The Canine Model of Human Cognitive Aging

The development of the canine model is based on over 16 years of research as is supported by the following:

1. Dogs, like humans develop cognitive dysfunction syndrome with advanced age

Like humans, aged dogs develop cognitive dysfunction syndrome, which ranges from a mild to global cognitive impairment, impacting learning, memory, attention and social interaction, sleep and activity. There is also considerable variability, however, with some dogs showing successful aging, others showed impaired cognitive function and still others showing a form of dementia, which has been labeled cognitive dysfunction syndrome. (See Adams et al. 2000 for discussion of variability)

2. Aged dogs model the brain pathology and cognitive decline of Alzheimer's disease

The beta amyloid hypothesis of Alzheimer's disease (AD) attributes the development of AD to the cellular production of a toxic substance known as beta amyloid protein.

The aged beagle dog provides a natural model of beta-amyloid pathology. Starting at around eight years of age, aged beagle dogs naturally develop beta-amyloid pathology, a hallmark feature of Alzheimer's disease in humans. Furthermore, like people, aged dogs primarily deposit the 42 amino acid peptide (see Cummings et al., 1996).

The similarity between human and canine brain aging also extends to more compartmentalized changes; both show selective loss of white matter, when compared to gray matter.

Localized lesions, which may be related to vascular dysfunction, is another feature that occurs with increasing frequency in advanced age in both dogs and humans.

Neuropsychological assessment of cognitive function of aged dogs characteristically reveals:

1. Deficits in complex learning and visuospatial memory. This is best illustrated by age-dependent deterioration in rate of learning a delayed-non-matching-to-position task (see Chan et al., 2002)
2. Executive function deficits, which include high level cognitive functions that are linked to the frontal lobes. These kinds of deficits can be revealed by difficulty in solving reversal learning problems (Tapp et al., 2003)

3. Role of the brain cholinergic system in cognitive aging in the dog

The cholinergic hypothesis, one of the most widely held models of Alzheimer's disease, postulates that dysfunction of the brain cholinergic system accounts for the cognitive decline associated with dementia. To investigate the role of the cholinergic system in canine aging, we showed that performance on memory tests was highly sensitive to treatment with scopolamine, a drug that disrupts brain cholinergic function. Furthermore, aged animals show an enhanced sensitivity to scopolamine, which is consistent with the cholinergic hypothesis (e.g., Araujo et al., 2005). We have also demonstrated that enhancement of the cholinergic system results in improved cognitive performance in aged dogs.

4. Changes in brain structure and aging

We have shown that brain aging in the dog is accompanied by loss of cortical volume, increased ventricular volume and decreased frontal lobe volume - all of which occurs during human aging (Tapp et al., 2004).