Publications by authors named "Olafur Kjartansson"

46 Publications

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

Neurology 2019 Jan 16. Epub 2019 Jan 16.

Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.

Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.

Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, = 1.77 × 10; and LINC00539/ZDHHC20, = 5.82 × 10. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits ( value for BI, = 9.38 × 10; = 5.23 × 10 for hypertension), smoking ( = 4.4 × 10; = 1.2 × 10), diabetes ( = 1.7 × 10; = 2.8 × 10), previous cardiovascular disease ( = 1.0 × 10; = 2.3 × 10), stroke ( = 3.9 × 10; = 3.2 × 10), and MRI-defined white matter hyperintensity burden ( = 1.43 × 10; = 3.16 × 10), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI ( ≤ 0.0022), without indication of directional pleiotropy.

Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
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http://dx.doi.org/10.1212/WNL.0000000000006851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369905PMC
January 2019

Prevalence of Multiple Sclerosis in Iceland.

Neuroepidemiology 2018 25;51(1-2):50-56. Epub 2018 Jun 25.

University of Iceland, School of Medicine, Reykjavik, Iceland.

Background: In this study, we examined multiple sclerosis (MS) point prevalence in the well-defined island population of Iceland.

Methods: This study included all registered residents of Iceland with MS on the prevalence day, December 31, 2007. All included patients met at least one of the following criteria: McDonald criteria; Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS; or criteria for primary progressive MS. The patients' medical records were reviewed, including all available MRI data acquired prior to the prevalence day.

Results: We identified 526 patients, of whom 73% (382) were women. The crude point prevalence of MS was 167.1 per 100,000 population on the prevalence day. With age adjustment made to the 2000 U.S. population, the prevalence was 166.5 per 100,000 population. The mean patient age on the prevalence day was 47 years(range 13-89) for both men and women. The mean age at diagnosis was 36 years (range 13-77): 35 years for women and 36 years for men.

Conclusion: MS prevalence was high in Iceland compared to the prevalence mentioned in reports from most of the world, and was similar to prevalence rates in other Nordic countries.
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http://dx.doi.org/10.1159/000489472DOI Listing
September 2019

Thyrotoxicosis in a 13-year-old girl following pituitary adenectomy for Cushing's disease.

Clin Case Rep 2017 08 6;5(8):1341-1343. Epub 2017 Jul 6.

Department of Pediatrics Children's Hospital Iceland Landspitali University Hospital Reykjavik Iceland.

Our objective is to report a case of thyrotoxicosis following pituitary adenectomy for Cushing's disease, the only pediatric case to our knowledge. No thyroid antibodies were detected, and the thyrotoxicosis was successfully treated for 3 months with no relapse after 5 years of follow-up. The cause of thyrotoxicosis remains unknown.
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http://dx.doi.org/10.1002/ccr3.1049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538062PMC
August 2017

Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study).

Stroke 2017 09 1;48(9):2353-2360. Epub 2017 Aug 1.

From the Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., O.K., E.F.G., G.E., V.G.); The University of Iceland, Reykjavik (T.A., P.V.J., V.G.); Department of Radiology, Leiden University Medical Center, the Netherlands (M.A.v.B.); Laboratory of Epidemiology and Population Science, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD (L.J.L.); and Department of Psychology, Reykjavik University, Iceland (M.K.J.).

Background And Purpose: The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia.

Methods: Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines.

Results: Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4).

Conclusions: Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels.
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http://dx.doi.org/10.1161/STROKEAHA.117.017357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588878PMC
September 2017

The AGES-Reykjavik study atlases: Non-linear multi-spectral template and atlases for studies of the ageing brain.

Med Image Anal 2017 Jul 6;39:133-144. Epub 2017 May 6.

Biospective Inc, Montreal, Canada.

Quantitative analyses of brain structures from Magnetic Resonance (MR) image data are often performed using automatic segmentation algorithms. Many of these algorithms rely on templates and atlases in a common coordinate space. Most freely available brain atlases are generated from relatively young individuals and not always derived from well-defined cohort studies. In this paper, we introduce a publicly available multi-spectral template with corresponding tissue probability atlases and regional atlases, optimised to use in studies of ageing cohorts (mean age 75 ± 5 years). Furthermore, we provide validation data from a regional segmentation pipeline to assure the integrity of the dataset.
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http://dx.doi.org/10.1016/j.media.2017.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545887PMC
July 2017

Space and location of cerebral microbleeds, cognitive decline, and dementia in the community.

Neurology 2017 May 3;88(22):2089-2097. Epub 2017 May 3.

From the Laboratory of Epidemiology and Population Sciences (J.D., O.M., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Icelandic Heart Association (S.S., G.E., O.K., V.G.), Kopavogur; Faculty of Medicine (P.V.J., V.G.), University of Iceland, Reykjavik; Department of Psychiatry and Neurology (O.L.L.), University of Pittsburgh, Pennsylvania; and Department of Radiology (M.A.v.B.), Leiden University Medical Center, the Netherlands.

Objective: To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people.

Methods: In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5.2 years later. Adjudicated incident dementia cases were diagnosed according to international guidelines.

Results: In the multiple linear regression models adjusted for demographic, genetic, cardiovascular risk, and other cerebrovascular MRI markers, the presence of CMBs located in deep or mixed (deep and lobar) areas was associated with a greater decline in all 3 cognitive domains. Mixed CMBs were the strongest correlate for decline in memory and speed. Compared to those with no CMBs, participants with ≥3 CMBs had a steeper decline in a composite measure of global cognitive function, memory, and speed. Among those with ≥3 deep or mixed CMBs, associations were strongest for memory; the association with speed was strongest in those having ≥3 strictly lobar CMBs. People with ≥3 CMBs, regardless of their locations, had a higher incidence of all-cause dementia and vascular dementia.

Conclusions: Mixed or a higher load of CMBs, with some specificity for location, is associated with accelerated cognitive decline in older people. These findings suggest a role for hypertensive vasculopathy and the combined effect of hypertensive and cerebral amyloid angiopathy in the pathogenesis of cognitive deterioration.
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http://dx.doi.org/10.1212/WNL.0000000000003983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447401PMC
May 2017

Extramedullary Cavernous Hemangioma with Intradural and Extradural Growth and Clinical Symptoms of Brown-Séquard Syndrome: Case Report and Review of the Literature.

World Neurosurg 2017 Feb 17;98:881.e5-881.e8. Epub 2016 Nov 17.

Department of Neurosurgery, Landspítali University Hospital, Reykjavík, Iceland; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

Background: Primary spinal tumors are rare. Symptoms depend on the size and location of the tumor.

Case Description: A patient presented with a rare clinical finding, Brown-Séquard syndrome. The symptoms were caused by an extramedullary tumor compressing on the thoracic spinal cord. Pathologic examination showed cavernous hemangioma with growth both intradurally and extradurally.

Conclusions: This is an extremely rare finding; to our knowledge, only 1 case report has been published before in which a spinal cavernous hemangioma had intradural and extradural growth. The clinical symptoms of Brown-Séquard syndrome have not been described before in the findings of spinal cavernous hemangiomas.
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http://dx.doi.org/10.1016/j.wneu.2016.11.026DOI Listing
February 2017

Late-life brain volume: a life-course approach. The AGES-Reykjavik study.

Neurobiol Aging 2016 May 19;41:86-92. Epub 2016 Feb 19.

Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA. Electronic address:

The "fetal-origins-of-adult-disease" hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Archived birth records of weight and height were abstracted for 1348 participants of the age, gene/environment susceptibility-Reykjavik study (RS; 2002-2006) population-based cohort, who participated in the original cohort of the RS (baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life age, gene/environment susceptibility-RS examination, a brain magnetic resonance imaging was acquired and from it, volumes of total brain, gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low ponderal index [PI]) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (body mass index >25 kg/m(2), hypertension, diabetes, "ever smokers") had smaller total brain volume later in life; B (95% confidence interval) were -10.9 mL (-21.0 to -0.9), -10.9 mL (-20.4 to -1.4), -20.9 mL (-46.9 to 5.2), and -10.8 mL (-19.3 to -2.2), respectively. These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory toward smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk.
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http://dx.doi.org/10.1016/j.neurobiolaging.2016.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751431PMC
May 2016

Midlife Cardiovascular Risk Factors and Late-Life Unrecognized and Recognized Myocardial Infarction Detect by Cardiac Magnetic Resonance: ICELAND-MI, the AGES-Reykjavik Study.

J Am Heart Assoc 2016 Feb 12;5(2). Epub 2016 Feb 12.

National Heart Lung and Blood Institute, NIH, Bethesda, MD.

Background: Associations of atherosclerosis risk factors with unrecognized myocardial infarction (UMI) are unclear. We investigated associations of midlife risk factors with UMI and recognized MI (RMI) detected 31 years later by cardiac magnetic resonance.

Methods And Results: The Reykjavik Study (1967-1991) collected serial risk factors in subjects, mean (SD) age 48 (7) years. In ICELAND-MI (2004-2007), 936 survivors (76 (5) years) were evaluated by cardiac magnetic resonance. Analysis included logistic regression and random effects modeling. Comparisons are relative to subjects without MI. At baseline midlife evaluation, a modified Framingham risk score was significantly higher in RMI and in UMI versus no MI (7.4 (6.3)%; 7.1 (6.2)% versus 5.4 (5.8)%, P<0.001). RMI and UMI were more frequent in men (65%, 64% versus 43%; P<0.0001). Baseline systolic and diastolic blood pressure were significantly higher in UMI (138 (17) mm Hg versus 133 (17) mm Hg; P<0.006; 87 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Diastolic BP was significantly higher in RMI (88 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Cholesterol and triglycerides were significantly higher in RMI (6.7 (1.1) mmol/L versus 6.2 (1.1) mmol/L; P=0.0005; and 1.4 (0.7) mmol/L versus 1.1 (0.7) mmol/L; P<0.003). Cholesterol trended higher in UMI (P=0.08). Serial midlife systolic BP was significantly higher in UMI versus no MI (β [SE] = 2.69 [1.28] mm Hg, P=0.04). Serial systolic and diastolic BP were significantly higher in RMI versus no MI (4.12 [1.60] mm Hg, P=0.01 and 2.05 [0.91] mm Hg, P=0.03) as were cholesterol (0.43 [0.11] mmol/L, P=0.0001) and triglycerides (0.3 [0.06] mmol/L, P<0.0001).

Conclusions: Midlife vascular risk factors are associated with UMI and RMI detected by cardiac magnetic resonance 31 years later. Systolic blood pressure was the most significant modifiable risk factor associated with later UMI.
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http://dx.doi.org/10.1161/JAHA.115.002420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802464PMC
February 2016

Birth size and brain function 75 years later.

Pediatrics 2014 Oct 1;134(4):761-70. Epub 2014 Sep 1.

Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland;

Background: There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations.

Methods: Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ∼75 years later underwent an examination that included brain MRI and extensive cognitive assessment.

Results: Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m(3)), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; βs (95% confidence intervals) were -1.0 (-1.9 to -0.0) and -0.5 (-1.0 to -0.0) mL. Furthermore, lower Ponderal index was associated with slower processing speed and reduced executive functioning but only in those with low education (β [95% confidence interval]: -0.136 [-0.235 to -0.036] and -0.077 [-0.153 to -0.001]).

Conclusions: This first study of its kind provides clinical measures suggesting that smaller birth size, as an indicator of a suboptimal intrauterine environment, is associated with late-life alterations in brain tissue volume and function. In addition, it shows that the effects of a suboptimal intrauterine environment on late-life cognitive function were present only in those with lower educational levels.
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http://dx.doi.org/10.1542/peds.2014-1108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179101PMC
October 2014

[Cerebral ischemia/infarction - diagnosis and treatment].

Laeknabladid 2014 07;100(7-8):393-401

Four hundred individuals suffer from ischemic stroke every year in Iceland, more than one daily. Cerebral ischemia is an emergency. Around two million brain cells die every minute after an occlusion of a cerebral artery. Therefore, it is of utmost importance that the patient is transported quickly to hospital, not least to receive thrombolytic treatment. Even though thrombolytic treatment can be given up to four and a half hours after the ictal event, time is brain and the effect of thombolysis reduces dramatically as times passes. For every two patients who are treated inside one hour, one recovers fully. When the treatment is administred between three and four and a half hours only one in 14 recovers fully. All patients with an acute stroke should be admitted to a stroke unit where a multidisciplinary focus on stroke causation and treatment is present, with emphasis on early rehabilitation. Secondary preventive treatment focusing on anti-thrombotic, hypertensive, diabetic, cholesterol lowering treatment, carotic endarterectomy and life style changes should be initiated as soon as possible.
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http://dx.doi.org/10.17992/lbl.2014.0708.553DOI Listing
July 2014

Joint effect of mid- and late-life blood pressure on the brain: the AGES-Reykjavik study.

Neurology 2014 Jun 4;82(24):2187-95. Epub 2014 Jun 4.

From the Laboratory of Epidemiology and Population Sciences (M.M., T.B.H., L.J.L.), Intramural Research Program, National Institute on Aging, Bethesda, MD; the Departments of Gerontology and Geriatrics (M.M.) and Radiology (M.v.B.), Leiden University Medical Center; Icelandic Heart Association (S.S., O.K., T.A., V.G.), Kopovagur; the Departments of Neurology & Radiology (O.K.) and Geriatrics (P.V.J.), Landspitali National University Hospital, Reykjavik, Iceland; the Department of Neurology (O.L.L.), University of Pittsburgh, PA; and the Faculty of Medicine (P.V.J.), University of Iceland, Reykjavik.

Objective: We hypothesized that in participants with a history of hypertension, lower late-life blood pressure (BP) will be associated with more brain pathology.

Methods: Participants are 4,057 older men and women without dementia with midlife (mean age 50 ± 6 years) and late-life (mean age 76 ± 5 years) vascular screening, cognitive function, and brain structures on MRI ascertained as part of the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

Results: The association of late-life BP to brain measures depended on midlife hypertension history. Higher late-life systolic and diastolic BP (DBP) was associated with an increased risk of white matter lesions and cerebral microbleeds, and this was most pronounced in participants without a history of midlife hypertension. In contrast, in participants with a history of midlife hypertension, lower late-life DBP was associated with smaller total brain and gray matter volumes. This finding was reflected back in cognitive performance; in participants with midlife hypertension, lower DBP was associated with lower memory scores.

Conclusion: In this large population-based cohort, late-life BP differentially affects brain pathology and cognitive performance, depending on the history of midlife hypertension. Our study suggests history of hypertension is critical to understand how late-life BP affects brain structure and function.
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http://dx.doi.org/10.1212/WNL.0000000000000517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113458PMC
June 2014

[Cerebral ischemia/infarction - epidemiology, causes and symptoms].

Laeknabladid 2014 05;100(5):271-9

Eight of ten strokes are due to cerebral ischemia, two from cerebal hemorrhage. Stroke is the most common cause of disability, the second commonest cause of dementia and the fourth commonest cause of death in the developed world. The incidence of stroke is 150-200/100.000 individuals/ year. One of every seven individuals suffers from stroke in their lifetime. In this article the epidemiology, risk factors, pathophysiology and symptoms of cerebral ischemia will be reviewed.
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http://dx.doi.org/10.17992/lbl.2014.05.543DOI Listing
May 2014

Diabetes, markers of brain pathology and cognitive function: the Age, Gene/Environment Susceptibility-Reykjavik Study.

Ann Neurol 2014 Jan;75(1):138-46

Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD; Aging Research Center, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.

Objective: We investigated whether, and the extent to which, vascular and degenerative lesions in the brain mediate the association of diabetes with poor cognitive performance.

Methods: This cross-sectional study included 4,206 participants (age > 65 years; 57.8% women) of the Age, Gene/Environment Susceptibility-Reykjavik Study. Data were collected through interview, clinical examination, psychological testing, and laboratory tests. The composite scores on memory, information-processing speed, and executive function were derived from a cognitive test battery. Markers of cerebral macrovascular (cortical infarcts), microvascular (subcortical infarcts, cerebral microbleeds, and higher white matter lesion volume), and neurodegenerative (lower gray matter, normal white matter, and total brain tissue volumes) processes were assessed on magnetic resonance images. Mediation models were employed to test the mediating effect of brain lesions on the association of diabetes with cognitive performance controlling for potential confounders.

Results: There were 462 (11.0%) persons with diabetes. Diabetes was significantly associated with lower scores on processing speed and executive function, but not with memory function. Diabetes was significantly associated with all markers of brain pathology. All of these markers were significantly associated with lower scores on memory, processing speed, and executive function. Formal mediation tests suggested that markers of cerebrovascular and degenerative pathology significantly mediated the associations of diabetes with processing speed and executive function.

Interpretation: Diabetes is associated with poor performance on cognitive tests of information-processing speed and executive function. The association is largely mediated by markers of both neurodegeneration and cerebrovascular disease. Older people with diabetes should be monitored for cognitive problems and brain lesions.
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http://dx.doi.org/10.1002/ana.24063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540233PMC
January 2014

[Spontaneus intracerebral haemhorrhage--review].

Laeknabladid 2013 09;99(9):391-7

Spontaneous intracerebral hemorrhage occurs when a blood vessel within the brain parenchyma ruptures without a near related trauma. It is the second most common form of stroke, accounting for approximately 10% to 15% of new strokes. The 30 day mortality is very high (25-50%). Hypertension is the most common cause. Unfortunately, surgery has not proven to be helpful except in certain exceptions such as in large cerebellar hemorrhage. Nonetheless, it is very important that patients with ICH are admitted to an intensive care or a stroke unit with close surveillance of consciousness, focal neurologic symptoms, blood pressure and fluid balance.
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http://dx.doi.org/10.17992/lbl.2013.09.509DOI Listing
September 2013

Migraine, depression, and brain volume: the AGES-Reykjavik Study.

Neurology 2013 Jun 22;80(23):2138-44. Epub 2013 May 22.

Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, National Institute on Aging, Bethesda, MD, USA.

Objective: To examine the joint association of migraine headache and major depressive disorder on brain volume in older persons without dementia.

Methods: Participants (n = 4,296, 58% women) from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study were assessed for migraine headache in 1967-1991 (age 51 years [range 33-65]) according to modified International Classification of Headache Disorders-II criteria. In 2002-2006 (age 76 years [range 66-96]), lifetime history of major depressive disorder (depression) was diagnosed according to DSM-IV criteria, and full-brain MRI was acquired, which was computer postprocessed into total brain volume (TBV) (gray matter [GM], white matter [WM], white matter hyperintensities) and CSF volume for each study subject. We compared brain tissue volumes by headache categories with or without depression using linear regression, adjusting for intracranial volume and other factors.

Results: Compared with the reference group (no headache, no depression) TBV and WM and GM volumes were smaller in those with both migraine and depression (TBV -19.2 mL, 95% confidence interval [CI] -35.3, -3.1, p = 0.02; WM -12.8 mL, CI -21.3, -4.3, p = 0.003; GM -13.0 mL, CI -26.0, 0.1, p = 0.05) but not for those with migraine alone (TBV 0.4 mL, WM 0.2 mL, GM 0.6 mL) or depression alone (TBV -3.9 mL, WM -0.9 mL, GM -2.9 mL).

Conclusions: Reporting both migraine and major depressive disorder was associated with smaller brain tissue volumes than having one or neither of these conditions. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae. Nonetheless, the number of subjects in the current study is relatively small and these findings need to be confirmed in future studies.
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http://dx.doi.org/10.1212/WNL.0b013e318295d69eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716352PMC
June 2013

[Cerebral sinus thrombosis - an uncommon but important differential diagnosis to headache, stroke and seizures. Cases and overview].

Laeknabladid 2013 04;99(4):189-95

Department of Neurology, Karolinska Hospital, Stodkholm, Sweden.

Thrombosis of the cerebral veins and sinuses is an unusual but important cause of increased intracranial pressure and stroke, especially in the young and middle aged. Pregnant women, especially during the puerperium, and individuals with thrombophilia are a special risk group. What makes the diagnosis difficult is the vast range of symptoms including: headache, nausea, vomiting, blurry vision, reduction of consciousness, aphasia and motor and sensory disturbances. We present four cases which reflect the diverse clinical presentation of the disease.
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http://dx.doi.org/10.17992/lbl.2013.04.492DOI Listing
April 2013

Incidence of first stroke: a population study in Iceland.

Stroke 2013 Jun 9;44(6):1714-6. Epub 2013 May 9.

Department of Neurology, Landspitali University Hospital, 108 Reykjavik, Iceland.

Background And Purpose: Iceland is an island in the North Atlantic with ≈319 000 inhabitants. The study determines the incidence of first stroke in the adult population of Iceland during 12 months, which has not been previously reported in the entire Icelandic population.

Methods: The study population consisted of all residents of Iceland, aged ≥ 18 years, during the 12-month study period. Cases were identified by multiple overlapping approaches. Medical records were reviewed to verify diagnosis, to determine stroke subtype and to determine selected risk factors.

Results: A total of 343 individuals, aged ≥ 18 years, had a first stroke during the study period. Incidence was 144 per 100 000 person years; 81% ischemic infarction; 9% intracerebral hemorrhage; 7% subarachnoid hemorrhage; and 3% unknown. Fifty percent of the individuals were men. Mean age for ischemic infarction and intracerebral hemorrhage was 71 years for men and 73 years for women. Atrial fibrillation was previously known in 18% with first ischemic stroke or intracerebral hemorrhage and another 6% were diagnosed on routine admission ECG. Long-term ECG study (24 hours) found that 12% (18/154) of the remaining individuals had paroxysmal atrial fibrillation.

Conclusions: Incidence of first stroke in Iceland is similar to other Western countries. The high number of paroxysmal atrial fibrillation found during the 24-hour ECG suggests that atrial fibrillation may be underdiagnosed in patients with stroke.
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http://dx.doi.org/10.1161/STROKEAHA.111.000222DOI Listing
June 2013

Temporal trends in the incidence of kidney stone disease.

Kidney Int 2013 Jan 19;83(1):146-52. Epub 2012 Sep 19.

Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.

Recent reports show an increased occurrence of kidney stone disease worldwide. To further evaluate and quantify this observation, we examined recent trends in the incidence of kidney stone disease in the adult population of Iceland over a 24-year period. Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases, radiologic and surgical procedure codes indicative of kidney stones in patients aged 18 years and older. The time trends in stone frequency of 5945 incident patients (63% men) were assessed by Poisson regression analysis. The majority of patients (90.5%) had symptomatic stone disease. The total incidence of kidney stones rose significantly from 108 per 100,000 in the first 5-year interval of the study to 138 per 100,000 in the last interval. The annual incidence of symptomatic stones did not increase significantly in either men or women. There was, however, a significant increase in the annual incidence of asymptomatic stones over time, from 7 to 24 per 100,000 for men and from 7 to 21 per 100,000 for women. The increase in the incidence of asymptomatic stones was only significant for women above 50 years of age and for men older than 40 years. Thus, we found a significant increase in the incidence of kidney stone disease resulting from increased detection of asymptomatic stones. This was largely due to a more frequent use of high-resolution imaging studies in older patients.
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http://dx.doi.org/10.1038/ki.2012.320DOI Listing
January 2013

Allocentric neglect strongly associated with egocentric neglect.

Neuropsychologia 2012 May 11;50(6):1151-7. Epub 2012 Apr 11.

Department of Psychology, University of South Carolina, Columbia, SC 29208, USA.

Following brain injury, many patients experience egocentric spatial neglect, where they fail to respond to stimuli on the contralesional side of their body. On the other hand, allocentric, object-based neglect refers to the symptom of ignoring the contralesional side of objects, regardless of the objects' egocentric position. There is an established tradition for considering these two phenomena as both behaviorally and anatomically dissociable. However, several studies and some theoretical work have suggested that these rather reflect two aspects of a unitary underlying disorder. Furthermore, in a recent large study Yue et al. [Archives of Physical Medicine and Rehabilitation 93 (2012) 156] reported that acute allocentric neglect is only observed in cases where substantial egocentric neglect is also present. In a new sample of right hemisphere stroke patients, we attempted to control for potential confounds by using a novel continuous measure for allocentric neglect (in addition to a recently developed continuous measure for egocentric neglect). Our findings suggest a strong association between egocentric and allocentric neglect. Consistent with the work of Yue et al. (2012), we found allocentric behavioral deficits only in conjunction with egocentric deficits as well as a large corresponding overlap for the anatomical regions associated with egocentric and with allocentric neglect. We discuss how different anatomical and behavioral findings can be explained in a unified physiologically plausible framework, whereby allocentric and egocentric effects interact.
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http://dx.doi.org/10.1016/j.neuropsychologia.2012.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358702PMC
May 2012

Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study.

Neuroimage 2012 Feb 13;59(4):3862-3870. Epub 2011 Nov 13.

The Icelandic Heart Association, Kopavogur, Iceland.

Imaging studies have reported conflicting findings on how brain structure differs with age and sex. This may be explained by discrepancies and limitations in study population and study design. We report a study on brain tissue volumes in one of the largest cohorts of individuals studied to date of subjects with high mean age (mean ± standard deviation (SD) 76 ± 6 years). These analyses are based on magnetic resonance imaging (MRI) scans acquired at baseline on 4303 non-demented elderly, and 367 who had a second MRI, on average 2.5 ± 0.2 years later. Tissue segmentation was performed with an automatic image analysis pipeline. Total brain parenchymal (TBP) volume decreased with increasing age while there was an increase in white matter hyperintensities (WMH) in both sexes. A reduction in both normal white matter (NWM)- and gray matter (GM) volume contributed to the brain shrinkage. After adjusting for intra-cranial volume, women had larger brain volumes compared to men (3.32%, p < 0.001) for TBP volume in the cross-sectional analysis. The longitudinal analysis showed a significant age-sex interaction in TBP volume with a greater rate of annual change in men (-0.70%, 95%CI: -0.78% to -0.63%) than women (-0.55%, 95%CI: -0.61% to -0.49%). The annual change in the cross-sectional data was approximately 40% less than the annual change in the longitudinal data and did not show significant age-sex interaction. The findings indicate that the cross-sectional data underestimate the rate of change in tissue volumes with age as the longitudinal data show greater rate of change in tissue volumes with age for all tissues.
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http://dx.doi.org/10.1016/j.neuroimage.2011.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712156PMC
February 2012

Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

Brain 2011 Nov;134(Pt 11):3398-407

Cardiovascular Engineering, Inc., Norwood, MA 02062, USA.

Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (-0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.
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http://dx.doi.org/10.1093/brain/awr253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212721PMC
November 2011

[Spontaneous subarachnoid haemorrhage--review].

Laeknabladid 2011 06;97(6):355-62

Taugadeild Karolinska sjúkrahússins í Stockholm.

Spontaneous subarachnoid hemorrhage is a bleeding in to the subarachnoid space without trauma. Aneurysms are the underlying cause in 80% of the cases. Among other causes are: arteriovenous malformations, anticoagulation, vasculitis or brain tumor. Spontaneous subarachnoid hemorrhage is a serious disease, where up to half of the patients die. Of those who survive, only half return to work and many have a reduced quality of life. To prevent rebleeding the aneurysm is closed either with endovascular coiling or neurosurgical clipping.
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http://dx.doi.org/10.17992/lbl.2011.06.377DOI Listing
June 2011

Incidence of multiple sclerosis in Iceland, 2002-2007: a population-based study.

Mult Scler 2011 Aug 20;17(8):909-13. Epub 2011 Apr 20.

Department of Neurology, Landspitali University Hospital, Reykjavik, Iceland.

Background: We conducted a study to determine the incidence of multiple sclerosis (MS) among the whole Icelandic population during a 6-year period (2002-2007).

Methods: We included all Icelandic residents diagnosed with MS during the study period. Cases were identified from records of the only neurology department in Iceland, plus the records of all practicing neurologists and all radiology departments. All patients had experienced at least two confirmed MS relapses (i.e. clinically definite MS) or had primary progressive MS as defined by the Poser criteria.

Results: We identified 136 individuals who met the inclusion criteria, including 102 (75%) women. The mean age at diagnosis was 36.3 years (women 35.7 years, men 38.3 years). Average annual incidence was 7.6 per 100,000 population. All but one patient (99%) had an MRI study done at diagnosis and 61% of these (83/135) fulfilled the Barkhof criteria for diagnosis of MS; one had a normal MRI. A visual evoked potential test was done in 68% (93/136) at the time of diagnosis and 44% (41/93) were abnormal. Spinal fluid was obtained from 78% (106/136), and 75% (80/106) had oligoclonal bands.

Conclusion: A total population study is the most reliable method of determining the spectrum of clinical symptoms and the results of investigations in MS patients at diagnosis.
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http://dx.doi.org/10.1177/1352458511402112DOI Listing
August 2011

[Cervical artery dissection - review].

Laeknabladid 2011 04;97(4):237-43

Taugadeild Karolinska, Sjúkrahússins í, Stokkhólmi.

In recent years carotid and vertebral artery dissections have been diagnosed more frequently, probably because new imaging techniques are more reliable and they are certainly less invasive. The cause of cervical artery dissections is largely unexplained but probably involves a combination of genetic and environmental factors such as trauma or infection. Most authors recommend intravenous heparin or low molecular weight heparin followed by oral warfarin to maintain INR between 2-3 for 3-6 months. If the artery has healed after 3-6 months of anti-coagulation all treatment can be stopped but if there is a remaining stenosis the patient can be put on aspirin 75-100 mg a day. The long-term prognosis of cervical artery dissection is favourable in the majority of patients. New dissections are uncommon.
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http://dx.doi.org/10.17992/lbl.2011.04.364DOI Listing
April 2011

[Wernicke's encephalopathy in chronic alcoholics].

Laeknabladid 2011 01;97(1):21-9

Taugalækningadeild Landspítala.

Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition. Clinically, its key features are mental status disorders and oculomotor abnormalities as well as stance and gait ataxia. The diagnosis of WE is frequently missed although delay of appropriate treatment can lead to death or Korsakoff's amnestic syndrome. It is therefore crucial in suspected cases of WE, not to await confirmation of diagnosis, but immediately administer high-dose intravenous thiamine and simultaneously treat magnesium deficiency. Alcoholics at risk of WE should on admission receive immediate prophylactic therapy with parenteral thiamine.
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http://dx.doi.org/10.17992/lbl.2011.01.338DOI Listing
January 2011

Impaired speech repetition and left parietal lobe damage.

J Neurosci 2010 Aug;30(33):11057-61

Department of Communication Sciences and Disorders, University of South Carolina, Columbia, South Carolina 29208, USA.

Patients with left hemisphere damage and concomitant aphasia usually have difficulty repeating others' speech. Although impaired speech repetition, the primary symptom of conduction aphasia, has been associated with involvement of the left arcuate fasciculus, its specific lesion correlate remains elusive. This research examined speech repetition among 45 stroke patients who underwent aphasia testing and MRI examination. Based on lesion-behavior mapping, the primary structural damage most closely associated with impaired speech repetition was found in the posterior portion of the left arcuate fasciculus. However, perfusion-weighted MRI revealed that tissue dysfunction, in the form of either frank damage or hypoperfusion, to the left inferior parietal lobe, rather than the underlying white matter, was associated with impaired speech repetition. This latter result suggests that integrity of the left inferior parietal lobe is important for speech repetition and, as importantly, highlights the importance of examining cerebral perfusion for the purpose of lesion-behavior mapping in acute stroke.
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http://dx.doi.org/10.1523/JNEUROSCI.1120-10.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936270PMC
August 2010

Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study.

Stroke 2010 May 1;41(5):891-7. Epub 2010 Apr 1.

National Institutes of Health, NIA/LEDB, 7201 Wisconsin Ave, Gateway Building, Suite 3C309, Bethesda, MD 20892-9205, USA.

Background And Purpose: Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function.

Methods: This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function.

Results: Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes.

Conclusions: In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology.
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http://dx.doi.org/10.1161/STROKEAHA.110.579581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298743PMC
May 2010

Ventricular dilation: association with gait and cognition.

Ann Neurol 2009 Oct;66(4):485-93

Department of Radiology, Leiden University Medical Center, The Netherlands.

Objective: Normal pressure hydrocephalus is characterized by gait impairment, cognitive impairment, and urinary incontinence, and is associated with disproportionate ventricular dilation. Here we report the distribution of ventricular volume relative to sulcal cerebrospinal fluid (CSF) volume, and the association of increasing ventricular volume relative to sulcal CSF volume with a cluster of gait impairment, cognitive impairment, and urinary incontinence in a stroke-free cohort of elderly persons from the general population.

Methods: Data are based on 858 persons (35.4% men; age range, 66-92 years) who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study. Gait was evaluated with an assessment of gait speed. Composite scores representing speed of processing, memory, and executive function were constructed from a neuropsychological battery. Bladder function was assessed with a questionnaire. Magnetic resonance brain imaging was followed by semiautomated segmentation of intracranial CSF volume. White matter hyperintensity (WMH) volume was assessed with a semiquantitative scale. For the analysis of ventricular dilation relative to the sulcal spaces, ventricular volume was divided by sulcal CSF volume (VV/SV).

Results: Disproportion between ventricular and sulcal CSF volume, defined as the highest quartile of the VV/SV z score, was associated with gait impairment (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3) and cognitive impairment (OR, 1.8; 95% CI, 1.1-3.0). We did not find an association between the VV/SV z score and bladder dysfunction.

Interpretation: The prevalence and severity of gait impairment and cognitive impairment increases with ventricular dilation in persons without stroke from the general population, independent of WMH volume.
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http://dx.doi.org/10.1002/ana.21739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530517PMC
October 2009

[Multiple sclerosis--symptoms, diagnosis and treatment].

Laeknabladid 2009 Sep;95(9):583-9

Taugalaekningadeild Landspítala.

Multiple sclerosis is an inflammatory disease of the central nervous system and a common cause of disability among young people. MS is thought to be an autoimmune disease involving both inheritance and environmental factors. The disease is characterized by relapses and the symptoms and course are highly variable. The diagnosis is primarily clinical and supported by results of diagnostic studies. The importance of timely diagnosis has increased with the availability of effective treatment. The purpose of this article is to review symptoms, signs, diagnosis and treatment of multiple sclerosis.
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September 2009