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  • 1. Adams, Hieab H. H.
    et al.
    Hibar, Derrek P.
    Chouraki, Vincent
    Stein, Jason L.
    Nyquist, Paul A.
    Renteria, Miguel E.
    Trompet, Stella
    Arias-Vasquez, Alejandro
    Seshadri, Sudha
    Desrivieres, Sylvane
    Beecham, Ashley H.
    Jahanshad, Neda
    Wittfeld, Katharine
    Van der Lee, Sven J.
    Abramovic, Lucija
    Alhusaini, Saud
    Amin, Najaf
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Arfanakis, Konstantinos
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Athanasiu, Lavinia
    Axelsson, Tomas
    Beiser, Alexa
    Bernard, Manon
    Bis, Joshua C.
    Blanken, Laura M. E.
    Blanton, Susan H.
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brickman, Adam M.
    Carmichael, Owen
    Chakravarty, M. Mallar
    Chauhan, Ganesh
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    Den Braber, Anouk
    Doan, Nhat Trung
    Ehrlich, Stefan
    Filippi, Irina
    Ge, Tian
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Gottesman, Rebecca F.
    Greven, Corina U.
    Grimm, Oliver
    Griswold, Michael E.
    Guadalupe, Tulio
    Hass, Johanna
    Haukvik, Unn K.
    Hilal, Saima
    Hofer, Edith
    Hoehn, David
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kasperaviciute, Dalia
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Liao, Jiemin
    Liewald, David C. M.
    Lopez, Lorna M.
    Luciano, Michelle
    Macare, Christine
    Marquand, Andre
    Matarin, Mar
    Mather, Karen A.
    Mattheisen, Manuel
    Mazoyer, Bernard
    Mckay, David R.
    McWhirter, Rebekah
    Milaneschi, Yuri
    Mirza-Schreiber, Nazanin
    Muetzel, Ryan L.
    Maniega, Susana Munoz
    Nho, Kwangsik
    Nugent, Allison C.
    Loohuis, Loes M. Olde
    Oosterlaan, Jaap
    Papmeyer, Martina
    Pappa, Irene
    Pirpamer, Lukas
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Puetz, Benno
    Rajan, Kumar B.
    Ramasamy, Adaikalavan
    Richards, Jennifer S.
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rommelse, Nanda
    Rose, Emma J.
    Royle, Natalie A.
    Rundek, Tatjana
    Saemann, Philipp G.
    Satizabal, Claudia L.
    Schmaal, Lianne
    Schork, Andrew J.
    Shen, Li
    Shin, Jean
    Shumskaya, Elena
    Smith, Albert V.
    Sprooten, Emma
    Strike, Lachlan T.
    Teumer, Alexander
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    Toro, Roberto
    Trabzuni, Daniah
    Vaidya, Dhananjay
    Van der Grond, Jeroen
    Van der Meer, Dennis
    Van Donkelaar, Marjolein M. J.
    Van Eijk, Kristel R.
    Van Erp, Theo G. M.
    Van Rooij, Daan
    Walton, Esther
    Westlye, Lars T.
    Whelan, Christopher D.
    Windham, Beverly G.
    Winkler, Anderson M.
    Woldehawariat, Girma
    Wolf, Christiane
    Wolfers, Thomas
    Xu, Bing
    Yanek, Lisa R.
    Yang, Jingyun
    Zijdenbos, Alex
    Zwiers, Marcel P.
    Agartz, Ingrid
    Aggarwal, Neelum T.
    Almasy, Laura
    Ames, David
    Amouyel, Philippe
    Andreassen, Ole A.
    Arepalli, Sampath
    Assareh, Amelia A.
    Barral, Sandra
    Bastin, Mark E.
    Becker, Diane M.
    Becker, James T.
    Bennett, David A.
    Blangero, John
    van Bokhoven, Hans
    Boomsma, Dorret I.
    Brodaty, Henry
    Brouwer, Rachel M.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Bulayeva, Kazima B.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cannon, Dara M.
    Cavalleri, Gianpiero L.
    Chen, Christopher
    Cheng, Ching -Yu
    Cichon, Sven
    Cookson, Mark R.
    Corvin, Aiden
    Crespo-Facorro, Benedicto
    Curran, Joanne E.
    Czisch, Michael
    Dale, Anders M.
    Davies, Gareth E.
    De Geus, Eco J. C.
    De Jager, Philip L.
    de Zubicaray, Greig I.
    Delanty, Norman
    Depondt, Chantal
    DeStefano, Anita L.
    Dillman, Allissa
    Djurovic, Srdjan
    Donohoe, Gary
    Drevets, Wayne C.
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Espeseth, Thomas
    Evans, Denis A.
    Fedko, Iryna
    Fernandez, Guillen
    Ferrucci, Luigi
    Fisher, Simon E.
    Fleischman, Debra A.
    Ford, Ian
    Foroud, Tatiana M.
    Fox, Peter T.
    Francks, Clyde
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Glahn, David C.
    Gollub, Randy L.
    Goring, Harald H. H.
    Grabe, Hans J.
    Green, Robert C.
    Gruber, Oliver
    Gudnason, Vilmundur
    Guelfi, Sebastian
    Hansell, Narelle K.
    Hardy, John
    Hartman, Catharina A.
    Hashimoto, Ryota
    Hegenscheid, Katrin
    Heinz, Andreas
    Le Hellard, Stephanie
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Ho, Beng-Choon
    Hoekstra, Pieter J.
    Hoffmann, Wolfgang
    Hofman, Albert
    Holsboer, Florian
    Homuth, Georg
    Hosten, Norbert
    Hottenga, Jouke-Jan
    Pol, Hilleke E. Hulshoff
    Ikeda, Masashi
    Ikram, M. Kamran
    Jack, Clifford R., Jr.
    Jenldnson, Mark
    Johnson, Robert
    Jonsson, Erik G.
    Jukema, J. Wouter
    Kahn, Rene S.
    Kanai, Ryota
    Kloszewska, Iwona
    Knopman, David S.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Lemaitre, Herve
    Liu, Xinmin
    Longo, Dan L.
    Longstreth, W. T., Jr.
    Lopez, Oscar L.
    Lovestone, Simon
    Martinez, Oliver
    Martinot, Jean-Luc
    Mattay, Venkata S.
    McDonald, Colm
    McIntosh, Andrew M.
    McMahon, Katie L.
    McMahon, Francis J.
    Mecocci, Patrizia
    Melle, Ingrid
    Meyer-Lindenberg, Andreas
    Mohnke, Sebastian
    Montgomery, Grant W.
    Morris, Derek W.
    Mosley, Thomas H.
    Muhleisen, Thomas W.
    Mueller-Myhsok, Bertram
    Nalls, Michael A.
    Nauck, Matthias
    Nichols, Thomas E.
    Niessen, Wiro J.
    Noethen, Markus M.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ohi, Kazutaka
    Olvera, Rene L.
    Ophoff, Roel A.
    Pandolfo, Massimo
    Paus, Tomas
    Pausova, Zdenka
    Penninx, Brenda W. J. H.
    Pike, G. Bruce
    Potkin, Steven G.
    Psaty, Bruce M.
    Reppermund, Simone
    Rietschel, Marcella
    Roffman, Joshua L.
    Romanczuk-Seiferth, Nina
    Rotter, Jerome I.
    Ryten, Mina
    Sacco, Ralph L.
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Schmidt, Reinhold
    Schofield, Peter R.
    Sigurdsson, Sigurdur
    Simmons, Andy
    Singleton, Andrew
    Sisodiya, Sanjay M.
    Smith, Colin
    Smoller, Jordan W.
    Soininen, Hindu.
    Srikanth, Velandai
    Steen, Vidar M.
    Stott, David J.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Tiemeier, Henning
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Tzourio, Christophe
    Uitterlinden, Andre G.
    Hernandez, Maria C. Valdes
    Van der Brug, Marcel
    Van der Lugt, Aad
    Van der Wee, Nic J. A.
    Van Duijn, Cornelia M.
    Van Haren, Neeltje E. M.
    Van't Ent, Dennis
    Van Tol, Marie Jose
    Vardarajan, Badri N.
    Veltman, Dick J.
    Vernooij, Meike W.
    Voelzke, Henry
    Walter, Henrik
    Wardlaw, Joanna M.
    Wassink, Thomas H.
    Weale, Michael E.
    Weinberger, Daniel R.
    Weiner, Michael W.
    Wen, Wei
    Westman, Eric
    White, Tonya
    Wong, Tien Y.
    Wright, Clinton B.
    Zielke, H. Ronald
    Zonderman, Alan B.
    Deary, Ian J.
    DeCarli, Charles
    Schmidt, Helena
    Martin, Nicholas G.
    De Craen, Anton J. M.
    Wright, Margaret J.
    Launer, Lenore J.
    Schumann, Gunter
    Fornage, Myriam
    Franke, Barbara
    Debette, Stephanie
    Medland, Sarah E.
    Ikram, M. Arfan
    Thompson, Paul M.
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016Ingår i: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, nr 12, s. 1569-1582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 2. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 7, s. 1199-1205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 3.
    Andersson, Linus
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Department of Occupational and Public Health Sciences, University of Gävle, Sweden.
    Claeson, Anna-Sara
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Short-term olfactory sensitization involves brain networks relevant for pain, and indicates chemical intolerance2017Ingår i: International journal of hygiene and environmental health (Print), ISSN 1438-4639, E-ISSN 1618-131X, Vol. 220, nr 2, s. 503-509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chemical intolerance is a medically unexplained affliction that implies deleterious reactions to non-toxic everyday chemical exposure. Sensitization (i.e. increased reactivity to repeated, invariant stimulation) to odorous stimulation is an important component in theoretical explanations of chemical intolerance, but empirical evidence is scarce. We hypothesized that (1) individuals who sensitize to repeated olfactory stimulation, compared with those who habituate, would express a lower blood oxygenated level dependent (BOLD) response in key inhibitory areas such as the rACC, and higher signal in pain/saliency detection regions, as well as primary and/or secondary olfactory projection areas; and (2) olfactory sensitization, compared with habituation, would be associated with greater self-reported chemical intolerance. More-over, we assessed whether olfactory sensitization was paralleled by comparable trigeminal processing - in terms of perceptual ratings and BOLD responses. We grouped women from a previous functional magnetic imaging study based on intensity ratings of repeated amyl acetate exposure over time. Fourteen women sensitized to the exposure, 15 habituated, and 20 were considered "intermediate" (i.e. neither sensitizers nor habituaters). Olfactory sensitizers, compared with habituaters, displayed a BOLD-pattern in line with the hypothesis, and reported greater problems with odours in everyday life. They also expressed greater reactions to CO2 in terms of both perceived intensity and BOLD signal. The similarities with pain are discussed.

  • 4.
    Andersson, Linus
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Claesson, Anna-Sara
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stenberg, Berndt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Brain responses to olfactory and trigeminal exposure in idiopathic environmental illness (IEI) attributed to smells: An fMRI study2014Ingår i: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 77, nr 5, s. 401-408Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Idiopathic environmental intolerance (IEI) to smells is a prevalent medically unexplained illness. Sufferers attribute severe symptoms to low doses of non-toxic chemicals. Despite the label, IEI is not characterized by acute chemical senses. Theoretical models suggest that sensitized responses in the limbic system of the brain constitute an important mechanism behind the symptoms. The aim was to investigate whether and how brain reactions to low-levels of olfactory and trigeminal stimuli differ in individuals with and without IEI. METHODS: Brain responses to intranasally delivered isoamyl acetate and carbon dioxide were assessed in 25 women with IEI and 26 non-ill controls using functional magnetic resonance imaging. RESULTS: The IEI group had higher blood-oxygenated-level-dependent (BOLD) signal than controls in the thalamus and a number of, mainly, parietal areas, and lower BOLD signal in the superior frontal gyrus. The IEI group did not rate the exposures as more intense than the control group did, and there were no BOLD signal differences between groups in the piriform cortex or olfactory regions of the orbitofrontal cortex. CONCLUSIONS: The IEI reactions were not characterized by hyper-responsiveness in sensory areas. The results can be interpreted as a limbic hyperreactivity and speculatively as an inability to inhibit salient extemal stimuli.

  • 5. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Kauppi, Karolina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017Ingår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, s. 209-216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

  • 6.
    Awad, Amar
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Hultling, Claes
    Department of Neurobiology, Care Sciences and Society (Neurorehabilitation), Karolinska Institute, Stockholm, Sweden.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Preserved somatosensory conduction in a patient with complete cervical spinal cord injury2015Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, nr 5, s. 426-431Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel ethodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury. Methods: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback. Results: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury. Conclusion: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

  • 7.
    Backman, Lars
    et al.
    Aging Research Center, Karolinska Institute and University of Stockholm, Stockholm,.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dopamine and training-related working-memory improvement2013Ingår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 37, nr 9, s. 2209-2219Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Converging evidence indicates that the neurotransmitter dopamine (DA) is implicated in working-memory (WM) functioning and that WM is trainable. We review recent work suggesting that DA is critically involved in the ability to benefit from WM interventions. Functional MRI studies reveal increased striatal BOLD activity following certain forms of WM interventions, such as updating training. Increased striatal BOLD activity has also been linked to transfer of learning to non-trained WM tasks, suggesting a neural signature of transfer. The striatal BOLD signal is partly determined by DA activity. Consistent with this assertion, PET research demonstrates increased striatal DA release during updating of information in WM after training. Genetic studies indicate larger increases in WM performance post training for those who carry advantageous alleles of DA-relevant genes. These patterns of results corroborate the role of DA in WM improvement. Future research avenues include: (a) neuromodulatory correlates of transfer; (b) the potential of WM training to enhance DA release in older adults; (c) comparisons among different WM processes (i.e., updating, switching, inhibition) regarding regional patterns of training-related DA release; and (d) gene-gene interactions in relation to training-related WM gains.

  • 8.
    Bergdahl, Jan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, Lars-Göran
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Treatment of chronic stress in employees: subjective, cognitive and neural correlates2005Ingår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 46, nr 5, s. 395-402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study reports the effect of an affect-focused intervention program, the Affect School, on stress, psychological symptoms, cognitive functioning and neural activity. Fifty employees in social service and education, with high levels of chronic stress, were randomly divided into a treatment (N= 27) and control (N= 23) group. Complete sets of data were available in 20 participants in the treatment group and 17 in the control group. The Perceived Stress Questionnaire assessed stress and the Symptom Check List-90 psychological symptoms before and after treatment. Episodic-memory functioning under focused and divided attention conditions was also assessed. Prior and after the Affect School, seven participants in the treatment group were studied with functional magnetic resonance imaging (fMRI) during episodic memory processing. After the Affect School there was a reduction in stress and psychological symptoms for the treatment group but not in the control group. The controls showed a reduction in episodic memory functioning whereas the performance of the treatment group remained intact. The fMRI scanning indicated a qualitative change in the neural network subserving episodic memory. These preliminary results suggest that the Affect School is effective on individuals with high stress.

  • 9. Bergdahl, Maud
    et al.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson, Lars-Göran
    Psykologiska institutionen, Stockholms universitet.
    Difference in apolipoprotein E type 4 allele (APOE e4) amongdentate and edentulous subjects2008Ingår i: Gerodontology, ISSN 0734-0664, E-ISSN 1741-2358, Vol. 25, nr 3, s. 179-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To evaluate the frequency of apolipoprotein (APOE) alleles and determine whether APOE type 4 allele (e4) was associated with edentulousness even when certain factors were controlled.Background: The APOE are important in lipid homeostasis, and APOE e4 has been found in many diseases and to have a negative impact on longevity. Tooth loss is more common in ill aged subjects with low income and education.Materials and methods: In a population-based study involving 1860 subjects between 35 and 85 years 1321 dentate (mean age = 54; 54% women, 46% men) and 539 edentulous (mean age = 72; 62% women, 38% men) subjects were studied. Logistic regression was performed with dentate/edentulous as dependent variables and years of education, socio-economic status, social network, stress level, handicap from birth, 23 various diseases and APOE e4 as covariates. Thereafter, APOE e4 frequencies were studied in 342 dentateand 336 edentulous subjects 50–85 years of age. The subjects were matched with regard to age, gender, years of education, living condition, stress level, handicap from birth and 23 various diseases.Results: APOE allele frequency in the total group was e2 = 7.8%, e3 = 76.4% and e4 = 15.8%. Age, living condition, years of education and APOE e4 were significant covariates in edentulous subjects (p £ 0.001).APOE e4 in the matched groups revealed significant differences between the dentate group and the edentulous group (v2 = 5.68; p = 0.017). There was no group effect (F(29,648) = 0.849; p < 0.696; Wilks’ lambda = 0.963). In the dentate group, the frequencies of APOE were: e2 = 8.8%, e3 = 77.9% ande4 = 13.3%. Corresponding frequencies of APOE in the edentulous group were: e2 = 6.6%, e3 = 75.4% and e4 = 18.0%.Conclusion: Despite matching both groups with regard to different background factors, the edentulous group had a higher frequency of APOE e4 than the dentate group. Thus, genetic factors might contribute to greater risk in developing complex oral diseases leading to tooth loss or just be an indication that the subjects in our study carrying APOE e4 are more fragile.

  • 10. Bergdahl, Maud
    et al.
    Habib, Reza
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nilsson, Lars-Göran
    Natural teeth and cognitive function in humans2007Ingår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 48, nr 6, s. 557-565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A number of neurobiological, psychological and social factors may account for cognitive impairment. In animal studies a relation between dental status and cognitive performance has been found. It is unclear whether such a relation exists for humans. In a first step we compared the performance of 1,351 participants (53% women, 47% men; age M = 54.0) with natural teeth to 487 edentulous participants (59% women, 41% men; age M = 71.3) on 12 cognitive tests. The natural teeth group had a lower mean age, fewer women, more years of education, higher mini-mental state (MMSE), and performed significantly higher on several cognitive tests. In a subsequent analysis, the cognitive performance of a subset of the participants (50–85 years) was examined. In this analysis, 211 had natural dentition and 188 were edentulous. The groups were matched for gender, age, social variables, diseases, stress and MMSE. The cognitive disadvantage of the edentulous group was still apparent. The results suggest that functional natural teeth relate to relatively preserved cognitive functioning in older age.

  • 11.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning2017Ingår i: Brain Injury: Accepted Abstracts from the International Brain Injury Association’s 12th World Congress on Brain Injury, 2017, Vol. 31, s. 755-755Konferensbidrag (Refereegranskat)
    Abstract [en]

    Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.

  • 12.
    Berginström, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning2018Ingår i: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, nr 4, s. 266-274Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).

    Setting: Neurorehabilitation clinic.

    Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).

    Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.

    Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.

    Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

  • 13. Bergouignan, Loretxu
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ehrsson, H. Henrik
    Out-of-body-induced hippocampal amnesia2014Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, nr 12, s. 4421-4426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed similar to 1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.

  • 14.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nordin, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson, Lars-Göran
    Aging Research Center, Karolinska Institutet.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Free Recall Episodic Memory Performance Predicts Dementia 10 Years Prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study2015Ingår i: Dementia and geriatric cognitive disorders extra, E-ISSN 1664-5464, Vol. 5, nr 2, s. 191-202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age-and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.

  • 15.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center (ARC), Karolinska Institute, Stockholm, Sweden.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default mode network: a multimodal approach2016Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 131, s. 133-141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One step toward healthy brain aging may be to entertain a physically active lifestyle. Studies investigating physical activity effects on brain integrity have, however, mainly been based on single brain markers, and few used a multimodal imaging approach. In the present study, we used cohort data from the Betula study to examine the relationships between scores reflecting current and accumulated physical activity and brain health. More specifically, we first examined if physical activity scores modulated negative effects of age on seven resting state networks previously identified by Salami, Pudas, and Nyberg (2014). The results revealed that one of the most age-sensitive RSN was positively altered by physical activity, namely, the posterior default-mode network involving the posterior cingulate cortex (PCC). Second, within this physical activity-sensitive RSN, we further analyzed the association between physical activity and gray matter (GM) volumes, white matter integrity, and cerebral perfusion using linear regression models. Regions within the identified DMN displayed larger GM volumes and stronger perfusion in relation to both current and 10-years accumulated scores of physical activity. No associations of physical activity and white matter integrity were observed. Collectively, our findings demonstrate strengthened PCC–cortical connectivity within the DMN, larger PCC GM volume, and higher PCC perfusion as a function of physical activity. In turn, these findings may provide insights into the mechanisms of how long-term regular exercise can contribute to healthy brain aging.

  • 16.
    Boraxbekk, Carl-Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Centrum för befolkningsstudier (CBS).
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Göteborgs Universitet.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Diet-Induced Weight Loss alters Functional Brain Responses during an Episodic Memory Task2015Ingår i: Obesity Facts, ISSN 1662-4025, E-ISSN 1662-4033, Vol. 8, s. 261-272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  • 17.
    Burzynska, A Z
    et al.
    Max Planck Institute for Human Development, Berlin.
    Preuschhof, C
    Max Planck Institute for Human Development, Berlin.
    Bäckman, L
    Max Planck Institute for Human Development, Berlin, Karolinska Institute.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Li, S-C
    Max Planck Institute for Human Development, Berlin.
    Lindenberger, U
    Max Planck Institute for Human Development, Berlin, .
    Heekeren, H R
    Max Planck Institute for Human Development, Berlin, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig.
    Age-related differences in white matter microstructure: region-specific patterns of diffusivity.2010Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 49, nr 3, s. 2104-2112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

  • 18. Bäckman, L
    et al.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Linderiberger, U
    Li, SC
    Farde, L
    The correlative triad among aging, dopamine, and cognition: Current status and future prospects2006Ingår i: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, ISSN 0149-7634, Vol. 30, nr 6, s. 791-807Artikel, forskningsöversikt (Övrig (populärvetenskap, debatt, mm))
  • 19.
    Bäckman, Lars
    et al.
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Karlsson, Sari
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Macdonald, Stuart WS
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden; Department of Psychology, University of Victoria, Canada .
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dopamine D(1) receptors and age differences in brain activation during working memory2011Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, nr 10, s. 1849-1856Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.

  • 20. Bäckman, Lars
    et al.
    Lindenberger, Ulman
    Li, Shu-Chen
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues2010Ingår i: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 34, nr 5, s. 670-677Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D(1) and D(2) receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.

  • 21. Bäckman, Lars
    et al.
    Nyberg, Lars
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi.
    Lindenberger, Ulman
    Li, Shu-Chen
    Farde, Lars
    The correlative triad among aging, dopamine, and cognition: current status and future prospects.2006Ingår i: Neuroscience and Biobehavioral Review, ISSN 0149-7634, Vol. 30, nr 6, s. 791-807Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance.

  • 22.
    Bäckman, Lars
    et al.
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Soveri, Anna
    Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
    Johansson, Jarkko
    Turku PET Center, University of Turku, Turku, Finland.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dahlin, Erika
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Neely, Anna S
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Virta, Jere
    Turku PET Center, University of Turku, Turku, Finland.
    Laine, Matti
    Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
    Rinne, Juha O
    Turku PET Center, University of Turku, Turku, Finland.
    Effects of working-memory training on striatal dopamine release2011Ingår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 333, nr 6043, s. 718-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.

  • 23. Bäckman, Lars
    et al.
    Waris, Otto
    Johansson, Jarkko
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Rinne, Juha O.
    Alakurtti, Kati
    Soveri, Anna
    Laine, Matti
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 7160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the lettermemory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.

  • 24. Cabeza, Roberto
    et al.
    Albert, Marilyn
    Belleville, Sylvie
    Craik, Fergus I. M.
    Duarte, Audrey
    Grady, Cheryl L.
    Lindenberger, Ulman
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Park, Denise C.
    Reuter-Lorenz, Patricia A.
    Rugg, Michael D.
    Steffener, Jason
    Rajah, M. Natasha
    Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing2018Ingår i: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 19, nr 11, s. 701-710Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.

  • 25. Cabeza, Roberto
    et al.
    Daselaar, Sander M
    Dolcos, Florin
    Prince, Steven E
    Budde, Matthew
    Nyberg, Lars
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Fysiologi. Umeå universitet, Samhällsvetenskaplig fakultet, Psykologi.
    Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval.2004Ingår i: Cerebral Cortex, ISSN 1047-3211, Vol. 14, nr 4, s. 364-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is controversial whether the effects of aging on various cognitive functions have the same common cause or several different causes. To investigate this issue, we scanned younger and older adults with functional magnetic resonance imaging (fMRI) while performing three different tasks: working memory, visual attention and episodic retrieval. There were three main results. First, in all three tasks, older adults showed weaker occipital activity and stronger prefrontal and parietal activity than younger adults. The occipital reduction is consistent with the view that sensory processing decline is a common cause in cognitive aging, and the prefrontal increase may reflect functional compensation. Secondly, older adults showed more bilateral patterns of prefrontal activity than younger adults during working memory and visual attention tasks. These findings are consistent with the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Finally, compared to younger adults, older adults showed weaker hippocampal formation activity in all three tasks but stronger parahippocampal activity in the episodic retrieval task. The former finding suggests that age-related hippocampal deficits may have a global effect in cognition, and the latter is consistent with an age-related increase in familiarity-based recognition. Taken together, the results indicate that both common and specific factors play an important role in cognitive aging.

  • 26.
    Dahlin, Erika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Bäckman, Lars
    Aging Research Center, Karolinska institutet,Stockholm.
    Stigsdotter Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Training of the executive component of working memory: subcortial areas mediate transfer effects2009Ingår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 27, nr 5, s. 405-419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Several recent studies show that training can improve working memory (WM) performance. In this review, many issues related to WM training, such as neural basis, transfer effects, and age-related changes are addressed.

    Method: We focus on our own studies investigating training on tasks taxing the executive updating function and discuss our findings in relation to results from other studies investigating training of the executive component of WM.

    Results: The review confirms positive behavioral effects of training on working memory. The most common neural pattern following training is fronto-parietal activity decreases. Increases in sub-cortical areas are also frequently reported after training, and we suggest that such increases indicate changes in the underlying skill following training. Transfer effects are in general difficult to demonstrate. Some studies show that older adults increase their performance after WM training. However, transfer effects are small or nonexistent in old age.

    Conclusions: The main finding in this review is that sub-cortical areas seem to have a critical role in mediating transfer effects to untrained tasks after at least some forms of working memory training (such as updating).

  • 27.
    Dahlin, Erika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bäckman, Lars
    Stigsdotter Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Plasticity of executive functioning in young and older adults: immediative training gains, transfer, and long-term maintenance2008Ingår i: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 23, nr 4, s. 720-730Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The authors investigated immediate training gains, transfer effects, and 18-month maintenance after 5 weeks of computer-based training in updating of information in working memory in young and older subjects. Trained young and older adults improved significantly more than controls on the criterion task (letter memory), and these gains were maintained 18 months later. Transfer effects were in general limited and restricted to the young participants, who showed transfer to an untrained task that required updating (3-back). The findings demonstrate substantial and durable plasticity of executive functioning across adulthood and old age, although there appear to be age-related constraints in the ability to generalize the acquired updating skill.

  • 28.
    Dahlin, Erika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stigsdotter-Neely, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, 11330 Stockholm, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Transfer of learning after updating training mediated by the striatum2008Ingår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 320, nr 5882, s. 1510-1512Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.

  • 29. Davies, G.
    et al.
    Armstrong, N.
    Bis, J. C.
    Bressler, J.
    Chouraki, V.
    Giddaluru, S.
    Hofer, E.
    Ibrahim-Verbaas, C. A.
    Kirin, M.
    Lahti, J.
    van der Lee, S. J.
    Le Hellard, S.
    Liu, T.
    Marioni, R. E.
    Oldmeadow, C.
    Postmus, I.
    Smith, A. V.
    Smith, J. A.
    Thalamuthu, A.
    Thomson, R.
    Vitart, V.
    Wang, J.
    Yu, L.
    Zgaga, L.
    Zhao, W.
    Boxall, R.
    Harris, S. E.
    Hill, W. D.
    Liewald, D. C.
    Luciano, M.
    Adams, H.
    Ames, D.
    Amin, N.
    Amouyel, P.
    Assareh, A. A.
    Au, R.
    Becker, J. T.
    Beiser, A.
    Berr, C.
    Bertram, L.
    Boerwinkle, E.
    Buckley, B. M.
    Campbell, H.
    Corley, J.
    De Jager, P. L.
    Dufouil, C.
    Eriksson, J. G.
    Espeseth, T.
    Faul, J. D.
    Ford, I.
    Gottesman, R. F.
    Griswold, M. E.
    Gudnason, V.
    Harris, T. B.
    Heiss, G.
    Hofman, A.
    Holliday, E. G.
    Huffman, J.
    Kardia, S. L. R.
    Kochan, N.
    Knopman, D. S.
    Kwok, J. B.
    Lambert, J-C
    Lee, T.
    Li, G.
    Li, S-C
    Loitfelder, M.
    Lopez, O. L.
    Lundervold, A. J.
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Mather, K. A.
    Mirza, S. S.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Oostra, B. A.
    Palotie, A.
    Papenberg, G.
    Pattie, A.
    Petrovic, K.
    Polasek, O.
    Psaty, B. M.
    Redmond, P.
    Reppermund, S.
    Rotter, J. I.
    Schmidt, H.
    Schuur, M.
    Schofield, P. W.
    Scott, R. J.
    Steen, V. M.
    Stott, D. J.
    Van Swieten, J. C.
    Taylor, K. D.
    Trollor, J.
    Trompet, S.
    Uitterlinden, A. G.
    Weinstein, G.
    Widen, E.
    Windham, B. G.
    Jukema, J. W.
    Wright, A. F.
    Wright, M. J.
    Yang, Q.
    Amieva, H.
    Attia, J. R.
    Bennett, D. A.
    Brodaty, H.
    de Craen, A. J. M.
    Hayward, C.
    Ikram, M. A.
    Lindenberger, U.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). ARC, Karolinska Institutet, Stockholm.
    Porteous, D. J.
    Raikkonen, K.
    Reinvang, I.
    Rudan, I.
    Sachdev, P. S.
    Schmidt, R.
    Schofield, P. R.
    Srikanth, V.
    Starr, J. M.
    Turner, S. T.
    Weir, D. R.
    Wilson, J. F.
    Van Duijn, C.
    Launer, L.
    Fitzpatrick, A. L.
    Seshadri, S.
    Jr, T. H. Mosley
    Deary, I. J.
    Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)2015Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, nr 2, s. 183-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

  • 30. Davies, Gail
    et al.
    Lam, Max
    Harris, Sarah E.
    Trampush, Joey W.
    Luciano, Michelle
    Hill, W. David
    Hagenaars, Saskia P.
    Ritchie, Stuart J.
    Marioni, Riccardo E.
    Fawns-Ritchie, Chloe
    Liewald, David C. M.
    Okely, Judith A.
    Ahola-Olli, Ari V.
    Barnes, Catriona L. K.
    Bertram, Lars
    Bis, Joshua C.
    Burdick, Katherine E.
    Christoforou, Andrea
    DeRosse, Pamela
    Djurovic, Srdjan
    Espeseth, Thomas
    Giakoumaki, Stella
    Giddaluru, Sudheer
    Gustavson, Daniel E.
    Hayward, Caroline
    Hofer, Edith
    Ikram, M. Arfan
    Karlsson, Robert
    Knowles, Emma
    Lahti, Jari
    Leber, Markus
    Li, Shuo
    Mather, Karen A.
    Melle, Ingrid
    Morris, Derek
    Oldmeadow, Christopher
    Palviainen, Teemu
    Payton, Antony
    Pazoki, Raha
    Petrovic, Katja
    Reynolds, Chandra A.
    Sargurupremraj, Muralidharan
    Scholz, Markus
    Smith, Jennifer A.
    Smith, Albert V.
    Terzikhan, Natalie
    Thalamuthu, Anbupalam
    Trompet, Stella
    van der Lee, Sven J.
    Ware, Erin B.
    Windham, B. Gwen
    Wright, Margaret J.
    Yang, Jingyun
    Yu, Jin
    Ames, David
    Amin, Najaf
    Amouyel, Philippe
    Andreassen, Ole A.
    Armstrong, Nicola J.
    Assareh, Amelia A.
    Attia, John R.
    Attix, Deborah
    Avramopoulos, Dimitrios
    Bennett, David A.
    Boehmer, Anne C.
    Boyle, Patricia A.
    Brodaty, Henry
    Campbell, Harry
    Cannon, Tyrone D.
    Cirulli, Elizabeth T.
    Congdon, Eliza
    Conley, Emily Drabant
    Corley, Janie
    Cox, Simon R.
    Dale, Anders M.
    Dehghan, Abbas
    Dick, Danielle
    Dickinson, Dwight
    Eriksson, Johan G.
    Evangelou, Evangelos
    Faul, Jessica D.
    Ford, Ian
    Freimer, Nelson A.
    Gao, He
    Giegling, Ina
    Gillespie, Nathan A.
    Gordon, Scott D.
    Gottesman, Rebecca F.
    Griswold, Michael E.
    Gudnason, Vilmundur
    Harris, Tamara B.
    Hartmann, Annette M.
    Hatzimanolis, Alex
    Heiss, Gerardo
    Holliday, Elizabeth G.
    Joshi, Peter K.
    Kahonen, Mika
    Kardia, Sharon L. R.
    Karlsson, Ida
    Kleineidam, Luca
    Knopman, David S.
    Kochan, Nicole A.
    Konte, Bettina
    Kwok, John B.
    Le Hellard, Stephanie
    Lee, Teresa
    Lehtimaki, Terho
    Li, Shu-Chen
    Liu, Tian
    Koini, Marisa
    London, Edythe
    Longstreth, Will T., Jr.
    Lopez, Oscar L.
    Loukola, Anu
    Luck, Tobias
    Lundervold, Astri J.
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lyytikainen, Leo-Pekka
    Martin, Nicholas G.
    Montgomery, Grant W.
    Murray, Alison D.
    Need, Anna C.
    Noordam, Raymond
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ollier, William
    Papenberg, Goran
    Pattie, Alison
    Polasek, Ozren
    Poldrack, Russell A.
    Psaty, Bruce M.
    Reppermund, Simone
    Riedel-Heller, Steffi G.
    Rose, Richard J.
    Rotter, Jerome I.
    Roussos, Panos
    Rovio, Suvi P.
    Saba, Yasaman
    Sabb, Fred W.
    Sachdev, Perminder S.
    Satizabal, Claudia L.
    Schmid, Matthias
    Scott, Rodney J.
    Scult, Matthew A.
    Simino, Jeannette
    Slagboom, P. Eline
    Smyrnis, Nikolaos
    Soumare, Aicha
    Stefanis, Nikos C.
    Stott, David J.
    Straub, Richard E.
    Sundet, Kjetil
    Taylor, Adele M.
    Taylor, Kent D.
    Tzoulaki, Ioanna
    Tzourio, Christophe
    Uitterlinden, Andre
    Vitart, Veronique
    Voineskos, Aristotle N.
    Kaprio, Jaakko
    Wagner, Michael
    Wagner, Holger
    Weinhold, Leonie
    Wen, K. Hoyan
    Widen, Elisabeth
    Yang, Qiong
    Zhao, Wei
    Adams, Hieab H. H.
    Arking, Dan E.
    Bilder, Robert M.
    Bitsios, Panos
    Boerwinkle, Eric
    Chiba-Falek, Ornit
    Corvin, Aiden
    De Jager, Philip L.
    Debette, Stephanie
    Donohoe, Gary
    Elliott, Paul
    Fitzpatrick, Annette L.
    Gill, Michael
    Glahn, David C.
    Hagg, Sara
    Hansell, Narelle K.
    Hariri, Ahmad R.
    Ikram, M. Kamran
    Jukema, J. Wouter
    Vuoksimaa, Eero
    Keller, Matthew C.
    Kremen, William S.
    Launer, Lenore
    Lindenberger, Ulman
    Palotie, Aarno
    Pedersen, Nancy L.
    Pendleton, Neil
    Porteous, David J.
    Raikkonen, Katri
    Raitakari, Olli T.
    Ramirez, Alfredo
    Reinvang, Ivar
    Rudan, Igor
    Rujescu, Dan
    Schmidt, Reinhold
    Schmidt, Helena
    Schofield, Peter W.
    Schofield, Peter R.
    Starr, John M.
    Steen, Vidar M.
    Trollor, Julian N.
    Turner, Steven T.
    Van Duijn, Cornelia M.
    Villringer, Arno
    Weinberger, Daniel R.
    Weir, David R.
    Wilson, James F.
    Malhotra, Anil
    McIntosh, Andrew M.
    Gale, Catharine R.
    Seshadri, Sudha
    Mosley, Thomas H., Jr.
    Bressler, Jan
    Lencz, Todd
    Deary, Ian J.
    Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function2018Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikel-id 2098Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic