title: The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease.
abstract: OBJECTIVE
  Based on the hippocampus disconnection hypothesis in Alzheimer disease (AD), which postulates that uncoupling from cortical inputs contributes to disinhibition-like changes in hippocampus activity, we suggested that in patients with AD, the more the intrinsic functional connectivity between hippocampus and precuneus is decreased, the higher hippocampal glucose metabolism will be.
  
  
  METHODS
  Forty patients with mild AD dementia, 21 patients with mild cognitive impairment, and 26 healthy controls underwent simultaneous PET/MRI measurements on an integrated PET/MR scanner. (18)F-fluorodeoxyglucose-PET was used to measure local glucose metabolism as proxy for neural activity, and resting-state functional MRI with seed-based functional connectivity analysis was performed to measure intrinsic functional connectivity as proxy for neural coupling. Group comparisons and correlation analysis were corrected for effects of regional atrophy, partial volume effect, age, and sex.
  
  
  RESULTS
  In both patient groups, intrinsic connectivity between hippocampus and precuneus was significantly reduced. Moreover, in both patient groups, glucose metabolism was reduced in the precuneus (AD < mild cognitive impairment < controls) while unchanged in the hippocampus. Critically, the lower connectivity between hippocampus and precuneus was in patients with AD dementia, the higher was hippocampus metabolism.
  
  
  CONCLUSIONS
  Results provide evidence that in patients with AD dementia, stronger decrease of intrinsic connectivity between hippocampus and precuneus is linked with higher intrahippocampal metabolism (probably reflecting higher neuronal activity). These data support the hippocampus disconnection hypothesis, i.e., uncoupling from cortical inputs may contribute to disinhibition-like changes of hippocampal activity with potentially adverse consequences on both intrahippocampal physiology and clinical outcome.
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria. masoud.tahmasian@lrz.tum.de.
authors: Masoud
authors: M
authors: Tahmasian
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Lorenzo
authors: L
authors: Pasquini
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Martin
authors: M
authors: Scherr
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Chun
authors: C
authors: Meng
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Stefan
authors: S
authors: Förster
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Satja
authors: S
authors: Mulej Bratec
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Kuangyu
authors: K
authors: Shi
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Igor
authors: I
authors: Yakushev
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Markus
authors: M
authors: Schwaiger
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Timo
authors: T
authors: Grimmer
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Janine
authors: J
authors: Diehl-Schmid
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Valentin
authors: V
authors: Riedl
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Christian
authors: C
authors: Sorg
authors: From the Departments of Neuroradiology (M.T., L.P., M. Scherr, C.M., S.M.B., V.R., C.S.), Nuclear Medicine (M.T., S.F., K.S., I.Y., M. Schwaiger, V.R., C.S., A.D.), and Psychiatry and Psychotherapy (M. Scherr, T.G., J.D.-S., C.S.) of Klinikum rechts der Isar, Technische Universität München; TUM-NIC Neuroimaging Center (M.T., L.P., M. Scherr, C.M., S.F., S.M.B., I.Y., V.R., C.S.), Technische Universität München, Munich; Graduate School of Systemic Neurosciences (C.M., S.M.B.), Ludwig Maximilians University, Munich; Department of Nuclear Medicine (M.T., A.D.), University Hospital of Cologne, Germany; Sleep Disorders Research Center (M.T.), Kermanshah University of Medical Sciences, Iran; and Department of Neurology (M. Scherr), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
authors: Alexander
authors: A
authors: Drzezga
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D063132:Connectome / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18