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  • 1.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Benedikz, Eirikur
    Department of Neurobiology, Division of Neurodegeneration, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy2012In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, no 2, p. 343-358Article in journal (Refereed)
    Abstract [en]

    The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.

  • 2.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Geriatrics.
    Lindström, Tobias
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, no 4, p. 1069-1082Article in journal (Refereed)
    Abstract [en]

    Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.

  • 3.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Geriatric Medicine in Norrköping.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Domert, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease2014In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 58, p. 29-39Article in journal (Refereed)
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.

  • 4. Allard, P
    et al.
    Englund, E
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Caudate nucleus dopamine D2 receptors in vascular dementia2002In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 14, no 1, p. 22-25Article in journal (Refereed)
    Abstract [en]

    Caudate nucleus dopamine (DA) D2 receptors were studied in patients with vascular dementia (VaD) and in a control group using [3H]raclopride as a radioligand. There was no significant difference in the number of DA D2 receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D2 receptors in Alzheimer's disease and Parkinson's disease. Copyright ⌐ 2002 S. Karger AG, Basel.

  • 5.
    Andersson, Lena B.
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Rehabilitation in Central County.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health-related quality of life and activities of daily living in 85-year-olds in sweden2014In: Health and Social Care in the Community, ISSN 0966-0410, Vol. 22, no 4, p. 368-374Article in journal (Refereed)
    Abstract [en]

    Few studies have examined health-related quality of life (HRQoL) with respect to daily living and health factors for relatively healthy elderly individuals. To this end, this study examines 85-year-olds’ reported HRQoL in relation to social support, perceived health, chronic diseases, health care use and instrumental activities of daily living. Data were collected from 360 participants (55% response rate) between March 2007 and March 2008 using a postal questionnaire and a home visit interview.  HRQoL was assessed using the EQ-5D-3L. For the items in the EQ-5D-3L, more problems were related to lower HRQoL. Restricted mobility and occurrence of pain/discomfort was common.  Lower HRQoL was associated with increased risk for depression, increased use of medication, increased number of chronic diseases, and more problems with instrumental activities of daily living (IADL). Health care use and health care costs was correlated to lower HRQoL.  HRQoL is of importance to health care providers and must be considered together with IADL in the elderly population when planning interventions. These should take into account the specific needs and resources of the older individuals.

  • 6.
    Andin, Josefine
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Enz, Albert
    Neuroscience Research, The Novartis Institutes for BioMedical Research, Basel, Switzerland.
    Gentsch, Conrad
    Neuroscience Research, The Novartis Institutes for BioMedical Research, Basel, Switzerland.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression2005In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 19, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

    Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.

  • 7.
    Andin, Josefine
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics.
    Hallbeck, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Mohammed, Abdul H
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Influence of environmental enrichment on steady-state mRNA levels for EAAC1, AMPA1 and NMDA2A receptor subunits in rat hippocampus2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1174, no 1, p. 18-27Article in journal (Refereed)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. © 2007.

  • 8.
    Andin, Josefine
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Mohammed, Abdul
    Division of Geriatric Medicine, Neurontec, Karolinska Institutet, Sweden.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Environmental enrichment induces changes in the mRNA expression of rat EAAC1 and NMDA but not in AMPAManuscript (preprint) (Other academic)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment has been shown on neuronal strucrure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g. Alzheimer's disease. Glutamatergic corticocortical pathways are imperative for cognitive functions, such as memory and learning, and long term porenriation relies on the AMPA and NMDAglutamate rcceptors. The glutamate signalling is also dependent on a fine-runed transport system, in the hippocampus primarily by theglutamate transporter EAACl. In this study we show how environmental enrichment modulates these parts of the glutamarergic system using in siru hybridization. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly decreased in hippocampal and cortical areas. We also provide further evidence about the upregulation of NMDA mRNA after environmental enrichement, and show it to have a regionally and hemisphere specific regulation. The current work also confirms that AMPA mRNA is nor per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.

  • 9.
    Andin, Josefine
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Stenfors, Carina
    Bioscience, Local Discovery, AstraZeneca R&D, Södertälje, Sweden.
    Ross, Svante B
    Bioscience, Local Discovery, AstraZeneca R&D, Södertälje, Sweden.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline2004In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 126, no 1, p. 74-77Article in journal (Refereed)
    Abstract [en]

    Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.

  • 10. Arnelo, Urban
    et al.
    Herrington, Margery
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Adrian, Thomas
    Reidelberger, Roger
    Larsson, Jörgen
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Strömmer, Lisa
    Ding, Xianzhong
    Permert, Johan
    Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.2000In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 887, p. 391-398Article in journal (Refereed)
  • 11. Berg, L
    et al.
    Gustafsson, L
    Hansson, G
    Klingen, S
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Näsman, B
    Passant, U
    Wahlund, U
    Wallin, A
    Harmonisering av demensdiagnoser - en nödvändig kvalitetssäkring.2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, p. 3531-3535Article in journal (Other academic)
  • 12.
    Bjartmar, Lisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Alkhori, Liza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ruud, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology.
    Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula2010In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1328, p. 24-33Article in journal (Refereed)
    Abstract [en]

    Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, is involved in activity-dependent synaptogenesis and synaptic plasticity. In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. This study demonstrates that NP2 mRNA is robustly expressed in the hippocampus and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is enhanced in the hippocampal subregions as well as in the MHb after long-term treatment with antidepressant drugs of various monoaminergic profiles, indicating a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant induced plasticity, but not EE induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.

  • 13.
    Bjartmar, Lisa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics.
    Johansson, Inga-Maj
    Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Ross, S-B
    Astra Arcus AB, Södertälje, Sweden.
    Seckl, JR
    Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK.
    Olsson, T
    Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden.
    Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat2000In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 151, no 1, p. 7-12Article in journal (Refereed)
    Abstract [en]

    There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase), with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.

  • 14.
    Domert, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Rao, Sahana Bhima
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Brorsson, Ann-Christin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Spreading of Amyloid-β Peptides via Neuritic Cell-to-cell Transfer Is Dependent on Insufficient Cellular Clearance2014In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 65, p. 82-92Article in journal (Refereed)
    Abstract [en]

    The spreading of pathology through neuronal pathways is likely to be the cause of the progressive cognitive loss observed in Alzheimer's disease (AD) and other neurodegenerative diseases. We have recently shown the propagation of AD pathology via cell-to-cell transfer of oligomeric amyloid beta (Aβ) residues 1-42 (oAβ1-42) using our donor-acceptor 3-D co-culture model. We now show that different Aβ-isoforms (fluorescently labeled 1-42, 3(pE)-40, 1-40 and 11-42 oligomers) can transfer from one cell to another. Thus, transfer is not restricted to a specific Aβ-isoform. Although different Aβ isoforms can transfer, differences in the capacity to clear and/or degrade these aggregated isoforms result in vast differences in the net amounts ending up in the receiving cells and the net remaining Aβ can cause seeding and pathology in the receiving cells. This insufficient clearance and/or degradation by cells creates sizable intracellular accumulations of the aggregation-prone Aβ1-42 isoform, which further promotes cell-to-cell transfer; thus, oAβ1-42 is a potentially toxic isoform. Furthermore, cell-to-cell transfer is shown to be an early event that is seemingly independent of later appearances of cellular toxicity. This phenomenon could explain how seeds for the AD pathology could pass on to new brain areas and gradually induce AD pathology, even before the first cell starts to deteriorate, and how cell-to-cell transfer can act together with the factors that influence cellular clearance and/or degradation in the development of AD.

  • 15.
    Dong, Huan-Ji
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Unosson, Mitra
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences.
    Obese very old women have low relative handgrip strength, poor physical function, and difficulty in daily living2015In: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 19, no 1, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate how anthropometric and body composition variables, and handgrip strength (HS) affect physical function and independent daily living in 88-year-old Swedish women.

    Participants: A cross-sectional analysis of 83 community-dwelling women, who were 88 years old with normal weight (n=30), overweight (n=29), and obesity (n=24) in Linköping, Sweden, was performed.

    Measures: Assessments of body weight (Wt), height, waist circumference (WC), and arm circumference were performed by using an electronic scale and measuring tape. Tricep skinfold thickness was measured by a skinfold calliper. Fat mass (FM) and fat-free mass (FFM) were measured by bioelectrical impedance analysis, and HS was recorded with an electronic grip force instrument. Linear regression was used to determine the contributions of parameters as a single predictor or as a ratio with HS to physical function (Short Form-36, SF-36PF) and instrumental activities of daily living (IADL).

    Results: Obese women had greater absolute FM and FFM, and lower HS corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI]) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, HS-based ratios explained more variance in SF-36PF scoring (R2: 0.52–0.54) than single anthropometric and body composition variables (R2: 0.45–0.51). WC, HS, and HS-based ratios (HS/Wt and HS/FFM) were also associated with the number of IADL with no difficulty.

    Conclusion: Obese very old women have a high WC, but their HS is relatively low in relation to their Wt and FFM. These parameters are better than BMI for predicting physical function and independent daily living.

  • 16.
    Dong, Huan-Ji
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Unosson, Mitra
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health Consequences Associated with Being Overweight or Obese: A Swedish Population-Based Study of 85-Year-Olds2012In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 60, no 2, p. 243-250Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine whether being overweight or obese is associated with significant health outcomes in an 85-year-old population. less thanbrgreater than less thanbrgreater thanDESIGN: A cross-sectional population-based study. less thanbrgreater than less thanbrgreater thanSETTING: Linkoping, Sweden. less thanbrgreater than less thanbrgreater thanPARTICIPANTS: Three hundred thirty-eight people born in 1922 were identified using the local authoritys register. less thanbrgreater than less thanbrgreater thanMEASUREMENTS: Data related to sociodemographic characteristics, health-related quality of life (HRQoL), assistance use, and the presence of diseases were collected using a postal questionnaire. Anthropometry and functional status were assessed during home and geriatric clinic visits. Diseases were double-checked in the electronic medical records, and information about health service consumption was obtained from the local healthcare register. less thanbrgreater than less thanbrgreater thanRESULTS: Overweight (body mass index (BMI) 25.0-29.9 kg/m(2)) and obese (BMI andgt;= 30.0 kg/m(2)) participants perceived more difficulty performing instrumental activities of daily living (IADLs) and had more comorbidity than their normal-weight counterparts (BMI 18.5-24.9 kg/m(2)), but their overall HRQoL and health service costs did not differ from those of normal-weight participants. After controlling for sociodemographic factors, being overweight did not influence IADLs or any comorbidity, but obese participants were more likely to perceive greater difficulty in performing outdoor activities (odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.1-4) and cleaning (OR = 2.2, 95% CI = 1.2-4.2) than their normal-weight counterparts. Although obesity was also associated with multimorbidity (OR = 3, 95% CI = 1.2-8), the health service cost of each case of multimorbidity (n = 251) was highest in normalweight participants and nearly three times as much as in obese participants (ratio: 2.9, 95% CI = 1.1-8.1). less thanbrgreater than less thanbrgreater thanCONCLUSION: For 85-year-olds, being obese, as opposed to overweight, is associated with self-reported activity limitations and comorbidities. Overweight older adults living in their own homes in this population had well-being similar to that of those with normal weight.

  • 17.
    Dong, Huan-Ji
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study2013In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 13, no 120Article in journal (Refereed)
    Abstract [en]

    Background

    As life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population.

    Methods

    Health and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients’ case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models.

    Results

    Cluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic–mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1–5.7) and women (OR = 3, 95% CI = 1.3–6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1–2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2–2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men’s cardiac cluster (OR = 1.6, 95% CI = 1–2.4) and one of the women’s aging clusters (OR = 0.5, 95% CI = 0.3–0.8) showed interaction effects on hospitalization.

    Conclusion

    In this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.

  • 18.
    Dong, Huan-Ji
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wressle, Ewa
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Marcusson, Jan
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Unaltered image of health maintenance: An observation of non-participants in a swedish cohort study of 85 to 86 years olds2015In: The Journal of Frailty & Aging, ISSN 2260-1341, Vol. 4, no 2, p. 93-99Article in journal (Refereed)
    Abstract [en]

    Background: Selection bias is often inevitable in epidemiologic studies. It is not surprising that study conclusions based on participants’ health status are frequently questioned. Objective: This study aimed to assess whether the non-participants affected the characteristics of a general population of the very old people. Design, Setting and Participants: Prospective, cross-sectional (N=650, aged 85 years old) analysis and 1-year follow-up (n=273), in Linköping, Sweden. Measurements: We analysed data on health-related factors from a postal questionnaire, a home visit and a clinic visit at baseline and at the 1-year follow-up. We calculated the effect size to evaluate the degree of differences between the groups. Results: A greater proportion of non-participants resided in sheltered accommodation or nursing homes (participants vs non-response vs refusal, 11% vs 22% vs 40, P<0.001, φ=0.24). During the home visit or clinic visit, a higher proportion of dropouts reported mid-severe problems in EQ-5D domains (mobility and self-care) and limitations in personal activities of daily living, but the differences between participants and dropouts were very small (φ<0.2). No significant difference was found between the groups with regard to emergency room visits or hospital admissions, despite the fact that more participants than dropouts (φ=0.23) had multimorbidities (≥2 chronic diseases). Living in sheltered accommodation or a nursing home (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.5-5), female gender (OR, 1.8; 95% CI, 1.1-3.1) and receiving more home visits in primary care (OR, 1.03; 95% CI, 1-1.06) contributed positively to drop out in the data collection stages over the study period. Conclusion: Non-participants were not considered to be a group with worse health. Mobility problems may influence very old people when considering further participation, which threatens attrition.

  • 19.
    Duits, Flora H.
    et al.
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    Teunissen, Charlotte E.
    Vrije University of Amsterdam, Netherlands.
    Bouwman, Femke H.
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    Visser, Pieter-Jelle
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands; University of Maastricht, Netherlands.
    Mattsson, Niklas
    Centre Imaging Neurodegenerat Disease, CA USA.
    Zetterberg, Henrik
    UCL Institute Neurol, England.
    Blennow, Kaj
    University of Gothenburg, Sweden.
    Hansson, Oskar
    Lund University, Sweden.
    Minthon, Lennart
    Lund University, Sweden.
    Andreasen, Niels
    Karolinska University Hospital, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wallin, Anders
    University of Gothenburg, Sweden.
    Olde Rikkert, Marcel
    Donders Institute Brain Cognit and Behav, Netherlands.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Greece.
    Parnetti, Lucilla
    University of Perugia, Italy.
    Herukka, Sanna-Kaisa
    University of Eastern Finland, Finland; Kuopio University Hospital, Finland.
    Hampel, Harald
    University of Paris 06, France; University of Paris 06, France.
    De Leon, Mony J.
    NYU, NY USA.
    Schroeder, Johannes
    Heidelberg University, Germany.
    Aarsland, Dag
    Stavanger University Hospital, Norway.
    Blankenstein, Marinus A.
    Vrije University of Amsterdam, Netherlands.
    Scheltens, Philip
    Vrije University of Amsterdam, Netherlands; Vrije University of Amsterdam, Netherlands.
    van der Flier, Wiesje M.
    Vrije University of Amsterdam, Netherlands.
    The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?2014In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 10, no 6, p. 713-723Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

  • 20. Eriksson, IS
    et al.
    Allard, P.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    (3H)tiagabine binding to GABA uptake sites in human brain.1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 18, no 1-2, p. 183-188Article in journal (Refereed)
    Abstract [en]

    The binding of [H-3]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3 carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GAB,4), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [H-3]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. B-max was 3.4 pmol/mg protein and K-d 16 nM in frontal cortex. The dissociation constants (K-d) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [H-3]tiagabine binding in human tissue. It is concluded that [H-3]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.

  • 21. Garcia, J.
    et al.
    Ahmadi, Ahmad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Wonnacott, A.
    University of Wales, College of Medicine, Cardiff, United Kingdom.
    Sutcliffe, W.
    University of Wales, College of Medicine, Cardiff, United Kingdom.
    Nagga, K.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Association of insulin-like growth factor-1 receptor polymorphism in dementia2006In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 22, no 5-6, p. 439-444Article in journal (Refereed)
    Abstract [en]

    There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1-2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females. Copyright © 2006 S. Karger AG.

  • 22.
    Hallbeck, Martin
    et al.
    Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Nath, Sangeeta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Neuron-to-Neuron Transmission of Neurodegenerative Pathology2013In: The Neuroscientist, ISSN 1073-8584, E-ISSN 1089-4098, Vol. 19, no 6, p. 560-566Article, review/survey (Refereed)
    Abstract [en]

    One of the hallmarks of neurodegenerative dementia diseases is the progressive loss of mental functions and the ability to manage activities of daily life. This progression is caused by the spread of the disease to more and more brain areas via anatomical connections. The pathophysiological process responsible for this spread of disease has long been sought after. There has been an increased understanding that the driving force of these neurodegenerative diseases could be the small, soluble intraneuronal accumulations of neurodegenerative proteins rather than the large, extracellular accumulations. Recently we have shown that the mechanism of spread of Alzheimer's disease most likely depends on the neuron-to-neuron spread of such soluble intraneuronal accumulations of -amyloid through neuritic connections. Similar transmissions have been shown for several other neurodegenerative proteins but little is known about the cellular mechanisms and about any potential strategies that might stop this spread. Resolving these questions requires good cellular models. We have established a unique model of synaptic transmission between human neuronal-like cells, something that has previously been difficult to target. This opens the possibility of developing potential inhibitors of progression of these devastating diseases.

  • 23.
    Johansson, Inga-Maj
    et al.
    Department of Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden.
    Bjartmar, Lisa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Ross, Svante
    Astra Arcus, Södertälje, Sweden.
    Seckl, Jonathan
    Department of Medicine, Western General Hospital, Edinburgh, Scotland, UK.
    Olsson, Tommy
    Department of Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden.
    Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats1998In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 62, no 1, p. 92-95Article in journal (Refereed)
    Abstract [en]

    Adult male rats were treated with the antidepressant drug amitriptyline for 21 days and the expression of specific transcription factors was examined. NGFI-A mRNA expression was increased in the hippocampus and in the cerebral cortex. MR mRNA was increased in the hippocampus while GR mRNA was increased in selective hippocampal regions. There was no change in the NGFI-B mRNA expression. Thus, NGFI-A may be a mediator of plasticity-related phenomena induced by antidepressant drugs.

  • 24.
    Johansson, Maria M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Cognition, daily living, and health-related quality of life in 85-year-olds in Sweden2012In: Aging, Neuropsychology and Cognition, ISSN 1382-5585, E-ISSN 1744-4128, Vol. 19, no 3, p. 421-432Article in journal (Refereed)
    Abstract [en]

    This study investigates how cognition influences activities of daily living and health-related quality of life in 85-year-olds in Sweden (n = 373). Data collection included a postal questionnaire comprising demographics and health-related quality of life measured by the EQ-5D. The ability to perform personal activities of daily living (PADL) was assessed during a home visit that included administering the Mini Mental State Examination (MMSE). Cognitive impairment was shown in 108 individuals (29%). The majority were independent with respect to PADL. A larger number of participants with cognitive impairment reported that they needed assistance in instrumental activities of daily living (IADL) compared to the group without cognitive impairment. Impaired cognition was significantly related to problems with IADL. Significant but low correlations were found between cognition and health-related quality of life – higher ratings on perceived quality of life correlated with higher results on the MMSE.

  • 25.
    Johansson, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Cognitive impairment and its consequences in everyday life: experiences of people with mild cognitive impairment or mild dementia and their relatives2015In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 27, no 6, p. 949-958Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to explore experiences of cognitive impairment, its consequences in everyday life and need for support in people with mild cognitive impairment (MCI) or mild dementia and their relatives.

    Methods: A qualitative approach with an explorative design with interviews was chosen. The participants included five people with MCI and eight people with mild dementia and their relatives. All participants were recruited at a geriatric memory clinic in Sweden. The Grounded Theory method was used.

    Results: The following categories emerged: noticing cognitive changes; changed activity patterns; coping strategies; uncertainty about own ability and environmental reactions; support in everyday life; support from the healthcare system; consequences in everyday life for relatives; and support for relatives. The main findings were that people with MCI and dementia experienced cognitive changes that could be burdensome and changed activity patterns. Most of them, however, considered themselves capable of coping on their own. The relatives noticed cognitive changes and activity disruptions to a greater extent and tried to be supportive in everyday life. Degree of awareness varied and lack of awareness could lead to many problems in everyday life.

    Conclusions: Perceived cognitive impairment and its consequences in everyday life were individual and differed among people with MCI or dementia and their relatives. Thus, healthcare professionals must listen to both people with cognitive impairment and their relatives for optimal individual care planning. Support such as education groups and day care could be more tailored towards the early stages of dementia.

  • 26.
    Johansson, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Development of an instrument for measuring activities of daily living in persons with suspected cognitive impairment2016In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, Vol. 23, no 3, p. 230-239Article in journal (Refereed)
    Abstract [en]

    Background: According to the Swedish National Board of Health and Welfare, structured assessment of function and activity has high priority when investigating for dementia.

    Aim/objectives: The aim was to develop and psychometrically test an instrument to measure self-reported and/or informant-reported ability to perform activities of daily living in persons with suspected cognitive impairment.

    Material and methods: The Cognitive Impairment in Daily Life (CID) instrument has been developed in several phases. Content validity was achieved through five expert panels using a Content Validity Index (CVI). The content was tested further in a pilot study of 51 patients and 49 relatives from primary care or a specialist memory clinic.

    Results: Content validity was good with a CVI index of 0.83. All patients considered that relevant activities were included. Most relatives considered that the activities included in the instrument were adequate and captured the patients’ difficulties in daily life. Some adjustments to the items and scale were suggested and these were done after each phase. In general, relatives indicated more difficulties than patients.

    Conclusion: The CID instrument seems promising in terms of content validity. Further testing of reliability and construct validity is ongoing.

  • 27.
    Johansson, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Segernäs Kvitting, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Clinical Utility of Cognistat in Multiprofessional Team Evalutations of Patients with Cognitive Impairment in Swedish Primary Care2014In: International Journal of Family Medicine, ISSN 2090-2042, E-ISSN 2090-2050, Vol. 2014, p. 649253-Article in journal (Refereed)
    Abstract [en]

    Background. Diagnostic evaluations of dementia are often performed in primary health care (PHC). Cognitive evaluation requires validated instruments.

    Objective. To investigate the diagnostic accuracy and clinical utility of Cognistat in a primary care population.

    Methods. Participants were recruited from 4 PHC centres; 52 had cognitive symptoms and 29 were presumed cognitively healthy. Participants were tested using the Mini-Mental State Examination (MMSE), the Clock Drawing Test (CDT), and Cognistat. Clinical diagnoses, based on independent neuropsychological examination and a medical consensus discussion in secondary care, were used as criteria for diagnostic accuracy analyses.

    Results. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.85, 0.79, 0.85, and 0.79, respectively, for Cognistat; 0.59, 0.91, 0.90, and 0.61 for MMSE; 0.26, 0.88, 0.75, and 0.46 for CDT; 0.70, 0.79, 0.82, and 0.65 for MMSE and CDT combined. The area under the receiver operating characteristic curve was 0.82 for Cognistat, 0.75 for MMSE, 0.57 for CDT, and 0.74 for MMSE and CDT combined.

    Conclusions. The diagnostic accuracy and clinical utility of Cognistat was better than the other tests alone or combined. Cognistat is well adapted for cognitive evaluations in PHC and can help the general practitioner to decide which patients should be referred to secondary care.

     

  • 28.
    Kalldalen, Anette
    et al.
    Jonköping University.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Nagga, Katarina
    Lund University.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Occupational Performance Problems in 85-Year-Old Women and Men in Sweden2012In: OTJR (Thorofare, N.J.), ISSN 1539-4492, E-ISSN 1938-2383, Vol. 32, no 2, p. 30-38Article in journal (Refereed)
    Abstract [en]

    An area of concern for occupational therapy is to increase preventive interventions among relatively healthy elderly individuals. The purpose of this study was to explore occupational performance problems among 85-year-old women and men in relation to demographic data, mental health, and health-related quality of life. Participants completed a postal questionnaire including the EuroQoL health-related quality of life measurement. Instruments used during a home visit were the Canadian Occupational Performance Measure, the Mini-Mental State Examination, and the Geriatric Depression scale. The sample comprised 380 individuals. Women experienced poorer health and more occupational performance problems in community management, household management, and quiet leisure than men. Impaired cognitive function, lower self-rated health, and higher risk of depression correlated with a larger number of occupational performance problems. Intervention planning should be based on individual perceptions of meaningful occupations and environmental considerations.

  • 29.
    Karlsson, Thomas
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Mårdh, Selina
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Emotion and recollective experience in Alzheimer’s diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Emotional changes are common in Alzheimer’s disease (AD). In addition, damage to brain regions involved in emotion is abundant in AD. Although these finding imply that emotion memory is severely compromised in AD, absolute or relative sparing of emotional memory has occasionally been reported. Hence, we wanted to clarify how well AD patients can remember emotion words. Eighteen AD patients and fifteen healthy older persons participated in the experiment. Participants studied neutral, positive, and negative words. Implicit and explicit memory was assessed in two tasks: a word-fragment completion task and a recognition task, respectively. In the latter task, participants were asked to provide recollective judgments when they indicated that they recognized a word from previous study. Results indicated that AD patients responded to valence, and in particular negative valence, similar to controls, that AD patients evidenced severe deficits as to recollective experience, and that implicit memory remained intact in AD.

  • 30.
    Källdalen, Anette
    et al.
    Jönköping University, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Interests among older people in relation to gender, function and health-related quality of life2013In: British Journal of Occupational Therapy, ISSN 0308-0226, E-ISSN 1477-6006, Vol. 76, no 2, p. 87-93Article in journal (Refereed)
    Abstract [en]

    Abstract

    Introduction: Older people should have opportunities to be active participants in society as aspects such as lifestyle, physical and social environment and physical and mental status have influence on active ageing. The purpose was to explore the interests pursued by 85-year-old people living in ordinary housing in relation to gender, cognition, depression and health-related quality of life.

    Method: A sample of 240 participants completed a postal questionnaire including the EuroQoL health-related quality of life measurement. Additional instruments used during a subsequent home visit were the Canadian Occupational Performance Measure, Mini Mental State Examination and Geriatric Depression scale.

    Results: Women experienced poorer health than men, lived alone to a greater extent and used more mobility devices. Compared to men, women had a larger number of interests within household management, but no gender differences in the leisure area. Lower number of interests in active recreation was associated with lower cognitive function, poorer health-related quality of life and a higher risk of depressive symptoms.

    Conclusion: The main finding is that engaging in active recreation interests is associated with better cognition, less depression and higher health-related quality of life in these 85-year-old people and is therefore a concern of occupational therapists.

  • 31.
    Landgren, Sara
    et al.
    University of Gothenburg, Sweden .
    von Otter, Malin
    University of Gothenburg, Sweden .
    Seibt Palmer, Mona
    University of Gothenburg, Sweden .
    Zetterstrom, Caroline
    University of Gothenburg, Sweden .
    Nilsson, Staffan
    Chalmers, Sweden .
    Skoog, Ingmar
    University of Gothenburg, Sweden .
    Gustafson, Deborah R.
    University of Gothenburg, Sweden .
    Minthon, Lennart
    Lund University, Sweden .
    Wallin, Anders
    University of Gothenburg, Sweden .
    Andreasen, Niels
    Karolinska Institute, Sweden .
    Bogdanovic, Nenad
    Karolinska Institute, Sweden .
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Blennow, Kaj
    University of Gothenburg, Sweden .
    Zetterberg, Henrik
    University of Gothenburg, Sweden UCL Institute Neurol, England .
    Kettunen, Petronella
    University of Gothenburg, Sweden .
    A novel ARC gene polymorphism is associated with reduced risk of Alzheimers disease2012In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 119, no 7, p. 833-842Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid beta (A beta) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute A beta application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and A beta(1-42). The AA genotype of the newly found 3-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.

  • 32.
    Lantz, Kristina
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Perceived participation and health-related quality of life in 85-year olds in Sweden2012In: OTJR (Thorofare, N.J.), ISSN 1539-4492, E-ISSN 1938-2383, Vol. 32, no 4, p. 117-125Article in journal (Refereed)
    Abstract [en]

    This study explores how 85-year-olds in Sweden perceive participation and autonomy in their life situations in relation to health-related quality of life and gender. A postal questionnaire included questions on socio-demographics, social network, assistive technology, community assistance, and the EQ-5D. During a home visit, an occupational therapist evaluated perceived participation and autonomy using the Impact on Participation and Autonomy Questionnaire. The majority perceived their participation as sufficient. Women had greater limitations than men in indoor and outdoor autonomy.  Only a few individuals reported many or severe problems with participation, mainly in mobility and leisure. Not having friends nearby, no close contact with neighbors, and living in community housing increased the risk of perceived problems. Sufficient participation was positively associated with higher HRQoL and facilitating participation is an area of interest for occupational therapists.

  • 33.
    Ludvigsson, Mikael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Milberg, Anna
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping.
    Markers of subsyndromal depression in very old persons.2016In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 31, no 6, p. 619-628Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate factors associated with subsyndromal depression (SSD) in very old persons, and to develop a model for prediction of SSD among very old persons.

    METHODS: A cross-sectional, population-based study was undertaken on 85-year-old persons in Sweden. Data were collected from a postal questionnaire, assessments in the participants' homes and at reception visits. Depressiveness was screened with GDS-15 (Geriatric Depression Scale), and the results were classified into three outcome categories: non-depression (ND), SSD and syndromal depression. Data were analysed with binary logistic, ordinal logistic and linear regression.

    RESULTS: With univariate logistic regression 20 factors associated with SSD were identified in very old persons, and the four hypothesized domains-sociodemographic factors, declining physical functioning, neuropsychiatric factors and existential factors-significantly related to SSD. The multivariate logistic model included seven independent factors that increase the likelihood of SSD instead of ND (lower self-perceived health, life not meaningful, problems with self-care, use of tranquilizing medication, no contact with neighbours, history of affective disorder and history of stroke). The ordinal logistic and the linear regression models resulted in seven partly different factors for predicting SSD and depressiveness, in the very old.

    CONCLUSIONS: The identified markers may help clinicians with the detection, prevention and treatment of SSD in very old persons. The findings indicate the importance of a comprehensive functional approach to diagnosing and treating depressiveness in this population, and the findings might be interpreted as offering support for the coexistence of a dimensional and a categorical view on depressive disorders.

  • 34.
    Ludvigsson, Mikael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Milberg, Anna
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Normal Aging or Depression? A Qualitative Study on the Differences Between Subsyndromal Depression and Depression in Very Old People.2015In: The Gerontologist, ISSN 0016-9013, E-ISSN 1758-5341, Vol. 55, no 5, p. 760-769Article in journal (Refereed)
    Abstract [en]

    Purpose of the Study: The aim of this study was to make a qualitative comparison of experiences of being in very old people with subsyndromal depression (SSD), in relation to the experiences of very old people with syndromal depression or nondepression. Through investigation and deeper understanding of the interface between depressive disease and normal aging, clinicians might give more accurate prevention or treatment to those very old persons who need such help.

    DESIGN AND METHODS: Semistructured qualitative interviews were conducted for 27 individuals of 87-88 years of age, who were categorized in the 3 strata of nondepressive, SSD, and syndromal depression. Transcripts were analyzed using qualitative content analysis within each stratum and later with a comparison between the strata.

    RESULTS: The content analysis resulted in 4 themes in people with SSD, as defined by a self-report depression screening instrument, giving a comprehensive picture of SSD in very old people, and also showed qualitative differences between the SSD, syndromal depression, and nondepressive groups. A main finding was that SSD differs qualitatively from syndromal depression but not clearly from nondepression.

    IMPLICATIONS: The results might indicate that SSD in very old people is not related to pathology but to normal aging, even though the condition correlates with negative health parameters. Overlooking certain psychosocial aspects of living in the very old may pose a risk of both underdiagnosis and overdiagnosis in the spectrum of depressive disorders.

  • 35.
    Marcusson, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Allard, P.
    Englund, E.
    Reduced number of caudate nucleus dopamine uptake sites in vascular dementia.1999In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 10, p. 77-80Article in journal (Refereed)
  • 36.
    Marcusson, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Blennow, Kaj
    Skoog, Ingmar
    Wallin, Anders
    Alzheimers sjukdom och andra kognitiva sjukdomar2003Other (Other (popular science, discussion, etc.))
  • 37.
    Marcusson, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Bullock, Roger
    Gauthier, Serge
    Kurz, Alexander
    Schwalen, Susanne
    Galantamine demonstrates efficacy and safety in elderly patients with Alzheimer disease2003In: Alzheimer Disease and Associated Disorders, ISSN 0893-0341, E-ISSN 1546-4156, Vol. 17, no SUPPL. 3Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease (AD) treatment guidelines state that cholinergic agents are not cost-effective in patients with more severe disease. Because many physicians may deem an older patient unlikely to respond to treatment, older AD patients may remain untreated. Galantamine (Reminyl), a novel cholinergic agent, is effective in mild to moderate AD. This post hoc analysis of pooled phase III galantamine clinical trials was designed to assess whether older (=80 years) and younger (=79 years) AD patients experience similar benefits with galantamine based on changes in the ADAS-cog and CIBIC-plus. Mean ADAS-cog scores for older patients treated with galantamine 24 mg/day significantly improved versus baseline and versus placebo at month 3. Cognitive improvement was maintained versus placebo at month 6, the ADAS-cog score for placebo patients dropped below baseline at month 6. Change in CIBIC-plus for galantamine was significantly different from placebo at months 5 to 6. Mean ADAS-cog score in older patients taking galantamine for 12 months remained above baseline. The score for patients taking placebo for 6 months before switching to galantamine did not differ significantly from baseline at 12 months but was lower than in patients receiving galantamine for 12 months. Incidence of adverse events in patients > 80 years was similar to that in the overall study population. Galantamine maintained cognitive and global function in patients > 80 years with mild to moderate AD for at least 5 to 6 months and cognitive efficacy for 12 months. Prescribing approved therapies such as galantamine for older patients with AD is recommended.

  • 38.
    Marcusson, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hoffman, W
    Klingen, S
    Minthon, L
    Sandman, PO
    Strömqvist, J
    Sundin, Y
    Wahlund, LO
    Wimo, A
    There is a need to reform dementia care. Resources are not used optimally--time for evidence-based care2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, p. 1022-1024Article in journal (Other academic)
  • 39.
    Marcusson, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    No association between the a2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression2000In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 107, no 8-9, p. 1065-1079Article in journal (Refereed)
    Abstract [en]

    A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the a2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE e4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE e4 allele. No change in A2M exon 17-18mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.

  • 40.
    Mattsson, N
    et al.
    University of Gothenburg.
    Rosen, E
    University of Gothenburg.
    Hansson, O
    Lund University.
    Andreasen, N
    Karolinska University Hospital.
    Parnetti, L
    University of Perugia.
    Jonsson, M
    University of Gothenburg.
    Herukka, S-K
    University of Eastern Finland.
    van der Flier, W M
    Vrije University of Amsterdam Medical Centre.
    Blankenstein, M A
    Vrije University of Amsterdam Medical Centre.
    Ewers, M
    University of Calif San Francisco.
    Rich, K
    NYU.
    Kaiser, E
    University of Heidelberg.
    Verbeek, M M
    Radboud University of Nijmegen Medical Centre.
    Olde Rikkert, M
    Radboud University of Nijmegen Medical Centre.
    Tsolaki, M
    Aristotle University of Thessaloniki.
    Mulugeta, E
    Kings College London.
    Aarsland, D
    Stavanger University Hospital.
    J Visser, P
    University of Maastricht.
    Schroeder, J
    University of Heidelberg.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    de Leon, M
    NYU.
    Hampel, H
    Goethe University of Frankfurt.
    Scheltens, P
    Vrije University of Amsterdam Medical Centre.
    Wallin, A
    University of Gothenburg.
    Eriksdotter-Jonhagen, M
    Karolinska University Hospital.
    Minthon, L
    Lund University.
    Winblad, B
    Karolinska University Hospital.
    Blennow, K
    University of Gothenburg.
    Zetterberg, H
    University of Gothenburg.
    Age and diagnostic performance of Alzheimer disease CSF biomarkers2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 78, no 7, p. 468-476Article in journal (Refereed)
    Abstract [en]

    Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. less thanbrgreater than less thanbrgreater thanMethods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. less thanbrgreater than less thanbrgreater thanResults: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. less thanbrgreater than less thanbrgreater thanConclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.

  • 41.
    Mattsson, Niklas
    et al.
    University of Gothenburg.
    Zetterberg, Henrik
    University of Gothenburg.
    Hansson, Oskar
    Lund University.
    Andreasen, Niels
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Parnetti, Lucilla
    University of Perugia, Italy.
    Jonsson, Michael
    University of Gothenburg.
    Herukka, Sanna-Kaisa
    University of Kuopio, Finland.
    van der Flier, Wiesje M.
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Blankenstein, Marinus A.
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Ewers, Michael
    University of Dublin, Ireland.
    Rich, Kenneth
    New York University, USA.
    Kaiser, Elmar
    University of Heidelberg, Germany.
    Verbeek, Marcel
    Radboud University Medical Centre, Nijmegen, the Netherlands.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Greece .
    Mulugeta, Ezra
    Stavanger University Hospital, Norway.
    Rosén, Erik
    University of Gothenburg.
    Aarsland, Dag
    Stavanger University Hospital, Norway.
    Jelle Visser, Pieter
    University of Maastricht, the Netherlands.
    Schroeder, Johannes
    University of Heidelberg, Germany.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    de Leon, Mony
    New York University, USA.
    Hampel, Harald
    University of Dublin, Ireland.
    Scheltens, Philip
    Vrije University Medical Center, Amsterdam, the Netherlands.
    Pirttilae, Tuula
    University of Kuopio, Finland.
    Wallin, Anders
    University of Gothenburg.
    Eriksdotter Jönhagen, Maria
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Minthon, Lennart
    Lund University.
    Winblad, Bengt
    Karolinska Institutet, Huddinge University Hospital, Stockholm.
    Blennow, Kaj
    University of Gothenburg.
    CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment2009In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 302, no 4, p. 385-393Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted.

    OBJECTIVE:

    To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI.

    DESIGN, SETTING, AND PARTICIPANTS:

    The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia.

    MAIN OUTCOME MEASURES:

    Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD.

    RESULTS:

    During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%.

    CONCLUSIONS:

    This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.

  • 42.
    Mårdh, Selina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Linnaeus Centre HEAD, Linköping University, Linköping, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Aspects of awareness in patients with Alzheimer's disease2013In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 25, no 7, p. 1167-1179Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of the present study was to gain insight into Alzheimer's disease (AD) patients' perception of the world through the study of a few aspects of awareness. The aspects in focus of the study were disease awareness, metacognition, managing of everyday life, and as a complement, the agreement (calibration) between patients and their spouses on the studied aspects was considered.

    Method: A mixed-method evaluation design was used involving 15 AD patients, their spouses, and 15 elderly healthy control subjects. The study comprised both a semistructured interview (AD patients and spouse) and a neuropsychological assessment (AD patients and control subjects).

    Results: The patients were aware of their disease and able to report on their illness. Despite this awareness, they were unable to realize and manage the practical and cognitive implications of their impairment. The results also indicate that patients and spouses were not well calibrated regarding thoughts about the disease and problems in handling the cognitive deterioration.

    Conclusions: The findings of our study have relevance to patients' well being and how they manage everyday life. An open dialogue on these issues between spouses and in the care for AD patients would hopefully enhance quality of life for all parties involved.

  • 43.
    Nath, Sangeeta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Roshan, Firoz
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Granseth, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid2012In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, no 26, p. 8767-8777Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of beta-amyloid (A beta) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble A beta oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric A beta. Additional studies conducted in a human donor-acceptor cell model show that this A beta transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular A beta oligomers play a role in neurodegeneration, and they explain the manner in which A beta can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.

  • 44.
    Neselius, Sanna
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Brisby, Helena
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Zetterberg, Henrik
    Sahlgrenska University Hospital, Mölndal, Sweden.
    Blennow, Kaj
    Sahlgrenska University Hospital, Mölndal, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Neurological Assessment and Its Relationship to CSF Biomarkers in Amateur Boxers2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, p. e0099870-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Mild traumatic brain injury (TBI) or concussion is common in many sports. Today, neuropsychological evaluation is recommended in the monitoring of a concussion and in return-to-play considerations. To investigate the sensitivity of neuropsychological assessment, we tested amateur boxers post bout and compared with controls. Further the relationship between neuropsychological test results and brain injury biomarkers in the cerebrospinal fluid (CSF) were investigated.

    METHOD:

    Thirty amateur boxers on high elite level with a minimum of 45 bouts and 25 non-boxing matched controls were included. Memory tests (Rey Osterrieth Complex Figure, Listening Span, Digit Span, Controlled Word Association Test, and computerized testing of episodic memory), tests of processing speed and executive functions (Trail Making, Reaction Time, and Finger Tapping) were performed and related to previously published CSF biomarker results for the axonal injury marker neurofilament light (NFL).

    RESULTS:

    The neurological assessment showed no significant differences between boxers and controls, although elevated CSF NFL, as a sign of axonal injury, was detected in about 80% of the boxers 1-6 days post bout. The investigation of the relationship between neuropsychological evaluation and CSF NFL concentrations revealed that boxers with persisting NFL concentration elevation after at least 14 days resting time post bout, had a significantly poorer performance on Trail Making A (p = 0.041) and Simple Reaction Time (p = 0.042) compared to other boxers.

    CONCLUSION:

    This is the first study showing traumatic axonal brain injury can be present without measureable cognitive impairment. The repetitive, subconcussive head trauma in amateur boxing causes axonal injury that can be detected with analysis of CSF NFL, but is not sufficient to produce impairment in memory tests, tests of processing speed, or executive functions. The association of prolonged CSF NFL increase in boxers with impairment of processing speed is an interesting observation, which needs to be verified in larger studies.

  • 45.
    Neselius, Sanna
    et al.
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Brisby, Helena
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Blennow, Kaj
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Zetterberg, Henrik
    Sahlgrens University Hospital, Sweden University of Gothenburg, Sweden .
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    CSF-Biomarkers in Olympic Boxing: Diagnosis and Effects of Repetitive Head Trauma2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4Article in journal (Refereed)
    Abstract [en]

    Background: Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur) boxing and cerebrospinal fluid (CSF) brain injury biomarkers. Methods: The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. Results: NFL (mean +/- SD, 5326 +/- 553 vs 135 +/- 51 ng/L p = 0.001), GFAP (496 +/- 238 vs 247 +/- 147 ng/L pless than0.001), T-tau (58 +/- 26 vs 49 +/- 21 ng/L pless than0.025) and S-100B (0.76 +/- 0.29 vs 0.60 +/- 0.23 ng/L p = 0.03) concentrations were significantly increased after boxing compared to controls. NFL (402 +/- 434 ng/L p = 0.004) and GFAP (369 +/- 113 ng/L p = 0.001) concentrations remained elevated after the rest period. Conclusion: Increased CSF levels of T-tau, NFL, GFAP, and S-100B in greater than80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury.

  • 46.
    Neselius, Sanna
    et al.
    Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden / Institution for Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, Gothenburg, Sweden / Inst. of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, Gothenburg, Sweden / Inst. of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Brisby, Helena
    Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden / Institution for Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Increased CSF Levels of Phosphorylated Neurofilament Heavy Protein following Bout in Amateur Boxers2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e81249-Article in journal (Refereed)
    Abstract [en]

    Introduction

    Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI.

    Materials and Methods

    Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up). The controls were tested once. CSF levels of neurofilament heavy (pNFH), amyloid precursor proteins (sAPPα and sAPPβ), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed.

    Results

    CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p<0.001). The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018). CSF pNFH concentrations correlated with NFL (r = 0.57 after bout and 0.64 at follow up, p<0.001). No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers.

    Conclusions

    Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI.

  • 47.
    Neselius, Sanna
    et al.
    Sahlgrens University Hospital, Sweden .
    Zetterberg, Henrik
    Sahlgrens University Hospital, Sweden .
    Blennow, Kaj
    Sahlgrens University Hospital, Sweden .
    Randall, Jeffrey
    Quanterix Corp, MA USA .
    Wilson, David
    Quanterix Corp, MA USA .
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Brisby, Helena
    Sahlgrens University Hospital, Sweden .
    Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma2013In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 27, no 4, p. 425-433Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to investigate if olympic (amateur) boxing is associated with elevation of brain injury biomarkers in peripheral blood compared to controls. less thanbrgreater than less thanbrgreater thanMaterials and methods: Thirty olympic boxers competing in at least 47 bouts were compared to 25 controls. Blood was collected from the controls at one occasion and from the boxers within 1-6 days after a bout and after a rest period of at least 14 days. Tau concentration in plasma was determined using a novel single molecule ELISA assay and S-100B, glial fibrillary acidic protein, brain-derived neurotrophic factor and amyloid beta 1-42 were determined using standard immunoassays. less thanbrgreater than less thanbrgreater thanResults: None of the boxers had been knocked-out during the bout. Plasma-tau was significantly increased in the boxers after a bout compared to controls (mean +/- SD, 2.46 +/- 5.10 vs. 0.79 +/- 0.961 ngL(-1), p = 0.038). The other brain injury markers did not differ between the groups. Plasma-tau decreased significantly in the boxers after a resting period compared to after a bout (p = 0.030). less thanbrgreater than less thanbrgreater thanConclusions: Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.

  • 48.
    Nägga, Katarina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Bogdanovic, N.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Gaba transporters (GAT-1) in Alzheimer´s disease.1999In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 106, no 11-12, p. 1141-1149Article in journal (Refereed)
    Abstract [en]

    The presynaptically located gamma-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [H-3]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [H-3]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.

  • 49.
    Nägga, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Dong, Huan-Ji
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Olin Skoglund, Sabina
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health-related factors associated with hospitalization for old people: Comparisons of elderly aged 85 in a population cohort study2012In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 54, no 2, p. 391-397Article in journal (Refereed)
    Abstract [en]

    The aim of this population-based study was to (1) describe living conditions and actual health care utilization among 85 year olds; (2) determine factors that affect hospital admissions in this age. The study was conducted on 85-year-old residents in Linkoping municipality, Sweden. The data collected included medical records, health care utilization during the preceding 12 months and a postal questionnaire on assistance, assistive technology, functional impairment, feelings of loneliness, worries and health-related quality of life measured by the EQ-5D. Out of 650 eligible individuals, 496 (78% of those alive) participated. Despite the prevalence of multi-morbidity (68%) and mental discomfort, the majority managed self-care (85%), usual activities (74%) and had high (andgt;60/100) self-rated health evaluated by a visual analog scale (VAS). The non-hospitalized group reported a better health status than the hospitalized group in terms of medical aspects, living conditions and subjective estimation. Factors associated with in-patient care were an increased number of general practitioner visits, more assistive technology, community assistance, multimorbidity and/or diagnosed congestive heart failure and arrhythmia.

  • 50.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Garcia-Colque, Jorge
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Zetterberg, Henrik
    Department of Clinical Neuroscience, Section of Experimental Neuroscience, University of Göteborg, Sahlgrenska University Hospital, Mölndal.
    Blennow, Kaj
    Department of Clinical Neuroscience, Section of Experimental Neuroscience, University of Göteborg, Sahlgrenska University Hospital, Mölndal and The Medical Research Council, AstraZeneca R&D, Mölndal.
    Gottfries, Johan
    Medicinal Chemistry, AstraZeneca R&D, Mölndal, Sweden.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Evaluation of factors of importance for clinical dementia diagnosis2005In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 19, no 5-6, p. 289-298Article in journal (Refereed)
    Abstract [en]

    Diagnosing clinical dementia is based on an assessment of different variables, such as the patient’s medical history, known risk factors, and biochemical features. Partial least squares discriminant analysis was used to evaluate variables of importance for diagnosing dementia in a clinical dementia population. Polymorphism for genotypes of glutathione S-transferase (GST) and sulfotransferase 1A1, hypothetically of importance in dementia disorders, was also included in the analysis. The study population consisted of 73 patients with Alzheimer’s disease (AD), 14 with mixed dementia, 75 patients with vascular dementia, and 28 control cases. We found that several of the variables, such as the presence of ApoE4 allele, high cerebrospinal fluid levels of total tau protein, low levels of β-amyloid(1–42), and a low score on the Mini-Mental State Examination, facilitated a discrimination between the diagnoses compared with the controls. The different diagnoses overlapped. There were indications that genotypes of GSTs contributed to a subgrouping within AD.

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