Biomedical subjects

Joseph A Araujo

Publications and source records attributed to Joseph A Araujo.

8 recordsLinked to original sources

PubMed2006

Visuospatial function in the beagle dog: an early marker of cognitive decline in a model of human aging and dementia.

Visuospatial learning and memory impairments are an early marker for age-related cognitive decline and Alzheimer's disease. Similar to humans, aged dogs show visuospatial learning and memory deficits (). One hundred and nine beagle dogs ranging between 0.25 and 11.99 years were tested on a visuospatial delayed non-matching to position (DNMP) task to better characterize the progression of visuospatial deficits in the dog. Age predicted 48.2% of the variability in learning the DNMP, with dogs ranging from 1 to 11.99 years generally making more errors with increasing age. By contrast, puppies (<1 year) likely were showing developmental deficits, possibly due to an immature prefrontal cortex. Mild visuospatial deficits were detected by 6 years, which precedes the typical onset of amyloid-beta (Abeta) accumulation in the dog brain by two years, and can serve as an early marker for cognitive decline in the dog. These findings suggest that (1) age-related changes in visuospatial function in the dog models that seen in humans, further validating the dog as a model for human aging and dementia; and (2) other mechanisms, such as oxidative stress, soluble Abeta oligomers or cholinergic deficits, are likely contributing to the early impairment.

Aging↗

PubMed2005

Behavior problems in geriatric pets.

Aging pets often suffer a decline in cognitive function (eg, memory,learning, perception, awareness) likely associated with age-dependent brain alterations. Clinically, cognitive dysfunction may result in various behavioral signs, including disorientation; forgetting of previously learned behaviors, such as house training; alterations in the manner in which the pet interacts with people or other pets;onset of new fears and anxiety; decreased recognition of people, places, or pets; and other signs of deteriorating memory and learning ability. Many medical problems, including other forms of brain pathologic conditions, can contribute to these signs. The practitioner must first determine the cause of the behavioral signs and then determine an appropriate course of treatment, bearing in mind the constraints of the aging process. A diagnosis of cognitive dysfunction syndrome is made once other medical and behavioral causes are ruled out.

Aging↗

PubMed2005

A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog.

Spatial discriminations can be performed using either egocentric information based on body position or allocentric information based on the position of landmarks in the environment. Beagle dogs ranging from 2 to 16 years of age were tested for their ability to learn a novel egocentric spatial discrimination task that used two identical blocks paired in three possible spatial positions (i.e. left, center and right). Dogs were rewarded for responding to an object furthest to either their left or right side. Therefore, when the center location was used, it was correct on half of the trials and incorrect on the other half. Upon successful acquisition of the task, the reward contingencies were reversed, and the dogs were rewarded for responding to the opposite side. A subset of dogs was also tested on an allocentric spatial discrimination task, landmark discrimination. Egocentric spatial reversal learning and allocentric discrimination learning both showed a significant age-dependent decline, while initial egocentric learning appeared to be age-insensitive. Intra-subject correlation analyses revealed a significant relationship between egocentric reversal learning and allocentric learning. However, the correlation only accounted for a small proportion of the variance, suggesting that although there might be some common mechanism underlying acquisition of the two tasks, additional unique neural substrates were involved depending on whether allocentric or egocentric spatial information processing was required.

Aging↗

PubMed2005

Effects of scopolamine challenge on regional cerebral blood volume. A pharmacological model to validate the use of contrast enhanced magnetic resonance imaging to assess cerebral blood volume in a canine model of aging.

Cognitive impairment resulting from disruption of cholinergic function may occur through modulation of cerebrovascular volume (CBV). In the present study, dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was used to examine cerebrovascular volume in young and old dogs during baseline and after administration of a cholinergic antagonist (scopolamine). In the first study, 24 animals (2-15 years of age) were given a baseline scan followed by a second scan after scopolamine administration (30 microg/kg). Gray matter rCBV was significantly higher than white matter rCBV during baseline and scopolamine administration. In the second study a subset of 7 dogs (4 young and 3 old) received scopolamine before anesthesia was induced for a second DSC-MRI scan. Consistent with the first study, gray matter rCBV was significantly higher than white matter rCBV. Scopolamine administered before anesthesia however, resulted in higher rCBV values compared to baseline in cerebral gray matter. Additionally, rCBVs were higher in young dogs at baseline in gray and white matter and marginally higher in gray matter when scopolamine was administered before anesthesia. These results indicate that in the dog, rCBV varies with brain compartment, decreases with age, and that DSC-MRI provides a measure of cerebrovascular function which may be related to age-dependent changes in cognition, brain structure, and neuropathology.

Aging↗

PubMed2005

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.

Acetylcholine↗

PubMed2005

Effect of feeding patterns on performance of a visuospatial memory task in the beagle dog: a novel cognitive-based protocol for assessing satiety.

The assessment of appetite suppressing effects, or satiating effects, of drugs or other treatments is typically based on the measurement of food consumption and body weight. The present study describes a novel cognitive-based protocol for assessing satiety in the dog based on response latency and performance accuracy on a canine test of spatial working memory, the three-component delayed-non-matching-to-position task (3cDNMP). We hypothesized that satiety, produced by providing food prior to testing, would reduce motivation to respond quickly and accurately on this food-reinforced task. Dogs were first over-trained on a variable-delay version of the 3cDNMP task. They were then pre-fed with either a single or a double portion of food prior to being tested on the same task. Pre-feeding slowed response latency, but had no effect on performance accuracy. A more pronounced increase in response latency was observed in young dogs than in old dogs when offered double portions of food. These results suggest, first, that spatial working memory capability is independent of motivation; second, that satiety is age sensitive; and third, that a cognitive protocol can provide a reliable method for evaluating the satiating effects of various foods and other compounds in the dog.

Aging↗

PubMed2005

The canine model of human cognitive aging and dementia: pharmacological validity of the model for assessment of human cognitive-enhancing drugs.

For the past 15 years we have investigated the aged beagle dog as a model for human aging and dementia. We have shown that dogs develop cognitive deficits and neuropathology seen in human aging and dementia. These similarities increase the likelihood that the model will be able to accurately predict the efficacy of Alzheimer's disease (AD) treatments as well as detect therapeutics with limited or no efficacy. Better predictive validity of cognitive-enhancing therapeutics (CETs) could lead to enormous cost savings by reducing the number of failed human clinical trials and also may reduce the likelihood of negative outcomes such as those recently observed in the AN-1792 clinical trials. The current review assesses the pharmacological validity of the canine model of human aging and dementia. We tested the efficacy of (1) CP-118,954 and phenserine, two acetylcholinesterase inhibitors, (2) an ampakine, (3) selegiline hydrochloride, two drugs that have failed human AD trials, and (4) adrafinil, a putative CET. Our research demonstrates that dogs not only develop isomorphic changes in human cognition and brain pathology, but also accurately predict the efficacy of known AD treatments and the absence or limited efficacy of treatments that failed clinical trials. These findings collectively support the utilization of the dog model as a preclinical screen for identifying novel CETs for both age-associated memory disorder and dementia.

Aging↗

PubMed2004

Comparison of the cognitive palatability assessment protocol and the two-pan test for use in assessing palatability of two similar foods in dogs.

OBJECTIVE: To compare preferences of dogs for 2 similar foods by use of 2 distinct methods (the cognitive palatability assessment protocol [CPAP] and the 2-pan test). ANIMALS: 13 Beagles. PROCEDURE: 6 dogs were trained in a 3-choice object-discrimination-learning task in which their nonpreferred objects were associated with a reward of a lamb-based or chicken-based food. The number of choices for each object was used to determine food preferences. Preference of the same foods was also assessed by use of a 2-pan test in which all 13 dogs were provided the 2 foods in identical bowls. The amount of each food consumed in 10 minutes was used to determine food preference. RESULTS: All dogs had a noticeable preference for the chicken-based food during the CPAP. Once established, preferences remained consistent and were not affected by satiety. The 2-pan test identified a preference for the chicken-based food in dogs with previous exposure to the food but only a weak and nonsignificant preference for the same food in dogs without previous exposure. Food preferences in the 2-pan test varied considerably. Total food consumption and the ability to detect a preference were reduced when dogs were fed prior to testing. CONCLUSIONS AND CLINICAL RELEVANCE: The CPAP provides a reliable measure of food preference that requires few test subjects. The 2-pan test reveals similar preferences but with variability in data that requires larger numbers of subjects and is susceptible to effects from prior exposure and feeding of the test foods to the subjects.

Analysis of Variance↗