title: Caffeine impact on working memory-related network activation patterns in early stages of cognitive decline.
abstract: OBJECTIVE
  Recent evidence indicates that caffeine may have a beneficial effect on cognitive decline and dementia. The current investigation assessed the effect of acute caffeine administration on working memory during the earliest stage of cognitive decline in elderly participants.
  
  
  METHODS
  The study includes consecutive 45 elderly controls and 18 individuals with mild cognitive impairment (MCI, 71.6 ± 4.7 years, 7 females). During neuropsychological follow-up at 18 months, 24 controls remained stable (sCON, 70.0 ± 4.3 years, 11 women), while the remaining 21 showed subtle cognitive deterioration (dCON, 73.4 ± 5.9 years, 14 women). All participants underwent an established 2-back working task in a crossover design of 200 mg caffeine versus placebo. Data analysis included task-related general linear model and functional connectivity tensorial independent component analysis.
  
  
  RESULTS
  Working memory behavioral performances did not differ between sCON and dCON, while MCI was slower and less accurate than both control groups (p < 0.05). The dCON group had a less pronounced effect of acute caffeine administration essentially restricted to the right hemisphere (p < 0.05 corrected) and reduced default mode network (DMN) deactivation compared to sCON (p < 0.01 corrected).
  
  
  CONCLUSIONS
  dCON cases are characterized by decreased sensitivity to caffeine effects on brain activation and DMN deactivation. These complex fMRI patterns possibly reflect the instable status of these cases with intact behavioral performances despite already existing functional alterations in neocortical circuits.
authors.affiliation: Affidea Centre de Diagnostic Radiologique de Carouge CDRC, Clos de la Fonderie 1, 1277 Carouge, Geneva, Switzerland. sven.haller@gmail.com.|Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden. sven.haller@gmail.com.
authors.forename: Sven
authors.initials: S
authors.lastname: Haller
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Medical Direction, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Montandon
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Medical Direction, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Cristelle
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Medical Direction, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Moser
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Medical Direction, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Simona
authors.initials: S
authors.lastname: Toma
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Medical Direction, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hofmeister
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Medical Direction, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Giannakopoulos
mesh_terms: D000368:Aged; D002110:Caffeine / Q000627:therapeutic use*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D011446:Prospective Studies
chemical_list: D002110:Caffeine
keywords: Aging; Blood oxygenation level dependent (BOLD); Caffeine; Functional magnetic resonance imaging (fMRI); Mild cognitive impairment (MCI)