Use of a delayed non-matching to position task to model age-dependent cognitive decline in the dog

Adams, Beth; Chan, Alan; Callahan, Heather; Siwak, Christina T.; Tapp, Dwight; Ikeda-Douglas, Candace J; Atkinson, Patricia; Head, Elizabeth; Cotman, Carl W.; Milgram, Norton W.

doi:10.1016/s0166-4328(99)00132-1

Cited by 104 publications

(42 citation statements)

References 40 publications

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“…Possibly a more important reason for the diversity in reversal learning data is individual differences associated with aging. Our studies of cognitive aging in beagle dogs have indicated that individual variability in cognitive performance increases with age such that at least three distinct populations of aged dogs can be identified: those that are severely cognitively impaired, those that show mild impairments, and those that perform at levels similar to those of young dogs (Milgram et al 1994;Head et al 1995;Cummings et al 1996a,b;Adams et al 2000a;Head et al 2001;Siwak et al 2002). To account for this age-associated increase in cognitive variability, the present study separated aged dogs into two distinct groups based on chronological age.…”

Section: Tapp Et Almentioning

confidence: 98%

Size and Reversal Learning in the Beagle Dog as a Measure of Executive Function and Inhibitory Control in Aging

Tapp¹,

Siwak²,

Estrada³

et al. 2003

Learn. Mem.

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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.Inhibitory control and performance monitoring are critical executive functions of the human brain which show decreased efficiency during normal aging (McDowd and Oseas

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Section: Tapp Et Almentioning

confidence: 98%

Size and Reversal Learning in the Beagle Dog as a Measure of Executive Function and Inhibitory Control in Aging

Tapp¹,

Siwak²,

Estrada³

et al. 2003

Learn. Mem.

181

140

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“…Procedural learning and memory, as well as simple discrimination learning, are generally insensitive to aging (Milgram et al 1994). By contrast, tests of executive function, such as discrimination reversal learning (Milgram et al 1994;Tapp et al 2003a), and working memory (Adams et al 2000b;Head et al 1995), such as a delayednonmatching-to-position (DNMP) task (Chan et al 2002), are highly sensitive to aging. In other instances, age sensitivity depends on prior test experience.…”

Section: Age-associated Cognitive Decline In Dogsmentioning

confidence: 99%

“…Using a cross-sectional approach, we have established that tasks dependent on frontal lobe function, in particular tests of executive function (Milgram et al 1994;Tapp et al 2003a) and visuospatial working memory (Chan et al 2002), are notably sensitive to age (Adams et al 2000b;Head et al 1995). In a study of 109 dogs (manuscript in preparation), a statistically significant impairment in both acquisition of the DNMP using a 5-s delay and memory capacity were detected as early as six years of age (Figure 1) (Araujo 2004;Araujo et al 2004a).…”

Section: Age-associated Cognitive Decline In Dogsmentioning

confidence: 99%

“…In a study of 109 dogs (manuscript in preparation), a statistically significant impairment in both acquisition of the DNMP using a 5-s delay and memory capacity were detected as early as six years of age (Figure 1) (Araujo 2004;Araujo et al 2004a). Aged dogs also demonstrate increased variability in which some show little or no impairment (successful agers) while at the other extreme are those incapable of learning (demented) (Adams et al 2000b). In aged dogs that perform equivalently to young dogs on the DNMP (successful agers), increasing memory load by adding an additional position results in a memory deficit (Tapp et al 2003b).…”

Section: Age-associated Cognitive Decline In Dogsmentioning

confidence: 99%

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Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging

Araujo

Studzinski

Head

et al. 2005

AGE

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The present review focuses on the utility of a canine model in evaluating nutritional interventions for age-related cognitive dysfunction. Aged dogs demonstrate progressive cognitive decline with concurrent amyloid-beta pathology that parallels the pathology observed in aging humans. Dogs, therefore, provide a natural model of human pathological aging. We have and are in the process of evaluating several nutritional-based interventions aimed at preventing cognitive decline and brain aging. In a three-year longitudinal study, we examined the effects of a diet enriched with antioxidants and mitochondrial cofactors on several measures of cognition and brain aging. Compared to controls, aged dogs on the enriched diet demonstrated both short-and long-term cognitive benefits, as well decreased deposition of amyloid-beta protein. The diet also reduced behavioral signs associated with canine Cognitive Dysfunction Syndrome when assessed in veterinary clinical trials. We also have preliminary evidence suggesting a beneficial effect of a proprietary blend of docosahexaenoic acid and phospholipids on both cognitive and physiological measures. Collectively, our data indicate (1) that the dog, either in the laboratory or in the clinic, provides an important tool for assessing nutritional interventions and (2) that combination interventions aimed at several mechanisms of pathological aging may prove more effective than single nutritive components in human trials.

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“…By means of a cognitive test apparatus (a canine adaptation of the Wisconsin General Test Apparatus) all laboratory behavioral tests (such as the object recognition memory task, delayed-non-matching-to-position task, delayed-non-matching-to-sample test), are conducted using food as a reward to motivate learning in the animal [83][84][85][86]. Aging dogs (mostly beagles) are diagnosed with substantial cognitive decline when they present reduced capacity in the learning of tasks such as object recognition memory [83], visuospatial learning and memory [87,88], allocentric spatial function [86], discrimination learning and discrimination reversal learning [89]. From all these studies two main conclusions have emerged: a) the detection of canine cognitive dysfunction depends on the cognitive process engaged, on the task used and on the relative level of difficulty; and b) the variability in the cognitive abilities of dogs increases with age.…”

Section: Behavioral Assessment Of Housed Dogsmentioning

confidence: 99%

Dogs with Cognitive Dysfunction Syndrome: A Natural Model of Alzheimer’s Disease

Bosch¹,

Pugliese²,

Gimeno-Bayón³

et al. 2012

CAR

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In the search for appropriate models for Alzheimer's disease (AD) involving animals other than rodents, several laboratories are working with animals that naturally develop cognitive dysfunction. Among the animals tested, dogs are quite unique in helping to elucidate the cascade of events that take place in brain amyloid-beta (Aβ) deposition aging, and cognitive deficit. Recent innovative research has validated human methods and tools for the analysis of canine neuropathology and has allowed the development of two different approaches to investigate dogs as natural models of AD. The first approach relates AD-like neuropathy with the decline in memory and learning ability in aged housed dogs in a highly controlled laboratory environment. The second approach involves research in family-owned animals with cognitive dysfunction syndrome. In this review, we compare the strengths and limitations of housed and family-owned canine models, and appraise their usefulness for deciphering the early mechanisms of AD and developing innovative therapies.KEYWORDS: aging, Amyloid-beta, animal model, canine cognitive dysfunction syndrome, family dog, therapies. 6 Why a canine model of AD?For years, the search for appropriate animal models for Alzheimer's disease (AD) has focused on a variety of manipulations to reproduce the disease in various species, such as yeast, Drosophyla melanogaster, Caenorabditis elegans, rodents, and rabbits, with a particular interest in obtaining knockout and transgenic animals (for a review, see [1]research is currently performed in the mouse because its brain structure is somewhat similar to that of humans, and it is amenable to highly sophisticated genetic engineering. Because age-related cognitive decline is a common feature of most mammals, other laboratories have focused on the few species that naturally develop cognitive dysfunction with various Alzheimer-like characteristics. These animals include the monkey, polar bear, cat and dog [2][3][4][5]. Canine models are currently considered a useful intermediate between genetically modified mouse models and humans [6,7]. Although many of the transgenic AD models have provided insights into the molecular mechanisms of the pathology, none of them encompass all the cognitive deficits observed in AD (see Table 1). One of the first transgenic mouse AD models was the amyloid precursor protein transgenic mouse, PDAPP mouse, which develops age-dependent amyloid beta accumulation and deposition in both diffuse and fibrillar neuritic plaques in the hippocampus, cerebral cortex, and corpus callosum [8]. Other models with AD-like pathology are apolipoprotein E (ApoE) or Tau transgenic mice, and also mice in which other genes have been modified. In more sophisticated approaches, important information has been gained from crossing PDAPP and ApoE models and with mice lacking or over-expressing genes for beta-secretase, alpha-secretase, or the insulin-degrading enzyme [9,10].All these models have provided valuable information on AD pathology and on the poss...

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Use of a delayed non-matching to position task to model age-dependent cognitive decline in the dog

Cited by 104 publications

References 40 publications

Size and Reversal Learning in the Beagle Dog as a Measure of Executive Function and Inhibitory Control in Aging

Size and Reversal Learning in the Beagle Dog as a Measure of Executive Function and Inhibitory Control in Aging

Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging

Dogs with Cognitive Dysfunction Syndrome: A Natural Model of Alzheimer’s Disease

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