• Atrial fibrillation is associated with reduced brain volume and cognitive function independent of cerebral infarcts.

      Stefansdottir, Hrafnhildur; Arnar, David O; Aspelund, Thor; Sigurdsson, Sigurdur; Jonsdottir, Maria K; Hjaltason, Haukur; Launer, Lenore J; Gudnason, Vilmundur; Univ Iceland, Fac Med, Reykjavik, Iceland, Landspitali Natl Univ Hosp Iceland, Dept Med, Cardiovasc Res Ctr, IS-101 Reykjavik, Iceland, Iceland Heart Assoc, Kopavogur, Iceland, Univ Iceland, Fac Psychol, Reykjavik, Iceland, Landspitali Natl Univ Hosp Iceland, Dept Neurol, IS-101 Reykjavik, Iceland, NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA, Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA (Lippincott Williams & Wilkins, 2013-04)
      Atrial fibrillation (AF) has been associated with cognitive decline independent of stroke, suggesting additional effects of AF on the brain. We aimed to assess the association between AF and brain function and structure in a general elderly population.
    • Cerebral infarcts and cognitive performance: importance of location and number of infarcts

      Saczynski, Jane S; Sigurdsson, Sigurdur; Jonsdottir, Maria K; Eiriksdottir, Gudny; Jonsson, Palmi V; Garcia, Melissa E; Kjartansson, Olafur; Lopez, Oscar; van Buchem, Mark A; Gudnason, Vilmunder; et al. (Lippincott Williams & Wilkins, 2009-03-01)
      BACKGROUND AND PURPOSE: Cerebral infarcts increase the risk for cognitive impairment. The relevance of location and number of infarcts with respect to cognitive function is less clear. METHODS: We studied the cross-sectional association between number and location of infarcts and cognitive performance in 4030 nondemented participants of the Age Gene/Environment Susceptibility-Reykjavik Study. Composite scores for memory, processing speed, and executive function were created from a neuropsychological battery. Subcortical, cortical, and cerebellar infarcts were identified on brain MRI. We performed linear regression analyses adjusted for demographic and vascular risk factors, depression, white matter lesions, and atrophy. RESULTS: Compared to participants with no infarcts, those with infarcts in multiple locations (n=287, 7%) had slower processing speed (beta=-0.19; P<0.001) and poorer memory (beta=-0.16; P<0.001) and executive function (beta=-0.12; P=0.003). Compared to no infarcts, the presence of either subcortical infarcts only (n=275; beta=-0.12; P=0.016) or cortical infarcts only (n=215; beta=-0.17; P=0.001) was associated with poorer memory performance. Compared to no infarcts, a combination of cortical and subcortical infarcts (n=45) was associated with slower processing speed (beta=-0.38; P<0.001) and poorer executive function (beta=-0.22; P=0.02), whereas a combination of cerebellar and subcortical infarcts (n=89) was associated with slower processing speed (beta=-0.15; P=0.04). Infarcts in all 3 locations was associated with slower processing speed (beta=-0.33; P=0.002). CONCLUSIONS: Having infarcts in >1 location is associated with poor performance in memory, processing speed, and executive function, independent of cardiovascular comorbidities, white matter lesions, and brain atrophy, suggesting that both the number and the distribution of infarcts jointly contribute to cognitive impairment.
    • Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study

      Vidal, Jean-Sébastien; Sigurdsson, Sigurdur; Jonsdottir, Maria K; Eiriksdottir, Gudny; Thorgeirsson, Gudmundur; Kjartansson, Olafur; Garcia, Melissa E; van Buchem, Mark A; Harris, Tamara B; Gudnason, Vilmundur; et al. (Lippincott Williams & Wilkins, 2010-05-01)
      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.
    • Correlation of echocardiographic findings with cerebral infarction in elderly adults: the AGES-Reykjavik study

      McAreavey, Dorothea; Vidal, Jean-Sébastien; Aspelund, Thor; Owens, David S; Hughes, Timothy; Garcia, Melissa; Sigurdsson, Sigurdur; Bjornsdottir, Halldora; Harris, Tamara B; Gudnason, Vilmundur; et al. (2010-10)
      BACKGROUND AND PURPOSE: Chronic effects of hypertension may be observed in multiple end organs. Previous reports suggest that cardiovascular morphological features can mirror cerebral infarction. In this cross-sectional analysis of elderly subjects, we investigated the relationship of a comprehensive set of echocardiographic measures with cerebral infarction detected by MRI. METHODS: We compared echocardiographically determined left ventricular (LV) mass, left atrial volume, aortic root diameter, mitral annular calcification, and measures of diastolic function with cerebral infarction determined by MRI using logistic regression in a random sample drawn from the Age Gene/Environment Susceptibility-Reykjavik Study cohort. The model was first adjusted for age and gender, and then for age, gender, and vascular risk factors. RESULTS: Among 692 subjects aged 75 (standard deviation, 6) years, 28% had at least 1 cerebral infarct. When adjusted for age and gender, the presence of cerebral infarction was modestly related to LV mass (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and left atrial volume (OR, 1.03; 95% CI, 1.01-1.05), as well as the lowest quartile of early-to-late pulsed Doppler velocity ratio (early-to-late pulsed Doppler velocity ratio <0.75; OR, 1.87; 95% CI, 1.22-2.87). The latter relation remained significant after adjustment for vascular risk factors and LV ejection fraction (OR, 1.82; 95% CI, 1.16-2.86). CONCLUSIONS: Of all echocardiographic parameters, LV filling abnormality as indicated by low early-to-late pulsed Doppler velocity ratio displayed the strongest association with cerebral infarction and this relationship was independent of vascular risk factors. This simple marker of cerebral infarction may be useful when evaluating older patients.
    • Immune reactions associated with cerebral amyloid angiopathy

      Yamada, M; Itoh, Y; Shintaku, M; Kawamura, J; Jensson, O; Thorsteinsson, L; Suematsu, N; Matsushita, M; Otomo, E; Department of Neurology, Tokyo Medical and Dental University, Japan. (Lippincott Williams & Wilkins Ltd, 1996-07-01)
      BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) occasionally coexists with cerebral vasculitis. An immune system may influence deposition or degradation of the amyloid in cerebral blood vessels. The purpose of this study was to elucidate immune reactions associated with CAA. METHODS: In 11 elderly patients with sporadic CAA, 2 patients with Icelandic familial CAA, and 2 patients with CAA and granulomatous angiitis, the cerebrovascular amyloid proteins and infiltrating inflammatory cells were analyzed immunohistochemically. RESULTS: In both sporadic CAA (beta-protein amyloid angiopathy) and Icelandic familial CAA (cystatin C amyloid angiopathy), leptomeningeal and cortical vessels were associated with an increase or activation of monocyte/macrophage lineage cells. In the cases of CAA with granulomatous angiitis, the vascular amyloid was of beta-protein and associated with infiltration of many monocyte/macrophage lineage cells, which included multinucleated giant cells containing the amyloid in the cytoplasm as well as T cells composed of CD4+ and CD8+ subsets. Amyloid P component, which was reported to be a common component of amyloid deposits and to prevent phagocytic proteolysis of amyloid fibrils of beta-protein, was negative for the vascular amyloid in a case of CAA with granulomatous angiitis but positive in the others. CONCLUSIONS: In both the beta-protein and cystatin C amyloid angiopathies, cerebrovascular amyloid deposition was associated with an increase or activation of monocyte/macrophage lineage cells. Prominent reactions of monocyte/macrophage lineage cells admixed with CD4+ and CD8+ T cells (granulomatous angiitis) were occasionally associated with beta-protein angiopathy. In some of these cases, the absence of amyloid P component might be related to pathogenesis of the granulomatous reaction.
    • Incidence of first stroke: a population study in Iceland.

      Hilmarsson, Agust; Kjartansson, Olafur; Olafsson, Elias; Landspitali Univ Hosp, Dept Neurol, IS-108 Reykjavik, Iceland, Landspitali Univ Hosp, Dept Radiol, IS-108 Reykjavik, Iceland, Univ Iceland, Sch Med, Reykjavik, Iceland (Lippincott Williams & Wilkins, 2013-06)
      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.
    • Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study.

      van Straaten, Elisabeth C W; Scheltens, Philip; Knol, Dirk L; van Buchem, Mark A; van Dijk, Ewout J; Hofman, Paul A M; Karas, Giorgos; Kjartansson, Olafur; de Leeuw, Frank-Erik; Prins, Niels D; et al. (Lippincott Williams & Wilkins, 2003-08-01)
      BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.