Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.