Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients. Today's technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility. In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation. One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly.

No description available.

Mild cognitive impairment (MCI) is a transition phase between normal aging and Alzheimer’s disease. Individuals with MCI show impairment in cognition as well as corresponding damage to areas of their brain. Performance on tasks such as discriminating objects with ambiguous features has been associated with damage to the perirhinal cortex, while scenes with structural (spatial) elements have been associated with damage to the hippocampus. In addition, attention is regarded as one of the first non-memory domains to decline in MCI. A relatively new MRI technique called diffusion tensor imaging (DTI) is sensitive to white matter microstructural integrity and has been associated with changes due to cognitive decline. 18 MCI (14 amnesic, 4 vascular) and 12 healthy matched controls were assessed in feature ambiguity, attention and structural learning to assess associated deficits in MCI. Associations with white matter microstructural integrity were then investigated. The MCI groups were discovered to perform worse than controls on the test of structural learning. In addition, altered attention networks were found in MCI and were associated with white matter microstructural integrity. No significant differences were found for feature ambiguity. These findings suggest there may be specific damage to the hippocampus while the perirhinal cortex may be preserved in MCI. Furthermore, dysfunction in attention was found to be associated with white matter microstructural integrity. These experimental tests may be useful in assessing dysfunction in MCI and identifying degeneration in white matter microstructural integrity. Further studies with larger sample sizes are needed to validate these findings.

Hensikt: Hensikten med studien var todelt. Den ene delen tok sikte på å belyse hvordan manved screeningkunne finne ut om personer med kognitiv svikt oppfyller helsekravene for fortsatt å kunne kjøre bil. Den andre delen så på ergoterapeutens rolle og kunnskapsgrunnlag i slike førerkortvurderinger. Metode:Tverrsnittsstudie hvor den ene delen varbygd på data fra 99 pasientjournaler med fokus på to nevropsykologiske tester(NorSDSA og UFOV)og en praktisk kjøretest(P-Drive). Den andre delen varbygd på data fra en webbasert spørreundersøkelse sendt ut til 1857 norske ergoterapeuter. Resultat:UFOV hadde signifikant korrelasjon med utfall i praktisk kjøretest, høy sensitivitet og høy PPV, slik at ved en ikke-godkjent UFOV er det grunn til å fortsette med praktisk kjøretest. NorSDSA hadde lav sensitivitet, men høy spesifisitet som indikerer atde som får godkjent på NorSDSA bør fortsette med en praktisk kjøretest.I praktisk kjøretest var det skår på kjørehandlingene «Løser problem, «Reaksjon» og «Oppmerksomhet mot venstre» som hadde størst sammenheng med resultatet av førerkortvurderingen. Det varfå ergoterapeuter i Norge som haddeførerkortvurderinger som sittarbeidsområde. Informantene i undersøkelsen opplevde at de kunne haen sentral rolle i å vurdere helsekravene for førerkort, men at de mangletbåde kunnskap, gyldige og pålitelige metoder og nasjonale retningslinjer for slike vurderinger. Konklusjon:Fra et folkehelseperspektiv, er utfordringentidlig å identifisere sjåfører med økt risiko, uten unødig begrense andre. Studien viser at det er behov for både å gjennomføre nevropsykologiske tester samt praktisk kjøretesti vurdering av helsekrav for personer med kognitiv svikt.Det er behov for mer forskning på området, og dessutenbehov for å utarbeide nasjonale retningslinjer.Ergoterapeutene oppfattet sinrolle i førerkortvurderinger som sentral med spesielt praktisk kjøretestsom et viktig bidrag. / Aim: The aim of thestudy was dual. First, itsought to determine whether individuals with cognitive impairments meet health requirements fordrivingsafety. Second, itexaminedthe role of occupational therapists and their knowledge of driver assessments. Method:For part 1, across-sectional study was applied, based partly on data from 99 patient records,focusing on two neuropsychological tests (NorSDSA and UFOV) and on-roaddriver performancetest(P-Drive). The second part wasbased on data from an online survey sent to 1.857 Norwegian occupational therapists. Result:UFOV had significant correlation with outcome in P-Drive, high sensitivity, and high PPV. A failed UFOV indicates a reason to continue with an on-roadtest. NorSDSA had low sensitivity but high specificity and high PPV. Passing NorSDSA indicates a reason to continue with an on-road test. The items in P-Drive that had the highest correlation with the result of the driving assessment were problem solving,reaction, and attention to the left.Few occupational therapists in Norway were involved in driving assessment. Survey participants felt that they might play a central role in assessing the health requirements for driving but lacked the knowledge, valid and reliable methods, and national guidelines for driving assessments. Conclusion: From a public health perspective, the challenge is to identify at-risk drivers as early as possible, without unnecessarily restricting other drivers. This study shows a need for conducting neuropsychological tests and for a practical driving test to assess people with cognitive impairment. This area requires further study, just as there is a need for national guidelines.Occupational therapists perceived a central role for them in driving assessment. They believed they could contribute most effectively through a driving test. / <p>ISBN 978-91-86739-50-8</p>

Objective: The Six Elements Task (SET; Shallice and Burgess, 1991; Burgess et al., 1996) measures examinees’ ability to plan and organize their behaviour, form strategies for novel problem solving, and self-monitor. The task has adequate specificity (Wilson et al., 1996), but questionable sensitivity to mild impairments in executive function (Jelicic, et al., 2001). The SET is vulnerable to practice effects. There is a limited range in possible scores, and ceiling effects are observed. This dissertation sought to evaluate the validity and clinical utility of a modification of the SET by increasing the difficulty of the test, and expanding the range of possible scores in order to make it more suitable for serial assessments. Participants and Methods: The sample included 26 individuals with mixed acquired brain injury, and 26 healthy matched controls (20 – 65 years). Participants completed a battery of neuropsychological tests on two occasions eight weeks apart. To control for confounding variables in executive function test performance, measures of memory, working memory, intelligence, substance abuse, pain, mood and personality were included. Self and informant reports of executive dysfunction were also completed. The two groups’ performances on the various measures were compared, and the external validity of the 12ET was examined. In addition, normative data and information for reliable change calculations were tabulated. Results: The ABI group exhibited very mild executive function deficits on established measures. The matched control group attempted more tasks on the 12ET, but the difference was non significant. Neither group tended to break the rule of the task. The 12ET showed convergent validity with significant correlations with measures of cognitive flexibility (Trailmaking B and Ruff Figural Fluency), and a measure of planning (Tower of London). The 12ET and published measures were also significantly correlated with intelligence in the brain-injured group. The 12ET did not show divergent validity with a test of visual scanning speed (Trailmaking A). No demographic variables were found to be significant predictors of 12ET performance at Time 2 over and above performance at Time 1, and both participant groups obtained the same benefit from practice. The 12ET did not suffer from ceiling effects on the second administration, and the test-retest reliability of the 12ET variables ranged from low (r = .22 for Rule Breaks in the brain-injured group) to high (r = .78 for Number of Tasks Attempted in the control group). Conclusions: Despite their (often severe) brain injuries, this sample of brain injured participants did not demonstrate executive impairments on many published tests and their scores were not significantly different from the control group’s scores. Therefore, it was not possible to determine if the 12ET was a more sensitive measure of mild executive deficits than the SET. However, the increase in range did reduce the tendency for participants to perform at ceiling levels. The 12ET showed a number of significant correlations with other executive measures, particularly for the brain-injured group, though these correlations may have been moderated by general intelligence. Two variables of the 12ET, deviation from the optimal amount of time per task and Number of Tasks Completed, showed promise as measures of reliable change in this sample over an 8-week interval.

The absence of gold standard criteria for mild cognitive impairment (MCI) impedes the comparison of research findings and the development of primary and secondary prevention strategies addressing the possible conversion to dementia. The objective of Study 1 was to compare the predictive ability of different MCI models as markers for incipient dementia in a longitudinal population-based Canadian sample. The utility of well-documented MCI criteria using data from persons who underwent a clinical examination in the second wave of the Canadian Study of Health and Aging (CSHA) was examined. Demographic characteristics, average neuropsychological test performance, and prevalence and conversion rates were calculated for each classification. Receiver operating characteristic (ROC) analyses were employed to assess the predictive power of each cognitive classification. The highest prevalence and conversion rates were associated with case definitions of multiple-domain MCI. The only diagnostic criteria to significantly predict dementia five years later was the Cognitive Impairment, No Dementia (CIND) Type 2 case definition. It is estimated that more restrictive MCI case definitions fail to address the varying temporal increases in decline across different cognitive domains in the progression from normal cognitive functioning to dementia. Using data from the CSHA, the objective of Study 2 was to elucidate the clinical correlates that best differentiate between cognitive classifications. A machine learning algorithm was used to identify the symptoms that best discriminated between: 1) not cognitively impaired (NCI) and CIND; 2) CIND & demented; and 3) converting and non-converting CIND participants. Poor retrieval was consistently a significant predictor of greater cognitive impairment across all three questions. While interactions with other predictors were noted when differentiating CIND from NCI and demented from non-demented participants, retrieval was the sole predictor of conversion to dementia over five years. Importantly, the limited specificity and predictive values of the respective algorithms caution against their use as clinical markers of CIND, dementia, or conversion. Rather, it is recommended that the predictors serve as markers for ongoing monitoring and assessment. Overall, the results of both studies suggest that the architecture of pathological cognitive decline to dementia may not be captured by a single set of diagnostic criteria.

Introduction Neuropsychological development is a genetically guided process which is continuously modified by socio-environmental factors. This thesis aimed to study the main socio-environmental determinants of neuropsychological development in different time-periods, such in the first two years of life, during preschool, and during preadolescence. This thesis also aimed to summarize the work done in environmental epidemiology on neuropsychological development in a novel conceptual framework. Methods This thesis is based on the data of the INMA (Infancia y Medio Ambiente) Project. The main objective of this project is to evaluate the impact of environmental exposures in children’s health in 7 population-based birth cohorts in different regions of Spain. The neuropsychological development of approximate total of 2,650 children was assessed at different time-periods following the same protocols. Results (1) Maternal cognitive capacities were positively related with child cognitive development early in life in more disadvantaged occupational social classes. (2) The levels of child cortisol were not related to child neuropsychological development during the second year of life. (3) Higher levels of long-chain polyunsaturated fatty acids in colostrum due to prolonged periods of breastfeeding improved early neuropsychological development of children, in particular in those children exposed to maternal smoking during pregnancy. (4) Prenatal exposure to PCBs (specially for PCB congener 153) impacted negatively on psychomotor development during the second year in life and on general neuropsychological development at the age of 4 years. (5) Postnatal exposure to organochlorine compounds was associated with a delay in reaction time (speed processing) during the preadolescent period. (6) The conceptual framework proposed will improve the quality of research in this area. Conclusions Social and cultural determinants such as maternal intelligence, educational level or occupational social class, are configuring the proximal environment in which a child develops and determine their neuropsychological development. Current levels of some organochlorine compounds, particularly polychlorinated byphenils, measured in blood samples (from umbilical cord, mothers, or children) are impairing on neuropsychological development in the general population. / Introducció El desenvolupament neuropsicològic infantil és un procés guiat genèticament, el qual és contínuament influenciat per factors socials i ambientals. L’objectiu d’aquesta tesis fou l’estudi dels principals determinants socio-ambientals del desenvolupament neuropsicològic infantil en diferents períodes de temps. Aquesta tesis també té l’objectiu de resumir en un marc conceptual els diferents components del desenvolupament neuropsicològic pel seu ús en estudis d’epidemiologia ambiental. Mètodes Aquesta tesis està basada en dades del projecte INMA (Infancia y Medio Ambiente). El principal objectiu d’aquest projecte és avaluar l’impacte de les exposicions ambientals en la salud infantil en 7 cohorts de població establides en diferents regions d’Espanya. Dintre del marc d’aquest projecte, s’ha avaluat el desenvolupament neuropsicològic d’aproximadament 2.650 nens en diferents moments, seguint els mateixos protocols. Resultats (1) Les capacitats cognitives maternes estan positivament relacionades amb el desenvolupament cognitiu infantil en les primeres etapes, en les classes socials ocupacionals menys afavorides. (2) Els nivells de cortisol infantil no mostren associació amb el desenvolupament neuropsicològic durant el segon any de vida. (3) Nivells elevats d’àcids grassos poliinsaturats de cadena llarga en conjunció amb períodes prolongats de lactancia materna afavoreixen el desenvolupament neuropsicològic a les primeres etapes, especialment en aquells nens de mares fumadores durant l’embaràs. (4) L’exposició prenatal a PCBs (espcialment, al congener 153) impacta negativament en el desenvolupament psicomotor infantil durant el segon any de vida i en el desenvolupament neuropsicològic general als 4 anys d’edat. (5) L’exposició postnatal a compostos organocloroats està associada a una capacitat de reacció (velocitat de processament) més alentida en etapes preadolescents. (6) L’ús del marc conceptual propossat tesis afavorirà la qualitat de l’investigació en aquesta àrea. Conclussions Els determinants socials, com l’intel•ligència materna, el nivell educatiu o la classe social basada en l’ocupació, configuren l’entorn més proper del nen i determinen el seu desenvolupament neuropsicològic. Els nivells actuals de certs compostos organoclorats, especialment els bifenils policlorinats, mesurats en mostres de sang (de cordó umbilical, mares o nens) mostren efectes negatius sobre el desenvolupament neuropsicològic en la població general. / Introducción El desarrollo neuropsicológico infantil es un proceso guiado genéticamente, el cual está contínuamente influenciado por factores sociales y ambientales. El objetivo de esta tesis fue estudiar los principales determinantes socio-ambientales del desarrollo neuropsicológico infantil en diferentes periodos de tiempo. Esta tesis también tenía como objetivo resumir en un marco conceptual el trabajo hecho en epidemiología ambiental en el estudio del desarrollo neuropsicológico infantil. Métodos Esta tesis está basada en datos del proyecto INMA (Infancia y Medio Ambiente). El principal objetivo de esto proyecto es evaluar el impacto de las exposiciones ambientales en la salud infantil en 7 cohortes de población establecidas en diferentes regiones de España. El desarrollo neuropsicológico de aproximadamente 2.650 niños ha sido evaluado en diferentes momentos siguiendo los mismos protocolos. Resultados (1) Las capacidades cognitivas maternas están positivamente relacionadas con el desarrollo cognitivo infantil en edades tempranas en las clases sociales ocupacionales menos aventajadas. (2) Los niveles de cortisol en el niño no se asocian con el desarrollo neuropsicológico durante el segundo año de vida. (3) Niveles altos de ácidos grasos poliinsaturados de cadena larga debido a periodos largos de lactancia materna mejoraron el desarrollo neuropsicológico a edades tempranas, especialmente en esos niños cuyas madres fumaron durante el embarazo. (4) La exposición prenatal a PCBs (espcialmente para el congener 153) impacta negativamente en el desarrollo psicomotor durante el segundo año de vida y en desarrollo neuropsicológico general a la edad de 4 años. (5) La exposición postnatal a compuestos organoclorados está asociado con una peor capacidad de tiempo de reacción (velocidad de procesamiento) durante la preadolescencia. (6) El marco conceptual propuesto mejorará la calidad de la investigación en esta área. Conclusiones Los determinantes sociales tales como inteligencia maternal, nivel educativo o clase social basada en la ocupación, configuran el entorno más cercano en el cual el niño se desarrolla y determinan su desarrollo neuropsicológico. Los niveles actuales de ciertos compuestos organoclorados, especialmente los bifeniles policlorinados, medidos en sangre (de cordón umbilical, madre, o niño) tienen efectos negativos sobre el desarrollo neuropsicológico de la población general.

Neuropsychological impairment following cardiopulmonary bypass (CPB) remains a serious consequence of otherwise successful surgery. The incidence of neuropsychological decline is poorly understood due to varied measurement intervals, and perhaps more importantly the use of unreliable detection and classification methods. The reported incidence varies considerably, ranging anywhere from 30% to 90% of subjects. While the nature of this impairment has not been fully elucidated, recent evidence suggests that microembolism during surgery may be the principal causative agent of postoperative cerebral dysfunction. The work described in this thesis investigates one possible source of microembolism leading to postoperative decline, namely thromboembolism arising from excessive activation of the haemostatic mechanism. Crucial to the accurate detection of significant decline in individual patients, this work also focuses on the development and use of meaningful criteria to be used when describing change in neuropsychological performance measures. The strong haemostatic activation during CPB is controlled by heparin anticoagulation. The clinical performance of the Hepcon heparin-monitoring instrument was compared to the activated clotting time (ACT), which is used in most cardiac centres. An analysis of samples from 42 elective coronary artery bypass grafting (CABG) patients shows that the ACT does not detect the significant decline in heparin concentration seen upon connection to CPB, in comparison to the Hepcon. The Hepcon appears to be in satisfactory agreement with laboratory anti-Xa analysis of heparin concentration, with the mean difference for the Hepcon at -0.46 U/ml, and the limits of agreement +/- 1.12 U/ml. Further analysis shows that that for 95% of cases, the Hepcon will give values that are between 0.53 and 1.27 times the value for anti-Xa. The loss of relationship between ACT and heparin concentration was further investigated by converting ACT values to heparin concentration. The results provide data on the degree of prolongation in ACT times brought about by factors associated with CPB. A methodology is presented by which users can adjust for the loss of relationship between ACT and heparin. This work also demonstrates that under normal usage of the ACT, the user may obtain values up to 3 times appropriate for the plasma heparin concentration. The computer-administered neuropsychological testing tool (the MicroCog) was validated using 40 age-matched control subjects. Using a two-week interval, the summary score correlation coefficients ranged from .49 to .84, with all scores demonstrating significant practice effects. Also presented are retest normative data that may be used to determine significant change in a homogeneous sample using both reliable change and regression models of analysis. The performance of four different models of change analysis was then analysed using data from the clinical group. The regression technique of analysis was shown to be the most useful prediction model as it provides correction for both practice effects and regression toward the mean in each individual. A novel statistical rationale is presented for the choice of criteria in the identification of patients that may be defined as overall impaired when using a battery of test scores. When using one-tailed prediction models for decline, the binomial distribution of scores was shown to be a useful descriptive statistic providing an estimate of change due to chance. When applied to a suitable selection of scores that minimise shared variance, a value +/- 20% of test scores used was demonstrated to be a rational cut-off for an individual to be classified as impaired. Using this methodology, 32.7% of patients were identified as significantly deteriorated in neuropsychological test function immediately prior to discharge from hospital. Patient age was shown to be a significant predictor of neuropsychological decline following CPB. No significant relationship was identified between thrombin generation and neuropsychological change scores, however problems with patient recruitment and retention limited the statistical power of this study. An intriguing relationship with heparin concentration was noted that might warrant further investigation. This work highlights the complex nature of post-bypass neuropsychological dysfunction and the complexities in assessing decline. The regression-based model was shown to be highly useful in the analysis of data from a suitably validated neuropsychological testing tool. The argument that no suitable criterion exists for the identification of patients as overall impaired has been challenged with the development of a rational cut-off based on the likely distribution of change scores across a series. The work presented here confirms the need for standardised testing methods based on sound statistical criteria. This work also highlights the problems associated with current methods for monitoring anticoagulation therapy during bypass surgery. Methodology is presented that allows adjustment of ACT results to account for CPB-induced prolongation of clotting times. Current techniques for heparin monitoring overestimate heparin levels on bypass by up to threefold, which may predispose to subclinical coagulation and increased delivery of protamine.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

The absence of gold standard criteria for mild cognitive impairment (MCI) impedes the comparison of research findings and the development of primary and secondary prevention strategies addressing the possible conversion to dementia. The objective of Study 1 was to compare the predictive ability of different MCI models as markers for incipient dementia in a longitudinal population-based Canadian sample. The utility of well-documented MCI criteria using data from persons who underwent a clinical examination in the second wave of the Canadian Study of Health and Aging (CSHA) was examined. Demographic characteristics, average neuropsychological test performance, and prevalence and conversion rates were calculated for each classification. Receiver operating characteristic (ROC) analyses were employed to assess the predictive power of each cognitive classification. The highest prevalence and conversion rates were associated with case definitions of multiple-domain MCI. The only diagnostic criteria to significantly predict dementia five years later was the Cognitive Impairment, No Dementia (CIND) Type 2 case definition. It is estimated that more restrictive MCI case definitions fail to address the varying temporal increases in decline across different cognitive domains in the progression from normal cognitive functioning to dementia. Using data from the CSHA, the objective of Study 2 was to elucidate the clinical correlates that best differentiate between cognitive classifications. A machine learning algorithm was used to identify the symptoms that best discriminated between: 1) not cognitively impaired (NCI) and CIND; 2) CIND & demented; and 3) converting and non-converting CIND participants. Poor retrieval was consistently a significant predictor of greater cognitive impairment across all three questions. While interactions with other predictors were noted when differentiating CIND from NCI and demented from non-demented participants, retrieval was the sole predictor of conversion to dementia over five years. Importantly, the limited specificity and predictive values of the respective algorithms caution against their use as clinical markers of CIND, dementia, or conversion. Rather, it is recommended that the predictors serve as markers for ongoing monitoring and assessment. Overall, the results of both studies suggest that the architecture of pathological cognitive decline to dementia may not be captured by a single set of diagnostic criteria.