How do we recognize brain aging in dogs?
While humans are afflicted by numerous tauopathies, each of which may have defining cognitive or anatomical dimension, emphasis
in dogs has been placed on a relatively nonspecific diagnosis of canine cognitive dysfunction (CD), sometimes also called
cognitive dysfunction syndrome. In dogs, CD is usually diagnosed because of a history of disorientation, alterations in social and interactive behaviors,
changes in locomotor behavior and sleep cycles and what is often called loss of housetraining. In early-onset CD, animals may have only slightly altered sleep cycles and appear more anxious. Alterations in social and
interactive behaviors may manifest early in the condition as an increased neediness but can change to a form of aloof disengagement
in social interactions with all species.
Estimates from numerous studies suggest that at least 25 percent of dogs older than 10 show one of these signs associated
with brain aging, and that by 15 years, more than 60 percent of dogs are affected to some extent.
What happens to cause deleterious brain aging changes?
If we understand what happens at the cellular and molecular level as brains age, the path to preventing or treating pathological
brain aging will become clearer. There are three main contributors to problematic, age-related brain changes: oxidative changes
associated with processes like free-radical formation; formation of lesions, including those composed of amyloid; and shifts
in oxygen and energy availability. All of these factors interact to compromise brain function.
Aging is associated with increased expression of genes associated with stress and inflammation. Changes in gene expression
are key to understanding why we and our pets may have difficulty learning with advancing age. As a result of these changes,
neuronal loss occurs in the hippocampus — the section of the brain primarily involved in associational learning. This loss
of neurons is associated with decreased expression of genes that affect the ability of neurons to send and receive signals.
Anything that causes inflammation or damage to neurons — oxidative assaults, illness, trauma — affects the neurochemicals
that allow neurons to talk to each other. To maintain efficient channels of communication between neurons, efficient and numerous
connections must exist. These connections are maintained by use because recalling and making molecular memory trigger a second
messenger system that ultimately stimulates an important neurotrophic factor called brain-derived neurotrophic factor (BDNF). BDNF, which stimulates cytosolic response element-binding protein (CREB), has three principal functions: 1) to enhance
growth of serotoninergic (5-HT) and norepinephrinergic (NE) neurons, 2) to protect these neurons from neurotoxic damage and
3) to help in remodeling neuronal receptors. By stimulating CREB, which facilitates protein transcription, BDNF plays a crucial
role in making and repairing all components of neurons.
Like humans, when canine neurons begin to suffer from oxidative assaults, amyloid deposition may occur. Dogs develop plaques
composed of beta-amyloid that are like those seen in humans. When amyloid deposition is extensive, it physically disrupts
communication between neurons, worsening the processes discussed previously.