title: Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: a BOLD and perfusion MRI study.
abstract: In young individuals, caffeine-mediated blockade of adenosine receptors and vasoconstriction has direct repercussions on task-related activations, changes in functional connectivity, as well as global vascular effects. To date, no study has explored the effect of caffeine on brain activation patterns during highly demanding cognitive tasks in the elderly. This prospective, placebo-controlled crossover design comprises 24 healthy elderly individuals (mean age 68.8 ± 4.0 years, 17 females) performing a 2-back working memory (WM) task in functional magnetic resonance imaging (fMRI). Analyses include complimentary assessment of task-related activations (general linear model, GLM), functional connectivity (tensorial independent component analysis, TICA), and baseline perfusion (arterial spin labeling). Despite a reduction in whole-brain global perfusion (-22.7%), caffeine-enhanced task-related GLM activation in a local and distributed network is most pronounced in the bilateral striatum and to a lesser degree in the right middle and inferior frontal gyrus, bilateral insula, left superior and inferior parietal lobule as well as in the cerebellum bilaterally. TICA was significantly enhanced (+8.2%) in caffeine versus placebo in a distributed and task-relevant network including the pre-frontal cortex, the supplementary motor area, the ventral premotor cortex and the parietal cortex as well as the occipital cortex (visual stimuli) and basal ganglia. The inverse comparison of placebo versus caffeine had no significant difference. Activation strength of the task-relevant-network component correlated with response accuracy for caffeine yet not for placebo, indicating a selective cognitive effect of caffeine. The present findings suggest that acute caffeine intake enhances WM-related brain activation as well as functional connectivity of blood oxygen level-dependent fMRI in elderly individuals.
authors.affiliation: Department of Imaging and Medical Informatics, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, Switzerland. Electronic address: sven.haller@hcuge.ch.
authors.forename: S
authors.initials: S
authors.lastname: Haller
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez
authors.forename: D
authors.initials: D
authors.lastname: Moser
authors.forename: S
authors.initials: S
authors.lastname: Toma
authors.forename: J
authors.initials: J
authors.lastname: Hofmeister
authors.forename: I
authors.initials: I
authors.lastname: Sinanaj
authors.forename: D
authors.initials: D
authors.lastname: Van De Ville
authors.forename: P
authors.initials: P
authors.lastname: Giannakopoulos
authors.forename: K-O
authors.initials: KO
authors.lastname: Lovblad
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D025341:Principal Component Analysis; D011597:Psychomotor Performance / Q000187:drug effects; D013113:Spin Labels
chemical_list: D000697:Central Nervous System Stimulants; D013113:Spin Labels; D002110:Caffeine; D010100:Oxygen
keywords: ASL; BOLD; CBF; CDR; Clinical Dementia Rating scale; DTI; FMRIB’s Software Library; FSL; GLM; ICs; MEG; PFC; SMA; TICA; WM; aging; arterial spin labeling; blood oxygen level dependent; caffeine; cerebral blood flow; cognition; diffusion tensor imaging; fMRI; functional magnetic resonance imaging; general linear model; independent components; magnetoencephalography; pre-frontal cortex; supplementary motor area; tensorial-independent component analysis; vPMC; ventral premotor cortex; working memory