Geneettisten ja ympäristötekijöiden merkitys toiminnanvajausten kehittymisessä - The Finnish Twin Study on Aging (FITSA)

Summary: Genetic and environmental factors in the disablement process. The Finnish Twin Study on Aging (FITSA)

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.

Genetically Determined Hypometabolism in Alzheimer’s Disease and Midlife Risk Factors for Cognitive Impairment

The role of genetic factors in the pathogenesis of Alzheimer’s disease (AD) is not completely understood. In order to improve this understanding, the cerebral glucose metabolism of seven monozygotic and nine dizygotic twin pairs discordant for AD was compared to that of 13 unrelated controls using positron emission tomography (PET). Traditional region of interest analysis revealed no differences between the non-demented dizygotic co-twins and controls. In contrast, in voxel-level and automated region of interest analyses, the non-demented monozygotic co-twins displayed a lower metabolic rate in temporal and parietal cortices as well as in subcortical grey matter structures when compared to controls. Again, no reductions were seen in the non-demented dizygotic co-twins. The reductions seen in the non-demented monozygotic co-twins may indicate a higher genetically mediated risk of AD or genetically mediated hypometabolism possibly rendering them more vulnerable to AD pathogenesis. With no disease modifying treatment available for AD, prevention of dementia is of the utmost importance. A total of 2 165 at least 65 years old twins of the Finnish Twin Cohort with questionnaire data from 1981 participated in a validated telephone interview assessing cognitive function between 1999 and 2007. Those subjects reporting heavy alcohol drinking in 1981 had an elevated cognitive impairment risk over 20 years later compared to light drinkers. In addition, binge drinking was associated with an increased risk even when total alcohol consumption was controlled for, suggesting that binge drinking is an independent risk factor for cognitive impairment. When compared to light drinkers, also non-drinkers had an increased risk of cognitive impairment. Midlife hypertension, obesity and low leisure time physical activity but not hypercholesterolemia were significant risk factors for cognitive impairment. The accumulation of risk factors increased cognitive impairment risk in an additive manner. A previously postulated dementia risk score based on midlife demographic and cardiovascular factors was validated. The risk score was found to well predict cognitive impairment risk, and cognitive impairment risk increased significantly as the score became higher. However, the risk score is not accurate enough for use in the clinic without further testing.

Ariel red "hunter twin" 500

kuv., 14 x 21 cm

New methods for controlling twin configurations and characterizing twin boundaries in 5M Ni-Mn-Ga for the development of applications

Traditional methods for studying the magnetic shape memory (MSM) alloys Ni-Mn-Ga include subjecting the entire sample to a uniform magnetic field or completely actuating the sample mechanically. These methods have produced significant results in characterizing the MSM effect, the properties of Ni-Mn-Ga and have pioneered the development of applications from this material. Twin boundaries and their configuration within a Ni-Mn-Ga sample are a key component in the magnetic shape memory effect. Applications that are developed require an understanding of twin boundary characteristics and, more importantly, the ability to predictably control them. Twins have such a critical role that the twinning stress of a Ni-Mn-Ga crystal is the defining characteristic that indicates its quality and significant research has been conducted to minimize this property. This dissertation reports a decrease in the twinning stress, predictably controlling the twin configuration and characterizing the dynamics of twin boundaries. A reduction of the twinning stress is demonstrated by the discovery of Type II twins within Ni-Mn-Ga which have as little as 10% of the twinning stress of traditional Type I twins. Furthermore, new methods of actuating a Ni-Mn-Ga element using localized unidirectional or bidirectional magnetic fields were developed that can predictably control the twin configuration in a localized area of a Ni-Mn-Ga element. This method of controlling the local twin configuration was used in the characterization of twin boundary dynamics. Using a localized magnetic pulse, the velocity and acceleration of a single twin boundary were measured to be 82.5 m/s and 2.9 × 107 m/s2, and the time needed for the twin boundary to nucleate and begin moving was less than 2.8 μs. Using a bidirectional magnetic field from a diametrically magnetized cylindrical magnet, a highly reproducible and controllable local twin configuration was created in a Ni-Mn-Ga element which is the fundamental pumping mechanism in the MSM micropump that has been co-invented and extensively characterized by the author.

Kulttuurierot kaksoiskaupunkiyhteistyössä Case: Imatra-Svetogorsk

The primary target of this study is to examine what kind of cultural differences have been noticed in co-operation concerning twin-city of Finnish town Imatra and Russian town Svetogorsk. The secondary purpose of the study is to analyse influences of cultural differences on leadership in this twin-city project and it's realizing. The case study has been carried out by qualitative research method. The research material has been gathered mainly by interviews. The results of the study show that cultural differences in twin-city co-operation are most clearly associated with the culture of the administration, attitude towards relations, communication style and the meaning of planning and time. The results also show that it has been realized both in Imatra and in Svetogorsk, that culture is a significant factor when people work together. Although its influence on leadership has not been analysed completely. The activities are mostly guided by common goals.

Tandem-GMA Welding of Low Alloy Structural Steel

The Tandem-GMAW method is the latest development as the consequences of improvements in the welding methods. The twin-wire and then the Tandem-method with the separate power sources has got a remarkable place in the welding of many types of materials with different joint types. The biggest advantage of Tandem welding method is the flexibility of choosing both the electrodes of different types from each other according to the type of the parent material. This is possible because of the feasibility of setting the separate welding parameters for both the wires. In this thesis work the effect of the variation in three parameters on the weld bead in Tandem-GMA welding method is studied. Theses three parameters are the wire feed rate in the slave wire, the wire feed rate in the master wire and the voltage difference in both the wires. The results are then compared to study the behaviour of the weld bead with the change in these parameters.

A Diagnostic view of the Genetics of CASADIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL, OMIM #125310) is an inherited vascular disease. The main symptoms include migraineous headache, recurrent strokes and progressive cognitive impairment. CADASIL is caused by mutations in the NOTCH3 gene which result in degeneration of vascular smooth muscle cells, arteriolar stenosis and impaired cerebral blood flow. The aims of this study were assessment of the genetic background of Finnish and Swedish CADASIL patients, analysis of genetic and environmental factors that may influence the phenotype, and identification of the optimal diagnostic strategy. The majority of Finnish CADASIL patients carry the p.Arg133Cys mutation. Haplotype analysis of 18 families revealed a region of linkage disequilibrium around the NOTCH3 locus, which is evidence for a founder effect and a common ancestral mutation. Despite the same mutational background, the clinical course of CADASIL is highly variable between and even within families. The association of several genetic factors with the phenotypic variation was investigated in 120 CADASIL patients. Apolipoprotein E allele 4 was associated with earlier occurrence of strokes, especially in younger patients. Study of a pair of monozygotic twins with CADASIL revealed environmental factors which may influence the phenotype, i.e. smoking, statin medication and physical activity. Knowledge of these factors is useful, since life-style choices may influence the disease progression. The clinical CADASIL diagnosis can be confirmed by detection of either the NOTCH3 mutation or granular osmiophilic material by electron microscopy in skin biopsy, although the sensitivity estimates have been contradictory. Comparison of these two methods in a group of 131 diagnostic cases from Finland, Sweden and France demonstrated that both methods are highly sensitive and reliable.

Kehittyneiden hitsausprosessien soveltuvuus alumiinin ja hiiliterästen hitsaukseen

Diplomityössä tutkitaan hitsausprosessien kehitystä. Työn kirjallisen osan alku kuvaa hitsauksen nykypäivää ja tulevaisuutta sekä millainen on hitsaava Suomi. Kehittyneiden hitsausprosessien tarkastelu on jaettu hiiliterästen ja alumiinien hitsausprosesseihin. Hiiliteräksien hitsauksen osalta työssä esitellään kitkahitsaus pyörivällä työkalulla, muunnettu lyhytkaarihitsaus, laserhitsaus, laser-hybridihitsaus ja kapearailohitsaus. Alumiinien hitsauksen osalta työssä esitellään laserhitsaus, muunnettu lyhytkaarihitsaus, kitkahitsaus pyörivällä työkalulla ja vaihtovirta MIG hitsaus. Diplomityön käytännönosuudessa todennettiin hitsausprosessien kehitys. Ensimmäisissä hitsauskokeissa hitsattiin merialumiinia eri kaarityypeillä. Vertailua tehdään pulssihitsauksen, lankapulssihitsauksen sekä CMT-kaarihitsauksen välillä. Koehitsaukset osoittavat CMT-hitsauksen tuottavan MIG-pulssihitsausta pienemmät hitsausmuodonmuutokset. CMT-hitsauksessa alumiinin oksidikerros aiheuttaa MIGpulssihitsausta vähemmän ongelmia, sillä kaari syttyy varmemmin suurillakin hitsausnopeuksilla, eikä hitsiin synny huokosia. Hitsausnopeudella 40 cm/min lankapulssihitsauksella ja MIG-pulssihitsauksella päittäisliitoksena hitsattujen vesileikattujen alumiinikappaleiden hitseihin ei syntynyt huokosia. Kokeen perusteella voidaan todeta, ettei oksidikerroksella ollut vaikutusta hitsin onnistumiseen. Hitsauskokeiden toinen osio tutkii hiilimangaaniteräksisen T-palkin kuitulaserhitsausta. Viiden kilowatin laserteholla hitsattiin onnistuneesti viisi metriä pitkiä T-palkkeja hitsausnopeudella 2 m/min. Takymetrimittauksella ja Tritop 3D-koordinaattimittauksella todennettiin laserhitsatun T-palkin hitsausmuodonmuutosten olevan huomattavasti Twin-jauhekaarihitsauksella hitsattua T-palkkia pienemmät.

Christina Rossetti's "Goblin market" : Milton revised or revived?

The present study examines Christina Rossetti's (1830-94) best-known poem "Goblin Market" (1859) as a response to John Milton's (1608-74) Paradise Lost (1667) and Paradise Regained (1674). Rossetti's poem relates to Milton's twin epics with a surprising degree of complexity, something that the thesis demonstrates through a large number of hitherto unexplored textual parallels. In its recontextualisation of Rossetti's poetry, this study balances interpretative strategies evolved by feminism with more historicist readings. SinceGilbert and Gubar's landmark feminist work of 1979, it has become something of a critical commonplace that Milton was a figure of patriarchal oppression whom women writers have challenged through revision. As a consequence, intertextual Rossetti studies have tended to emphasise such a revisionist element in her achievement. But if we place "Goblin Market" within the larger context of Rossetti's thoughts on religion and poetry throughout her writing, and if we de-emphasise the dichotomy between Rossetti and her male precursor, alternative patterns of reading begin to emerge. This thesis argues that Rossetti's aim was not only to revise Milton but also to revive him. It develops this point in several ways: first, by introducing the subject and theoretically arguing that literary allusiveness is not necessarily a matter of oedipal or feminist envy only (Chapter One); second, by determining the nature and extent of Rossetti's Miltonic allusions in terms of theme, imagery and language (Chapter Two);and third, by examining their function in terms of argument (Chapters Three andFour). I n an age of increasing religious doubt, Rossetti's poetry provided a subtle challenge not so much to Milton as to the emerging scepticism and aestheticism in Victorian society and its art-world, and not least to the secular tendencies of the second generation of Pre-Raphaelites, including Dante Gabriel Rossetti. Christina Rossetti was ahead of her time (and perhaps ours) in seeing the feminist potential in both John Milton and the Christian message. In the soul's relation to Christ, gender does not matter. What matters is the individual's quest for salvation, a quest in which poetry is a sacramental act, with a transformative, unifying function. Rossetti's poems both depict and constitute such a quest for union with God, on the assumption that God's word offers a pathway that is open to men as well as women.

Cargo Traffic on the Helsinki-Tallinn Route

The twin-city model has found to increase economical activity and well-being. The similar economical, social and cultural background of Finland and Estonia as well as the EU integration give good preconditions to create a twin-city of Helsinki and Tallinn. The relatively long distance between Helsinki and Tallinn is challenging. Therefore, good transport infrastructure and functioning connections are required to form a twin-city of Helsinki and Tallinn. The connections between these cities can be considered also in broader perspective than only from the viewpoint of the twin-city concept. New markets areas have been emerged in Europe due to collapse of planned economy and integration of Europe. Also the transport routes to the markets are changing. The Hel-sinki-Tallinn sea route can be considered as a fast route to the new markets in the Cen-tral and Eastern Europe. The Helsinki-Tallinn sea route is also a potential route to the Western European markets. This study provides an analysis of transport and cargo flows between Finland and Esto-nia for regional and local planners. The main purpose of the study is to clarify the pre-sent situation of the seaborne cargo flows on the Helsinki-Tallinn route and how the cargo flows will develop in the future. The study focuses on the following thematic enti-ties: the Finnish and Estonian seaborne transport system and cargo flows, the structure and volume of the cargo flows on the Helsinki-Tallinn route, the hinterland cargo flows on the Helsinki-Tallinn route and the transport methods used on the Helsinki-Tallinn route. The study was carried out as a desk research, a statistical analysis and an inter-view study during the spring–autumn 2011. The study reveals that during the period 2002–2010 the volume of the seaborne cargo traffic between Finland and Estonia has increased significantly while the trend of the trade volume between Finland and Estonia has remained nearly constant. This indicates that the route via Estonia is increasingly used in the Finnish foreign trade. Because the ports of Helsinki and Tallinn are the main ports in the cargo traffic between Finland and Estonia, the role of the Helsinki-Tallinn route as a sea leg in the hinterland connections of Finland has increased. The growth of the cargo volume on the Helsinki-Tallinn route was estimated to continue on the annual level of 10 % during the next couple of years. In the long run the growth of the cargo volumes depends on the economical and indus-trial development of the former Eastern European countries. If the IMO’s sulphur regu-lations will come in force, the Helsinki-Tallinn route will become one of the main routes also to the Western European markets, besides of the route via Sweden. The study also shows that the fast and reliable connections year round on the Helsinki-Tallinn route have made it possible for service and logistics companies to reconsider their logistics strategies in a new way in the both side of the Gulf of Finland. Anyway, the ropax concept is seen as the only economical profitable solution on the Helsinki-Tallinn route because cargo and passenger traffic are supporting each other. The trucks (vehicle combinations) will remain the main mode of transport on the Helsinki-Tallinn route because general cargo is the main commodity on the route. IMO’s sulphur regula-tions and the changes in the structure of the Finnish industry may create prerequisites for rail road transport in the hinterland connections of Finland. The twin-city model has found to increase economical activity and well-being. The similar economical, social and cultural background of Finland and Estonia as well as the EU integration give good preconditions to create a twin-city of Helsinki and Tallinn. The relatively long distance between Helsinki and Tallinn is challenging. Therefore, good transport infrastructure and functioning connections are required to form a twin-city of Helsinki and Tallinn. The connections between these cities can be considered also in broader perspective than only from the viewpoint of the twin-city concept. New markets areas have been emerged in Europe due to collapse of planned economy and integration of Europe. Also the transport routes to the markets are changing. The Hel-sinki-Tallinn sea route can be considered as a fast route to the new markets in the Cen-tral and Eastern Europe. The Helsinki-Tallinn sea route is also a potential route to the Western European markets. This study provides an analysis of transport and cargo flows between Finland and Esto-nia for regional and local planners. The main purpose of the study is to clarify the pre-sent situation of the seaborne cargo flows on the Helsinki-Tallinn route and how the cargo flows will develop in the future. The study focuses on the following thematic enti-ties: the Finnish and Estonian seaborne transport system and cargo flows, the structure and volume of the cargo flows on the Helsinki-Tallinn route, the hinterland cargo flows on the Helsinki-Tallinn route and the transport methods used on the Helsinki-Tallinn route. The study was carried out as a desk research, a statistical analysis and an inter-view study during the spring–autumn 2011. The study reveals that during the period 2002–2010 the volume of the seaborne cargo traffic between Finland and Estonia has increased significantly while the trend of the trade volume between Finland and Estonia has remained nearly constant. This indicates that the route via Estonia is increasingly used in the Finnish foreign trade. Because the ports of Helsinki and Tallinn are the main ports in the cargo traffic between Finland and Estonia, the role of the Helsinki-Tallinn route as a sea leg in the hinterland connections of Finland has increased. The growth of the cargo volume on the Helsinki-Tallinn route was estimated to continue on the annual level of 10 % during the next couple of years. In the long run the growth of the cargo volumes depends on the economical and indus-trial development of the former Eastern European countries. If the IMO’s sulphur regu-lations will come in force, the Helsinki-Tallinn route will become one of the main routes also to the Western European markets, besides of the route via Sweden. The study also shows that the fast and reliable connections year round on the Helsinki-Tallinn route have made it possible for service and logistics companies to reconsider their logistics strategies in a new way in the both side of the Gulf of Finland. Anyway, the ropax concept is seen as the only economical profitable solution on the Helsinki-Tallinn route because cargo and passenger traffic are supporting each other. The trucks (vehicle combinations) will remain the main mode of transport on the Helsinki-Tallinn route because general cargo is the main commodity on the route. IMO’s sulphur regula-tions and the changes in the structure of the Finnish industry may create prerequisites for rail road transport in the hinterland connections of Finland.

Welding development of crane main girder

Konecranes Corporation manufactures huge steel structures in 16 factories worldwide, in which the environment and quality varies. The company has a desire to achieve the same weld quality in each factory, regardless of the manufacturing place. The main subject of this master’s thesis was to develop the present box girder crane welding process, submerged arc welding and especially the fillet welding. Throughput time and manufacturing costs can be decreased by welding the full penetration fillet weld without a bevel, changing present groove types for more appropriate ones and by achieving the desired weld quality on the first time. Welding experiments of longitudinal fillet welding were made according to the present challenges, which the manufacturing process is facing. In longitudinal fillet welding tests the main focus was to achieve full penetration fillet weld for 6, 8 and 10 millimeters thick web plates with single and twin wire submerged arc welding. Full penetration was achieved with all the material thicknesses, both with single and twin wire submerged arc welding processes. The main problem concerning the weld was undercutting and shape of the weld bead. The question about insufficiency of presently used power sources with twin wire was risen up during testing, due to the thicknesses that require high welding current. Bigger power source is required when box girders are welded nonstop, if twin wire is used. For single wire process the penetration was achieved with significantly less amperage than with twin wire.

Solar Twins and Solar Analogues in Galactic Surveys.

The Sun is a crucial benchmark for how we see the universe. Especially when it comes to the visible range of the spectrum, stars are commonly compared to the Sun, as it is the most thoroughly studied star. In this work I have focussed on two aspects of the Sun and how it is used in modern astronomy. Firstly, I try to answer the question on how similar to the Sun another star can be. Given the limits of observations, we call a solar twin a star that has the same observed parameters as the Sun within its errors. These stars can be used as stand-in suns when doing observations, as normal night-time telescopes are not built to be pointed at the Sun. There have been many searches for these twins and every one of them provided not only information on how close to the Sun another star can be, but also helped us to understand the Sun itself. In my work I have selected _ 300 stars that are both photometrically and spectroscopically close to the Sun and found 22 solar twins, of which 17 were previously unknown and can therefore help the emerging picture on solar twins. In my second research project I have used my full sample of 300 solar analogue stars to check the temperature and metallicity scale of stellar catalogue calibrations. My photometric sample was originally drawn from the Geneva-Copenhagen-Survey (Nordström et al. 2004; Holmberg et al. 2007, 2009) for which two alternative calibrations exist, i.e. GCS-III (Holmberg et al. 2009) and C11 (Casagrande et al. 2011). I used very high resolution spectra of solar analogues, and a new approach to test the two calibrations. I found a zero–point shift of order of +75 K and +0.10 dex in effective temperature and metallicity, respectively, in the GCS-III and therefore favour the C11 calibration, which found similar offsets. I then performed a spectroscopic analysis of the stars to derive effective temperatures and metallicities, and tested that they are well centred around the solar values.

Kylmälaitekoneikon runkorakenteen kehittäminen

Kylmälaitekoneikot ovat kylmäkomponentteja sisältäviä rakenteita, joiden avulla toteutetaan suurten tilojen, kuten elintarvikemyymälöiden sisäilman jäähdytys. Lisäksi koneikkojen avulla jäähdytetään matalampiin lämpötiloihin pienempiä kylmähuoneita. Osa koneikoista ottaa talteen kylmäprosessissa syntyvän lämmön, jota hyödynnetään tilojen lämmityksessä. Tämän diplomityön tavoitteena oli suunnitella ja mitoittaa kahdeksalle eri kylmälaitekoneikolle entistä kustannustehokkaammat runkorakenteet, jotka ovat niin kestäviä, että koneikkoja on mahdollista pinota tilan säästämiseksi kolme päällekkäin. Lisäksi runkorakenteilta vaadittiin helppoa kuljetettavuutta, hyviä kiinnitysominaisuuksia ja korroosionkestävyyttä. Aluksi työssä selvitettiin runkorakenteisiin kohdistuvat vaatimukset, jonka jälkeen materiaalin valinta tehtiin materiaaliin kohdistuvien vaatimusten perusteella. Rakenteiden palkit mitoitettiin tarvittavan taivutusvastuksen ja kiepahduksen mukaan. Pilarit puolestaan mitoitettiin nurjahduksen ja kaksiaksiaalisen taivutustilan perusteella. Tämän jälkeen mitoitettiin eri sauvojen väliset hitsi- ja ruuviliitokset siten, että rakenne hajoaa ylikuormitustilanteessa mahdollisimman turvallisesti. Työssä tehdyt laskelmat varmennettiin elementtimenetelmän avulla ja lopullisille rakenteille tehtiin elementtimenetelmällä vielä ominaistaajuusanalyysejä. Lopuksi työssä suunniteltiin runkorakenteille sopiva korroosionsuojaus.

Genetics of inherited small vessel diseases – in search of a novel small vessel disease and modifiers of the clinical course of CADASIL

The genetic and environmental risk factors of vascular cognitive impairment are still largely unknown. This thesis aimed to assess the genetic background of two clinically similar familial small vessel diseases (SVD), CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) and Swedish hMID (hereditary multi-infarct dementia of Swedish type). In the first study, selected genetic modifiers of CADASIL were studied in a homogenous Finnish CADASIL population of 134 patients, all carrying the p.Arg133Cys mutation in NOTCH3. Apolipoprotein E (APOE) genotypes, angiotensinogen (AGT) p.Met268Thr polymorphism and eight NOTCH3 polymorphisms were studied, but no associations between any particular genetic variant and first-ever stroke or migraine were seen. In the second study, smoking, statin medication and physical activity were suggested to be the most profound environmental differences among the monozygotic twins with CADASIL. Swedish hMID was for long misdiagnosed as CADASIL. In the third study, the CADASIL diagnosis in the Swedish hMID family was ruled out on the basis of genetic, radiological and pathological findings, and Swedish hMID was suggested to represent a novel SVD. In the fourth study, the gene defect of Swedish hMID was then sought using whole exome sequencing paired with a linkage analysis. The strongest candidate for the pathogenic mutation was a 3’UTR variant in the COL4A1 gene, but further studies are needed to confirm its functionality. This study provided new information about the genetic background of two inherited SVDs. Profound knowledge about the pathogenic mutations causing familial SVD is also important for correct diagnosis and treatment options.