Assessing brain aging in cats

Assessing brain aging in cats

Are we paying enough attention to cats—both young and old?
Oct 01, 2010

Cats are more common as pets in North America than dogs are, and, on average, they live longer. Indeed, the aged and aging cat population is increasing, but cats have been relatively neglected in the animal brain-aging debate.

Because cats can be naturally independent, we may resort to neglecting their behaviors and cognitive well-being. Thus, we may not be adequately addressing the emotional needs of young and middle-aged cats, and we may need to rethink how we assess brain aging in them.

What we know about cats' brains

Since the 1970s, cats have been the subject of much basic neuroscience research. For example, early studies used cats as models for human seizure activity and damage or lesions.

Interestingly, early studies showed cats with septal lesions experienced dramatic increases in social awareness (based on how much time they spent watching cats with whom they were housed).1 Those with amygdaloid lesions doubled their baseline activities.

These findings may be relevant to aging cats given what we know about the distribution of beta-amyloid and neprilysin, an enzyme that degrades beta-amyloid, in cat brains.2 The distribution of these compounds is regionally sensitive.

Amyloid distribution is most common in the cerebral cortex and the hippocampus, and there is one report of amyloid distribution in the distal olfactory neurons of aged dogs (no equivalent study exists for cats).

Neprilysin distribution appears relatively high in the striatum, globus pallidus and substantia nigra. In contrast, its distribution is low in the cerebral cortex. Neprilysin activity is greatest in the thalamus/striatum followed, in order, by the cerebral cortex (in which executive function and implementation of learning occurs), the hippocampus (where much associational learning occurs) and the white matter.

Not all brain lesions are the same. The conventional wisdom holds that cats may form amyloid plaques but do not appear to develop the neurofibrillary tangles and plaques common in Alzheimer's disease. Beta-amyloid plaques can vary in type and length of termini they express, and these are found in different types of lesions. An early study of three older cats and 20 older dogs found plaques in their brains that contained residues of 42 amino acid (beta-amyloid42) but not 40 (beta-amyloid40), which is commonly found in a subset of human neuritic plaques and cerebrovascular deposits.3 Amyloid lesions appear in the brains of cats at about 10 years of age. In one study assessing 19 cats aged 16 weeks to 14 years, all expressed amyloid precursor protein constitutively in neurons and blood vessels.4 Staining for beta-amyloid was most pronounced in the deep cortical areas of the anterior/midcerebrum of cats older than 10 years. Clearly, amyloid deposition can affect brain function in cats.

Other physiological factors that can affect brain function

Feline cardiovascular changes that can occur with aging (e.g., anemia, decreased cardiac output and perfusion, systemic hypertension, changes in viscosity) may predispose some cats to, or worsen, brain aging.5 Older cats can experience infarcts of periventricular vessels. Any such pathology will worsen risks associated with reactive oxygen species such as free radicals (e.g., hydrogen peroxide, superoxide, nitric oxide). While these compounds are the normal detritus of mitochondrial metabolism, with advancing age, they are not removed as well by endogenous antioxidants (e.g., superoxide dismutase) and free radical scavengers (e.g., vitamins A, C and E) because their production becomes overwhelming. Such changes provide a good environment for the development of tauopathies, including those associated with amyloid deposition. When taken as a whole, these neuropathologic changes put feline brains at the risk of multiplicative assaults.

Like people, aging cats experience changes in how they digest and use food. Mean energy requirements do not decrease in aging cats; in fact, they actually may increase. Digestive efficiency changes; that is, older cats may not digest proteins or fats as well as they did when young.6 As a result, geriatric cats (those older than 11 years) may often be underweight despite the problem with obesity in the overall cat population.