However, if the rats were divided into cognitively impaired and not impaired groups, using the value of 2 standard deviations from the mean performance of the 3-month-old rats as the criterion, 8% of the rats were already cognitively impaired at 12 months and 45% at 18 months of age.16 Similarly, 50% of female Dark Agouti rats already showed a learning deficit at 14 months of age, using a complex maze task, and 71% of

the rats were impaired at 26 months of age.17 However, dividing the rats into cognitively impaired and not impaired groups was too strict a criterion to identify MCI rats, which presumably fall into the not impaired group. More subtle criteria are therefore needed. Inhibitors,research,lifescience,medical For instance, by YM155 testing Fischer-344 male rats in the Morris water maze, Lindner et al18 were able to detect a difference in performance, evaluated as distance swam, between 2- and 16-month-old rats and observed

that Inhibitors,research,lifescience,medical the aging rats had more impairment in the reference memory task, which was tested by keeping the target location in the Inhibitors,research,lifescience,medical same place, but using a longer intertrial interval than in the working memory task, in which the target location was changed, but the intertrial interval was short. Increasing the retention time, ie, the interval between acquisition and testing, is a simple and effective procedure for unmasking memory deficits in aging rats. In a non-matching-to-sample task, 15- and 24-month-old Sprague-Dawley rats did not

show any deficit if the delay between the sample and choice responses was 0 s, but an impairment was revealed when variable 0 to 24 s delay intervals were introduced.19 By increasing the delay, memory impairment was detected in 17-month-old rats performing a delayed alternation task.20 Inhibitors,research,lifescience,medical Fourteen months is also the age at which a decline in memory ability, tested by an allocentric place determination task in a water maze,21 was detected in Fisher-344 rats, individually followed throughout their life, as a decrease in accuracy. The decline progressed with age Inhibitors,research,lifescience,medical and could be reversed by inhibiting cholinesterase with physostigmine at the age of 22 to 23 months, but not at 26 to 27 months. An improvement in spatial learning was reported in navigation in a water maze, evaluated as time required to reach the platform, in 20-month-old Lister hooded rats receiving 17-DMAG (Alvespimycin) HCl 40 to 80 mg/day aspirin in their drinking water.22 The above data, some of which are also presented in Table II for an easier comparison, make it possible to answer the question regarding the age at which cognitive impairment can be detected in the rat. It appears that the possibility of detecting an initial cognitive impairment in animals, mimicking MCI in humans, depends on many factors: the task that the animals are trained to acquire, the procedure used to train them to meet the criterion, the strain, and, most importantly, the interval between acquisition and recall.