Chronic antioxidant and mitochondrial cofactor administration improves discrimination learning in aged but not young dogs.

The present experiment was part of a 3-year longitudinal study examining the effects of age and antioxidant treatment on cognitive decline in beagles. Two size-concept tasks were administered following pretraining on a series of two-choice (six subtests) and three-choice size discrimination tasks. Thirty-nine young and aged dogs were matched for age and cognitive ability then divided into four treatment groups. A combined antioxidant-mitochondrial cofactor treatment led to significantly improved performance in aged dogs on the first subtest of the two-choice size discrimination series. Treated aged dogs did not significantly differ from the young. Aged dogs on the antioxidant diet continued to perform better than aged controls on the second and third subtests, but these effects did not achieve significance. Young dogs performed significantly better than the aged dogs on the second and third subtests. The remaining two-choice tasks of the discrimination series were comparatively easy, leading to a floor effect. The antioxidant animals performed better on the three-choice size discrimination, but not on the two size-concept tasks. Antioxidants improved the performance of aged dogs on the initial learning tests, suggesting a selective improvement of factors related to the aging process and specific cognitive processes rather than general cognitive enhancement.

Frontal lobe volume, function, and beta-amyloid pathology in a canine model of aging.

Application of magnetic resonance imaging (MRI) techniques reveals that human brain aging varies across cortical regions. One area particularly sensitive to normal aging is the frontal lobes. In vitro neuropathological studies and behavioral measures in a canine model of aging previously suggested that the frontal lobes of the dog might be sensitive to aging. In the present study, MRI scans were acquired to compare age-related changes in frontal lobe volume with changes in executive functions and beta-amyloid pathology in the frontal cortex of beagle dogs aged 3 months to 15 years. Decreases in total brain volume appeared only in senior dogs (aged 12 years and older), whereas frontal lobe atrophy developed earlier, appearing in the old dogs (aged 8-11 years). Hippocampal volume also declined with age, but not occipital lobe volume past maturity. Reduced frontal lobe volume correlated with impaired performance on measures of executive function, including inhibitory control and complex working memory, and with increased beta-amyloid accumulation in the frontal cortex. Age-related hippocampal atrophy also correlated with complex working memory but not inhibitory control, whereas occipital lobe volume did not correlate with any cognitive measure. These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging.

Concept abstraction in the aging dog: development of a protocol using successive discrimination and size concept tasks.

The present study examined the effects of age on concept learning in beagle dogs. In experiment one, subjects were tested on a series of 2-choice size discrimination (2CSD) tasks, in which the correct response was to always approach the larger or smaller of the two blocks. Compared to old and senior dogs, young and middle-aged dogs solved the initial training subtest faster and were more successful at transferring this learning to subsequent tests. The second experiment extended the task by using three rather than two objects and introducing novel objects to test concept acquisition. Young and middle-aged dogs made fewer errors than old or senior dogs on a 3-choice size discrimination (3CSD) task. Transfer performance was above chance for all four groups on the 3CSD and first 3-choice size concept (CSC) task and for the young dogs on the second 3CSC but did not differ from the original learning criterion in any group. Age impairments in concept learning may account for differences in transfer performance on both 3CSC tests.

Long-term treatment with antioxidants and a program of behavioral enrichment reduces age-dependent impairment in discrimination and reversal learning in beagle dogs.

The effects of long-term treatment with both antioxidants and a program of behavioral enrichment were studied as part of a longitudinal investigation of cognitive aging in beagle dogs. Baseline performance on a battery of cognitive tests was used to assign 48 aged dogs (9-12 years) into four cognitively equivalent groups, of 12 animals per group: Group CC (control food-control environment), group CE (control food-enriched environment); Group AC (antioxidant fortified food-control environment); Group AE (fortified food-enriched environment). We also tested a group of young dogs fed the control food and a second group fed the fortified food. Both groups of young dogs received a program of behavioral enrichment. To evaluate the effects of the interventions on cognition after 1 year, the dogs were tested on a size discrimination learning task and subsequently on a size discrimination reversal learning task. Both tasks showed age-sensitivity, with old dogs performing more poorly than young dogs. Both tasks were also improved by both the fortified food and the behavioral enrichment. However, in both instances the treatment effects largely reflected improved performance in the combined treatment group. These results suggest that the effectiveness of antioxidants in attenuating age-dependent cognitive decline is dependent on behavioral and environmental experience.

Adrafinil disrupts performance on a delayed nonmatching-to-position task in aged beagle dogs.

Previous studies in humans and dogs have reported beneficial effects of adrafinil on specific cognitive functions. The effects in dogs are limited to a single study examining discrimination learning. We wanted to further explore the cognitive effects of adrafinil in dogs. The purpose of the present study was to determine the effect of oral administration of adrafinil on visuospatial function in dogs. Eighteen aged beagle dogs were tested on a delayed nonmatching-to-position (DNMP) task 2 h following one of three possible treatments; 20 mg/kg of adrafinil, 10 mg/kg of adrafinil or a placebo control. All dogs were tested under each treatment for eight test sessions. A 2-day washout period was given between treatments and the order of treatments was varied. Treatment with 20 mg/kg of adrafinil produced a significant impairment in working memory as indicated by an increase in the number of errors over the 8-day test period. The disturbance of memory functions from adrafinil could be a result of increased noradrenergic transmission in the prefrontal cortex.

Locomotor activity rhythms in dogs vary with age and cognitive status.

Beagle dogs exhibited diurnal patterns of locomotor activity that varied as a function of age, cognitive status, and housing environment. Aged dogs housed in an indoor facility showed a delayed onset of activity following lights on and displayed shorter bouts of activity, with more rest periods during the day, compared with young dogs. Cognitively impaired aged dogs were more active and showed a delayed peak of activity compared with unimpaired aged dogs. Housing in continuous light did not disrupt activity rhythms. The effect of age was less prominent in dogs housed in an indoor/outdoor facility. This suggests that bright sunlight and natural light-dark transitions are better able to consolidate and synchronize the activity rhythms of the dogs.

Effects of age on measures of complex working memory span in the beagle dog (Canis familiaris) using two versions of a spatial list learning paradigm.

The present study used two versions of a spatial list learning (SLL) paradigm to examine the effects of increased cognitive load on visuospatial working memory processes in young and old beagle dogs. In the first experiment, young, and a select group of old dogs were first presented with one item, then two, and then three, and were rewarded for responding to the novel position. The dogs were able to learn the task at short delays, but compared with young dogs, old dogs performed worse at delays of 10 sec, and could not reach longer delays. Analysis of errors indicated that memory was best for end items in the spatial list and that within sessions, the number of errors in later trials was greater than the number of errors in earlier trials. A second version of the task, a modified SLL (mSLL) was developed to control for the use of non-mnemonic strategies on the SLL task. In this version, the first two items were presented individually. Acquisition and maximal memory performance were better in the young relative to the old dogs. Similar to the original SLL design, memory for early list items was worse than memory for later list items in both young and old dogs. The within-session pattern of errors however, did not change from trial to trial on the mSLL. The present results suggest that multiple working memory processes are engaged during complex tests of visuospatial function and the neuroanatomical substrates controlling these processes are affected differentially by age in the beagle dog.

Size and reversal learning in the beagle dog as a measure of executive function and inhibitory control in aging.

Several studies converge on the idea that executive processes age earlier than other cognitive processes. As part of a larger effort to investigate age-related changes in executive processes in the dog, inhibitory control was measured in young, middle-aged, old, and senior dogs using size discrimination learning and reversal procedures. Compared to young and middle-aged dogs, old and senior dogs were impaired on both the initial learning of the size task and the reversal of original reward contingencies. Impaired performance in the two aged groups was characterized as a delay in learning the correct stimulus-reward contingencies and, among the senior dogs in particular, an increase in perseverative responding. These separate patterns of reversal impairments in the old and senior dogs may reflect different rates of aging in subregions of the frontal cortex.

Age-dependent decline in locomotor activity in dogs is environment specific.

A decrease in motor activity is an expected concomitant of normal aging and has been reported in humans and nonhuman mammals. We have previously failed to find age differences in open-field locomotor activity in beagle dogs. We now report an age-associated decline when activity measures are taken in the home cage. Locomotor activity of young and aged dogs was examined in both open-field and home-cage environments. Dogs were given six activity tests (two open field, two morning and two afternoon home-cage tests) every second day. Aged dogs were less active than young dogs in the home cage but not in the open field. Activity also varied as a function of sex and housing condition. Behavioral activity is a complex manifestation of many underlying factors.