Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.

Autor: Franzmeier N; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany., Düzel E; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany., Jessen F; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924 Cologne, Germany., Buerger K; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany., Levin J; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany., Duering M; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany., Dichgans M; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Haass C; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Biomedical Center, Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany., Suárez-Calvet M; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Biomedical Center, Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany., Fagan AM; Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA.; Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA., Paumier K; Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA., Benzinger T; Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA.; Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA., Masters CL; The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia., Morris JC; Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA.; Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA., Perneczky R; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Nußbaumstr. 7, 80336 Munich, Germany.; Neuroepidemiology and Ageing Research Unit, School of Public Health, The Imperial College of Science, Technology and Medicine, Exhibition Road, SW7 2AZ London, UK.; West London Mental Health Trust, 13 Uxbridge Road, UB1 3EU London, UK., Janowitz D; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany., Catak C; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany., Wolfsgruber S; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Wagner M; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Teipel S; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.; Department of Psychosomatic, University of Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany., Kilimann I; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany., Ramirez A; Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924 Cologne, Germany.; Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.; Institute of Human Genetics, University of Bonn, 53127, Bonn, Germany., Rossor M; Dementia Research Centre, University College London, Queen Square, London, UK., Jucker M; Hertie Institute for Clinical Brain Research, Tübingen, Germany and German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Chhatwal J; Departments of Neurology, Massachusetts General Hospital, Charlestown HealthCare Center, Charlestown, Massachusetts 02129, USA.; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown HealthCare Center, Charlestown, Massachusetts 02129, USA., Spottke A; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Neurology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Boecker H; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Radiology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Brosseron F; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Falkai P; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Nußbaumstr. 7, 80336 Munich, Germany., Fliessbach K; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Heneka MT; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Laske C; Dementia Research Centre, University College London, Queen Square, London, UK.; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany., Nestor P; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.; Queensland Brain Institute, University of Queensland, Brisbane, Australia., Peters O; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité, Hindenburgdamm 30, 12203 Berlin, Germany., Fuentes M; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany., Menne F; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Psychiatry and Psychotherapy, Charité, Hindenburgdamm 30, 12203 Berlin, Germany., Priller J; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Neuropsychiatry, Charite - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Spruth EJ; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Neuropsychiatry, Charite - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Franke C; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.; Department of Neuropsychiatry, Charite - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Schneider A; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Kofler B; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Westerteicher C; German Center for Neurodegenerative Diseases (DZNE), Bonn, Sigmund-Freud-Str. 27, 53127 Bonn, Germany.; Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany., Speck O; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.; Leibniz Institute for Neurobiology, Magdeburg, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany.; Department of Biomedical Magnetic Resonance, Leipziger Str. 44, 39120 Magdeburg, Germany., Wiltfang J; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany.; iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal., Bartels C; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany., Araque Caballero MÁ; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany., Metzger C; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany., Bittner D; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany., Weiner M; University of California at San Francisco, 505 Parnassus Ave, San Francisco, CA94143, USA., Lee JH; Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea., Salloway S; Department of Neurology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA., Danek A; German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.; Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany., Goate A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Schofield PR; Neuroscience Research Australia, Barker Street Randwick, Sydney 2031, Australia.; School of Medical Sciences, University of New South Wales, Sydney 2052, Australia., Bateman RJ; Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA.; Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.; Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, USA., Ewers M; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377 Munich, Germany.
Jazyk: angličtina
Zdroj: Brain : a journal of neurology [Brain] 2018 Apr 01; Vol. 141 (4), pp. 1186-1200.
DOI: 10.1093/brain/awy008
Abstrakt: Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.
Databáze: MEDLINE