses were conducted to test associations between the neuropsychological data and selected frontal white matter (WM) tracts, including the genu and body of the corpus callosum (CC); right and left cingulum bundle (CB); right and left uncinate fasciculus (UF); right and left anterior corona radiata (CR) and the right and left superior longitudinal fasciculus (SLF). Results: No significant between-group differences were detected for performance in any of the neuropsychological domains assessed. No relationship between FA or MD and the GNS was demonstrated in the tracts of interest. After adjusting for age and gender, significant group differences in FA and MD were detected across several regions of interest (ROI), however, these did not survive corrections for multiple comparisons. Conclusion: Cognitive performance and white matter integrity did not differ between young MA dependent subjects and healthy controls. Whatever differences that were found in white matter did not survive correction for multiple comparisons. These findings may reflect one or more of several possibilities: that brain function and structure is relatively preserved in younger individuals; or that differences were too small to be detected in this sample. Further studies should explore the effects of aging, poly-substance abuse and HIV coinfection on neurocognitive functioning and structural brain integrity in methamphetamine users.

Two dopaminergic altering drugs, haloperidol and carbidopa + levodopa, and juice only conditions, were given to six squirrel monkeys in factorial combination with two novel environments and an alone condition. The point of this research was to assess differences in subjects' adaptation to various stimulus conditions under the differential influence of the two drug conditions. Control conditions for both drug and environmental variables were included in the design, which provided a baseline for comparison with active variables. Although no significant interactions between drugs and environments were found, some interesting reactions to the non-drug-laced vehicle were noted. The drugs, haloperidol and carbidopa-levodopa, have been used in many past comparative studies. However, the thrust of most research has been focused upon changes in movement capability, or deterioration of movement ability. Extrapyramidal side-effects, such as bizarre facial and tongue movement and postural changes, have generally been included in these investigations. Little attention has been placed upon adaptive change to novel environments, which may occur with these drugs. This research represents an initial investigation of such changes, an important consideration in view of their widespread use as therapeutic agents with humans.

abstract / Psychiatry / Doctoral / Doctor of Philosophy

Dissertation (PhD)--University of Stellenbosch, 2006. / Bibliography. Also available via the Internet.

Issued also as Schulte's thesis, Leiden. / Text in Latin and Dutch, with summary in English and Russian.

Syftet med denna uppsats har varit att belysa neuropsykiatriska utredningar utifrån ett klientperspektiv. Uppsatsen bygger på kvalitativa intervjuer med sex informanter som har genomgått en neuropsykiatrisk utredning. Avsikten med studien var att få en djupare och tydligare kunskap om klienternas upplevelse av att genomgå en neuropsykiatrisk utredning. Våra frågeställningar har belysts utifrån tre teman förväntningar, upplevelse och bemötande. Resultatet visade att det finns flera aspekter i utredningen som har upplevts som problematiska utifrån ett klientperspektiv, men också aspekter utanför utredningen som upplevts som bekymmersamma utifrån klienternas utsagor. De negativa upplevelserna från utredningen visade sig vara den neuropsykiatriska utredningens tidsomfattning som ansågs vara för lång, även återkopplingsmötet bedömdes vara för komplicerat och förvirrande. Flera informanter beskrev att de sökt hjälp tidigare, men att någon diagnos aldrig har fastställts, vilket bidrog till att samtliga informanter var ytterst angelägna om att genomgå en utredning. Resultatet visade att det fanns ett behov av att få prata och beskriva sina svårigheter, vilket det neuropsykiatriska utredningsteamet kunnat tillgodose genom sin professionalitet och goda kunskaper. Informanterna upplevde en lättnad efter fastställd diagnos och för många betydde en utredning att de fått rätsida på svårigheter som varit påtagliga under större delen av deras liv. Det finns i empirin tendenser till ett stort behov av att få uttrycka sig och en upplevelse av kunskapsbrist från omgivningen.

Previous studies have shown that dietary supplementation of curcumin or omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid can reduce behavioural deficits and β-amyloid (Aβ) pathology in several models of Alzheimer’s disease (AD), including Tg2576 mice. However, no study to date had examined the effect of omega-3 PUFA and curcumin co-supplementation on behaviour or β-amyloid pathology in mouse models of AD. Further to this, no study to date had examined the effect of longitudinal omega-3 PUFA or curcumin supplementation provided from an early age before significant pathological development in the Tg2576 model. This was deemed important since human studies have suggested that lifelong dietary choices before disease development are an important factor in disease risk. Finally, although a plethora of studies has examined the effect of omega-3 PUFA supplementation, none has accurately examined its effect against an appropriate control diet. For example, some control diets contained differential levels of fatty acids such as excess total fat and omega-6 PUFAs. Such differences in the control diet may have contributed to the observed beneficial effects of dietary omega-3 PUFA supplementation, particularly since these dietary factors can exacerbate pathological processes related to AD. Using this experimental design, chapter 3 found longitudinal dietary supplementation of omega-3 PUFA docosahexaenoic acid (DHA) from an early age in Tg2576 mice provided some protection from cognitive decline that was limited to later but not early stages of pathology. In contrast to previous reports however, Aβ pathology was unaltered by DHA supplementation. Providing DHA supplementation from an even earlier age, chapter 4 showed that DHA reduced behavioural deficits at an early age (prior to Aβ pathology), although interestingly, these effects were less robust at the later age. Chapter 5 examined longitudinal supplementation of curcumin, fish oil containing omega-3 PUFAs (DHA and eicosapentaenoic acid, EPA) and their co-supplementation from an early age in Tg2576 mice. The results consistently revealed no beneficial effects of dietary supplementation on behaviour or Aβ pathological measures. The findings from this thesis indicate that dietary supplementation of DHA relative to a suitable control diet can provide only limited protection against behavioural deficits in Tg2576 mice. In contrast, fish oil supplementation containing omega-3 PUFAs DHA and EPA provided no protection, indicating that DHA monotherapy may be a more advisable treatment. The null effects of curcumin supplementation at earlier stages relative to previous studies suggest that curcumin may only be effective during advanced stages of pathology, although further investigation is needed. Finally, the null effects of curcumin and fish oil/omega-3 PUFA co-supplementation suggest that this is not an optimal intervention strategy in reducing Aβ-induced changes.

Objective: There is emerging evidence that exercise may modify disease progression and improve function in a number of neurodegenerative diseases, but this has not been systematically studied in Huntington.s disease (HD). The purpose of this study was to evaluate feasibility, acceptability and benefits of an exercise programme in people with HD. Methods: Using a randomised controlled trial design, 25 participants with manifest HD were allocated to either intervention (home-based exercise; n=13) or control (usual care;n=12) groups. Participants were assessed at baseline and eight weeks later. Eleven participants from the exercise and 10 from the control group completed the intervention study. The primary outcome was gait variability (stride time coefficient of variation (CV)). Secondary outcomes included other measures of gait, disease-specific motor scale and measures of balance, muscle strength, mobility and community walking, functional performance in ADL and quality of life. These measures were included to reflect a range of physical impairments and activity limitations seen in people with HD. Analysis of covariance was used to compare follow-up scores across groups after adjustment for differences at baseline. Effect sizes were calculated for outcome measures based on differences in change scores between groups. Process interviews were conducted at the end of the study to determine acceptability of the intervention to participants. Cross sectional investigation of outcome measures was undertaken initially to investigate discriminant and concurrent validity as well as test re-test reliability and minimal detectable change (MDC95) along the broad spectrum of the disease. Baseline data from 25 participants with manifest HD (who went on to participate in the intervention), in addition to data from 17 individuals with pre-manifest HD and 25 healthy controls were analysed. This data was of use in interpreting the results from the interventional study. In particular, the MDC95 data helped in determining of whether any statistical significant changes due to the intervention are clinically meaningful. Results: Measures of gait variability, some measures of balance, community walking and measures of functional performance in ADL were able to distinguish between people with manifest HD and pre-manifest HD as well as between people with pre-manifest HD and healthy controls suggesting good discriminant validity. All these outcomes had also good concurrent validity with a disease specific motor score. The test re-tests reliability scores for the majority of the outcomes were high and the MDC95 scores were low, suggesting that the individual variability on these outcomes were low. Adherence rates to the exercise programme were high (78.8% of participants reported completion of at least 78% of the prescribed sessions). Participants in the intervention group demonstrated significant improvement in stride time CV (95% CI (-11.5, -0.6))based on complete case analysis. Significant differences between groups were also observed in the disease-specific motor scale and in measures of balance, mobility,community walking and functional performance in ADL, but not muscle strength and health-related quality of life. Effect sizes were large (>0.8) for the majority of the outcomes. The magnitude of the change as a result of the exercise intervention exceeded the calculated MDC95 values for some of the outcomes, which suggest that most of the observed changes are clinically meaningful. Qualitative feedback from the participants who completed the exercise programme suggested high levels of acceptability with positive impact on general health and mobility. Participants identified barriers and facilitators that affected performing the exercises at home and described management strategies that helped adherence to the exercise programme. Conclusions: This study was the first systematic trial to demonstrate that a short-term structured exercise programme is acceptable and can be safely delivered in a home environment; achieve good adherence; and positively affect body function and activity in people with HD. The sensitivity of the outcomes as determined in the cross-sectional study, to mobility deficits the in pre-manifest HD group is important. These outcomes has the potential to be used in future studies of exercise interventions in the premanifest stage which aim to target such deficits early in the disease life cycle, before they begin to impact on a person.s ability to participate in the community. Overall the data presented from this study provides a platform for further investigations to extend these findings about the role of exercise and physical activity in people with HD. Larger and more detailed studies are needed to replicate findings from this study in othercontexts and variations in dose.

People with Parkinson's disease report high levels of non-motor symptoms, including anxiety and depression, that are difficult to treat pharmacologically. Mindfulness-based interventions have been shown to be effective in other long-term conditions. This pilot study explored how a mindfulness-based intervention may have had an effect and for whom, with a view to informing future studies. Volunteers were randomised to a remote delivery, eight-week mindfulness cognitive behavioural group therapy intervention (n=40) or wait-list (n=38), and measures for psychological outcomes and putative mediators were taken at baseline, 4 weeks, 8 weeks and 20-week follow-up. The study showed that all the outcome measures changed in a positive health direction in the intervention group. The intervention had a small effect on decentering (d=.36) and acceptance (d=.27) by mid-point, before depression at 8 weeks (d=-.28) and anxiety at follow-up (d=-.29), indicating an indirect effect between trial arm and levels of distress. Mediation and moderation analysis were conducted using PROCESS, time-lagging the mediators to the outcome variables, but no combined or individual indirect effects had confidence intervals entirely above or below zero, thus mediation cannot be confirmed. When the end of intervention mediators were analysed with the follow-up levels of anxiety and depression, there is evidence of inconsistent mediation, or possible suppression effects. Moderation analysis revealed that the effect on anxiety levels was moderated by gender, with women benefitting more from the mindfulness intervention. Moderated mediation analysis also indicated that the effect of the trial arm on levels of acceptance was conditional by age and time since diagnosis, and the effect of trial arm on levels of mindfulness skills by age, meaning that younger, newly-diagnosed patients were more able to increase mindfulness skills and acceptance.