Six new tri- and tetracyclic nitrogen bridgehead compounds known to be moderate to potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were tested in vivo as experimental therapeutics for treatment of Alzheimer's disease. Cognitive impairment in rats was reversibly induced by scopolamine (CAS 51-34-3). The effect of the new substances was evaluated in an eight-arm radial maze and run times (1), errors (2), correct choices (3), correct choices per second (4), speed (5), and running distance (6) were recorded. For optimisation of data analysis a new strategy was used: A score was created on the basis of the 6 parameters described with score 1 for controls and score 4 for scopolamine rats. Scores above 4 indicate an impairment of cognition function compared to scopolamine. After equimolar dosage compared to the reference drug rivastigmine (CAS 123441-03-2), two of the new substances slightly improved cognition in rats, but only to a significantly lower degree compared to the irreversible inhibitor rivastigmine. Surprisingly, the other four compounds did not improve or even worsened the scopolamine effect on working memory.