In experimental colonies of beagles, careful studies of learning ability and memory have shown that cognitive function declines
with age.17 As would be expected, some dogs experience a more severe decline than others, and the most severely affected dogs have been
compared to people with Alzheimer's disease. As cognitive testing has not been standardized in pet dogs, the diagnosis of
canine cognitive dysfunction in this group depends on animals showing one or more of the following changes: disorientation,
disruption of activity and sleep, changes in housetraining, and changes in interactions with family members.16 The older the dog, the more likely it is to have abnormalities in one or more category. However, because older dogs are more
likely to also have orthopedic, metabolic, and cardiovascular disease, all of which could affect behavior in these categories,
it is difficult to determine the extent to which neurodegenerative disease is contributing to the clinical signs.
Far less information is published about cognitive dysfunction in cats. Experimental behavioral studies in aged cats also suggest
that their cognitive function declines.18
Cerebral microvascular disease
Do strokes occur in dogs and cats?
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Cerebral microvascular disease is the second most common cause of cerebral neurodegeneration in people, producing a disease
called vascular dementia.19 Although dogs and cats do not suffer from vascular disease to the same extent as people do, the advent of MRI has improved
our ability to diagnose CNS vascular diseases. This area is still emerging in veterinary medicine. No published reports exist
of vascular dementia in dogs and cats that corresponds to the disease in people. Focal large infarcts have been described
in dogs and cats for many years (see boxed text titled "Do strokes occur in dogs and cats?").20 In both species, large strokes affecting the forebrain can result in persistent behavioral changes, but this is a distinct
process when compared with the insidious loss of neurons secondary to repeated microvascular events as seen in people. As
more aged dogs and cats undergo MRI studies of their brains, descriptions of changes that represent microvascular disease
may emerge.
Q:
What types of age-related changes occur in the canine brain?
The histopathologic changes associated with aging have been described in a number of studies in dogs. Beta-amyloid protein
accumulates in diffuse deposits in the prefrontal cortex, entorhinal cortex, and hippocampus. The deposits are detected first
in the prefrontal cortex, and their principal constituent is the β-amyloid 1-42 protein, the insoluble fragment that is thought
to be neurotoxic.21 Apoptosis of neurons is also detected and tends to localize to those areas where amyloid accumulation is most prevalent.22 Evidence for progressive accumulation of oxidative damage also exists.23 These changes have been likened to the early changes seen in the brains of patients with Alzheimer's disease. Unlike Alzheimer's
disease patients, however, dogs do not develop mature amyloid plaques with cores and do not develop neurofibrillary tangles.
The cerebral vasculature also shows pathologic changes with age. A shorter fragment of β-amyloid protein, the β-amyloid 1-40
fragment, accumulates in the walls of blood vessels, although the significance of these changes is not known.24 Dogs with hypothyroidism may develop cerebrovascular atherosclerosis, but unlike in people, this is not a change seen simply
with age in dogs.25
Other reported aging changes include loss of spiral ganglion neurons in the inner ear associated with deafness26 and diffuse gliosis.27 Myelinated tracts develop nonspecific changes with age; in dogs over 12 years of age, white matter tracts, such as the corona
radiata and corpus callosum, develop pallor and gliosis with accumulation of perivascular macrophages.28
Intracytoplasmic neuronal inclusions called Lafora's bodies are encountered in the brains of aged dogs, their frequency apparently correlating to age. Finally, accumulation of a pigment
called lipofuscin is a common event in numerous organs, including those in the CNS. The pigment is brown and granular and tends to lie eccentrically
between the nucleus and axon hillock of neuronal cell bodies. In severely affected neurons, it may be perinuclear or fill
the entire cytoplasm. Less dense deposits may be found in astrocytes and oligodendrocytes.29
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