Several studies converge on the idea that executive processes age earlier than other cognitive processes. As part of a larger effort to investigate age-related changes in executive processes in the dog, inhibitory control was measured in young, middle-aged, old, and senior dogs using size discrimination learning and reversal procedures. Compared to young and middle-aged dogs, old and senior dogs were impaired on both the initial learning of the size task and the reversal of original reward contingencies. Impaired performance in the two aged groups was characterized as a delay in learning the correct stimulus-reward contingencies and, among the senior dogs in particular, an increase in perseverative responding. These separate patterns of reversal impairments in the old and senior dogs may reflect different rates of aging in subregions of the frontal cortex.Inhibitory control and performance monitoring are critical executive functions of the human brain which show decreased efficiency during normal aging (McDowd and Oseas

Aging and age-related disorders such as Alzheimer's disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a longterm treatment with an antioxidant fortified diet and a program of behavioral enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food-control behavioral enrichment (CC); control food -behavioral enrichment (CE); antioxidant food-control behavioral enrichment (CA); and enriched environment -antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4- Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurobiol Aging. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Neurobiol Aging. 2008 January ; 29(1): 51-70. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increas...

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Application of magnetic resonance imaging (MRI) techniques reveals that human brain aging varies across cortical regions. One area particularly sensitive to normal aging is the frontal lobes. In vitro neuropathological studies and behavioral measures in a canine model of aging previously suggested that the frontal lobes of the dog might be sensitive to aging. In the present study, MRI scans were acquired to compare age-related changes in frontal lobe volume with changes in executive functions and ␤-amyloid pathology in the frontal cortex of beagle dogs aged 3 months to 15 years. Decreases in total brain volume appeared only in senior dogs (aged 12 years and older), whereas frontal lobe atrophy developed earlier, appearing in the old dogs (aged 8 -11 years). Hippocampal volume also declined with age, but not occipital lobe volume past maturity. Reduced frontal lobe volume correlated with impaired performance on measures of executive function, including inhibitory control and complex working memory, and with increased ␤-amyloid accumulation in the frontal cortex. Age-related hippocampal atrophy also correlated with complex working memory but not inhibitory control, whereas occipital lobe volume did not correlate with any cognitive measure. These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging.