title: Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer's Disease.
abstract: Very early Alzheimer's disease (AD) - i.e., AD at stages of mild cognitive impairment (MCI) and mild dementia - is characterized by progressive structural and neuropathologic changes, such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex and also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC) patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON,n= 33) and patients with AD in the stages of MCI (AD-MCI,n= 38) and mild dementia (AD-D,n= 36). Outcome measures were voxel-based morphometry (VBM) values and region-of-interest-based iFC maps of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D). Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D), particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions, including that of amygdala.
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Ortner
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pasquini
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Barat
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Department of Psychiatry, University Hospital of Rion, University of Patras, Rion Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: Department of Nuclear Medicine, Klinikum Bayreuth , Bayreuth , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Diehl-Schmid
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Zimmer
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universität München , Munich , Germany.
authors.forename: Afra
authors.initials: A
authors.lastname: Wohlschläger
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Peters
keywords: Alzheimer’s dementia; Alzheimer’s disease; amygdala; fMRI; intrinsic functional connectivity; mild cognitive impairment