Page 696 - Small Animal Clinical Nutrition 5th Edition

Cognitive Dysfunction in Dogs 721

VetBooks.ir Box 35-3. Similarities Between Neurologic Diseases in People and Those Found in Dogs.

The original rationale for conducting laboratory-based studies on canine
cognition was to develop a model of human age-related cognitive dysfunc-
tion. The population of aged dogs tested to date display many similar char-
acteristics to those observed in the aged human population. Like people,
dogs show age-related individual variability in their learning, memory and
cognitive abilities, and these impairments vary as a function of task. Some
old dogs perform neuropsychological tests quite well for their age (success-
ful agers), others are mildly impaired (similar to age-associated memory
impairments in people) and still others are severely impaired (similar to
dementia in people). Furthermore, neuropsychological tests developed for
use in dogs have been adapted to test people. Preliminary evidence sug-
gests that these adapted canine tasks are successful in discriminating
healthy and cognitively impaired subpopulations of people.
Aged dogs develop similar neuropathological features to those in both
successfully aging people and patients with Alzheimer’s disease. As in peo-
ple, beta-amyloid (Aβ) protein is deposited in the aging dog brain, and shows
a selective distribution that changes as a function of age. Immunostaining of
the frontal cortex with an anti-Aβ marker reveals morphologic similarities
between Aβ plaques in the brains of normal and cognitively impaired people
and beagles, making it very difficult to distinguish one species from another
based on plaque deposition (Figure 1). Furthermore, the extent to which
they possess these biologic markers is correlated with their cognitive abili-
ties across the lifespan. For instance, results from a recent study show that
decreased brain volume and increased Aβ load accumulation in the frontal
cortex of aged dogs are correlated with deficits in complex discrimination
and reversal learning.
Taken together, these findings suggest that the canine model can be used
effectively for studying the etiology of age-related cognitive decline and
dementia and their prevention and treatment in people. There are many
research endeavors currently underway to determine if similar positive
effects on cognition with antioxidant dietary intervention will be evident in
people. This research represents a unique and exciting approach in translat-
ing what we know in dogs to aged and diseased human populations.

The Bibliography for Box 35-3 can be found at www.markmorris.org.
Figure 1. Comparable beta-amyloid (Aβ) immunostaining in the canine and human brain. The frontal cortex of a cognitively normal 13-
year-old beagle (A) and 90-year-old female (B) illustrates a similar pattern of senile Aβ plaque deposition in the deeper cortical layers.
Frontal cortex sections of a severely impaired 12-year-old beagle (C) and 86-year-old individual (D) with Alzheimer’s disease show
extensive Aβ pathology throughout all layers of cortex, whereas the molecular layer is largely spared (vertical line = molecular layer,
arrow = compact plaque, all bars = 200 mm). (Reproduced with permission from Head E, Milgram NW, Cotman CW. Neurobiological
models of aging in the dog and other vertebrate species. In: Hof P, Mobbs C, eds. Functional Neurobiology of Aging. New York, NY:
Academic Press, 2001; 457-468.)

increased error scores across all tasks (Cummings et al, 1996) of endothelial cells, astrocytes, pericytes and basement mem-
(Figure 35-2). branes surrounding the brain. The BBB allows for selective
transport of nutrients from the blood to neuronal cells (Khan,
Functional Changes in the Aging Brain 2005). An MRI study involving 18 beagles (four to 15 years
In addition to macroscopic and microscopic morphologic old) showed a non-significant increase in BBB permeability
changes in the aging canine brain, there is also evidence of with age; surprisingly, one six-year-old beagle, in which no
functional change. pathology was expected, had severe BBB leakage and dysfunc-
tion, enlarged ventricles, Aβ deposition and cognitive dysfunc-
CHANGES IN THE BLOOD-BRAIN tion (Su et al, 1998). Another study reported a direct link
BARRIER WITH AGE between vascular Aβ deposition and vessel wall integrity; lep-
The BBB is a collective term for the complex vascular system tomeninges obtained from old dogs affected by cerebral amy-