title: Functional connectivity increase in the default-mode network of patients with Alzheimer's disease after long-term treatment with Galantamine.
abstract: Acetylcholinesterase inhibitors (AChEIs) are efficacious for the treatment of mild to moderate forms of Alzheimer's dementia (AD). Default-mode network (DMN) connectivity is considered to be early impaired in AD. Long-term effects of AChEIs on the DMN in AD have not yet been investigated. Twenty-eight AD patients and 11 age-matched healthy volunteers (HC) participated in the prospective study. AD patients were randomly assigned to either a pharmacotherapy arm (Galantamine, AD G) or to a placebo arm (AD P+G) for the period of 6 months followed by open-label Galantamine therapy from month 7-12. All subjects underwent neuropsychological testing, resting-state functional and structural MRI at baseline and after 12 months, AD patients additionally in between after 6 months. Thirteen AD patients completed the treatment trial and underwent all functional MRI follow-up sequences of good quality. Functional connectivity significantly increased within the AD G group in the posterior cingulate cortex and in the Precuneus between baseline and 12 months follow-up (pcorr<0.05). Between-group analyses demonstrated that functional connectivity in the AD G group significantly increased in the posterior cingulate cortex as well as in the Precuneus compared to the HC group and in the anteromedial aspect of the temporal lobes compared to the AD P+G group, respectively, at 12 months follow-up (pcorr<0.05). Cognitive performance remained stable within groups over time indicating that resting-state fMRI may be sensitive for the detection of pharmacologically induced effects on brain function of AD patients.
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany. Electronic address: Janusch.Blautzik@med.uni-muenchen.de.
authors.forename: Janusch
authors.initials: J
authors.lastname: Blautzik
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Keeser
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Paolini
authors.affiliation: Department of Neurology, Ludwig-Maximilians-University, Munich, Germany; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kirsch
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Berman
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Coates
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reiser
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meindl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005702:Galantamine / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D012146:Rest; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D005702:Galantamine; D010100:Oxygen
keywords: Alzheimer׳s disease; Default-mode network; Galantamine; Resting-state functional connectivity; Voxel-based morphometry