Amyloid PET imaging with [11C]PIB enabled detection of Aβ for the first time in vivo. However, [11C]PIB is a small molecule that binds only the insoluble Aβ plaque. Rather, the soluble Aβ aggregates are considered the cause of Alzheimer’s disease (AD). As such, a more sensitive and specific PET tracer is needed for tracking longitudinal AD pathology. Soluble Aβ aggregates likely interact with the metabotropic glutamate receptor 5 (mGluR5) to cause neurotoxic effects. However, with [11C]ABP688 PET we were unable to detect aberrant mGluR5 binding in AD mouse models, although we find elevated mGluR5 protein levels with immunoblotting. Antibodies are highly specific large molecules that can bind specifically to soluble Aβ aggregates, thus they can be a good marker for AD pathology. Unfortunately, due to their large size they cannot cross the blood-brain barrier (BBB). However, it is possible to shuttle antibodies into the brain by taking advantage of endogenous transporter systems on the BBB. By creating bispecific antibodies binding both to soluble Aβ aggregates and to the transferrin receptor (BBB target), we successfully transported the antibody into the brain and could visually detect soluble Aβ aggregates with PET. Recombinant expression further improved and optimized antibody design, creating smaller bispecific antibody-based constructs that had better pharmacokinetic properties allowing for earlier PET scanning (1 day instead of 3), and more sensitive signal. Lastly, using TCO-tetrazine click chemistry, we indirectly labeled our antibodies with fluorine-18, and could successfully perform PET already 11 h post-injection with a fluorine-18 labeled antibody.

Physical health can be measured in several ways both based on subjective experiences and with objective tools. However, mental health can only be measured through subjective experiences and sensations, which can be biased. Therefore, researchers adopted the notion of an objective tool to assess well-being as a complement to existing self-reported scales and suggested that heart rate variability (HRV) might be an indicator of well-being. Hence, this thesis investigates the relationship between subjective well-being (SWB) and HRV, particularly high frequency-HRV (HF-HRV). Three hypotheses, which included different forms of well-being, were developed to test the relationship. And the hypotheses were: Cognitive well-being correlates positively with HF-HRV. Positive affect correlates positively with HF-HRV, and negative affect correlates negatively with HF-HRV. A total of 19 healthy Swedish females aged from 20-35 participated and answered questionnaires measuring SWB. After they completed the SWB-scales, their heart rate was measured and then converted into HF-HRV data. The findings revealed no correlations between the cognitive SWB and HF-HRV, neither to affective SWB.

Med en ökande livslängd blir metoder för att förhindra åldersrelaterad kognitiv förlust allt viktigare. Hippocampusformationen som består av gyrus dentatus, subiculum, entorinalkortex och hippocampus, har en viktig roll när det kommer till bland annat minne, inlärning och beslutsfattande: Samtidigt som området är känsligt för åldrande har subregioner uppvisat hög plastisk kapacitet och kan påverkas positivt av bland annat kognitiv stimulans. Vidare har intresset för meditation ökat inom forskningsvärlden och utvecklingen av hjärnavbildningstekniker har möjliggjort för djupare förståelse över meditationens effekter på hjärnan. I denna litteraturstudie har det undersökts huruvida meditation kan ha inverkan på hippocampusformationen med avseende på volym och funktion. Detta har gjorts genom studier som använt hjärnavbildningstekniker, mer specifikt magnetresonanstomografi (fMRI), magnetencefalografi (MEG) och positronemissionstomografi (PET). Litteraturundersökningen visar att erfarna meditationsutövare har mer grå hjärnmassa och funktionell anslutning inom vissa hippocampusområden, framförallt hippocampus och subiculum. I aktuell studie diskuteras bland annat potentiella mekanismer och orsaker bakom resultaten, meditation som potentiell teknik gällande förebyggande av kognitiv förlust, utvecklingspotential gällande meditation för kliniskt värde samt problematik associerad till forskningen inom området. Resultatet indikerar positiva effekter av meditation på hippocampusformationen, något som kan göra meditation till en potentiell förebyggande åtgärd för att förhindra åldersrelaterad kognitiv förlust kopplad till hippocampusformationen. Samtidigt behövs mer forskning inom området och resultaten bör tolkas med försiktighet då det i nuläget bara finns ett begränsat antal studier inom området. / With increasing life expectancy, methods to prevent age-related cognitive loss are becoming increasingly important. Hippocampal formation, which consists of the dentate gyrus, subiculum, entorhinal cortex and hippocampus, plays an important role when it comes to, among other things, memory, learning and decision-making. At the same time as the area is sensitive to aging, subregions have shown high plastic capacity and can be positively affected by for example cognitive stimuli. Furthermore, interest in meditation has increased in the world of research and the development of brain imaging techniques has enabled a deeper understanding of the effects of meditation on the brain. This literature study investigated whether meditation may have an impact on hippocampal formation in terms of volume and function. This has been done through studies that have used brain imaging techniques, more specifically magnetic resonance imaging (fMRI), magnetic encephalography (MEG) and positron emission tomography (PET). The literature review shows that experienced meditation practitioners have more gray matter and functional connection in certain hippocampal areas, especially the hippocampus and subiculum. The current study has also discussed potential mechanisms and reasons behind the results, meditation as a potential technology regarding prevention of cognitive loss, development potential regarding meditation for clinical value and problems associated with research in the field. The results indicate positive effects of meditation on hippocampal formation, which may make meditation a potential preventive practice when it comes to age-related cognitive loss associated to hippocampal formation. At the same time, more research is needed in the area and the results should be interpreted with caution as there are currently few studies in the area.

The present work consists of a research of the process of memorizing a music score and performing it with its main goal being to understand which is the better and the most efficient process of learning and memorizing it. The piece that has been chosen for this project is Sonata n.1 op.120 in F minor for clarinet and piano by Johannes Brahms.The project is based on two methods and some strategies made by psychologists and musicians that suggest to do a theoretical analysis of the piece and afterwards, define some points (cues) that will help the musician to remember. The work consists in to apply these strategies in the practice sessions, in lessons with teachers and in concerts and observe if they have been successful. This paper concludes with the results of the practical part and with a discussion about them and about the experience to play the piece. / <p>Sounding part of the project:</p><p>Johannes Brahms - Sonata n.1 op. 120 in F minor for Clarinet and Piano</p><p></p><p>Clarinet: Clara Vilanova</p><p>Piano: Erik Lanninger</p><p></p><p>The concert took place on May 3rd, 2021 in Nathan Milstein Hall in the Royal College of Music in Stockholm</p>

The Swedish Red Cross (SRK) plays an important humanitarian role by selling donated clothes in order to collect more money to help people in need. An extended network of 251 second-hand stores is built nationwide, where donors leave their clothes and buyers can buy them at competitive prices. However, an amount of these clothes remain unsold and ends up being shipped to textile recycling centers. The organization plans to build some Regional Sorting Facilities, where a careful sorting will take place and the clothes will be stored, until they will be redistributed to other stores within thecountry.This project aims to find the optimal number and location of these facilities in a way that the transportation cost from stores to facilities is minimized. SRKs Logistics Department operationalizes this aim to the following objective: place a minimum number of facilities such that at least 50% of the stores or 50% of the produced revenues are reached in less than 90 minutes of driving time. Thus, modern GIS software is used in a Location-Allocation analysis to solve the p-median problem. The core of the methodology in this thesis is the well known Vertex Substitution heuristic algorithm (Teitz &amp; Bart).Empirical evaluations of seven (7) scenarios comprised of optimally placing an increasing number of facilities from one (1) to seven (7) reveal that five (5) facilities is sufficient to meet the operational objective with the minimal number of resources/facilities. The solutions for all scenarios are analyzed in terms of statistics (Key Performance Indicators) and are illustrated on maps.

Introduktion: Alzheimers sjukdom är en neurodegenerativ sjukdom som orsakas av ansamling av amyloid-β (Aβ) i hjärnan. Prevalensen av Alzheimers sjukdom ökar, och symtom inkluderar minnesförlust, ångest, depression, förvirring, nedsatt omdöme och desorientering. Ålder och genetiska varianter är två riskfaktorer för att utveckla Alzheimers sjukdom. Det finns två modeller som förklarar hur sjukdomen kan uppstå, 1) den amyloida hypotesen som beskriver hur deposition av Aβ leder till ökad aggregation av proteinet tau vilket orsakar celldöd och neurodegeneration, och 2) den kolinerga hypotesen vilken beskriver att Aβ-plack minskar produktionen av acetylkolin vilket leder minskad aktivitet i kolinerga nerver. Det är främst entorhinala cortex och hippocampus som drabbas. Diagnostisering görs genom medicinska och neurologiska undersökningar och genom standardiserade test/instrument. I dagläget kan symtom av Alzheimers sjukdom behandlas med acetylkolinesterasinhibitorer och memantin. Ett annat behandlingssätt är att använda monoklonala antikroppar som riktats mot Aβ för att minska belastningen av Aβ i hjärnan. För att bedöma effekt av sådana läkemedel används bedömningsmetoder baserade på kognitiva och funktionella tester.  Syfte: Syftet med detta arbete var att undersöka effektivitet och säkerhet av anti-Aβ antikroppar för behandling av Alzheimers sjukdom, vilket gjordes genom att analysera kognitiv förmåga, biomarkörer och biverkningar.  Metod: Detta arbete är en litteraturstudie som baserades på fem läkemedelsstudier vilka erhölls från databasen PubMed. Sökord som användes vid litteratursökning var ”aducanumab”, ”lecanemab”, ”donanemab”, ”crenezumab” och ”bapineuzumab”.  Resultat: Hög dos aducanumab i studien EMERGE och lecanemab visade statistiskt signifikant förändring på alla utfallsvariabler, och analys av biomarkörer visade minskad amyloid-belastning i hjärnan. Donanemab visade statistiskt signifikant skillnad på den primära utfallsvariabeln och på analys av biomarkörer, men resultat på sekundära utfallsvariabler var inte statistiskt signifikanta. Crenezumab visade endast statistiskt signifikant förändring på den primära utfallsvariabeln i CREAD2. Bapineuzumab visade ingen statistiskt signifikant skillnad på någon utfallsvariabel eller på förändringar i biomarkörer. De resultat som var statistiskt signifikanta indikerade minskad kognitiv försämring hos patienterna. ARIA var en vanlig biverkning hos alla läkemedel utom crenezumab, men förekomsten av ARIA var i de flesta fall mild till måttlig. Andra vanliga biverkningar inkluderade infusionsrelaterade reaktioner, huvudvärk och fall.  Slutsats: Baserat på resultaten från detta arbete dras slutsatsen att aducanumab, lecanemab och donanemab var de läkemedel med högst effektivitet. Framtiden ser mest lovande ut för aducanumab och lecanemab med anledning av positiva resultat på primära och sekundära utfallsvariabler och biomarkörer samt FDAs godkännande av läkemedlen i USA. Förekomsten av ARIA påverkar säkerheten av läkemedlen och därför behöver fler studier genomföras för att undersöka deras säkerhet ytterligare. / Background: Alzheimer’s disease is a neurodegenerative disease that is caused by accumulation of amyloid-β (Aβ) in the brain. The prevalence of Alzheimer’s disease is increasing, and symptoms of the disease include memory loss, anxiety, depression, confusion, impaired judgment and disorientation. Age and genetic variants are the two main risk factors for developing Alzheimer’s disease. There are two models which describe the development of the disease, 1) the amyloid hypothesis which describes how the deposition of Aβ leads to increased aggregation of the protein tau, which causes neuronal cell death and neurodegeneration, and 2) the cholinergic hypothesis which describes that Aβ plaques decrease the production of acetylcholine, this causes less activity in cholinergic neurons. The two areas in the brain which are mainly affected by neurodegeneration are the entorhinal cortex and the hippocampus. Diagnosing Alzheimer’s disease is done by medicinal and neurological assessments and by using standardized tests/instruments. Currently only symptomatic treatments for Alzheimer’s disease are available; acetylcholine esterase inhibitors and memantine. Another treatment method is using monoclonal antibodies against Aβ to decrease the Aβ load in the brain. To assess the effectiveness of these drugs assessment methods based on cognitive and functional tests can be used.  Aim: This study aimed to analyse the efficacy and safety of anti-Aβ antibodies as a treatment for Alzheimer’s disease, which was done by analysing cognitive ability, biomarkers and adverse events.  Method: This literature study was based on 5 clinical randomized controlled trials which were obtained from the PubMed database. Keywords that were used in the searches were “aducanumab”, “lecanemab”, “donanemab”, “crenezumab” and “bapineuzumab”.  Results: High-dose aducanumab in the study EMERGE and lecanemab showed statistically significant differences on all endpoints, and analysis of biomarkers showed a decrease in amyloid load in the brain. Donanemab showed statistically significant differences on the primary endpoint and analysis of biomarkers but results on secondary endpoints were not statistically significant. Crenezumab only showed statistically significant change on the primary endpoint in CREAD2. Bapineuzumab did not show statistically significant differences on any endpoint or on changes in levels of biomarkers. Statistically significant results on primary and secondary endpoints indicated decreased cognitive impairment among the patients. ARIA was a common adverse event in all drugs, with exception of crenezumab, but the occurrence of ARIA was in most cases mild to moderate. Other common adverse events were infusion-related reactions, headaches and falls.  Conclusion: With consideration of the results of this paper a conclusion can be drawn that aducanumab, lecanemab and donanemab have been shown to be effective on primary endpoints and analysis of biomarkers. The drugs that seem the most promising are aducanumab and lecanemab, mainly because they showed efficacy on both primary and secondary endpoints, and biomarkers and because of the FDA’s recent approval of both drugs in the US. The occurrence of ARIA is something that affects the safety of these drugs and because of this more studies are needed to further assess their safety.

Mitochondria are dynamic organelles that function in a complex interconnected network within the cell. Neurons are sensitive and highly energy demanding cells in the brain which require a functioning mitochondrial network that is able to provide ATP and modulate calcium. Mitochondrial networks have yet to be explored which gives rise to the need for specific and efficient molecular tools. In this project, I designed and produced adeno-associated virus vectors carrying a fluorescent reporter gene for imaging mitochondrial networks under human synapsin 1 promoter to target neurons specifically. The design of each vector was conducted with careful consideration of the different components in the plasmid design that are important for optimal expression, which resulted in two constructs; one self-complementary adeno-associated virus vector that marks the mitochondria and one single-stranded that marks mitochondria and the membrane of neurons.  The modularity of viral vectors allows the usage of different serotypes which adapt the vector to the cell type and the model. For this project I chose the serotypes 1 for neurons in vitro and PHP.eB which suits in vivo models since it has better permeability to the blood brain barrier. The production was conducted in human embryonic kidney cells using the triple-plasmid transfection method, followed by extraction and purification. The existence of viral particles was verified through transmission electron microscopy and the DNA titer of the vector through quantitative polymerase chain reaction. The produced adeno-associated virus vectors were delivered into young brain organoids which were not able to express the reporter gene, probably due to not fully developed neurons. The fluorescent protein expression targeting specifically mitochondria and the membrane was however verified in the human embryonic kidney cells during the packaging stages.

Obsessive compulsive disorder (OCD) is one of the most disabling psychiatric disorder. About 10% of patients with OCD do not respond to pharmacological treatment. However, deep brain stimulation (DBS) has advanced as an alternative treatment. In 2002, two patients who suffered from co-morbidity of Parkinson’s disease (PD) and OCD were treated with DBS for their PD, with DBS-electrodes placed in the subthalamic nucleus (STN). Surprisingly, not only PD symptoms but also OCD symptoms were improved. This was the first time that patients with OCD were treated with DBS in STN and it was found to markedly improve their symptoms. When performing DBS in patients with OCD, as well as for treating PD, several side-effectshave been observed. The side-effects can be both physical and psychological. In this project,the aim is to investigate the efficiency and side-effects of DBS in OCD, correlated with the position of the electrode in, or near, the STN. To address the aim, 10 published reports were analysed. It was found that all electrode positions reported resulted in great improvement of OCD symptoms. In fact, 88% of patients had significant improvement. There was no clear correlation between position of the electrode and number or type of side-effect. However, there was a trend that patients with the electrode placed in associative/limbic STN suffered from more side-effects. In conclusion, this project demonstrates that there might be a correlation between target for electrode stimulation and side-effects. It would be interesting analyse this closer, including additional electrode target areas, but also consider other possible explanations for the variety of side-effects caused by DBS for OCD.

During roughly forty years of a woman’s life-span, the fertile female human body prepares itself monthly for the possibility of pregnancy. Science has shown that the fluctuation of the sex steroids progesterone and estrogen have a crucial role in the female body's physiology, determining the menstrual cycle and its general phases. This biological dance of hormones governing the cycle influences a lot of physical, mental and cognitive aspects of life for a fertile ovulating woman. Although the question of whether these changes also affect women's cognitive performance is still unclear, some evidence has been gathered that could bring us closer to answers. Recent research findings show that this hormonal interplay might have a significant role in cognitive and psychological development - modulating brain activity, cognitive performance, higher cognition, emotional status, sensory processing, appetite and more. This thesis aims to uncover to what extent the menstrual cycle affects brain functions, neurobiology, mood, well-being and cognitive performance in menstruating cisgender women.

Meditation has been practiced around the world for thousands of years and has during the past decade become increasingly popular in the Western world. Meditation can be seen as a form of mental exercise and refers to a family of complex emotional and attentional regulatory practices that involves different attentional, cognitive monitoring and awareness processes. Clinical research on meditation has demonstrated that meditation seem to reduce stress, anxiety, and depression. Recent interest in how meditation affect the human brain and body have lead to an increase in research regarding the neural correlates of meditation, structural changes induced by meditation, and the potential attentional and emotional benefits mediated by meditation. This thesis investigates expert related changes in neural activity, brain structure, and attentional performance induced by focused attention meditation (FAM) and open monitoring meditation (OMM). The research on meditation and the brain is still in its infancy but despite this, there seem to be some converging evidence of meditation’s impact on the human brain and mind. The results from the included studies in this thesis indicates that expert meditators show greater activation in some meditation related brain areas, as well as less activation in other areas when compared to novice meditators. The results also suggest that long-term meditation practice induce some structural changes in the brain and that meditation seem to enhance the practitioners’ attentional control.