title: Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.
abstract: Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.|Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Germany.|Department of Neurology, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Peter
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.|Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Jacob
authors.initials: J
authors.lastname: Lahr
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.|Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Germany.|Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Germany.
authors.forename: Lora
authors.initials: L
authors.lastname: Minkova
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Eliza
authors.initials: E
authors.lastname: Lauer
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Grothe
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.|Department of Neurology, Faculty of Medicine, University of Freiburg, Germany.|Department of Neuroradiology, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Köstering
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.|Department of Neurology, Faculty of Medicine, University of Freiburg, Germany.|BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Kaller
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Freiburg, Germany.|Centre for Geriatric Medicine and Gerontology, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Heimbach
authors.affiliation: Centre for Geriatric Medicine and Gerontology, Faculty of Medicine, University of Freiburg, Germany.|Centre for Psychiatry Emmendingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.affiliation: Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Normann
authors.affiliation: Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nissen
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Reis
authors.affiliation: Freiburg Brain Imaging, Faculty of Medicine, University of Freiburg, Germany.|Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Freiburg, Germany.|Centre for Geriatric Medicine and Gerontology, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D060825:Cognitive Dysfunction / Q000150:complications* / Q000473:pathology*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D061212:Memory, Episodic; D008875:Middle Aged; D009433:Neural Inhibition / Q000502:physiology; D009483:Neuropsychological Tests; D016548:Prosencephalon / Q000000981:diagnostic imaging / Q000378:metabolism; D012044:Regression Analysis; D050781:Transcranial Magnetic Stimulation; D014706:Verbal Learning / Q000502:physiology*
chemical_list: D000109:Acetylcholine
keywords: Basal forebrain cholinergic system; mediation; mild cognitive impairment; short afferent inhibition