Livskvalitet och kognitiv funktion hos kvinnor med autoimmunt betingad hög ämnesomsättning och dess association till strukturella förändringar i hjärnan
Project number : 225961
Created by: Mats Holmberg, 2017-04-27
Last revised by: Mats Holmberg, 2019-01-07
Project created in: FoU i Västra Götalandsregionen

PublishedPublished

1. Översiktlig projektbeskrivning

Engelsk titel

Diffuse autoimmune hyperthyroidism and its association to mental
fatigue and changes in medial temporal lobe structures

Populärvetenskaplig sammanfattning av projektet

Graves sjukdom är ett vanligt tillstånd med 2-3% prevalens som i huvudsak drabbar kvinnor. Patienterna är svårt sjuka med sänkt livskvalitet och uttalade neuropsykiatriska symtom som stresskänslighet, nedsatt minnesfunktion och trötthet förutom rent kroppsliga symtom. Ofta kvarstår dessa symtom under lång tid, även sedan hormonnivåerna normaliserats. Patienten kan vara sjukskriven länge och en del återfår aldrig sin hälsa trots att de har normala koncentrationer av sköldkörtelhormon.

Bakgrunden till patientens ofta långvariga sjukdomstillstånd torde vara en påverkan på det centrala nervsystemet. Den kliniska bilden i det sena skedet med depression, psykisk uttröttbarhet och minnessvårigheter liknar den ”hjärntrötthet” som ses efter många fall av hjärnskada. Det är också sannolikt från djurförsök att sköldkörtelhormon har en direkt påverkan på hjärnan.

I studien undersöks 50 kvinnor med nydebuterad Graves´ sjukdom rörande livskvalitet och de genomgår en neuropsykiatrisk och neuropsykologisk bedömning av kognitiva funktioner. Hjärnstrukturer såsom hippocampus och amygdala undersöks med magnetkamera och hjärnans syreförbrukning under mentalt arbete undersöks med functional Near Infrared Spectroscopy (fNIRS). Undersökningarna upprepas efter 7,5 och 15 månader efter det att medicinsk behandling påbörjats, vilket innebär att patienten vid det tredje undersökningstillfället bör ha haft normala koncentrationer av sköldkörtelhormon i ett år.

En kontrollgrupp på 50 personer undersöks enligt samma protokoll vid start och efter 15 månader.

Vi kartlägger de förändringar i livskvalitet och psykisk funktion som ses vid Graves´ sjukdom, i vilken grad de normaliseras efter terapi, och i vilken mån de är associerade med förändringar i hjärnan och/eller hjärnans funktion. Vi vill öka kunskapen om bakgrunden till de nedsättningar av livskvalitet och psykisk funktion som ses vid Graves´ sjukdom för att om möjligt förebygga, prediktera och förhindra dessa.

Graves sjukdom är ett vanligt tillstånd med 2-3% prevalens som i huvudsak drabbar kvinnor. Patienterna är svårt sjuka med sänkt livskvalitet och uttalade neuropsykiatriska symtom som stresskänslighet, nedsatt minnesfunktion och trötthet förutom rent kroppsliga symtom. Ofta kvarstår dessa symtom under lång tid, även sedan hormonnivåerna normaliserats. Patienten kan vara sjukskriven länge och en del återfår aldrig sin hälsa trots att de har normala koncentrationer av sköldkörtelhormon.

Bakgrunden till patientens ofta långvariga sjukdomstillstånd torde vara en påverkan på det centrala nervsystemet. Den kliniska bilden i det sena skedet med depression, psykisk uttröttbarhet och minnessvårigheter liknar den ”hjärntrötthet” som ses efter många fall av hjärnskada. Det är också sannolikt från djurförsök att sköldkörtelhormon har en direkt påverkan på hjärnan.

I studien undersöks 50 kvinnor med nydebuterad Graves´ sjukdom rörande livskvalitet och de genomgår en neuropsykiatrisk och neuropsykologisk bedömning av kognitiva funktioner. Hjärnstrukturer såsom hippocampus och amygdala undersöks med magnetkamera och hjärnans syreförbrukning under mentalt arbete undersöks med functional Near Infrared Spectroscopy (fNIRS). Undersökningarna upprepas efter 7,5 och 15 månader efter det att medicinsk behandling påbörjats, vilket innebär att patienten vid det tredje undersökningstillfället bör ha haft normala koncentrationer av sköldkörtelhormon i ett år.

En kontrollgrupp på 50 personer undersöks enligt samma protokoll vid start och efter 15 månader.

Vi kartlägger de förändringar i livskvalitet och psykisk funktion som ses vid Graves´ sjukdom, i vilken grad de normaliseras efter terapi, och i vilken mån de är associerade med förändringar i hjärnan och/eller hjärnans funktion. Vi vill öka kunskapen om bakgrunden till de nedsättningar av livskvalitet och psykisk funktion som ses vid Graves´ sjukdom för att om möjligt förebygga, prediktera och förhindra dessa.

Vetenskaplig sammanfattning av projektet

Background

Diffuse autoimmune hyperthyroidism or Graves´ disease is a common condition mainly affecting women, where the prevalence is 2-3%. The disease is most common among women in the age when most have a full time workload and a growing family. The high levels of thyroid hormones in hyperthyroidism affect most organ systems of the body through genomic pathways. There are also non-genomic effects, e.g. on mitochondria and on the receptors of sympathetic nerves. The increased production of thyroid hormones in Graves´ disease is driven by autoantibodies directed against the TSH receptor. In most cases, this autoimmunity will also affect other tissues, above all the orbital tissue by mechanisms not fully understood.

Quality of life and neuropsychiatric symptoms

The début of Graves´ disease may be associated with negative life events and stress (1). Moreover, in the disease situation psychiatric symptoms are often striking with symptoms of unrest, stress intolerance, fatigue, memory impairment and compromised well-being (2-4). Patients may also experience depression and a form of “reversible dementia” (5). The mentioned symptoms are consistent with the presence of an astheno-emotional syndrome (6,7). Recovery of wellbeing is delayed for months after euthyroidism is achieved in many patients, and some will never regain full pre morbid health (2,4,8). The impaired mental health rather than somatic symptoms is the major cause of the prolonged inability to return to full-time work.

Medial temporal lobe pathology

Hippocampus is part of the limbic system of the brain and has an important role in forming and retrieving new memories. Thyroid hormone receptors (TR) is distributed among all areas of the brain (12). Two distinct genes, TRalpha and TRbeta, encode several receptor isoforms with specific functions defining the tissue specific action of thyroid hormone. The highest level of rTR alpha 1 transcript is found in the hippocampus, and granular layer of the cerebellar cortex (12). Data from TRalpha 1 knock-out mice indicate that TRalpha1 is involved in the regulation of hippocampal structure and function as these mice show considerable behavioural changes (13). Also, data from thyrectomized rats infer improved hippocampal-dependent learning and memory after thyroxine substitution (14). There are at present no human data on the receptor isoform distribution among brain areas. However, in a recent report there was no association with medial temporal brain structure and polymorphisms of diodinases convering T4 to T3 (15). In another study higher T4 within the normal was correlated with lower volume of the hippocampal structure (16).

Glucocorticoids have an impact on hippocampal volume. In patients with Cushings syndrome, a condition with markedly elevated glucocorticoids chronically, hippocampal volume is reduced (17). With the cure of the disease and normalisation of glucocorticoid levels hippocampal volume is increased accompanied by an improvement in the patients’ cognitive functioning demonstrating the plasticity of this brain area (17,18). Hyperthyroidism is a protein catabolic state (19) as is glucocorticoid excess and it is likely that the neuropsychology associated with Graves´ disease is due to direct action of thyroid hormone on the brain. It is therefore of interest to study brain structures which may be involved in the pathogenesis of the symptoms, such as the medial temporal regions including the hippocampus and the amygdala. In many neuropsychiatric disorders (20), the volume of the hippocampus area, as determined by MRI, is reduced. In some of these disorders changes have been reported in other medial temporal structures such as the amygdala.

Study Design

This is a case-controlled prospective trial with at least 15-month open treatment period in the patients. Matched controls will be studied twice with at least 15 months in-between while patients will be studied at diagnosis and after at least 15 months, allowing for a period of at least 6 months of euthyroidism. Euthyroidism is defined as a serum TSH concentration between 0.4-2.0 mIU/L combined with normal free T4 and T3 levels. Thyroid hormone levels are checked five times at the visits and in between the visits. Blood for the freezer is also saved. Treatment of hyperthyroidism will be the conventional therapy most suitable for the patients by anti thyrostatic drug (ATD), 131I radiotherapy or surgery. Hypothyroidism is prevented by early commencement of thyroxine treatment. The treatment follows the local treatment scheme for patients with Graves’ disease in this age group.

Study population

Patients: The aim is to include around 60 consecutive premenopausal adult women with Graves Disease (GD) presenting at the Thyroid Units at Sahlgrenska University Hospital, the Hospital in Kungälv, Skaraborgs Hospital, Skövde and The Hospital in Borås according to the following criteria. Blood specimens from patients shall be sent to Sahlgrenska University Hospital instead of local laboratory to avoid recruitment bias due to different thyroid hormone analysis methods.

Inclusion criteria
  • Premenopausal women (>18 years of age).
  • Newly diagnosed Graves’ disease.
  • FT4 ≥ 50 pmol/L (reference 12-22) and/or T3 ≥ 6 (1.3-3.1 nmol/L.
  • Positive TSH receptor antibodies and/or homogenous uptake at technetium scintigraphy
Exclusion criteria
  • Other concomitant illnesses affecting QoL such as other endocrine diagnoses heart failure, respiratory insufficiency, active malignancy and current or recent psychosis diagnosis.
  • Patient who may not attend to the protocol according to the investigators opinion.
  • TAO with concomitant steroid medication or TAO where the use of steroids will be very likely within the next 15 months
  • Concomitant or recent illness with steroid treatment
  • Contraindications for MRI
  • GD caused by Cordarone medication

For the final analyses we aim at 40 patients remaining in the study after 15 months. As 10% of GD patients will have severe TAO and 40% of these cases will develop after the debut of GD some women will be treated with high doses of steroids intravenously or orally after inclusion in the study. We will in those cases include another patient. An initial inclusion level of 60 patients may be sufficient.

Controls: Controls matched for age and gender are recruited randomly from the Swedish Tax Agency for the Göteborg area. Controls will also be matched for smoking habits as chronic nicotine treatment reversed the hypothyroidism-induced learning and memory impairment seen in rats (23) and for educational level.

Power calculations

Power calculations are not possible as similar previous studies are not available, but based on changes in hippocampus volume in patients being cured for Cushing’s disease and using an 1,5 T MR scanner, a sample size of approximately 40 subjects for within-individual comparison would be sufficient in order to detect a mean volumetric change of 10% with an 80% probability and with a 5% significance level. However, with a 3T scanner much smaller changes can be reliably detected.

These figures, which have been used to determine the sample size of the present study, relate to paired comparisons of successive manual segmentations of the hippocampus. It is generally agreed that longitudinal comparisons using serial registration methods are more sensitive (17). Although there are no published MRI studies of medial brain structures in thyroid disease we are therefore confident that the study power will be sufficient to detect any clinically meaningful changes in hippocampal volume over time.

Somatic evaluation: The clinical visits will be performed at baseline and after at least 15 months with clinical status, body weight, length, ECG,  measurement of thyroid associated hormones (F-T4, T3, FT3, T4, TSH and TRAb), and blood specimens for futures analyses. There will also be general questions about ethnicity, socioeconomic status, smoking, snuff, alcohol, stress, pregnancies, heredity, low dose irradiation and other previous and current diseases, and ongoing medications.

MR of brain and analysis of medial temporal data: The patients will be scanned with a 3 T Philips scanner at the Sahlgrenska University Hospital. A 3D-FFE T1 sequence with ≤1 mm cubic voxels will be used for the segmentation of medial temporal structures. Whole brain transversal T1 and sagittal T2 sections (3-5mm slices) are added in order to exclude other pathology and to improve the estimation of intracranial volume. The images of the hippocampi and nearby structures will be analyzed with several methods in order to ensure that a maximum of information is extracted. Manual segmentation of the images will be done by two independent raters using custom software developed in a recent project (24). The volume of the hippocampus will be normalized by the total intracranial volume. Automatic segmentation will be done with the Freesurfer software, which is a less exact but faster method that gives information about many brain structures. Longitudinal comparisons will also be made using serial registration and difference imaging. An experienced radiologist will inspect the MR images for visually apparent structural changes of the brain.

Neuropsychological assessment: The neuropsychological examination will comprise information processing speed, attention, working memory and verbal fluency. The following tests will be included: Trail Making Test A and B (visual scanning, flexibility and divided attention) (27), and two extended versions of these with higher load on divided attention (28), digit symbol (measure motor and mental speed) and digit span (auditory working memory) both subtests of WAIS-III (29), letter verbal fluency (subtest of D-KEFS) (30), reading speed (31) and a newly constructed ccomputer test measuring the simultaneous capacity of working memory and processing speed. These cognitive functions seem to be most easily affected among patients with Graves´thyroxicosis (32,33).

The tests will be administered in a standardized sequence and are divided into two sessions of one to one and a half hours. Verbal tests will vary with nonverbal in each session, and sequence is also decided on the consideration of risk of contamination on the memory tests.

Clinical neuropsychiatric assessment: Depressive and anxiety symptoms will be assessed by a clinical interview based on the Comprehensive Psychopathological Rating Scale (CPRS) for depression and anxiety (34). A self-evaluation of mental fatigue and associated symptoms will be performed using a questionnaire (35) based on the LM system for organic mental syndromes (6,36,37) followed by a structured interview with focus on the same symptoms.

Quality of life and well-being: Socioeconomic status is registered. Self-reported questionnaires will be used at entry into the trial and at study end. Questionnaires to be used are the ThyrPro (38) The Social Readjustment Scale (18) and PGWB (Psychological Well Being).

Study organisation

The patients will be seen at the Centre of Endocrinology and Metabolism (CEM) at Sahlgrenska University Hospital, Göteborg. The principal investigator will be contacted by colleagues if an eligible patient is referred and the study nurse will arrange for the first visit.

11. References

1.         Winsa B, Adami HO, Bergstrom R, Gamstedt A, Dahlberg PA, Adamson U, Jansson R, Karlsson A. Stressful life events and Graves' disease. LancetEM 1991; 338:1475-1479

2.         Watt T, Groenvold M, Rasmussen AK, Bonnema SJ, Hegedus L, Bjorner JB, Feldt-Rasmussen U. Quality of life in patients with benign thyroid disorders. A review. Eur J EndocrinolEM 2006; 154:501-510

3.         Elberling TV, Rasmussen AK, Feldt-Rasmussen U, Hording M, Perrild H, Waldemar G. Impaired health-related quality of life in Graves' disease. A prospective study. Eur J EndocrinolEM 2004; 151:549-555

4.         Berg G, Michanek A, Holmberg E, Nystrom E. Clinical outcome of radioiodine treatment of hyperthyroidism: a follow-up study. J Intern MedEM 1996; 239:165-171

5.         Fukui T, Hasegawa Y, Takenaka H. Hyperthyroid dementia: clinicoradiological findings and response to treatment. J Neurol SciEM 2001; 184:81-88

6.         Lindqvist G aMH. Organisk Psykiatri (Organic Psychiatry)EM· Stockholm: Almqvist & Wiksell.

7.         Rodholm M, Starmark JE, Svensson E, Von Essen C. Astheno-emotional disorder after aneurysmal SAH: reliability, symptomatology and relation to outcome. Acta Neurol ScandEM 2001; 103:379-385

8.         Perrild H, Hansen JM, Arnung K, Olsen PZ, Danielsen U. Intellectual impairment after hyperthyroidism. Acta Endocrinol (Copenh)EM 1986; 112:185-191

12.       Bradley DJ, Young WS, 3rd, Weinberger C. Differential expression of alpha and beta thyroid hormone receptor genes in rat brain and pituitary. Proc Natl Acad Sci U S AEM 1989; 86:7250-7254

13.       Guadano-Ferraz A, Benavides-Piccione R, Venero C, Lancha C, Vennstrom B, Sandi C, DeFelipe J, Bernal J. Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits. Mol PsychiatryEM 2003; 8:30-38

14.       Alzoubi KH, Gerges NZ, Aleisa AM, Alkadhi KA. Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: Behavioral, electrophysiological, and molecular studies. HippocampusEM 2009; 19:66-78

15.       de Jong FJ, Peeters RP, den Heijer T, van der Deure WM, Hofman A, Uitterlinden AG, Visser TJ, Breteler MM. The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe. The Journal of clinical endocrinology and metabolismEM 2007; 92:636-640

16.       de Jong FJ, den Heijer T, Visser TJ, de Rijke YB, Drexhage HA, Hofman A, Breteler MM. Thyroid hormones, dementia, and atrophy of the medial temporal lobe. J Clin Endocrinol MetabEM 2006; 91:2569-2573

17.       Starkman MN, Giordani B, Gebarski SS, Berent S, Schork MA, Schteingart DE. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease. Biol PsychiatryEM 1999; 46:1595-1602

18.       Starkman MN, Giordani B, Gebarski SS, Schteingart DE. Improvement in learning associated with increase in hippocampal formation volume. Biol PsychiatryEM 2003; 53:233-238

19.       Lonn L, Stenlof K, Ottosson M, Lindroos AK, Nystrom E, Sjostrom L. Body weight and body composition changes after treatment of hyperthyroidism. The Journal of clinical endocrinology and metabolismEM 1998; 83:4269-4273

23.       Alzoubi KH, Aleisa AM, Gerges NZ, Alkadhi KA. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J Neurosci ResEM 2006; 84:944-953

24.       Eckerstrom C, Olsson E, Borga M, Ekholm S, Ribbelin S, Rolstad S, Starck G, Edman A, Wallin A, Malmgren H. Small baseline volume of left hippocampus is associated with subsequent conversion of MCI into dementia: the Goteborg MCI study. J Neurol SciEM 2008; 272:48-59

27.       Lezak MD, Howieson DB, Loring DW, eds. Neuropsychological assessmentEM[. ]4th ed. New York:: Oxford University Press; 2004.

28.       Johansson B, Berglund P, Rönnbäck L. Mental fatigue and impaired information processing after mild and moderate traumatic brain injury. Brain InjuryEM 2009; 23:1027-1040

29.       Wechsler D, ed. Wechsler Adult Intelligence Scale – third edition, WAIS-III, Swedish versionEM· Pearson Assessment; 2003.

30.       Ellis DC, Kaplan E, Kramer JH, eds. Delis-Kaplan Executive Function System – D-KEFSEM· San Antonio, TX: The Psychological Corporation; 2001.

31.       Madison S. LäsdiagnosEM· Lund: Läs och skrivcentrum.

32.       Vogel A, Elberling TV, Hörding M, Dock J, Rasmussen ÅK, U F-R, Perrild H, Waldemar G. Affective symptoms and cognitive functions in the acute phase of Graves´thyrotoxicosis. PsychoneuroendocrinologyEM 2007; 32:36-43

33.       Samuels MH. Cognitive function in untreated hypthyroidism and hyperthyroidism. Curr Opin Endocrinol Diabetes ObesEM 2008; 15:429-433

34.       Svanborg P, Åsberg M. A new self-rating scale for depression and anxiety states based on the Comprehensive Psychopathological Scale. Acta Psychiatr ScandEM 1994; 89:21-28

35.       Johansson B, Starmark A, Berglund P, Rödholm M, Rönnbäck L. A self-assessment questionnaire for mental fatigue and related symptoms after neurological disorders and injuries. Brain InjuryEM 2010; 24:2-12

36.       Lindqvist G aMH. Classification and Diagnosis in Organic Psychiatry. Acta Psychiatrica ScandinavicaEM 1993; 88

37.       Rödholm M. Astheno-emotional disorder after aneurysmal subarachnoid hemorrhage. Classification, outcome, and relation to anxiety and depressive disorders. Gothenburg, University of Gothenburg; 2003.

38.       Watt T, Hegedus L, Groenvold M, Bjorner JB, Rasmussen AK, Bonnema SJ, Feldt-Rasmussen U. Validity and reliability of the novel thyroid-specific quality of life questionnaire, ThyPRO. Eur J EndocrinolEM 162:161-167

Typ av projekt

Forskningsprojekt

MeSH-termer för att beskriva typ av studier

checked Longitudinella studier (Longitudinal Studies)
checked Prospektiva studier (Prospective Studies)
checked Fall-kontrollstudier (Case-Control Studies)
checked Kohortstudier (Cohort Studies)


(Only selected options are displayed. Click here to display all options)

MeSH-termer för att beskriva ämnesområdet

information Added MeSH terms
Hyperthyroidism
Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.
Graves Disease
A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy).
Graves Ophthalmopathy
An autoimmune disorder of the EYE, occurring in patients with Graves disease. Subtypes include congestive (inflammation of the orbital connective tissue), myopathic (swelling and dysfunction of the extraocular muscles), and mixed congestive-myopathic ophthalmopathy.
Magnetic Resonance Imaging
Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.
Quality of Life
A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.
Psychiatry
The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders.

Projektets delaktighet i utbildning

checked Avhandling


(Only selected options are displayed. Click here to display all options)

2. Projektorganisation och finansiering

Arbetsplatser involverade i projektet

information Added workplaces
Regioner - Västra Götalandsregionen - Specialiserad vård - Sahlgrenska Universitetssjukhuset - Område 6 - Medicin, Sahlgrenska workplace verified by Västra Götalandsregionen on 2018-02-27
Företag - Privata vårdgivande bolag - inom Västra Götalandsregionen - Specialiserad vård - Capio Lundby Närsjukhus workplace verified by Västra Götalandsregionen on 2018-02-27
Regioner - Västra Götalandsregionen - Specialiserad vård - Kungälvs sjukhus workplace verified by Västra Götalandsregionen on 2018-02-27
Regioner - Västra Götalandsregionen - Specialiserad vård - Södra Älvsborgs sjukhus (SÄS) workplace verified by Västra Götalandsregionen on 2018-02-27

Coworker

Helge Malmgren
Emeritus professor, Institutionen för medicin
Daniel Ruhe
Systemutvecklare, Göteborgs universitet
Simon Skau
Institutionen för neurovetenskap och fysiologi
Rolf A. Heckemann
Professor i medicinsk bildbehandling och bildanalys, Institutionen för neurovetenskap och fysiologi
Birgitta Johansson
Docent, Universitetssjukhusöverpsykolog, specialist i neuropsykologi, Neurosjukvård
Peter Berglund
Överläkare, Psykiatri kognition och äldrepsykiatri
Niklas Klasson
Doktorand, Sektionen för psykiatri och neurokemi
Göran Starck
Universitetssjukhusöveringejör, 1:e Ingenjör, Diagnostisk strålningsfysik, Institutionen för fysik
Lina Bunketorp Käll
Physiotherapist, Avancerad Rekonstruktion av Extremiteter (C.A.R.E)

Tutor

Helena Filipsson Nyström
Docent, Universitetssjukhusöverläkare, Medicin, Sahlgrenska

Finansiering

Grants

Fredrik och Ingrid Thurings stiftelse
50 000 SEK (applied sum: 200 000 SEK)
Helena Filipsson Nyström

2013, CogThyr

Svenska Läkaresällskapet (SLS-326461)
164 800 SEK (applied sum: 500 000 SEK)
Helena Filipsson Nyström

2013, CogThyr och RTX

Svenska Endokrinföreningen
100 000 SEK (applied sum: 100 000 SEK)
Helena Filipsson Nyström

2012, CogThyr

Göteborgs Läkaresällskap (GLS-252341)
100 000 SEK (applied sum: 150 000 SEK)
Helena Filipsson Nyström

2012, CogThyr

Förlängt starta upp LUA
600 000 SEK (applied sum: 600 000 SEK)
Helena Filipsson Nyström

2012, Samtliga studier

SU-fonderna
90 000 SEK (applied sum: 500 000 SEK)
Helena Filipsson Nyström

2011, CogThyr

Starta upp LUA 2010 (ALFGBG)
600 000 SEK (applied sum: 1 000 000 SEK)
Helena Filipsson Nyström

2011, CogThyr, RTX, TT-12, Jod

Fredrik och Ingrid Thurings stiftelse
100 000 SEK (applied sum: 100 000 SEK)
Helena Filipsson Nyström

2011, CogThyr

Åke Wibergs stiftelse
70 000 SEK (applied sum: 528 000 SEK)
Helena Filipsson Nyström

2011, CogThyr

FOU VGR
267 000 SEK (applied sum: 500 000 SEK)
Helena Filipsson Nyström

2011, CogThyr

Göteborgs Läkaresällskap ( GLS-97391)
95 000 SEK (applied sum: 150 000 SEK)
Helena Filipsson Nyström

2010, CogThyr

FOU VGR (VGFOUREG-73701)
305 000 SEK (applied sum: 500 000 SEK)
Helena Filipsson Nyström

2009, CogThyr


Livskvalitet och kognitiv funktion hos kvinnor med autoimmunt betingad hög ämnesomsättning och dess association till strukturella förändringar i hjärnan, from FoU i Västra Götalandsregionen
http://www.researchweb.org/is/html/vgr/project/225961