Bakgrund: Unified Parkinson’s Disease Rating Scale är ett bedömningsinstrument som är frekvent använt, både i Sverige och internationellt, inom vården för personer med Parkinsons sjukdom. Under 2001 granskades och reviderades instrumentet vilket resulterade i en ny version benämnt Movement Disorder Society Unified Disease Rating Scale. Del III av MDSUPDRS syftar till att undersöka motoriska symtom och anses viktiga i bland annat fysioterapeuters utredning och som utvärdering efter behandling. I dagsläget saknas en svensk validerad översättning av del III. Syfte: Syftet med detta arbete var att översätta del III av bedömningsinstrumentet MDSUPDRS från engelska till svenska och därefter undersöka innehållsvaliditet för den svenska versionen. Metod: Översättningen skedde genom forward translation, backward translation samt analys av innehållsvaliditet genom Content Validity Index (CVI). Översättningen undersöktes med hjälp av fem forskningspersoner, sakkunniga inom området. Validitet analyserades under två skattningsomgångar utifrån följande CVI-delar med tillhörande referensvärden: I-CVI (0,80), S-CVI/AVE (0,90) och S-CVI/UA (0,80). Resultat: Efter två omgångar skattade samtliga forskningspersoner 20 av 24 frågor som relevanta med ett I-CVI-värde på 1,0. Resterande fyra frågor uppnådde ett I-CVI-värde på 0,80. Värdena för S-CVI/AVE och S-CVI/UA var 0,97 respektive 0,83, vilket innebar att dessa översteg de uppsatta referensvärdena. Skalan kan därmed i sin helhet ses som valid, då samtliga CVI-värden uppnådde de uppsatta referensvärdena. Slutsats: Den översatta versionen kan i sin helhet betraktas som valid. / Background: The Unified Parkinson’s Disease Rating Scale is a frequently used assessment tool world wide in clinics in care of people with Parkinson’s disease. In 2001, the assessment tool were reviewed and revised, which was titled Movement Disorder Society Unified Parkinson’s Disease Rating Scale. Part III of MDS-UPDRS aims to investigate motor symptoms and is considered important in, among other things, physiotherapists' investigation, and as evaluation after treatment. Currently, a Swedish validated translation of Part III is lacking. Aim: The aim of this study is to translate part III of MDS-UPDRS from english to swedish, and then analyze content validity for the swedish version. Method: The translation was done with the use of forward translation, backward translation and the content validity was analyzed with Content Validity Index (CVI). The translation were analyzed in two rounds, with help by five individual proficient to the area. The content validity were set by following domains and reference values: I-CVI (0,80), S-CVI/AVE (0,90) and SCVI/UA (0,80). Results: After two rounds, 20 questions out of 24 reached an I-CVI of 1,0. The remaining four questions reached an I-CVI of 0,80. The values of S-CVI/AVE and S-CVI/UA were 0,97 and 0,83 which meant that it exceeded the set reference values. The integer scale can be considered valid based on the reference values on S-CVI/AVE and S-CVI/UA. Conclusion: The integer translated version of MDS-UPDRS part III can be considered valid.

La maladie de Parkinson (MP) se caractérise par une dégénérescence progressive et irréversible des neurones dopaminergiques de la substance noire induisant une perte de dopamine (DA) dans les structures cibles. Lorsque cette perte DA se situe entre 60 % et 80 %, les patients présentent des symptômes moteurs (rigidité, tremblement, akinésie) et non-moteurs très variés (dépression, anxiété, apathie). Ces derniers apparaissent avant et/ou en même temps que les symptômes moteurs. La dopathérapie permet de contrecarrer certains symptômes, mais tous ne sont pas sensibles à cette médication. Parallèlement à la dégénérescence DA, le système sérotoninergique (5-HT) serait aussi altéré de façon précoce dans la maladie. Cette dégénérescence est liée par l’expression de symptômes moteurs et non-moteurs. Néanmoins, aucun lien causal n’a été mis en évidence entre cette lésion 5-HT et la symptomatologie parkinsonienne. Ainsi, il était primordial de déterminer le rôle de la 5-HT dans 1) l’expression des troubles moteurs et non-moteurs 2) dans la réponse au traitement sérotoninergique et dopaminergique. Nous avons utilisé un nouveau modèle animal primate ayant une lésion 5-HT (via la MDMA) puis une lésion DA (via le MPTP). Ce modèle nous permet de mettre en évidence l’impact d’une lésion 5-HT précoce dans la symptomatologie. Des approches comportementales, pharmacologiques, d’imagerie et de neuroanatomie ont été utilisées. La lésion 5-HT a induit un trouble anxieux chez les animaux lésés à la MDMA, qui ne sont pas contrecarrer avec un traitement sérotoninergique (antidépresseur). Cette lésion a également induit une sévérité et une progression plus rapide des symptômes moteurs induits par la lésion DA / Parkinson’s disease (PD) is characterized by a progressive and irreversible degeneration of dopaminergic (DA) neurons localized in the substantia nigra, leading to a loss of dopamine within the target structures. When the loss of DA reaches 60 to 80 %, PD patients develop a wide range of motor (rigidity, tremor, akinesia fro example) and non-motor (depression, anxiety, apathy for example) symptoms. Dopatherapy allows the reduction of symptoms expression. But some motor and non-motor symptoms are not counteracted by those DA drugs. In addition to DA degeneration, patients present an early serotonergic (5-HT) lesion. This lesion is linked to the severity of some motor and non-motor symptoms. However, there is no causal link established between 5-HT lesion and parkinsonian symptoms. Therefore, it was essential to determine the role of 5-HT 1) in the expression of motor and non-motor symptoms 2) and in the response of DA and 5-HT treatments. For that, we used a new monkey model of PD, exhibiting a 5-HT lesion (with MDMA ‘”ecstasy”)) followed by a DA lesion (with MPTP). This model allowed us to evaluate the impact of an early 5-HT lesion on parkinsonian symptoms. We used different approaches: PET imaging, pharmacology, behavioral and neuroanatomy. The MDMA-driven early 5-HT lesion induced an anxious-like behavior on MDMA treatedmonkeys. This behavioral modification was not counteracted by 5-HT drugs (antidepressant). This MDMA lesion has also increased the severity and the progression of parkinsonian symptoms induced by DA lesion with MPTP

<p>The aim was to describe and explore the food-related work and eating habits of older community-dwelling women, with Parkinson’s disease, rheumatoid arthritis or stroke or without these diseases. The major focus is on health perceptions, eating habits and meal support. A theoretical framework based on cultural and health theories was adopted. A total of 91 women between 64 and 88 years were visited in their homes, a food survey was performed consisting of a 24h recall and an estimated three-day food diary was introduced. Seventy-two of the women also took part in qualitative interviews with an ethnographic approach. Approximately one week later, another 24h recall was carried out at a second visit, or for the non-disabled women by telephone. The analyses revealed that many women were influenced by the prevailing health message and tried to eat a healthy diet. It was also important to them to enjoy their preferred foods, but this gave some women a bad conscience, while others perceived their usual foods as wholesome to eat. Health promotion for older women needs to incorporate the women’s own cultural context, their perceptions of food-related health, and their wish to adhere to their usual habits. Women with disease, frailty and who had become alone reported simplified food-related work and poor eating habits. However, management of these duties was highly valued, and women strove to cook by themselves as long as possible when disability became a threat. This resulted in a trend towards less nourishing cooked meals for women with disabilities. Thus, many women with these diseases living at home need support with their meals. This has to be planned in collaboration with the woman and build on her cultural values. The help must be performed with respect for the woman’s sense of order, be given sufficient time, and acknowledge her self-determination.</p>

The aim was to describe and explore the food-related work and eating habits of older community-dwelling women, with Parkinson’s disease, rheumatoid arthritis or stroke or without these diseases. The major focus is on health perceptions, eating habits and meal support. A theoretical framework based on cultural and health theories was adopted. A total of 91 women between 64 and 88 years were visited in their homes, a food survey was performed consisting of a 24h recall and an estimated three-day food diary was introduced. Seventy-two of the women also took part in qualitative interviews with an ethnographic approach. Approximately one week later, another 24h recall was carried out at a second visit, or for the non-disabled women by telephone. The analyses revealed that many women were influenced by the prevailing health message and tried to eat a healthy diet. It was also important to them to enjoy their preferred foods, but this gave some women a bad conscience, while others perceived their usual foods as wholesome to eat. Health promotion for older women needs to incorporate the women’s own cultural context, their perceptions of food-related health, and their wish to adhere to their usual habits. Women with disease, frailty and who had become alone reported simplified food-related work and poor eating habits. However, management of these duties was highly valued, and women strove to cook by themselves as long as possible when disability became a threat. This resulted in a trend towards less nourishing cooked meals for women with disabilities. Thus, many women with these diseases living at home need support with their meals. This has to be planned in collaboration with the woman and build on her cultural values. The help must be performed with respect for the woman’s sense of order, be given sufficient time, and acknowledge her self-determination.

Hintergrund: Die Parkinson-Krankheit (PK) ist häufig durch Demenz und Depression gekennzeichnet, die den Krankheitsverlauf erschweren und das Risiko einer Pflegebedürftigkeit zusätzlich erhöhen können. Über die genauen Zusammenhänge zwischen PK und diesen Komplikationen liegen für Ambulanzpatienten jedoch bislang keine Zahlen vor. Patienten und Methode: Bundesweit wurden 1449 Patienten mit PK von 315 niedergelassenen Fachärzten untersucht. Neben dem neurologischen Zustand und der Pflegebedürftigkeit wurden auch demenzielle Syndrome nach DSM-IV-Kritierien sowie Depressionen mit der Montgomery-Asberg Depression Rating Scale (MADRS) dokumentiert. Ergebnisse: Insgesamt 18,3% der Patienten waren pflegebedürftig, hiervon hatten 51,9% und 43,2% die Pflegestufen I und II. Auch nach Kontrolle des PK-Schweregrads hatten Patienten mit Depression (OR=2,8, 95%-KI:1,8–4,3), Demenz (OR=2,7; 95%-KI:1,8–4,1) bzw. mit beiden Störungen (OR=3,9, 95%-KI:2,5–6,0) ein höheres Risiko für Pflegebedürftigkeit als Patienten ohne diese Störungen. Patienten ≥76 Jahre hatten ein 4fach höheres Risiko für eine Pflegestufe als Patienten ≤65 Jahre (OR=3,5, 95%-KI:2,3–5,5). Über die Altersgruppen hinweg nahm das Risiko, pflegebedürftig zu werden, bei depressiven Patienten am stärksten zu (von 11,9% auf 42,0%). Schlussfolgerung: Das Risiko für eine Pflegebedürftigkeit ist bei Demenz und Depression stark erhöht. Die Daten legen insbesondere für die Depression als Einzelkomplikation eine vergleichbar hohe Krankheitslast nahe wie für die Demenz. / Background: Parkinson’s disease (PD) is frequently accompanied by dementia or depression which can aggravate the clinical picture of the disease and increase the risk of care dependency (CD). Little is known about the associations between PD, these neuropsychiatric comorbidities and CD in outpatients. Patients and methods: A nationwide sample of outpatients (n=1,449) was examined by office-based neurologists (n=315) comprising the documentation of the general, neurological status and the degree of CD. The dementia status was clinically rated according to the established DSM-IV criteria. Depression was screened with the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Overall, 18.3% of all patients were care dependent. Even after adjustment for PD severity, patients with depression (OR=2.8; 95% CI 1.8–4.3), dementia (OR=2.7; 95% CI 1.8–4.1) or both (OR=3.9; 95% CI 2.5–60,0) were at higher risk for CD than patients without dementia or depression. Patients aged ≥76 years were fourfold more likely to be care dependent than patients aged ≤65 years (OR=3.5; 95% CI 2.3–5.5). Across all age groups, patients with depression featured the highest increments (from 11.9 to 42.0%). Conclusion: The risk for CD is substantially elevated in outpatients with PD when further neuropsychiatric symptoms are present. The data suggest that depression contributes equally to disability as does dementia.

Background: Parkinson’s disease (PD) is often accompanied by non-motor complications, such as dementia, depression, and psychotic symptoms, which worsen the prognosis and increase the personal and socioeconomic burden of disease. Prevalence estimates of these complications are quite variable and are lacking for the outpatient care sector. Methods: As part of a larger, nationwide, cross-sectional epidemiological study in n=315 neurological outpatient settings in Germany, this paper estimates the frequency of dementia and cognitive impairment in n=873 outpatients meeting the UK Brain Bank criteria for idiopathic PD. Assessments were based on a clinical interview and neuropsychological assessments, including the Hoehn & Yahr rating and Unified Parkinson’s Disease Rating Scale (UPDRS). Cognitive impairment was assessed by the Mini-Mental State Exam (MMSE), Clock Drawing Test (CDT) and the Parkinson Neuropsychometric Dementia Assessment (PANDA) and the clinician’s diagnosis of dementia was based on the diagnostic criteria of DSMIV. Results Using standardized cutoff scores, the prevalence of cognitive impairment in the study sample as measured by various methods was 17.5% by MMSE (≤ 24), 41.8% by CDT (≥ 3), 43.6% by PANDA (≤ 14), and 28.6% met the DSM-IV criteria for dementia. All estimates increased with age and PD severity. Gender was an inconsistent contributor while illness duration had no significant impact on cognition. Multiple regression analyses revealed PD severity to be the strongest predictor of dementia risk (OR=4.3; 95 % CI: 2.1–9.1), while neuropsychiatric syndromes had independent, although modest additional contributions (OR=2.5, 95% CI: 1.6–3.8). Conclusion: Estimates of cognitive impairment and dementia in PD patients are largely dependent on the diagnostic measure used. Using established clinical diagnostic standards for dementia the overall rate on routine outpatient neurological care is 28.6%, but using more sensitive neuropsychological measures, rates for cognitive impairment might be up to 2-fold higher. The MMSE revealed strikingly low sensitivity. Neuropsychiatric syndromes, in addition to PD severity and age, have an independent – although modest – additional contribution to patients’ risk for cognitive impairment and dementia.

Parkinson's Disease can be treated by a micro-electrode guided neurosurgery called a Pallidotomy or Deep Brain Stimulus. A new software program, called Onetrack, is being developed and incorporates a three dimensional virtual model of the brain, a advanced digital signal processor and a knowledge based system (KBS). This thesis discusses the design and development of this KBS. The purpose of the KBS is to assist the surgical team in identifying the different anatomical structures and neuronal cell types of the brain. Therefore, improving the efficiency of the procedure.

The pre-symptomatic stage of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) occurs several decades before the clinical onset. Changes in the lysosomal network, i.e. the autophagosomal, endosomal and lysosomal vesicular system, are among the first alterations observed. There are currently no treatments to slow or cure neurodegenerative diseases, and there is a great need for discovery of treatment targets in cellular pathways where pathology pre-dates the neuronal death. It is also crucial to be able to diagnose neurodegenerative diseases earlier, both to enable early intervention treatment and aid in selecting clinical trial populations before the patient has widespread pathology. This thesis aims at investigating the potential of lysosomal network proteins as biomarkers and therapeutic targets in neurodegenerative disease. A targeted search for lysosomal network proteins was performed in cerebrospinal fluid (CSF) from AD patients, and seven proteins: early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), lysozyme, microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were elevated. The levels of EEA1, LAMP-1, LAMP-2, LC3, lysozyme and Rab3 were also measured in CSF from parkinsonian syndrome patients: PD, clinically diagnosed 4-repeat tauopathy, pathologically confirmed corticobasal degeneration (CBD) and pathologically confirmed progressive supranuclear palsy (PSP) patients. LAMP-1 and LAMP-2 were decreased in PD. LC3 and lysozyme levels were increased in 4-repeat tauopathy patients. EEA1 was decreased and lysozyme increased in PSP, and LAMP-1, LAMP-2, LC3 and lysozyme were increased in CBD. The lysosomal network proteins had different CSF protein profiles in all the parkinsonian syndromes, as well as in AD. It should be emphasized that only a select few of the lysosomal network proteins were observed to be changed, rather than a general change in lysosomal network proteins, which implicates the involvement of these seven proteins in specific pathological processes. The most interesting candidates, LAMP-2 and lysozyme, were selected for further study for their involvement in the pathology of AD. Lysozyme was found to co-localise with Aβ plaques in AD patients and overexpression prolonged survival and improved the activity in a Drosophila model of AD. Lysozyme was found to alter the aggregation pathway of Aβ1-42, to counteract the formation of toxic Aβ species and to protect from Aβ1-42 induced cell toxicity. Aβ1-42 in turn was found to increase the expression of lysozyme in both neuronal and glial cells. These data suggest that lysozyme levels rise in AD as a compensatory response which is protective against Aβ associated toxicity. LAMP-2 mRNA and protein were found increased in brain areas relevant for AD pathology and various cellular models showed complex involvement of LAMP-2 in Aβ related pathology, with extensive crosstalk between LAMP-2 and Aβ. Exposure to oligomeric Aβ1-42 caused an upregulation of LAMP-2 and in turn, overexpression of LAMP-2 caused a reduction in secreted levels of Aβ1-42, as well as changing the generation pattern of Aβ and affecting clearance and secretion of Aβ1-42. These data indicate that the increased levels of LAMP-2 in AD could be an attempt to regulate Aβ generation and secretion. In summary, this thesis reports that utilising lysosomal network proteins as biomarkers and novel therapeutic targets for neurodegenerative diseases holds great promise.

No description available.

Bakgrund: Deep Brain Stimulation (DBS) i nucleus subthalamicus (STN) och i kaudala zona incerta (cZi) har visat positiva effekter på motoriska symtom (rörelseförmåga och balans) vid Parkinsons sjukdom. Efter DBS har dock negativa taleffekter noterats, inklusive nedsatt artikulatorisk precision och stabilitet. Nedsatt artikulatorisk precisionoch stabilitet påverkar klusilproduktionen mest vilket kan resultera i att klusilexplosionen uteblir eller att multipla explosioner uppstår. Mål: Att undersöka artikulatorisk precision och stabilitet vid klusilexplosionen efter DBS i STN respektive cZi. Metod: I studien deltog 19 patienter varav 9 deltagare stimulerats i STN och 10 deltagare i cZi. Talinspelningar gjordes innan operation och ett år efter operation med DBSstimulering på och av. Klusilerna i talmaterialet delades in i tre kategorier, de med en klusilexplosion, de med två eller flera klusilexplosioner samt de utan klusilexplosion. Hypotesprövning gjordes gällande fördelningen av klusiler med multipla explosioner samt klusiler utan explosion mellan och inom patientgrupperna samt inom respektive klusil. Resultat: Multipla explosioner ökade hos cZi-patienterna och minskade hos STNpatienterna. Klusiler som saknade explosion ökade hos STN-patienterna medan de minskade hos cZi-patienterna. För båda patientgrupperna ökade multipla explosioner och klusiler utan explosion då stimuleringen var på jämfört med av. Skillnaderna mellan och inom grupperna var inte signifikanta. Slutsats: Artikulatorisk precision och stabilitet påverkades efter DBS i form av bristande stabilitet, för kort slutningsrörelse och felaktig koordination av slutningsrörelsen. Detta resulterade i multipla explosioner och uteblivna explosioner med olika effekter för elektrodlokalisationerna. / Background: Deep Brain Stimulation (DBS) in Subthalamicus Nucleus (STN) and Caudala zona incerta (cZi) have shown positive effects on motor symptoms in Parkinson‘s disease. Negative effects on speech after DBS has been noted including reduced articulatory precision. Reduced articulatory precision and stability affects the production of stop consonants and as a result, loss of burst or multiple burst can occur. Aim: To investigate articulatory precision and stability regarding the burst in stop consonants after DBS of STN or cZi. Method: The study included 19 patients with 9 patients stimulated in STN and 10 patientsin cZi. Speech recordings were made before surgery and one year after with stimulation ON and OFF. The stop consonants were divided into three categories, those with one burst, those with two or more bursts (multiple burst) and those with loss of burst. Hypothesis testing was done on the categorization of the stop consonants in and between the groups and between the stop consonants types. Results: Multiple burst increased in the cZi group and decreased in the STN group. Stop consonants with loss of burst increased in the STN group but decreased in the cZi group. For both groups multiple burst and stop consonants with loss of burst increased with stimulation on. The differences between and within the groups were not significant. Conclusion: Articulatory precision and stability were affected by DBS with decreased stability, shortened occlusion and incorrect coordination. As a result multiple burst and loss of burst occurred in both groups. / Speech, voice and swallowing outcomes after deep brain stimulation of the zona incerta and the pedunculopontine nucleus in Parkinson’s disease: Comparsion with stimulation of the subthalamic nucleus