Masoud Tahmasian1, Lorenzo Pasquini2, Martin Scherr2, Chun Meng2, Stefan Förster2, Satja Mulej Bratec2, Kuangyu Shi2, Igor Yakushev2, Markus Schwaiger2, Timo Grimmer2, Janine Diehl-Schmid2, Valentin Riedl2, Christian Sorg2, Alexander Drzezga2. 1. 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. 2. 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.
Abstract
OBJECTIVES: 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. CONCLUSION: 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.
OBJECTIVES: 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. CONCLUSION: 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: Masoud Tahmasian; Simon B Eickhoff; Kathrin Giehl; Frank Schwartz; Damian M Herz; Alexander Drzezga; Thilo van Eimeren; Angela R Laird; Peter T Fox; Habibolah Khazaie; Mojtaba Zarei; Carsten Eggers; Claudia R Eickhoff Journal: Cortex Date: 2017-04-08 Impact factor: 4.027
Authors: Nicolai Franzmeier; Jinyi Ren; Alexander Damm; Gemma Monté-Rubio; Mercè Boada; Agustín Ruiz; Alfredo Ramirez; Frank Jessen; Emrah Düzel; Octavio Rodríguez Gómez; Tammie Benzinger; Alison Goate; Celeste M Karch; Anne M Fagan; Eric McDade; Katharina Buerger; Johannes Levin; Marco Duering; Martin Dichgans; Marc Suárez-Calvet; Christian Haass; Brian A Gordon; Yen Ying Lim; Colin L Masters; Daniel Janowitz; Cihan Catak; Steffen Wolfsgruber; Michael Wagner; Esther Milz; Sonia Moreno-Grau; Stefan Teipel; Michel J Grothe; Ingo Kilimann; Martin Rossor; Nick Fox; Christoph Laske; Jasmeer Chhatwal; Peter Falkai; Robert Perneczky; Jae-Hong Lee; Annika Spottke; Henning Boecker; Frederic Brosseron; Klaus Fliessbach; Michael T Heneka; Peter Nestor; Oliver Peters; Manuel Fuentes; Felix Menne; Josef Priller; Eike J Spruth; Christiana Franke; Anja Schneider; Christine Westerteicher; Oliver Speck; Jens Wiltfang; Claudia Bartels; Miguel Ángel Araque Caballero; Coraline Metzger; Daniel Bittner; Stephen Salloway; Adrian Danek; Jason Hassenstab; Igor Yakushev; Peter R Schofield; John C Morris; Randall J Bateman; Michael Ewers Journal: Mol Psychiatry Date: 2019-03-21 Impact factor: 15.992
Authors: Lars Michels; Florian Riese; Rafael Meyer; Andrea M Kälin; Sandra E Leh; Paul G Unschuld; Roger Luechinger; Christoph Hock; Ruth O'Gorman; Spyros Kollias; Anton Gietl Journal: Front Aging Neurosci Date: 2021-04-23 Impact factor: 5.750