Tests of Cognitive Function and Brain Regions Important for Cognitive Function

One of the most controversial issues pertaining to management of the perimenopausal transition is that of neuroprotection and maintenance of cognitive function. The rhesus macaque provides a highly useful model for performing tasks that provide specific information on neural systems. This allows for characterization of age-related changes in cognitive function with females during the perimenopausal transition and with surgical removal of ovarian steroids. Moreover, selected interventions may be tested for their efficacy in enhancing cognitive performance in aging individuals. A few of these tests will be briefly described below because these tests provide methods for assessment of age-related changes in motor capabilities and cognitive function.

MOVEMENT ANALYSIS PANEL (mMAP)

Several behavioral studies have been conducted in monkeys, including assessments of general locomotor activity, motor performance, and simple cognitive tasks. Regarding general locomotor activity, two studies have been published indicating age-related declines in activity of male and female rhesus monkeys measured by an infrared/ultrasonic apparatus placed on the home cage of the monkeys (Weed et al., 1997; Moscript et al., 2000). Monkeys may be assessed for motor performance in the Movement Analysis Panel (mMAP), which has proven to be age-sensitive in rhesus monkeys. This task evaluates the response time required to retrieve a food reward from different manipulanda located in a box mounted to the home cage of the monkey. The simplest task is a flat platform; the next most difficult is a straight rod, and the most difficult is hook. Figure 38.1 shows an apparatus with an individual performing the task using the mMAP (Ingram et al., unpublished data).

Tasks on visual-motor skill have been demonstrated to be age-sensitive (Bachevalier et al., 1991; Grondin

Figure 38.1 This photograph shows a rhesus monkey retrieving a food reward in the mMAP apparatus. This test allows for assessment of motor control.

2003) and involve deficits in the nigral-striatal pathways. The prefrontal cortex is involved with working memory/executive function, whereas the temporal lobe-hippocampal region is involved in spatial memory (Bartus, 1978; Rapp, 1989). It is clear that consistent with a recent report (Lacreuse et al., 1995) female rhesus monkeys are faster in this task than males.

SPATIAL-DELAYED RECOGNITION SPAN TEST (SPATIAL-DRST)

Spatial-DRST is a memory test that depends on the integrity of the hippocampus (Beason-Held et al., 1999). It requires the subject to identify, trial-by-trial, the new location of a stimulus among an increasing array of serially presented identical stimuli. Different versions of this test have been used in normal aged humans and in a variety of neurologic patient populations. In monkeys, the spatial-DRST has been used to examine age-related impairments of rhesus macaques, to examine sex differences in young and old rhesus monkeys (Lacreuse et al., 1999) and to compare the performance of aged OVX and age-matched intact female rhesus monkeys (Lacreuse et al., 2000). This test appears to be useful in detecting memory loss during aging.

OBJECT-DELAYED RECOGNITION SPAN TEST (OBJECT-DRST)

Object-DRST follows the same rules as spatial-DRST, but the stimuli are different objects instead of identical disks. The objects are randomly drawn from a pool of 3000 color clipart objects. On each trial, the position of the stimuli changes in a random fashion so that the monkey is able to identify the new stimulus based only on visual, rather than spatial cues. The mean number of objects that the monkey is able to correctly identify before making an error and the mean response times will be recorded. The object-DRST is a task of visual recognition memory that is sensitive to hippocampal lesions in monkeys (Beason-Held et al., 2005).

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