title: Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.
abstract: Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.
authors.affiliation: Department of Imaging and Medical Informatics, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Haller
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Montandon
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Cristelle
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Moser
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Simona
authors.initials: S
authors.lastname: Toma
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hofmeister
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Indrit
authors.initials: I
authors.lastname: Sinanaj
authors.affiliation: Department of Imaging and Medical Informatics, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Karl-Olof
authors.initials: KO
authors.lastname: Lovblad
authors.affiliation: Department of Mental Health and Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Giannakopoulos
mesh_terms: D000368:Aged; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018592:Cross-Over Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects; D012815:Signal Processing, Computer-Assisted; D066127:White Matter / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine
keywords: Blood oxygenation level dependent; caffeine; functional magnetic resonance imaging; mild cognitive impairment