Pattern separation and goal-directed behavior in the aged canine.

The pattern separation task has recently emerged as a behavioral model of hippocampus function and has been used in several pharmaceutical trials. The canine is a useful model to evaluate a multitude of hippocampal-dependent cognitive tasks that parallel those in humans. Thus, this study was designed to evaluate the suitability of pattern separation task(s) for detecting age-related changes in canines. We also assessed the dogs' ability to show pattern separation and discrimination reversal, which provides a novel extension of the pattern separation learning literature. Our data show that aged dogs are impaired on a complex pattern separation task (six-well task) relative to easier tasks (four-well or six-well pattern discrimination task), and that the age-related deficits are due to loss of perceptual and inhibitory control in addition to the loss of spatial discrimination and pattern separation ability. Our data also suggest that aged animals show pattern separation deficits when the objects are brought progressively closer together while changing the location of both correct and incorrect objects. However, if the location of any one object is fixed the animals tend to use alternate strategies. Overall, these data provide important insight into age-related pattern separation deficits in a higher animal model and offers additional means for evaluating the impact of lifestyle and pharmaceutical interventions on episodic memory in preclinical trials.

Cognitive domains in the dog: independence of working memory from object learning, selective attention, and motor learning.

Cognition in dogs, like in humans, is not a unitary process. Some functions, such as simple discrimination learning, are relatively insensitive to age; others, such as visuospatial learning can provide behavioral biomarkers of age. The present experiment sought to further establish the relationship between various cognitive domains, namely visuospatial memory, object discrimination learning (ODL), and selective attention (SA). In addition, we also set up a task to assess motor learning (ML). Thirty-six beagles (9-16 years) performed a variable delay non-matching to position (vDNMP) task using two objects with 20- and 90-s delay and were divided into three groups based on a combined score (HMP = 88-93 % accuracy [N = 12]; MMP = 79-86 % accuracy [N = 12]; LMP = 61-78 % accuracy [N = 12]). Variable object oddity task was used to measure ODL (correct or incorrect object) and SA (0-3 incorrect distractor objects with same [SA-same] or different [SA-diff] correct object as ODL). ML involved reaching various distances (0-15 cm). Age did not differ between memory groups (mean 11.6 years). ODL (ANOVA P = 0.43), or SA-same and SA-different (ANOVA P = 0.96), performance did not differ between the three vDNMP groups, although mean errors during ODL was numerically higher for LMP dogs. Errors increased (P < 0.001) for all dogs with increasing number of distractor objects during both SA tasks. vDNMP groups remained different (ANOVA P < 0.001) when re-tested with vDNMP task 42 days later. Maximum ML distance did not differ between vDNMP groups (ANOVA P = 0.96). Impaired short-term memory performance in aged dogs does not appear to predict performance of cognitive domains associated with object learning, SA, or maximum ML distance.

Olfactory discrimination and generalization of ammonium nitrate and structurally related odorants in Labrador retrievers.

A critical aspect of canine explosive detection involves the animal's ability respond to novel, untrained odors based on prior experience with training odors. In the current study, adult Labrador retrievers (N = 15) were initially trained to discriminate between a rewarded odor (vanillin) and an unrewarded odor (ethanol) by manipulating scented objects with their nose in order to receive a food reward using a canine-adapted discrimination training apparatus. All dogs successfully learned this olfactory discrimination task (≥80 % correct in a mean of 296 trials). Next, dogs were trained on an ammonium nitrate (AN, NH4NO3) olfactory discrimination task [acquired in 60-240 trials, with a mean (±SEM) number of trials to criterion of 120.0 ± 15.6] and then tested for their ability to respond to untrained ammonium- and/or nitrate-containing chemicals as well as variants of AN compounds. Dogs did not respond to sodium nitrate or ammonium sulfate compounds at rates significantly higher than chance (58.8 ± 4.5 and 57.7 ± 3.3 % correct, respectively). Transfer performance to fertilizer-grade AN, AN mixed in Iraqi soil, and AN and flaked aluminum was significantly higher than chance (66.7 ± 3.2, 73.3 ± 4.0, 68.9 ± 4.0 % correct, respectively); however, substantial individual differences were observed. Only 53, 60, and 64 % of dogs had a correct response rate with fertilizer-grade AN, AN and Iraqi soil, and AN and flaked aluminum, respectively, that were greater than chance. Our results suggest that dogs do not readily generalize from AN to similar AN-based odorants at reliable levels desired for explosive detection dogs and that performance varies significantly within Labrador retrievers selected for an explosive detection program.

Acquisition of a visual discrimination and reversal learning task by Labrador retrievers.

Optimal cognitive ability is likely important for military working dogs (MWD) trained to detect explosives. An assessment of a dog's ability to rapidly learn discriminations might be useful in the MWD selection process. In this study, visual discrimination and reversal tasks were used to assess cognitive performance in Labrador retrievers selected for an explosives detection program using a modified version of the Toronto General Testing Apparatus (TGTA), a system developed for assessing performance in a battery of neuropsychological tests in canines. The results of the current study revealed that, as previously found with beagles tested using the TGTA, Labrador retrievers (N = 16) readily acquired both tasks and learned the discrimination task significantly faster than the reversal task. The present study confirmed that the modified TGTA system is suitable for cognitive evaluations in Labrador retriever MWDs and can be used to further explore effects of sex, phenotype, age, and other factors in relation to canine cognition and learning, and may provide an additional screening tool for MWD selection.

Cognitive enhancement in middle-aged and old cats with dietary supplementation with a nutrient blend containing fish oil, B vitamins, antioxidants and arginine.

Cognitive dysfunction syndrome is a major disease affecting old cats and is the consequence of severe and irreversible loss of brain cells and brain atrophy. The present study focused on the hypothesis that the optimal strategy for promoting successful brain ageing is to target risk factors associated with brain ageing and dementia. We used a nutritional strategy involving supplementation with a blend of nutrients (antioxidants, arginine, B vitamins and fish oil) to test this hypothesis. Middle-aged and old cats between 5·5 and 8·7 years of age were assigned to cognitively equivalent control or treatment groups based on prior cognitive experience and performance on baseline cognitive tests. The cats in the treatment group were maintained on a diet supplemented with the nutrient blend and the cats in the control group were maintained on the identical base diet without the additional supplementation. After an initial wash-in period, all cats were tested on a battery of cognitive test protocols. The cats fed the test diet showed significantly better performance on three of four test protocols: a protocol assessing egocentric learning, a protocol assessing discrimination and reversal learning and a protocol focused on acquisition of a spatial memory task. The results support the hypothesis that brain function of middle-aged and old cats can be improved by the nutrient blend that was selected to minimise or eliminate the risk factors associated with brain ageing and dementia.

Sphingolipids and DHA Improve Cognitive Deficits in Aged Beagle Dogs.

Canine cognitive dysfunction syndrome (CDS) is a disorder found in senior dogs that is typically defined by the development of specific behavioral signs which are attributed to pathological brain aging and no other medical causes. One way of objectively characterizing CDS is with the use of validated neuropsychological test batteries in aged Beagle dogs, which are a natural model of this condition. This study used a series of neuropsychological tests to evaluate the effectiveness of supplementation with a novel lipid extract containing porcine brain-derived sphingolipids (Biosfeen®) and docosahexaenoic acid (DHA) for attenuating cognitive deficits in aged Beagles. Two groups (n = 12), balanced for baseline cognitive test performance, received a daily oral dose of either test supplement, or placebo over a 6-month treatment phase. Cognitive function was evaluated using the following tasks: delayed non-matching to position (DNMP), selective attention, discrimination learning retention, discrimination reversal learning, and spatial discrimination acquisition and reversal learning. The effect of the supplement on brain metabolism using magnetic resonance spectroscopy (MRS) was also examined. A significant decline (p = 0.02) in DNMP performance was seen in placebo-treated dogs, but not in dogs receiving the supplement, suggesting attenuation of working memory performance decline. Compared to placebo, the supplemented group also demonstrated significantly improved (p = 0.01) performance on the most difficult pattern of the spatial discrimination task and on reversal learning of the same pattern (p = 0.01), potentially reflecting improved spatial recognition and executive function, respectively. MRS revealed a significant increase (p = 0.048) in frontal lobe glutamate and glutamine in the treatment group compared to placebo, indicating a physiological change which may be attributed to the supplement. Decreased levels of glutamate and glutamine have been correlated with cognitive decline, suggesting the observed increase in these metabolites might be linked to the positive cognitive effects found in the present study. Results of this study suggest the novel lipid extract may be beneficial for counteracting age-dependent deficits in Beagle dogs and supports further investigation into its use for treatment of CDS. Additionally, due to parallels between canine and human aging, these results might also have applicability for the use of the supplement in human cognitive health.

Synergistic effects of long-term antioxidant diet and behavioral enrichment on beta-amyloid load and non-amyloidogenic processing in aged canines.

A long-term intervention (2.69 years) with an antioxidant diet, behavioral enrichment, or the combined treatment preserved and improved cognitive function in aged canines. Although each intervention alone provided cognitive benefits, the combination treatment was additive. We evaluate the hypothesis that antioxidants, enrichment, or the combination intervention reduces age-related beta-amyloid (Abeta) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Abeta neuropathology in plaques, biochemically extractable Abeta(40) and Abeta(42) species, soluble oligomeric forms of Abeta, and various proteins in the beta-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Abeta pathology were observed in animals receiving the combined antioxidant and enrichment treatment. Specifically, Abeta plaque load was significantly decreased in several brain regions, soluble Abeta(42) was decreased selectively in the frontal cortex, and a trend for lower Abeta oligomer levels was found in the parietal cortex. Reductions in Abeta may be related to shifted APP processing toward the non-amyloidogenic pathway, because alpha-secretase enzymatic activity was increased in the absence of changes in beta-secretase activity. Although enrichment alone had no significant effects on Abeta, reduced Abeta load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. Abeta measures did not correlate with cognitive performance on any of the six tasks assessed, suggesting that modulation of Abeta alone may be a relatively minor mechanism mediating cognitive benefits of the interventions. Overall, the data indicate that multidomain treatments may be a valuable intervention strategy to reduce neuropathology and improve cognitive function in humans.

Effect of trans-fat, fructose and monosodium glutamate feeding on feline weight gain, adiposity, insulin sensitivity, adipokine and lipid profile.

The incidence of obesity and type 2 diabetes mellitus (T2DM) is increasing, and new experimental models are required to investigate the diverse aspects of these polygenic diseases, which are intimately linked in terms of aetiology. Feline T2DM has been shown to closely resemble human T2DM in terms of its clinical, pathological and physiological features. Our aim was to develop a feline model of diet-induced weight gain, adiposity and metabolic deregulation, and to examine correlates of weight and body fat change, insulin homeostasis, lipid profile, adipokines and clinical chemistry, in order to study associations which may shed light on the mechanism of diet-induced metabolic dysregulation. We used a combination of partially hydrogenated vegetable shortening and high-fructose corn syrup to generate a high-fat-high-fructose diet. The effects of this diet were compared with an isoenergetic standard chow, either in the presence or absence of 1.125 % dietary monosodium glutamate (MSG). Dual-energy X-ray absorptiometry body imaging and a glucose tolerance test were performed. The present results indicate that dietary MSG increased weight gain and adiposity, and reduced insulin sensitivity (P < 0.05), whereas high-fat-high-fructose feeding resulted in elevated cortisol and markers of liver dysfunction (P < 0.01). The combination of all three dietary constituents resulted in lower insulin levels and elevated serum ß-hydroxybutyrate and cortisol (P < 0.05). This combination also resulted in a lower first-phase insulin release during glucose tolerance testing (P < 0.001). In conclusion, markers of insulin deregulation and metabolic dysfunction associated with adiposity and T2DM can be induced by dietary factors in a feline model.

Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs.

The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5.5 % MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of beta-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source.

Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine.

Aged dogs demonstrate cognitive decline that is linked to brain aging. The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles. Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase. Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting. These findings suggest that the nutraceutical supplement can improve memory in aged dogs.

Efficacy of a Therapeutic Diet on Dogs With Signs of Cognitive Dysfunction Syndrome (CDS): A Prospective Double Blinded Placebo Controlled Clinical Study.

Cognitive dysfunction syndrome (CDS) is a common condition in senior dogs, which may be analogous to dementia such as Alzheimer's disease (AD) in people. In humans, AD has been associated with many risk factors such as reduced cerebral glucose metabolism, docosahexaenoic acid (DHA) deficiency, chronic oxidative stress, and chronic inflammation. By targeting some of these risk factors, we have developed two nutritional solutions (medium chain triglyceride, MCT and Brain Protection Blend, BPB) to enhance cognitive function and slow aging-induced cognitive decline. These have been positively evaluated in colony housed senior dogs and cats. The objective of this clinical study was to evaluate the effects of diets with MCTs and the BPB on client-owned dogs with CDS. Participating veterinary clinics screened senior dogs for signs of CDS as determined by a Senior Canine Behavior Questionnaire and a Canine Medical Health Questionnaire. Eighty-seven dogs were randomly enrolled into one of three diet groups with 29 dogs per group: Control, 6.5% MCT oil + BPB (6.5% MCT diet), 9% MCT oil + BPB (9% MCT diet). Diets were fed for a period of 90 days, and each dog's CDS signs were re-evaluated at day 30 and day 90. All 6 categories of the CDS signs were significantly improved (p <0.05) in the dogs given the 6.5% MCT diet at the end of the 90-day study. Control only improved in 4 out 6 categories. The 9% MCT diet only improved in dogs that accepted the diet. The results from this dog study confirm the benefits of MCT and BPB in managing clinical signs of CDS in dogs. The results support our hypothesis that targeting known risk factors associated with brain aging and AD is able to improve symptoms of CDS in dogs. These data may facilitate the development of similar nutrient blends to manage MCI and AD.

Cognitive decline and human (Homo sapiens) aging: an investigation using a comparative neuropsychological approach.

Using a comparative neuropsychological approach, the authors compared performance of younger and healthy older adults ages 65 and over on tasks originally developed to measure cognition in animals. A battery of 6 tasks was used to evaluate object discrimination, egocentric spatial abilities, visual and spatial working memory, and response shifting. Older adults performed more poorly than younger adults on tasks that evaluate egocentric spatial abilities, response shifting, and to a lesser extent object recognition. The two groups did not differ for tasks that evaluate spatial working memory and object discrimination. The impairments the authors observed in tasks that evaluate response shifting and object recognition are consistent with those found in canines and primates as well as those found in Alzheimer's disease. The results are consistent with the notion that cognitive processes supported by the amygdala and the orbitofrontal cortex are among the first to decline with increasing age in both humans and animals.

Neuroprotective effects of cognitive enrichment.

Cognitive enrichment early in life, as indicated by level of education, complexity of work environment or nature of leisure activities, appears to protect against the development of age-associated cognitive decline and also dementia. These effects are more robust for measures of crystallized intelligence than for measures of fluid intelligence and depend on the ability of the brain to compensate for pathological changes associated with aging. This compensatory ability is referred to as cognitive reserve. The cognitive reserve hypothesis suggests that cognitive enrichment promotes utilization of available functions. Alternatively, late life cognitive changes in cognition may be linked to a factor, such as cholinergic dysfunction, that is also present early in life and contributes to the reduced levels of early life cognitive enrichment. Beneficial effects of environmental enrichment early in life have also been observed in rodents and primates. Research with rodents indicates that these changes have structural correlates, which likely include increased synapses in specific brain regions. Dogs also show age-dependent cognitive decline, and both longitudinal and cross-sectional studies indicate that this decline can be attenuated by cognitive enrichment. Furthermore, cognitive enrichment has differential effects, improving some functions more than others. From a neurobiological perspective, behavioral enrichment in the dog may act to promote neurogenesis later in life. This can be distinguished from nutritional interventions with antioxidants, which appear to attenuate the development of neuropathology. These results suggest that a combination of behavioral and nutritional or pharmacological interventions may be optimal for reducing the rate of age-dependent cognitive decline.

Extensive spatial training does not negate age differences in response latency.

Previously, Nippak et al. [Nippak, P.M.D., Chan, A.D.F., Campbell, Z., Muggenburg, B., Head, E., Ikeda-Douglas, C., Murphy, H., Cotman, C.W., Milgram, N.W., 2003. Response latency in the canine: mental ability or mental strategy? Behav. Neurosci. 117 (5), 1066-1075] reported that young dogs respond significantly slower than aged dogs during the acquisition of a three-component delayed non-match to position (3-DNMP) task. Thus, we examined how age influences response latency (RL) when animals are trained extensively on the 3-DNMP task. Animals were separated into two groups based on their task sophistication. The first group comprised young (N=5) and aged (N=10) dogs that received extensive spatial training on a two-component delayed non-match to position task (2-DNMP) before 3-DNMP testing, while the second group of young (N=8) and aged (N=11) animals received extensive training on a variety of other non-spatial cognitive tasks between each 3-DNMP test period. RL age differences were absent following extensive 3-DNMP testing; however, other age-dependent performance differences emerged: all young animals learned the task and displayed RL slowing and superior response accuracy (RA) on the center-incorrect (CI) subtest, while several aged animals failed to learn the task and displayed no RL or RA subtest variations even when they acquired the task. Toates's [Toates, F., 1998. The interaction of cognitive and stimulus-response processes in the control of behaviour, Neurosci. Biobehav. Rev. 22 (1), 59-83] theory of RL and mental strategy was proposed to explain these age differences in response strategies: the fast-responding aged animals utilized stimulus-response strategies, while the slow-responding young animals adopted cognitive strategies, a specific requirement for solving the CI subtest.

Diurnal changes in core body temperature, day/night locomotor activity patterns, and actigraphy-generated behavioral sleep in aged canines with varying levels of cognitive dysfunction.

Core body temperature (CBT) rhythm, locomotor activity, and actigraphy-sleep were evaluated in geriatric dogs with cognitive dysfunction. Dogs (n=33; 9-16 yrs) performed a spatial working memory task and divided into three memory groups: Low, Moderate, and High, with subsequent evaluation of learning and attention. Rectal CBT was recorded 6 times over a 17.5 h period and Actiwatch® activity monitoring system for 5 days while housed indoors with 12 h light/dark schedule. Rhythm of daily activity data was evaluated using the traditional cosinor analysis and generation of non-parametric measures of interdaily stability, intradaily variability, and relative amplitude. CBT differed with time (F (5, 130)=11.36, p<0.001), and was the highest at 19:00C. CBT at 19:00 was positively related (p<0.01) to memory (r(31)=0.50) and 3-domain cognitive performance index (memory, learning, attention; r(31)=0.39). Total daytime or night-time activity did not differ between memory groups, but hourly counts at 8:00 were positively related (p<0.05) to memory (r(31)=0.52), learning (r(31)=0.36), and 3-domain cognitive performance index (r(31)=0.53). There were no significant differences between age or memory groups for any circadian rhythm measures. Daytime naps were inversely related to memory accuracy (r(31)=-0.39; p<0.05) and BT at 15:00 (r(30)=-0.51; p<0.01). Lower peak BT and increased napping may predict some aspects of cognitive performance of working memory, learning, and/or attention processes in these geriatric dogs, but minimal diurnal rhythm disruption of locomotor activity is observed when these cognitive processes decline.

Effect of mitochondrial cofactors and antioxidants supplementation on cognition in the aged canine.

A growing body of research has focused on modifiable risk factors for prevention and attenuation of cognitive decline in aging. This has led to an unprecedented interest in the relationship between diet and cognitive function. Several preclinical and epidemiologic studies suggest that dietary intervention can be used to improve cognitive function but randomized controlled trials are increasingly failing to replicate these findings. Here, we use a canine model of aging to evaluate the effects of specific components of diet supplementation which contain both antioxidants and a combination of mitochondrial cofactors (lipoic acid [LA] and acetyl-l-carnitine) on a battery of cognitive functions. Our data suggest that supplementation with mitochondrial cofactors, but not LA or antioxidant alone, selectively improve long-term recall in aged canines. Furthermore, we found evidence that LA alone could have cognitive impairing effects. These results contrast to those of a previous longitudinal study in aged canine. Our data demonstrate that one reason for this difference may be the nutritional status of animals at baseline for the 2 studies. Overall, this study suggests that social, cognitive, and physical activity together with optimal dietary intake (rather than diet alone) promotes successful brain aging.

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.

An investigation of the relationship between response latency across several cognitive tasks in the beagle dog.

Response latencies (RLs) extracted from simple motor tasks are a commonly used index of human intelligence. To date few human or animal studies have investigated the relationship between an individuals RL scores across a number of diverse cognitive tasks: Does RL remain consistent between individuals across several cognitive domains? Thus, the current study examined how RL measures gathered from beagle dogs (n=13) tested on three different cognitive tasks were related. RL scores were collected following both discrimination and reversal learning and a test of visuospatial memory, the 3 component delayed non-matching to position (3-DNMP) task. RL scores were recorded from the time the choice stimulus was presented until the animal selected a response. Results indicated that strong correlations emerged between 3-DNMP RLs and both the discrimination and reversal RLs, indicating that animals that responded fast on the 3-DNMP task also responded fast on the discrimination and reversal tasks. Interestingly, 3-DNMP RLs were more strongly correlated with reversal learning RLs. Finally, when mean RL performance across the three tasks was examined, strong RL differences emerged indicating that animals displayed significantly slower RLs on the 3-DNMP task than on the discrimination task, while reversal RLs remained indistinguishable from both. In conclusion, RLs show high between task correlations, indicating individual differences, and also vary between tasks, probably because of differences in task difficulty. These results further validate the use of RLs as an index of cognition, and also highlight the importance of further studies using animal models.

A novel method for assessing contrast sensitivity in the beagle dog is sensitive to age and an antioxidant enriched food.

Tasks requiring visual discrimination are commonly used in assessment of canine cognitive function. However, little is known about canine visual processing, and virtually nothing is known about the effects of age on canine visual function. This study describes a novel behavioural method developed to assess one aspect of canine visual function, namely contrast sensitivity. Four age groups (young, middle aged, old, and senior) were studied. We also included a group of middle aged to old animals that had been maintained for at least 4 years on a specially formulated food containing a broad spectrum of antioxidants and mitochondrial cofactors. Performance of this group was compared with a group in the same age range maintained on a control diet. In the first phase, all animals were trained to discriminate between two high contrast shapes. In the second phase, contrast was progressively reduced by increasing the luminance of the shapes. Performance decreased as a function of age, but the differences did not achieve statistical significance, possibly because of a small sample size in the young group. All age groups were able to acquire the initial discrimination, although the two older age groups showed slower learning. Errors increased with decreasing contrast with the maximal number of errors for the 1% contrast shape. Also, all animals on the antioxidant diet learned the task and had significantly fewer errors at the high contrast compared with the animals on the control diet. The initial results suggest that contrast sensitivity deteriorates with age in the canine while form perception is largely unaffected by age.

Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging.

Memory decline in human aging and dementia is linked to dysfunction of the cholinergic system. Aging dogs demonstrate cognitive impairments and neuropathology that models human aging and dementia. This paper reviews recent evidence suggesting cholinergic involvement in canine cognitive aging based on studies with the anti-cholinergic drug, scopolamine, and a novel acetylcholinesterase inhibitor, phenserine. In particular, we examine: (1) the cognitive specificity of scopolamine's impairment in dogs, (2) the effect of age on scopolamine impairment and (3) the effect of phenserine on cognitive performance in dogs. Our findings indicate that working memory performance is disrupted by scopolamine at doses that do not disrupt non-cognitive behavior or long-term, semantic-like, memory, as indicated by performance of previously learned discriminations. This pattern of deficits is also seen in human and canine aging. We demonstrate that aged dogs are more sensitive to the impairing effects of scopolamine than young dogs, suggesting a decrease in cholinergic tone with increasing age. Dogs receiving phenserine demonstrate improved learning and memory compared to placebo controls. Our findings suggest that cholinergic decline could result in memory impairment, but that the memory impairment may be secondary to deficits in attention and/or encoding of new information. Together, these results suggest that the canine cholinergic system declines with age and that the aged dog is a unique model for screening therapeutics and for examining the relationship between amyloid pathology and cholinergic dysfunction in age-dependent cognitive decline.