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  • 1.
    af Edholm, Karolina
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Lidman, Christer
    Karolinska University Hospital, Solna, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences.
    Solders, Göran
    Karolinska Institutet, Stockholm, Sweden.
    Paucar, Martin
    Karolinska University Hospital, Solna, Sweden.
    Clinical Reasoning: Leg weakness and stiffness at the emergency room2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 6, p. E622-E625Article in journal (Other academic)
    Abstract [en]

    A 48-year-old woman from the Maghreb came to the emergency department with insidious gait difficulties, urgency, and constipation starting 6 months prior to the visit. The patient's complaints consisted of weakness, stiffness, and pain in her legs. Her medical history consisted of Hashimoto thyroiditis and breast cancer, with the latter having motivated surgery 4 months prior to admission. Histopathologic examination had demonstrated ductal cancer sensitive to estrogen and mapping with sentinel node biopsy ruled out metastasis. For that reason, the patient was treated with local radiation given weekly over 1 month and treatment with tamoxifen was started. Physical examination upon admission demonstrated weakness and spasticity in both legs. Reflexes were brisk; bilateral nonsustained foot clonus and Babinski sign were also present. Bilateral dorsal flexion was reduced, but vibration and sensation to touch and pinprick were normal. Sphincter tonus was reduced; systemic manifestations such as myalgias, fever, skin rashes, uveitis, sicca, and arthritic joints were absent.

  • 2.
    Aghajani, Moji
    et al.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands; Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
    Colins, Olivier F.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands; School of Law, Psychology, and Social Work, Örebro University, Örebro, Sweden.
    Klapwijk, Eduard T.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.
    Veer, Ilya M.
    Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany.
    Andershed, Henrik
    Örebro University, School of Law, Psychology and Social Work.
    Popma, Arne
    Department of Child and Adolescent Psychiatry, VU University Medical Center, Amsterdam, the Netherlands; Faculty of Law, Leiden University, Institute of Criminal Law and Criminology, Leiden, the Netherlands.
    van der Wee, Nic J.
    Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
    Vermeiren, Robert R. J. M.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.
    Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders2016In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 37, no 11, p. 4017-4033Article in journal (Refereed)
    Abstract [en]

    Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile.

  • 3.
    Aghanavesi, Somayeh
    et al.
    Department of Computer Engineering, Dalarna University, Borlänge, Sweden.
    Bergquist, Filip
    Department of Pharmacology, Institute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden.
    Nyholm, Dag
    Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Senek, Marina
    Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Memedi, Mevludin
    Örebro University, Örebro University School of Business.
    Motion sensor-based assessment of Parkinson's disease motor symptoms during leg agility tests: results from levodopa challenge2019In: IEEE journal of biomedical and health informatics, ISSN 2168-2194, E-ISSN 2168-2208Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is a degenerative, progressive disorder of the central nervous system that mainly affects motor control. The aim of this study was to develop data-driven methods and test their clinimetric properties to detect and quantify PD motor states using motion sensor data from leg agility tests. Nineteen PD patients were recruited in a levodopa single dose challenge study. PD patients performed leg agility tasks while wearing motion sensors on their lower extremities. Clinical evaluation of video recordings was performed by three movement disorder specialists who used four items from the motor section of the Unified PD Rating Scale (UPDRS), the treatment response scale (TRS) and a dyskinesia score. Using the sensor data, spatiotemporal features were calculated and relevant features were selected by feature selection. Machine learning methods like support vector machines (SVM), decision trees and linear regression, using 10-fold cross validation were trained to predict motor states of the patients. SVM showed the best convergence validity with correlation coefficients of 0.81 to TRS, 0.83 to UPDRS #31 (body bradykinesia and hypokinesia), 0.78 to SUMUPDRS (the sum of the UPDRS items: #26-leg agility, #27-arising from chair and #29-gait), and 0.67 to dyskinesia. Additionally, the SVM-based scores had similar test-retest reliability in relation to clinical ratings. The SVM-based scores were less responsive to treatment effects than the clinical scores, particularly with regards to dyskinesia. In conclusion, the results from this study indicate that using motion sensors during leg agility tests may lead to valid and reliable objective measures of PD motor symptoms.

  • 4.
    Aghanavesi, Somayeh
    et al.
    Computer Engineering, School of Technology and Business Studies, Dalarna University, Borlänge, Sweden.
    Memedi, Mevludin
    Örebro University, Örebro University School of Business.
    Westin, Jerker
    Computer Engineering, School of Technology and Business Studies, Dalarna University, Borlänge, Sweden.
    Measuring temporal irregularity in spiral drawings of patients with Parkinson’s disease2017In: Abstracts of the 21st International Congress of Parkinson's Disease and Movement Disorders, John Wiley & Sons, 2017, Vol. 32, p. s252-s252, article id 654Conference paper (Other (popular science, discussion, etc.))
    Abstract [en]

    Objective: The aim of this work is to evaluate clinimetric properties of a method for measuring Parkinson’s disease (PD) upper limb temporal irregularities during spiral drawing tasks.

    Background: Basal ganglia fluctuations of PD patients are associated with motor symptoms and relating them to objective sensor-based measures may facilitate the assessment of temporal irregularities, which could be difficult to be assessed visually. The present study investigated the upper limb temporal irregularity of patients at different stages of PD and medication time points.

    Methods: Nineteen PD patients and 22 healthy controls performed repeated spiral drawing tasks on a smartphone. Patients performed the tests before a single levodopa dose and at specific time intervals after the dose was given. Three movement disorder specialists rated the videos of patients' performance according to six items of UPDRS-III, dyskinesia (Dys), and Treatment Response Scale (TRS). A temporal irregularity score (TIS) was developed using approximate entropy (ApEn) method. Differences in mean TIS between two groups of patients and healthy subjects, and also across four subject groups: early, intermediate, advanced patients and, healthy subjects were assessed. The relative ability of TIS to detect changes from baseline (no medication) to later time points when patients were on medication was assessed. Correlations between TIS and clinical rating scales were assessed by Pearson correlation coefficients and test-retest reliability of TIS was measured by intra-class correlation coefficients (ICC).

    Results: The mean TIS was significantly different between healthy subjects and patients (P<0.0001). When assessing the changes in relation to treatment, clinical-based scores (TRS and Dys) had better responsiveness than TIS. However, the TIS was able to capture changes from Off to On, and the wearing off effects. Correlations between TIS and clinical scales were low indicating poor validity. Test-retest reliability correlation coefficient of the mean TIS was good (ICC=0.67).

    Conclusions: Our study found that TIS was able to differentiate spiral drawings drawn by patients from those drawn by healthy subjects. In addition, TIS could capture changes throughout the levodopa cycle.TIS was weakly correlated to clinical ratings indicating that TIS measures high frequency upper limb temporal irregularities that could be difficult to be detected during clinical observations.

  • 5.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden ; .
    Thelin, Eric Peter
    Department of Clinical Neuroscience, Karolinska Institutet Solna, Stockholm, Sweden.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Bellander, Bo Michael
    Department of Clinical Neuroscience, Karolinska Institutet Solna, Stockholm, Sweden.
    Riddez, Louis
    Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Talving, Peep
    Department of Surgery, Tartu University Hospital, Tartu, Estonia.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; Division of Trauma and Emergency Surgery, Department of Surgery, Orebro University Hospital, Orebro, Sweden.
    β-Blocker after severe traumatic brain injury is associated with better long-term functional outcome: a matched case control study2017In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 43, no 6, p. 783-789Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Severe traumatic brain injury (TBI) is the predominant cause of death and disability following trauma. Several studies have observed improved survival in TBI patients exposed to β-blockers, however, the effect on functional outcome is poorly documented.

    METHODS: Adult patients with severe TBI (head AIS ≥ 3) were identified from a prospectively collected TBI database over a 5-year period. Patients with neurosurgical ICU length of stay <48 h and those dying within 48 h of admission were excluded. Patients exposed to β-blockers ≤ 48 h after admission and who continued with treatment until discharge constituted β-blocked cases and were matched to non β-blocked controls using propensity score matching. The outcome of interest was Glasgow Outcome Scores (GOS), as a measure of functional outcome up to 12 months after injury. GOS ≤ 3 was considered a poor outcome. Bivariate analysis was deployed to determine differences between groups. Odds ratio and 95% CI were used to assess the effect of β-blockers on GOS.

    RESULTS: 362 patients met the inclusion criteria with 21% receiving β-blockers during admission. After propensity matching, 76 matched pairs were available for analysis. There were no statistical differences in any variables included in the analysis. Mean hospital length of stay was shorter in the β-blocked cases (18.0 vs. 26.8 days, p < 0.01). The risk of poor long-term functional outcome was more than doubled in non-β-blocked controls (OR 2.44, 95% CI 1.01-6.03, p = 0.03).

    CONCLUSION: Exposure to β-blockers in patients with severe TBI appears to improve functional outcome. Further prospective randomized trials are warranted.

  • 6. Ahlström, Gerd
    et al.
    Lindvall, B.
    Wenneberg, Stig
    Örebro University, Department of Nursing and Caring Sciences.
    Gunnarsson, Lars-Gunnar
    Örebro University, Department of Clinical Medicine.
    A comprehensive rehabilitation programme tailored to the needs of adults with muscular dystrophy2006In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 20, no 2, p. 132-141Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess if activities of daily living (ADL), coping and quality of life could be improved in adults with muscular dystrophy through a comprehensive rehabilitation programme. DESIGN: Quasi-experimental, controlled clinical study comparing patients with similar age and disease aspects. SETTING: Two different counties in Sweden, being either study or control setting. SUBJECTS: The study group comprised 37 adults (21 women, 16 men; mean age 50 years), while the control group comprised 39 people (25 women, 14 men; mean age 46 years). INTERVENTIONS: Four rehabilitation sessions tailored to different medical, physical and psychosocial needs of the patients, comprising a total of 10 days over a period of 18 months. MAIN MEASURES: ADL, the Mental Adjustment to Cancer Scale measuring coping strategies, the Sickness Impact Profile measuring health-related quality of life, the Hospital Anxiety and Depression Scale, and the Psychosocial Well-being Questionnaire. RESULTS: No significant differences were found between groups with regard to the outcome measures. There was increased dependence on others in ADL after 18 months in both groups, but it was more pronounced in the control group. Furthermore, a clear trend was observed in the data with regard to coping patterns, the control group using more coping strategies such as 'Helplessness/hopelessness' (P= 0.057), 'Anxious preoccupation' (P = 0.085) and 'Fatalistic' (P= 0.073) when being compared to the study group. CONCLUSIONS: No apparent effects on ADL were found from the rehabilitation programme, although there was a tendency of reduction of maladaptive coping patterns in the study group. This initial study may provide the rationale and basis for a randomized controlled trial.

  • 7.
    Ahola-Erkkilä, Sofia
    et al.
    Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.
    Carroll, Christopher J.
    Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.
    Peltola-Mjösund, Katja
    Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.
    Tulkki, Valtteri
    Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppänen-Laakso, Tuulikki
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Tyynismaa, Henna
    Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.
    Suomalainen, Anu
    Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki, University Central Hospital, Helsinki, Finland.
    Ketogenic diet slows down mitochondrial myopathy progression in mice2010In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, no 10, p. 1974-1984Article in journal (Refereed)
    Abstract [en]

    Mitochondrial dysfunction is a major cause of neurodegenerative and neuromuscular diseases of adult age and of multisystem disorders of childhood. However, no effective treatment exists for these progressive disorders. Cell culture studies suggested that ketogenic diet (KD), with low glucose and high fat content, could select against cells or mitochondria with mutant mitochondrial DNA (mtDNA), but proper patient trials are still lacking. We studied here the transgenic Deletor mouse, a disease model for progressive late-onset mitochondrial myopathy, accumulating mtDNA deletions during aging and manifesting subtle progressive respiratory chain (RC) deficiency. We found that these mice have widespread lipidomic and metabolite changes, including abnormal plasma phospholipid and free amino acid levels and ketone body production. We treated these mice with pre-symptomatic long-term and post-symptomatic shorter term KD. The effects of the diet for disease progression were followed by morphological, metabolomic and lipidomic tools. We show here that the diet decreased the amount of cytochrome c oxidase negative muscle fibers, a key feature in mitochondrial RC deficiencies, and prevented completely the formation of the mitochondrial ultrastructural abnormalities in the muscle. Furthermore, most of the metabolic and lipidomic changes were cured by the diet to wild-type levels. The diet did not, however, significantly affect the mtDNA quality or quantity, but rather induced mitochondrial biogenesis and restored liver lipid levels. Our results show that mitochondrial myopathy induces widespread metabolic changes, and that KD can slow down progression of the disease in mice. These results suggest that KD may be useful for mitochondrial late-onset myopathies.

  • 8.
    Alaie, Iman
    et al.
    Dept Psychol, Uppsala Univ, Uppsala, Sweden.
    Frick, Andreas
    Dept Psychol, Uppsala Univ, Uppsala, Sweden.
    Marteinsdottir, Ina
    Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Hartvig, Per
    Dept Drug Design & Pharmacol, Univ Copenhagen, Copenhagen, Denmark.
    Tillfors, Maria
    Örebro University, School of Law, Psychology and Social Work.
    Eriksson, Elias
    Dept Pharmacol, Univ Gothenburg, Gothenburg, Sweden.
    Fredrikson, Mats
    Dept Psychol, Uppsala Univ, Uppsala, Sweden.
    Furmark, Tomas
    Dept Psychol, Uppsala Univ, Uppsala, Sweden.
    Serotonin Synthesis Rate and the Tryptophan Hydroxylase-2 G-703T Polymorphism in Social Anxiety Disorder2014In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 75, no 9, p. 357S-357SArticle in journal (Other academic)
  • 9.
    Amer, Ahmed
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Eliasson, Ann-Christin
    Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Peny-Dahlstrand, Marie
    Regional Rehabilitation Centre, Queen Silvia Children's Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hermansson, Liselotte
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Prosthetics and Orthotics, Örebro University Hospital, Örebro, Sweden.
    Validity and test-retest reliability of Children's Hand-use Experience Questionnaire in children with unilateral cerebral palsy2016In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 58, no 7, p. 743-749Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the validity of the internet-based version of the Children's Hand-use Experience Questionnaire (CHEQ) by testing the new four-category rating scale, internal structure, and test-retest reliability.

    Method: Data were collected for 242 children with unilateral cerebral palsy (CP) (137 males and 105 females; mean age 9y 10mo, SD 3y 5mo, range 6-18y). Twenty children from the study sample (mean age 11y 8mo, SD 3y 10mo) participated in a retest within 7 to 14 days. Validity was tested by Rasch analysis based on a rating scale model and test-retest reliability by Kappa analysis and intraclass correlation coefficient (ICC).

    Results: The four-category rating scale was within recommended criteria for rating scale structure. One item was removed because of misfit. CHEQ showed good scale structure according to the criteria. The effective operational range was >90% for two of the CHEQ scales. Test-retest reliability for the three CHEQ scales was: grasp efficacy, ICC=0.91; time taken, ICC=0.88; and feeling bothered, ICC=0.91.

    Interpretation: The internet-based CHEQ with a four-category rating scale is valid and reliable for use in children with unilateral CP. Further studies are needed to investigate the validity of the internet-based version of CHEQ for children with upper limb reduction deficiency or obstetric brachial plexus palsy and the validity of the recommended improvements to the current version.

  • 10.
    Andersson, Åsa G.
    et al.
    Karolinska institutet, Stockholm, Sweden; Örebro University Hospital, Örebro, Sweden.
    Seiger, Åke
    Karolinska institutet, Stockholm, Sweden.
    Appelros, Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Karolinska institutet, Stockholm, Sweden; Örebro University Hospital, Örebro, Sweden.
    Hip fractures in persons with stroke2013In: Stroke Research and Treatment, ISSN 2090-8105, E-ISSN 2042-0056, Vol. 2013, article id 954279Article in journal (Refereed)
    Abstract [en]

    Background. Our aim was to determine the incidence of hip fractures within two years after stroke, to identify associated factors, to evaluate which test instruments that best could identify people at risk, and to describe the circumstances that prevailed when they sustained their hip fractures. Method. A total of 377 persons with first-ever stroke were followed up for a 24-month period. Stroke severity, cognition, and associated medical conditions were registered. The following test instruments were used: National Institutes of Health Stroke Scale, Mini-Mental State Examination, Berg Balance Scale, Timed Up & Go, and Stops Walking When Talking. Result. Sixteen of the persons fractured their hip within the study period, which corresponds to an incidence of 32 hip fractures per 1000 person-years. Persons with fractures more often had impaired vision and cognitive impairment and more had had previous fractures. Of the investigated test instruments, Timed Up & Go was the best test to predict fractures. Conclusion. The incidence of hip fractures in persons with stroke was high in this study. Persons with previous fractures, and visual and cognitive defects are at the greatest risk. Certain test instruments could be used in order to find people at risk, which should be targeted for fall preventive measures.

  • 11.
    Appelros, Peter
    Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Cognitive impairment in lacunar strokes2014In: European Neurological Review, ISSN 1758-3837, Vol. 9, no 1, p. 64-67Article in journal (Refereed)
    Abstract [en]

    Vascular cognitive impairment is closely related to stroke. Each condition is a risk factor for the other. Cognitive impairment is a symptom that makes it difficult for a stroke patient to live at home. In this review paper, different types of vascular cognitive impairment are discussed, with emphasis on cognitive impairment related to lacunar strokes (LACS). Symptoms, diagnostics, epidemiology, treatment, and prognosis are surveyed. LACS are often associated with leukoaraiosis, which is related to subcortical ischemic vascular dementia. Even if LACS often are mild, they may therefore be associated with cognitive impairment on longer term.

  • 12.
    Appelros, Peter
    Örebro University, Department of Clinical Medicine.
    Heart failure and stroke2006In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 37, no 7, p. 1637-1637Article in journal (Refereed)
  • 13.
    Appelros, Peter
    Örebro University, Department of Clinical Medicine.
    Prevalence and predictors of pain and fatigue after stroke: a population-based study2006In: International Journal of Rehabilitation Research, ISSN 0342-5282, E-ISSN 1473-5660, Vol. 29, no 4, p. 329-333Article in journal (Refereed)
    Abstract [en]

    Pain and fatigue are two often overlooked symptoms after stroke. Their prevalence and determinants are not well understood. In this study patients with first-ever stroke (n=377) were examined at baseline and after 1 year. General characteristics of the patients, as well as stroke type, stroke severity and risk factors were registered at baseline. After 1 year survivors (n=253) were examined with respect to residual impairment, disability, cognition and depression. They were asked whether they had experienced pain and/or fatigue which had started after the stroke, and which the patient felt to be stroke related. Twenty-eight patients (11%) had stroke-associated pain and 135 (53%) had stroke-associated fatigue. Pain was associated with depression and different manifestations of stroke severity, especially degree of paresis at baseline. Fatigue was more associated with physical disability. In univariate analysis, fatigue was also associated with sleep disturbances. In conclusion, it is important to be aware of the occurrence of pain and fatigue after stroke, because these symptoms are common, they impair quality of life and they are potentially treatable. Post-stroke depression may coexist with pain and fatigue. The detection of one symptom should lead to consideration of the others. Follow-up and individual assessment of stroke patients is crucial.

  • 14.
    Appelros, Peter
    et al.
    Örebro University, Department of Clinical Medicine.
    Andersson, A. G.
    Changes in mini mental state examination score after stroke: lacunar infarction predicts cognitive decline2006In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 13, no 5, p. 491-495Article in journal (Refereed)
    Abstract [en]

    Stroke and cognitive impairment are inter-related. The purpose of this study was to show the natural evolution of cognitive performance during the first year after a stroke, and to show which factors that predict cognitive decline. Subjects were patients with a first-ever stroke who were treated in a stroke unit. A total of 160 patients were included. At baseline patients were evaluated with regard to stroke type, stroke severity, pre-stroke dementia and other risk factors. Mini Mental State Examinations (MMSE) were performed after 1 week and after 1 year. Patients had a median increase of 1 point (range -8 to +9) on the MMSE. Thirty-two pre cent of the patients deteriorated, 13% were unchanged, and 55% improved. Lacunar infarction (LI) and left-sided stroke were associated with a failure to exhibit improvement. Patients with LI had an average decline of 1.7 points, whilst patients with other stroke types had an average increase of 1.8 points. Most stroke survivors improve cognitively during the first year after the event. The outcome for LI patients is worse, which suggests that LI may serve as a marker for concomitant processes that cause cognitive decline.

  • 15.
    Appelros, Peter
    et al.
    Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Háls Berglund, Maria
    Riksstroke, Medicincentrum, University Hospital of Norrland, Umeå, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Long-Term Risk of Stroke after Transient Ischemic Attack2017In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 43, no 1-2, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context.

    Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstroke's TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Cox's regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve.

    Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low.

    Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice.

  • 16.
    Appelros, Peter
    et al.
    Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Jonsson, Fredrik
    Riks-Stroke, Department of Medicine, Umeå University Hospital, Umeå, Sweden.
    Åsberg, Signild
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Asplund, Kjell
    Riks-Stroke, Department of Medicine, Umeå University Hospital, Umeå, Sweden.
    Glader, Eva-Lotta
    Riks-Stroke, Department of Medicine, Umeå University Hospital, Umeå, Sweden.
    Åsberg, Kerstin Hulter
    Department of Medicine, Enköping Hospital, Enköping, Sweden.
    Norrving, Bo
    Department of Neurology, Lund University Hospital, Lund, Sweden.
    Stegmayr, Birgitta
    Riks-Stroke, Department of Medicine, Umeå University Hospital, Umeå, Sweden.
    Terént, Andreas
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Trends in stroke treatment and outcome between 1995 and 2010: observations from Riks-Stroke, the Swedish stroke register2014In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 37, no 1, p. 22-29Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Continuous changes in stroke treatment and care, as well as changes in stroke characteristics, may alter stroke outcome over time. The aim of this paper is to describe time trends for treatment and outcome data, and to discuss if any such changes could be attributed to quality changes in stroke care.

    METHODS: Data from Riks-Stroke, the Swedish stroke register, were analyzed for the time period of 1995 through 2010. The total number of patients included was 320,181. The following parameters were included: use of computed tomography (CT), stroke unit care, thrombolysis, medication before and after the stroke, length of stay in hospital, and discharge destination. Three months after stroke, data regarding walking, toileting and dressing ability, as well social situation, were gathered. Survival status after 7, 27 and 90 days was registered.

    RESULTS: In 1995, 53.9% of stroke patients were treated in stroke units. In 2010 this proportion had increased to 87.5%. Fewer patients were discharged to geriatric or rehabilitation departments in later years (23.6% in 2001 compared with 13.4% in 2010), but more were discharged directly home (44.2 vs. 52.4%) or home with home rehabilitation (0 vs. 10.7%). The need for home help service increased from 18.2% in 1995 to 22.1% in 2010. Regarding prevention, more patients were on warfarin, antihypertensives and statins both before and after the stroke. The functional outcome measures after 3 months did improve from 2001 to 2010. In 2001, 83.8% of patients were walking independently, while 85.6% were independent in 2010. For toileting, independence increased from 81.2 to 84.1%, and for dressing from 78.0 to 80.4%. Case fatality (CF) rates after 3 months increased from 18.7% (2001) to 20.0% (2010). This trend is driven by patients with severe strokes.

    CONCLUSIONS: Stroke outcomes may change over a relatively short time period. In some ways, the quality of care has improved. More stroke patients have CT, more patients are treated in stroke units and more have secondary prevention. Patients with milder strokes may have benefited more from these measures than patients with severe strokes. Increased CF rates for patients with severe stroke may be caused by shorter hospital stays, shorter in-hospital rehabilitation periods and lack of suitable care after discharge from hospital.

  • 17.
    Appelros, Peter
    et al.
    Örebro University, Department of Clinical Medicine.
    Nydevik, Ingegerd
    Terént, Andreas
    Living setting and utilisation of ADL assistance one year after a stroke with special reference to gender differences2006In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 28, no 1, p. 43-49Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine living setting and need for ADL assistance before and one year after a first-ever stroke with special focus on gender differences. METHODS: One-year survivors from a population-based stroke study (n = 377) were studied with regard to place of living, need for ADL assistance and who provided the help. Stroke severity, cognitive impairment, post-stroke depression as well as risk factors were evaluated. RESULTS: Before the stroke 48 patients (13%) lived in special housing (service flats or nursing homes), and one year after the stroke, 50 of the survivors (20%) lived in such accommodations. Before the stroke, 80 (21%) of the patients needed help with their personal ADL, while 90 (36%) needed help after one year. The increased need was fulfilled by relatives. Female spouses more often helped their male counterparts, and they tended to accept a heavier burden. Age, living alone, stroke severity, cognitive impairment, pre-stroke ADL dependency and depression were predictors for special housing. CONCLUSIONS: In a time when more and more stroke survivors are cared for at home, it is important to pay attention to the situation of the caregivers. Female caregivers seem to be in an especially exposed position by accepting a heavier burden.

  • 18.
    Axén, Iben
    et al.
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden.
    Bergström, Gunnar
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden.
    Using few and scattered time points for analysis of a variable course of pain can be misleading: an example using weekly text message data2014In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 14, no 8, p. 1454-1459Article in journal (Refereed)
    Abstract [en]

    Background context: Because low back pain (LBP) is a fluctuating condition, the diversity in the prediction literature may be due to when the outcome is measured.

    Purpose: The objective of this study was to investigate the prediction of LBP using an outcome measured at several time points.

    Study design/setting: A multicenter clinical observational study in Sweden.

    Patient sample: Data were collected on 244 subjects with nonspecific LBP. The mean age of the subjects was 44 years, the mean pain score at inclusion was 4.4/10, and 51% of the sample had experienced LBP for more than 30 days the previous year.

    Outcome measures: The outcome used in this study was the “number of days with bothersome pain” collected with weekly text messages for 6 months.

    Methods: In subjects with nonspecific LBP, weekly data were available for secondary analyses. A few baseline variables were chosen to investigate prediction at different time points: pain intensity, the presence of leg pain, duration of LBP the previous year, and self-rated health at baseline. Age and gender acted as additional covariates.

    Results: In the multilevel models, the predictive variables interacted with time. Thus, the risk of experiencing a day with bothersome LBP varied over time. In the logistic regression analyses, the predictive variable's previous duration showed a consistent predictive ability for all the time points. However, the variables pain intensity, leg pain, and self-rated health showed inconsistent predictive patterns.

    Conclusions: An outcome based on frequently measured data described the variability in the prediction of future LBP over time. Prediction depended on when the outcome was measured. These results may explain the diversity of the results of the predictor studies in the literature.

  • 19. Bahmanyar, S.
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Hillert, J.
    Ekbom, A.
    Olsson, T.
    Cancer risk among patients with multiple sclerosis and their parents2009In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 72, no 13, p. 1170-1177Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

  • 20.
    Bejerot, Susanne
    et al.
    Norra Stockholms psykiatri, Stockholm, Sweden.
    Bruno, Kai
    BUP Brommaplan, Stockholm, Sweden.
    Gerland, Gunilla
    Lindquist, Lars
    Infektionskliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Nordin, Viviann
    Sachsska barn- och ungdomssjukhuset, Södersjukhuset, Stockholm, Sweden.
    Pelling, Henrik
    BUP-kliniken, Akademiska sjukhuset, Uppsala, Sweden.
    Humble, Mats B.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Misstänk PANDAS hos barn med akuta neuropsykiatriska symptom. Infektion bakom sjukdomen [Suspect PANDAS in children with acute neuropsychiatric symptoms. Infection behind the disease]: långvarig antibiotikabehandling bör övervägas  [long-term antibiotic therapy should be considered]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 41, p. 1803-1803, article id CDCDArticle in journal (Refereed)
  • 21.
    Bejerot, Susanne
    et al.
    Örebro University, School of Medical Sciences.
    Edman, Gunnar
    Department of Clinical Sciences, Danderyds Sjukhus, Karolinska Institutet, Solna, Sweden..
    Frisén, Louise
    Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
    Humble, Mats B.
    Örebro University, School of Medical Sciences.
    Evidence-Based Brief Obsessive-Compulsive Scale2017In: Journal of Central Nervous System Disease, ISSN 1179-5735, E-ISSN 1179-5735, Vol. 9, article id UNSP 1179573517702867Article in journal (Other academic)
  • 22.
    Bejerot, Susanne
    et al.
    Norra Stockholms psykiatri, Stockholm, Sweden.
    Gardner, Ann
    Järvapsykiatrin, institutionen för klinisk neurovetenskap, Karolinska institutet, Stockholm, Sweden.
    Humble, Mats B.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Diagnostik och terapi utmanar än, trots snabb tillväxt av kunskap [Diagnosis and therapy are still challenging, despite the rapid growth of knowledge]2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 39, p. 1638-1641, article id CYRHArticle, review/survey (Refereed)
    Abstract [sv]

    Psychiatric diagnoses are not reflections of the aetiology of the disorder, but rather lists of symptoms with considerable overlaps, which hamper research and may cause confusion. The diagnoses of autism spectrum disorder, attention deficit hyperactivity disorder and tic disorder are often comorbid along with a number of other symptomatic syndromes. Individual immune responsivity is possibly involved in pathophysiological mechanisms. Multiple environmental factors may contribute to the clinical phenotypes. Recent research supports to some extent the involvement of dietary and nutritional factors in ADHD. In spite of impressive progress in the molecular biological understanding of the pathophysiology of these disorders, treatment options are still limited and more research is warranted.

  • 23.
    Bejerot, Susanne
    et al.
    Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nordin, Viviann
    Karolinska Institutet, Stockholm, Sweden.
    Autismspektrumsyndrom ersätter Aspergers syndrome och autism [Autism spectrum syndrome replaces Asperger syndrome and autism].2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 39, p. 1660-1663, article id CUH6Article in journal (Refereed)
    Abstract [sv]

    Autism spectrum disorder describes a behaviourally defined impairment in social interaction and communication, along with the presence of restricted interests and repetitive behaviours. Although the etiology is mostly unknown, it is evident that biological factors affect the brain and result in the autistic clinical presentation. Assessment for diagnosing autism spectrum disorder should be comprehensive in order to cover all sorts of problems related to the disorder. Knowledge and experience from working with neurological and psychiatric disorders are a prerequisite for quality in the examination. Up to now, there is no cure for autism spectrum disorder, but support and adaptations in education are nevertheless important for obtaining sufficient life quality for the patients and the family.

  • 24.
    Bejerot, Susanne
    et al.
    Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institute, Stockholm, Sweden .
    Rydén, Eleonore M.
    Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institute, Stockholm, Sweden .
    Arlinde, Christina M
    Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institute, Stockholm, Sweden .
    Two-year outcome of treatment with central stimulant medication in adult attention-deficit/hyperactivity disorder: a prospective study2010In: Journal of Clinical Psychiatry, ISSN 0160-6689, E-ISSN 1555-2101, Vol. 71, no 12, p. 1590-1597Article in journal (Refereed)
    Abstract [en]

    Background: Given that adults with ADHD continue to use stimulants for extended periods of time, studies on the long-term effectiveness and adverse events are warranted. The aims of this study were to investigate factors associated with persistence in treatment in an exploratory manner and to document side effects and reasons for discontinuation.

    Method: The current study describes the systematic follow-up of 133 psychiatric patients with DSM-IV-diagnosed ADHD treated with central stimulants at a specialized outpatient unit between January 1, 2001, and August 31, 2006. A standardized questionnaire, derived from the Targeted Attention-deficit Disorder Symptoms Rating Scale, was used in order to measure improvement of the following target symptoms: hyperactivity, impulsivity, irritability, distractibility, structure/organization problems, inattention, and restlessness.

    Results: Eighty percent of the patients were successfully treated with stimulants at the 6- to 9-month follow-up. Fifty percent remained in treatment after 2 years or more. Forty-five percent were treated for comorbid anxiety and/or depression during the study period. Only 15% dropped out because of lack of efficacy. The amount of clinical response over the first 6 to 9 months (but not at 6 weeks) predicted adherence to treatment at 2 years. The patients' heart rate increased from a least squares mean ± SE of 70 ± 2.2 to 80 ± 2.1 bpm (P = .00003) while blood pressure remained unchanged at the ≥ 2-year follow-up. Severe side effects or drug abuse were not detected in this cohort.

    Conclusions: The long-term treatment outcome shows that stimulants are effective in adult ADHD and side effects tend to be mild.

  • 25.
    Benoit, Daniel L
    et al.
    nstitution for Surgical Sciences, Section of Sports Medicine, Karolinska Institute, Stockholm, Sweden; Department of Orthopaedics, Karolinska Hospital, Stockholm, Sweden; Department of Mechanical Engineering, University of Delaware, 106 Spencer Lab, Newark, DE 19711, United States.
    Ramsey, Dan K
    Department of Physical Therapy, University of Delaware, Newark, DE, United States.
    Lamontagne, Mario
    School of Human Kinetics, University of Ottawa, Ottawa, Canada; Department of Mechanical Engineering, University of Ottawa, Ottawa, Canada.
    Xu, Lanyi
    School of Human Kinetics, University of Ottawa, Ottawa, Canada.
    Wretenberg, Per
    Örebro University Hospital. Department of Orthopaedics, Karolinska Hospital, Stockholm, Sweden; Institution for Surgical Sciences, Section of Orthopaedics, Karolinska Institute, Stockholm, Sweden.
    Renström, Per
    Institution for Surgical Sciences, Section of Sports Medicine, Karolinska Institute, Stockholm, Sweden; Department of Orthopaedics, Karolinska Hospital, Stockholm, Sweden.
    Effect of skin movement artifact on knee kinematics during gait and cutting motions measured in vivo2006In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 24, no 2, p. 152-164Article in journal (Refereed)
    Abstract [en]

    Eight healthy male subjects had intra-cortical bone-pins inserted into the proximal tibia and distal femur. Three reflective markers were attached to each bone-pin and four reflective markers were mounted on the skin of the tibia and thigh, respectively. Roentgen-stereophotogrammetric analysis (RSA) was used to determine the anatomical reference frame of the tibia and femur. Knee joint motion was recorded during walking and cutting using infrared cameras sampling at 120Hz. The kinematics derived from the bone-pin markers were compared with that of the skin-markers. Average rotational errors of up to 4.4 degrees and 13.1 degrees and translational errors of up to 13.0 and 16.1mm were noted for the walk and cut, respectively. Although skin-marker derived kinematics could provide repeatable results this was not representative of the motion of the underlying bones. A standard error of measurement is proposed for the reporting of 3D knee joint kinematics.

  • 26.
    Bergh, Cecilia
    et al.
    Örebro University, School of Medical Sciences.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Appelros, Peter
    Department of Neurology, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Determinants in adolescence of stroke-related hospital stay duration in men: a national cohort study2016In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 47, no 9, p. 2416-2418Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke.

    Methods: Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first.

    Results: Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45).

    Conclusions: Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors.

  • 27.
    Bergh, Cecilia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Physiotherapy, Örebro University Hospital, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nilsagård, Ylva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Appelros, Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Departnment of Epidemiology and Public Health, University College London, London, UK; Cinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Stress resilience in male adolescents and subsequent stroke risk: cohort study2014In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 12, p. 1331-1336Article in journal (Refereed)
    Abstract [en]

    Objective Exposure to psychosocial stress has been identified as a possible stroke risk, but the role of stress resilience which may be relevant to chronic exposure is uncertain. We investigated the association of stress resilience in adolescence with subsequent stroke risk.

    Methods Register-based cohort study. Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Cox regression estimated the association of stress resilience with stroke, after adjustment for established stroke risk factors.

    Results Some 3411 diagnoses of first stroke were identified. Lowest stress resilience (21.8%) compared with the highest (23.7%) was associated with increased stroke risk, producing unadjusted HR (with 95% CIs) of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to 1.63) after adjustment for markers of socioeconomic circumstances in childhood; and after further adjustment for markers of development and disease in adolescence (blood pressure, cognitive function and pre-existing cardiovascular disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further adjustment for markers of physical fitness (BMI and physical working capacity) in adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude associations for fatal rather than non-fatal, and for haemorrhagic rather than ischaemic stroke.

    Conclusions Stress susceptibility and, therefore, psychosocial stress may be implicated in the aetiology of stroke. This association may be explained, in part, by poorer physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress.

  • 28.
    Bergström, Gunnar
    et al.
    Division of Intervention and Implementation Research, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Bergström, Cecilia
    Division of Intervention and Implementation Research, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Hagberg, Jan
    Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bodin, Lennart
    Division of Intervention and Implementation Research, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Jensen, Irene
    Division of Intervention and Implementation Research, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    A 7-year follow-up of multidisciplinary rehabilitation among chronic neck and back pain patients: Is sick leave outcome dependent on psychologically derived patient groups?2010In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 14, no 4, p. 426-433Article in journal (Refereed)
    Abstract [en]

    A valid method for classifying chronic pain patients into more homogenous groups could be useful for treatment planning, that is, which treatment is effective for which patient, and as a marker when evaluating treatment outcome. One instrument that has been used to derive subgroups of patients is the Multidimensional Pain Inventory (MPI). The primary aim of this study was to evaluate a classification method based on the Swedish version of the MPI, the MPI-S, to predict sick leave among chronic neck and back pain patients for a period of 7 years after vocational rehabilitation. As hypothesized, dysfunctional patients (DYS), according to the MPI-S, showed a higher amount of sickness absence and disability pension expressed in days than adaptive copers (AC) during the 7-years follow-up period, even when adjusting for sickness absence prior to rehabilitation (355.8days, 95% confidence interval, 71.7; 639.9). Forty percent of DYS patients and 26.7% of AC patients received disability pension during the follow-up period. However, this difference was not statistically significant. Further analyses showed that the difference between patient groups was most pronounced among patients with more than 60days of sickness absence prior to rehabilitation. Cost-effectiveness calculations indicated that the DYS patients showed an increase in production loss compared to AC patients. The present study yields support for the prognostic value of this subgroup classification method concerning long-term outcome on sick leave following this type of vocational rehabilitation.

  • 29.
    Biström, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Andersen, O.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Alonso-Magdalena, L.
    Department of Neurology, Skåne University Hospital, Malmö, Sweden.
    Gunnarsson, Martin
    Örebro University, School of Medical Sciences. Department of Neurology.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Hultdin, J.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    High serum concentrations of vitamin D may protect against multiple sclerosis2018In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, no Suppl. 2, p. 1001-1002Article in journal (Other academic)
  • 30.
    Biström, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Hultdin, J.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Andersen, O.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Alonso-Magdalena, L.
    Department of Neurology, Skåne University Hospital, Malmö, sweden.
    Jons, D.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Gunnarsson, Martin
    Örebro University, School of Medical Sciences. Department of Neurology.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Leptin levels are associated with multiple sclerosis risk2019In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, no Suppl. 2, p. 904-904Article in journal (Other academic)
    Abstract [en]

    Introduction: One environmental factor that in the last decade repeatedly has been linked to increased risk of developing multiple sclerosis (MS) is overweight, including obesity, early in life. The incidence of both MS and overweight are increasing, making elucidation of this connection important. The adipokine leptin is strongly correlated to both body mass index and total fat mass and the peptide hormone insulin is associated with obesity and type 2 diabetes, making leptin and insulin suitable biomarkers to investigate the connection between overweight and MS.

    Objectives: To determine if leptin or insulin are risk factors for developing relapsing MS.

    Aims: To further the understanding of how overweight influence MS risk.

    Methods: In this case-control study, we compared concentrations of leptin and insulin in 649 individuals that later developed relapsing-remitting MS with 649 matched controls. Cases were matched for biobank, sex, date of sampling and age with decreasing priority. Only prospectively collected samples from individuals below the age of 40 were included in the study. Conditional logistic regression was performed on log10 transformed and z-scored values for the entire group, separately for men and women and divided into age groups.

    Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals below 20 years of age (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.9) and for all men (OR 1.4, 95% CI 1.0–2.0). In contrast, for women aged 30-39 years there was a lower risk of MS with increased leptin levels (OR 0.74, 95% CI 0.54–1.0) when adjusting for insulin levels. No statistically significant association was found between insulin levels and MS risk.

    Conclusions: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals. The age dependent relationship between leptin and MS risk in women - for whom leptin levels are several-fold higher than in men - suggests a possible role for leptin as being the link between MS risk and being overweight early in life.

  • 31. Bjerkenstedt, Lars
    et al.
    Farde, Lars
    Terenius, Lars
    Edman, Gunnar
    Venizelos, Nikolaos
    Örebro University, Department of Clinical Medicine.
    Wiesel, Frits-Axel
    Support for limited brain availability of tyrosine in patients with schizophrenia2006In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 9, no 2, p. 247-255Article in journal (Refereed)
    Abstract [en]

    Several mechanisms have been suggested to account for altered dopaminergic neurotransmission in schizophrenia. The brain is the only organ for which amino-acid transport is limited and competition for transport over the blood-brain barrier (BBB) occurs at physiological plasma concentrations. One line of research suggests that patients with schizophrenia have altered brain levels of the essential amino acid tyrosine, the precursor for the synthesis of dopamine. The most common hypothesis is that less tyrosine is available because of competition with elevated levels of other amino acids. By consequence, the synthesis of dopamine in the brain will decrease. In contrast, another line of evidence suggests a change in the affinity for one of the transport proteins. A limitation of this research has been that the systems for amino-acid transport across the BBB have not been fully characterized at a molecular or functional level. The L system is the major system for transport of tyrosine across cell membranes including the BBB. The A system is also involved in this transport. Earlier in-vitro studies using fibroblasts have demonstrated a normal L system in schizophrenia but nevertheless reduced tyrosine transport. The combination of molecular research, fibroblast techniques, and brain imaging provides a new basis for clinical research on the role of amino-acid membrane transport in schizophrenia.

  • 32.
    Björk, Tabita
    et al.
    Psychiatric Research Centre, Örebro County Council, Örebro, Sweden; Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Brus, Ole
    Örebro University Hospital, Örebro, Sweden.
    Osika, Walter
    Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Primary Care and Public Health, Charing Cross Hospital, Imperial College, London, UK.
    Laterality, hand control and scholastic performance: a British birth cohort study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 2, article id e000314Article in journal (Refereed)
    Abstract [en]

    Objectives: To use simple measures of laterality and hand control that can identify a greater risk of poorer scholastic ability, potentially signalling suboptimal hemispheric lateralisation.

    Design: Analysis of material from a birth cohort study.

    Setting: Members of the National Child Development Study, a British birth cohort study following people born in 1958.

    Participants: 10 612 children who undertook tests at age 11 years.

    Primary outcome measures: Teacher-administered tests of non-verbal general ability, verbal general ability, reading comprehension and mathematics.

    Results: Linear regression produced associations (and 95% CIs) with tests of verbal general ability, non-verbal general ability, reading comprehension and mathematics scores for the lowest third (compared with highest) of a left-hand control test involving picking up matches of -1.21 (-1.73 to -0.68; p<0.001), -0.72 (-1.14 to -0.29; p=0.001), -0.70 (-1.06 to -0.35; p<0.001) and -1.32 (-1.90 to -0.73; p<0.001). Among those in the lowest third of the right-hand control test score, mixed-handedness compared with right-handedness was associated with poorer scholastic performance, with regression coefficients (and 95% CIs; p values) of 1.90 (-3.01 to -0.80; p=0.001), -1.25 (-2.15 to -0.35; p=0.007), -1.28 (2.04 to -0.53; p=0.001) and -1.33 (-2.53 to -0.13; p=0.030). The estimates are for a point change in the scholastic test scores, after adjustment for sex, left-hand motor function and social class. Statistically significant associations with mixed-handedness were only observed for the lowest third of right-hand motor function.

    Conclusions: Measures involving poorer left-hand motor function may represent useful markers of reduced cognitive function possibly reflecting suboptimal hemispheric lateralisation. Crude measures of laterality such as reported non-right-handedness may be more useful for research when combined with measures of motor function.

  • 33.
    Bloniecki, Victor
    et al.
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
    Aarsland, Dag
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Cummings, Jeffrey
    Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
    Falahati, Farshad
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
    Winblad, Bengt
    Department of Neurobiology, Caring Sciences and Society (NVS), Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institute, Huddinge, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 57, no 2, p. 387-393Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment for neuropsychiatric symptoms (NPS) in dementia is insufficient. Antipsychotics and acetylcholinesterase inhibitors are used generating symptomatic improvements in behavior and cognition, but few studies have investigated their effect on Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF).

    OBJECTIVE: This is a secondary analysis based on an earlier clinical trial comparing the treatment effects on NPS. The aim of this study was to examine whether treatment with risperidone and galantamine affect levels of the biomarkers T-Tau, P-Tau, Aβ1-42, and Aβ42/40-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS.

    METHODS: 83 patients (mean + SD 77.9.6±7.7 years) with dementia and NPS were randomized to galantamine (n = 44) or risperidone (n = 39) treatment. CSF samples were collected at baseline and after 12 weeks.

    RESULTS: Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of Aβ1 - 42 was significantly associated with reduction of irritability at follow up. Low baseline levels of Aβ1-42, Aβ42/40, and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF Aβ1-42 levels in patients treated with risperidone were significantly decreased at follow up, showing an 8% (40 pg/mL) reduction as compared with baseline (p = 0.03).

    CONCLUSIONS: Our results suggest that risperidone may affect the CSF profile of AD biomarkers indicating more amyloid pathology. Treatment with galantamine did not affect the CSF biomarkers in any direction. The AD CSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.

  • 34.
    Bloniecki, Victor
    et al.
    Division of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Aarsland, Dag
    Center for Alzheimer Research, Division for Neurogeriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
    Cummings, Jeffrey
    Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nev., USA.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Agitation in dementia: relation to core cerebrospinal fluid biomarker levels2014In: Dementia and geriatric cognitive disorders extra, E-ISSN 1664-5464, Vol. 4, no 2, p. 335-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and Aβ1-42.

    METHODS: One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points).

    RESULTS: Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95).

    CONCLUSIONS: Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD.

  • 35.
    Boersma, Katja
    Örebro University, School of Law, Psychology and Social Work.
    Is the search for a "pain personality" of added value to the Fear-Avoidance-Model (FAM) of chronic pain?2017In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, no October, p. 226-227Article in journal (Refereed)
  • 36.
    Boersma, Katja
    et al.
    Örebro University, School of Law, Psychology and Social Work.
    Linton, Steven J.
    Örebro University, School of Law, Psychology and Social Work.
    Editorial comment on Nina Kreddig's and Monika Hasenbring's study on pain anxiety and fear of (re) injury in patients with chronic back pain: Sex as a moderator2017In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 16, p. 89-90, article id S1877-8860(17)30050-2Article in journal (Refereed)
  • 37.
    Borgestig, Maria
    et al.
    Department of Social and Welfare Studies, Linköping University, Linköping, Sweden; Folke Bernadotte Regional Habilitation Centre and Department of Women´s and Children´s Health, Uppsala University, Uppsala, Sweden.
    Rytterström, Patrik
    Department of Social and Welfare Studies, Linköping University, Linköping, Sweden.
    Hemmingsson, Helena
    Department of Social and Welfare Studies, Linköping University, Linköping, Sweden.
    Gaze-based assistive technology used in daily life by children with severe physical impairments: parents’ experiences2017In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, no 5, p. 301-308Article in journal (Refereed)
    Abstract [en]

    Objective: To describe and explore parents’ experiences when their children with severe physical impairments receive gaze-based assistive technology (gaze-based assistive technology (AT)) for use in daily life.

    Methods: Semi-structured interviews were conducted twice, with one year in between, with parents of eight children with cerebral palsy that used gaze-based AT in their daily activities. To understand the parents’ experiences, hermeneutical interpretations were used during data analysis.

    Results: The findings demonstrate that for parents, children’s gaze-based AT usage meant that children demonstrated agency, provided them with opportunities to show personality and competencies, and gave children possibilities to develop. Overall, children’s gaze-based AT provides hope for a better future for their children with severe physical impairments; a future in which the children can develop and gain influence in life.

    Conclusion: Gaze-based AT provides children with new opportunities to perform activities and take initiatives to communicate, giving parents hope about the children’s future.

  • 38.
    Borgestig, Maria
    et al.
    Department of Social and Welfare Studies, Linköping University, Linköping, Sweden; Department of Women´s and Children´s Health, Uppsala University, Uppsala, Sweden; Folke Bernadotte Regional Habilitation Centre, Uppsala University, Uppsala, Sweden.
    Sandqvist, Jan
    Department of Social and Welfare Studies, Linköping University, Linköping, Sweden.
    Ahlsten, Gunnar
    School of Occupational Therapy & Social Work, Curtin University, Perth WA, Australia; School of Occupational Therapy, La Trobe University, Melbourne VIC, Australia; Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University & Pain and Rehabilitation Centre (UHL), County Council, Linköping, Sweden.
    Falkmer, Torbjorn
    Avdelningen för samhällsmedicin, Linköpings universitet, Linköping, Sweden.
    Hemmingsson, Helena
    Department of Social and Welfare Studies, Linköping University, Linköping, Sweden.
    Gaze-based assistive technology in daily activities in children with severe physical impairments: an intervention study2017In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, no 3, p. 129-141Article in journal (Refereed)
    Abstract [en]

    Objective: To establish the impact of a gaze-based assistive technology (AT) intervention on activity repertoire, autonomous use, and goal attainment in children with severe physical impairments, and to examine parents’ satisfaction with the gaze-based AT and with services related to the gaze-based AT intervention.

    Methods: Non-experimental multiple case study with before, after, and follow-up design. Ten children with severe physical impairments without speaking ability (aged 1–15 years) participated in gaze-based AT intervention for 9–10 months, during which period the gaze-based AT was implemented in daily activities.

    Results: Repertoire of computer activities increased for seven children. All children had sustained usage of gaze-based AT in daily activities at follow-up, all had attained goals, and parents’ satisfaction with the AT and with services was high.

    Discussion: The gaze-based AT intervention was effective in guiding parents and teachers to continue supporting the children to perform activities with the AT after the intervention program.

  • 39.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Verhey, Frans R.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Ramakers, Inez H. G. B.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Jacobs, Heidi I. L.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Soininen, Hilkka
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter & Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Hampel, Harald
    AXA Research Fund and UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France; Institut du cerveau et de la moelle (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Memory and Dementia Center, 3rd Department of Neurology, “G Papanicolau” General Hospital, Thessaloniki, Greece.
    Wallin, Åsa K.
    Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
    van Buchem, Mark A.
    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
    Oleksik, Ania
    Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
    Verbeek, Marcel M.
    Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, The Netherlands.
    Olde Rikkert, Marcel
    Radboudumc Alzheimer Centre, Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
    van der Flier, Wiesje M.
    Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Scheltens, Philip
    Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Aalten, Pauline
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands; Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Vos, Stephanie J. B.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline2017In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 9, no 1, article id 101Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia.

    METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ1-42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics.

    RESULTS: MTA and t-tau were elevated in the Aβ - WMH+, Aβ + WMH-, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline.

    CONCLUSIONS: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.

  • 40.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Vos, Stephanie J. B.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Jansen, Willemijn J.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Vandenberghe, Rik
    University Hospital Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences KU Leuven, Leuven, Belgium.
    Gabel, Silvy
    Laboratory for Cognitive Neurology, Department of Neurosciences KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven, Belgium.
    Estanga, Ainara
    Center for Research and Advanced Therapies CITA-Alzheimer Foundation, San Sebastián, Spain.
    Ecay-Torres, Mirian
    Center for Research and Advanced Therapies CITA-Alzheimer Foundation, San Sebastián, Spain.
    Tomassen, Jori
    Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center VU University Amsterdam, Amsterdam, Netherlands.
    den Braber, Anouk
    Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center VU University Amsterdam, Amsterdam, Netherlands; Department of Biological Psychology VU University Amsterdam, Amsterdam, Netherlands.
    Lleó, Alberto
    Department of Neurology Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Sala, Isabel
    Department of Neurology Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Wallin, Anders
    Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.
    Kettunen, Petronella
    Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Molinuevo, José L.
    Alzheimer's Disease & Other Cognitive Disorders Unit, Hopsital Clínic Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Barcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.
    Rami, Lorena
    Alzheimer's Disease & Other Cognitive Disorders Unit, Hopsital Clínic Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
    Chetelat, Gaël
    Institut National de la Santé et de la Recherche Médicale UMR-S U1237, Université de Caen-Normandie GIP Cyceron, Caen, France.
    de la Sayette, Vincent
    Institut National de la Santé et de la Recherche Médicale U1077, Université de Caen Normandie Ecole Pratique des Hautes Etudes, Caen, France; CHU de Caen Service de Neurologie, Caen, France.
    Tsolaki, Magda
    1st Department of Neurology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, Norrtälje Hospital Tiohundra, Norrtälje, Sweden.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
    Novak, Gerald P.
    Janssen Pharmaceutical Research and Development, Titusville, NJ, United States.
    Ramakers, Inez
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Verhey, Frans R.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.2018In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 10, article id 193Article in journal (Refereed)
    Abstract [en]

    We investigated whether amyloid-β (Aβ) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had Aβ status and neuropsychological data available. Linear mixed models were used to assess the associations of Aβ and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with Aβ status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without Aβ pathology (Aβ- norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the Aβ- norms rightfully identified an additional group of individuals at risk of dementia. For non-memory test we found no difference. We confirmed the relationship between Aβ and cognition in cognitively normal individuals. The Aβ- norms for memory tests in combination with published norms improve prognostic accuracy of dementia.

  • 41.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands.
    Vos, Stephanie J.
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
    Kornhuber, Johannes
    Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
    Wiltfang, Jens
    Department of Psychiatry and Psychotherapy, University Medical Center (UMC), Georg-August-University, Göttingen, Germany.
    Maier, Wolfgang
    Department of Psychiatry and Psychotherapy, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
    Peters, Oliver
    Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
    Rüther, Eckhart
    Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
    Engelborghs, Sebastiaan
    Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
    Niemantsverdriet, Ellis
    Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
    De Roeck, Ellen Elisa
    Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; Department of Clinical and Lifespan Psychology, Vrije Universiteit Brussel, Brussels, Belgium.
    Tsolaki, Magda
    3rd Department of Neurology, Aristotle University of Thessaloniki, Memory and Dementia Center, “G Papanicolau” General Hospital, Thessaloniki, Greece.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    Vandenberghe, Rik
    Department of Neurology, University of Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium.
    Lleó, Alberto
    Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Alcolea, Daniel
    Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Frisoni, Giovanni B.
    Geneva Neuroscience Center, University Hospital and University of Geneva, Geneva, Switzerland; IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Galluzzi, Samantha
    IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Nobili, Flavio
    Clinical Neurology, Department of Neurosciences (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy.
    Morbelli, Silvia
    Nuclear Medicine, Department of Health Science (DISSAL), University of Genoa IRCCS AOU San Martino-IST, Genoa, Italy.
    Drzezga, Alexander
    Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
    Didic, Mira
    AP-HM Hôpitaux de la Timone, Service de Neurologie et Neuropsychologie, Marseille, France; Aix-Marseille Université, INSERM, Institut de Neurosciences des Systèmes, Marseille, France.
    van Berckel, Bart N.
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
    Salmon, Eric
    Department of Neurology and Memory Clinic, CHU Liège, Liège, Belgium; GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium.
    Bastin, Christine
    GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium.
    Dauby, Solene
    Department of Neurology and Memory Clinic, CHU Liège, Liège, Belgium.
    Santana, Isabel
    Department of Neurology and Memory Clinic, CHU Liège, Liège, Belgium.
    Baldeiras, Inês
    Center for Neuroscience and Cell Biology, Faculty of Medicine, Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
    de Mendonça, Alexandre
    Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Portugal.
    Silva, Dina
    Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Portugal.
    Wallin, Anders
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nordlund, Arto
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Coloma, Preciosa M.
    Real World Data Science (RWD-S) Neuroscience and Established Products, F. Hoffmann-La Roche Ltd. Pharmaceuticals Division, Basel, Switzerland.
    Wientzek, Angelika
    PDB RWD (Real World Data) Team, Roche Products Limited, Welwyn Garden City, UK; Epidemiologische Beratung und Literatur-Recherche “conepi”, Herrsching, Germany.
    Alexander, Myriam
    PDB RWD (Real World Data) Team, Roche Products Limited, Welwyn Garden City, UK.
    Novak, Gerald P.
    Janssen Pharmaceutical Research and Development, Titusville, NJ, USA.
    Gordon, Mark Forrest
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA.
    Wallin, Åsa K.
    Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
    Hampel, Harald
    Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, AXA Research Fund & UPMC Chair, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Paris, France; Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
    Soininen, Hilkka
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
    Herukka, Sanna-Kaisa
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
    Scheltens, Philip
    Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Verhey, Frans R.
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands; Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    The frequency and influence of dementia risk factors in prodromal Alzheimer's disease2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 56, p. 33-40Article in journal (Refereed)
    Abstract [en]

    We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.

  • 42.
    Bos, Isabelle
    et al.
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Vos, Stephanie
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Verhey, Frans
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Scheltens, Philip
    Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
    Teunissen, Charlotte
    Neurochemistry Lab and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, the Netherlands.
    Engelborghs, Sebastiaan
    Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
    Sleegers, Kristel
    Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Frisoni, Giovanni
    University of Geneva, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Blin, Olivier
    Mediterranean Institute of Cognitive Neuroscience, Aix Marseille University, Marseille, France.
    Richardson, Jill C.
    Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
    Bordet, Régis
    University of Lille, Inserm, CHU Lille, Lille, France.
    Tsolaki, Magda
    1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
    Popp, Julius
    Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland; Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Peyratout, Gwendoline
    Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Martinez-Lage, Pablo
    Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Tainta, Mikel
    Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Lleó, Alberto
    Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Psychiatry Norrtälje Hospital Tiohundra, Norrtäije, Sweden.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
    Vandenberghe, Rik
    University Hospital Leuven, Leuven, Belgium.
    Westwood, Sarah
    University of Oxford, Oxford, United Kingdom.
    Dobricic, Valerija
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
    Barkhof, Frederik
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
    Legido-Quigley, Cristina
    Steno Diabetes Center, Copenhagen, Denmark; King's College London, London, UK.
    Bertram, Lars
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; School of Public Health, Imperial College London, London, UK; Department of Psychology, University of Oslo, Oslo, Norway.
    Lovestone, Simon
    University of Oxford, Oxford, United Kingdom.
    Streffer, Johannes
    Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Early Clinial Neurology, UCB Biopharma SPRL, Braine-l'Alleud, Belgium.
    Andreasson, Ulf
    Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden.
    Blennow, Kaj
    Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK.
    Visser, Pieter Jelle
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
    Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum2019In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 5, p. 644-654Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).

    METHODS: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.

    RESULTS: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.

    DISCUSSION: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.

  • 43.
    Brander, Gustaf
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Isomura, Kayoko
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Chang, Zheng
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Association of Tourette Syndrome and Chronic Tic Disorder With Metabolic and Cardiovascular Disorders2019In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, no 4, p. 454-461Article in journal (Refereed)
    Abstract [en]

    Importance: There are limited data concerning the risk of metabolic and cardiovascular disorders among individuals with Tourette syndrome (TS) or chronic tic disorder (CTD).

    Objective: To investigate the risk of metabolic and cardiovascular disorders among individuals with TS or CTD over a period of 40 years.

    Design, Settings, and Participants: This longitudinal population-based cohort study included all individuals living in Sweden between January 1, 1973, and December 31, 2013. Families with clusters of full siblings discordant for TS or CTD were further identified. Data analyses were conducted from August 1, 2017, to October 11, 2018.

    Exposures: Previously validated International Classification of Diseases diagnoses of TS or CTD in the Swedish National Patient Register.

    Main Outcomes and Measures: Registered diagnoses of obesity, dyslipidemia, hypertension, type 2 diabetes, and cardiovascular diseases (including ischemic heart diseases, arrhythmia, cerebrovascular diseases and transient ischemic attack, and arteriosclerosis).

    Results: Of the 14 045 026 individuals in the cohort, 7804 individuals (5964 males [76.4%]; median age at first diagnosis, 13.3 years [interquartile range, 9.9-21.3 years]) had a registered diagnosis of TS or CTD in specialist care. Of 2 675 482 families with at least 2 singleton full siblings, 5141 families included siblings who were discordant for these disorders. Individuals with TS or CTD had a higher risk of any metabolic or cardiovascular disorders compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99; 95% CI, 1.90-2.09) and sibling controls (aHR for any disorder, 1.37; 95% CI, 1.24-1.51). Specifically, individuals with TS or CTD had higher risks for obesity (aHR, 2.76; 95% CI, 2.47-3.09), type 2 diabetes (aHR, 1.67; 95% CI, 1.42-1.96), and circulatory system diseases (aHR, 1.76; 95% CI, 1.67-1.86). The risk of any cardiometabolic disorder was significantly greater in males than in females (aHR, 2.13; 95% CI, 2.01-2.26 vs aHR, 1.79; 95% CI, 1.64-1.96), as was the risk of obesity (aHR, 3.24; 95% CI, 2.83-3.70 vs aHR, 1.97; 95% CI, 1.59-2.44). The risks were already evident from childhood (the groups were significantly different by age 8 years) and were significantly reduced with the exclusion of individuals with comorbid attention-deficit/hyperactivity disorder (aHR, 1.52; 95% CI, 1.42-1.62), while excluding other comorbidities did not significantly affect the results. Compared with patients with TS or CTD who were not taking antipsychotics, patients with a longer duration of antipsychotic treatment (>1 year) had significantly lower risks of metabolic and cardiovascular disorders.

    Conclusions and Relevance: The findings of this study suggest that TS and CTD are associated with a substantial risk of metabolic and cardiovascular disorders. The results highlight the importance of carefully monitoring cardiometabolic health in patients with TS or CTD across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder.

  • 44.
    Brander, Gustaf
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mina
    Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Karolinska Institutet, Stockholm, Sweden.
    Serlachius, Eva
    Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences.
    Mataix-Cols, David
    Karolinska Institutet, Stockholm, Sweden.
    Is Tic-Related OCD a Familial Subtype of the Disorder?: A Swedish Population Cohort Study2019In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 85, no 10, p. S221-S221Article in journal (Other academic)
  • 45.
    Brander, Gustaf
    et al.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rydell, Mina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul S.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Serlachius, Eva
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 5, p. 1189-1197Article in journal (Refereed)
    Abstract [en]

    Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

  • 46.
    Brenner, P.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Burkill, S.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Umeå University, Umeå, Sweden.
    Moore, A.
    Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland.
    Geissbuehler, Y.
    Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, S.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medicine, Örebro University, Sweden. DepDepartment of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Multiple sclerosis and risk of completed and attempted suicide - a national cohort study2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no Suppl. 11, p. 23-24Article in journal (Other academic)
    Abstract [en]

    Introduction: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated.

    Objectives: To estimate attempted suicide and completed suicide risks among MS patients using national registers and to assess if the inverse association of higher-level education with completed suicide is affected by MS.

    Methods: A total of 29,617 Swedish MS patients were identified through the Swedish Patient Register and matched (by birth year, sex, vital status at diagnosis and region) with 296,164 people without MS from the general population. Cox regression estimated hazard ratios (HR) (with 95% confidence intervals) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education level, decade of study entry, and previous suicide attempts.

    Results: The adjusted HR for attempted suicide among MS patients is 2.18 (1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (1.53-2.30). Overall, men were at higher risk of completing suicide, while women were at higher risk of attempting suicide. Higher education is inversely associated with completed suicide among the non-MS cohort with an HR of 0.68, (0.51-0.91), but not among MS patients, where the HR is 1.10, (0.60-2.04). MS patients were less likely to use a violent method than the non-MS cohort.

    Conclusion: MS patients are at higher risk of both attempted and completed suicide, and the risk increase is present in both men and women. Possibly the stress and perceived prognosis associated with an MS diagnosis increases the risk of suicide. MS appears to eliminate the protective association of higher education with completed suicide.

  • 47.
    Bridel, Claire
    et al.
    Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Centre, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Gunnarsson, Martin
    Örebro University, School of Medical Sciences.
    Weiss, Edward J.
    UCL Institute of Neurology, London, England.
    Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis2019In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, no 9, p. 1035-1048Article, review/survey (Refereed)
    Abstract [en]

    Key Points: QuestionHow do levels of neurofilament light in cerebrospinal fluid (cNfL) compare between neurological conditions and with healthy controls?

    Findings: Among 10 059 individuals in this systematic review and meta-analysis, cNfL was elevated in most neurological conditions compared with healthy controls, and the magnitude of the increase varies extensively. Although cNfL overlaps between most clinically similar conditions, its distribution did not overlap in frontotemporal dementia and other dementias or in Parkinson disease and atypical parkinsonian syndromes.

    Meaning: The cNfL is a marker of neuronal damage and may be useful to differentiate some clinically similar conditions, such as frontotemporal dementia from Alzheimer disease and Parkinson disease from atypical parkinsonian syndromes.

    This systematic review and meta-analysis assesses the associations of age, sex, and diagnosis with neurofilament light in cerebrospinal fluid and evaluates its potential in discriminating clinically similar conditions.

    Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.

    Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.

    Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.

    Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.

    Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.

    Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses.

    Results: Data were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n=2795), dementias and predementia stages (n=4284), parkinsonian disorders (n=984), and HC (n=1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.

    Conclusions and Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

  • 48.
    Brikell, I.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ghirardi, L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Chang, Z.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, B. M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Kuja-Halkola, R.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    ADHD medications and the risk of epileptic seizures: a pharmacoepidemiological study using nationwide register data2017In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 27, no Suppl. 4, p. S1113-S1114Article in journal (Other academic)
    Abstract [en]

    Background: Attention-deficit/hyperactivity disorder (ADHD) affects 10–30% of children with epilepsy, making it one of the most common comorbidities in epilepsy. Stimulant medications are first line pharmacological treatment of ADHD, yet there areconcerns regarding the safety of stimulant treatment in patients with comorbid ADHD and epilepsy. This is due to the long held view that stimulants may lower the seizure threshold and increase seizure frequency [1]. Evidence for such an effect are however inconsistent and largely based on studies with small sample sizes, highly selected patient populations and observational studies that have not sufficiently addressed issues of confounding [2]. The aim of this pharmacoepidemiological register based study wastherefore to estimate the risk of seizures in relation to ADHD medication use in a population based cohort of individuals with a history of seizures.

    Methods: Using Swedish national registers, we identified a cohort of 62,361 individuals (48% female) born in Sweden between 1960 and 2004, with at least one seizure episode according to ICD codes. Each individual was followed from January 1st 2006, their first seizure or age five, up until December 31st 2013 or death, whichever came first. We identified periods of ADHD medication use (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, and atomoxetine) from the Swedish National Prescribed Drug Register. A period was defined as on-medication when two consecutive prescriptions where no more than 183 days apart, and off-medication if more than 183 daysapart. We obtained information on medical visit for unplanned seizures events from the Swedish National Patient register using ICD codes. We estimated the population level association between ADHD medications and the rate of seizures during medicated and non-medication periods using a cox proportional hazards regression model. To adjust for individual-specific confounding that may influence both seizure risk and the likelihood of receiving ADHD medication, we used a stratified Cox regression model to estimate the rate of seizures during medicated and non-medicated periods, within the same individual.

    Preliminary Result: A total of 59,749 seizure events occurred during 361,501 person years of follow-up. ADHD medications were not associated with the rate of seizures at the population level (HR = 1.06, 95%CI 0.91–1.23). In the within-individual analysis, ADHD medication periods were associated with a reduced rate of seizures (HR = 0.70, 95%CI 0.62–0.79), compared to non-medicated periods. Estimates did not differ across sex, nor in age restricted analyses including only ages 5 and 20 years. All analyses were adjusted for age as a time-varying covariate. Population level analyses were additionally adjusted for sex.

    Conclusions: Our findings suggest that ADHD medications are not associated with an increased risk of seizures. Rather, results from the within-individual analysis, which adjusts for factors that are constant within the individual, such as genetic factors and underlying disorder severity, suggest a protective effect of ADHD medication treatment on seizure rates. Next, we will study the effect of concurrent antiepileptic medication use and whether the observed effect differs by stimulant and non-stimulant ADHD medications. We will also further investigate possible mechanisms contributing to the observed protective effect of ADHD medications on seizure rates.

    References

    [1] Williams, A.E., Giust, J.M., Kronenberger, W.G., Dunn, D.W., 2016. Epilepsy and attention-deficit hyperactivity disorder: links, risks, and challenges. Neuropsychiatr Dis Treat 12, 287–296.

    [2] Ravi, M., Ickowicz, A., 2016. Epilepsy, Attention-Deficit/Hyperactivity Disorder and Methylphenidate: Critical Examination of Guiding Evidence. Journal of the Canadian Academy of Child and Adolescent Psychiatry 25 (1), 50.

  • 49.
    Brikell, Isabell
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Chen, Qi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA.
    Wiggs, Kelsey K.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Quinn, Patrick D.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA.
    Chang, Zheng
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy2019In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 60, no 2, p. 284-293Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) affects 10%-30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy.

    METHODS: A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within-individual to adjust for unmeasured, time?constant confounding.

    RESULTS: Among 995 individuals who initiated ADHD medication during follow-up, within-individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person-years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57-0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders.

    SIGNIFICANCE: We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.

  • 50.
    Brikell, Isabell
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ghirardi, Laura
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States.
    Dunn, David W.
    Department of Psychiatry, Riley Child and Adolescent Psychiatry Clinic, Indiana University School of Medicine, Indiana University Health Physicians, Indianapolis Indiana, United States.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Dalsgaard, Søren
    National Centre for Register-Based Research, Department of Economics, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark; Department for Child and Adolescent Psychiatry, Hospital of Telemark, Kragerø, Norway.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study2018In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.

    METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.

    RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = 20.16-0.79).

    CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.

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