Caffeine impact on working memory-related network activation patterns in early stages of cognitive decline

Purpose 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). Conclusion 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.