Frontal Lobe Volume, Function, and β-Amyloid Pathology in a Canine Model of Aging

Abstract

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.

Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging

“…By the 1950s, researchers observed BAlzheimer's-like^plaque pathology (Dahme 1962(Dahme , 1967(Dahme , 1968Osetowska 1966), which is a result of Ab protein deposition (Cummings et al 1996c). More recent studies have found that dogs have reduced levels of endogenous antioxidants , cortical atrophy (Tapp et al 2004a), ventricular enlargement (Tapp et al 2004a;Su et al 1998), myelin degeneration (Ferrer et al 1993), and accumulation of degraded proteins (Borras et al 1999). However, the canine and human neuropathology is not identical.…”

“…Both cognitive dysfunction and cortical atrophy are linked to Ab deposition in the dog (Tapp et al 2004a;Cummings et al 1996b). As mentioned previously, Ab typically is deposited early in the prefrontal cortex of both dogs (Head et al 2000) and humans (Braak and Braak 1997).…”

“…Cognitive tasks thought to be dependent on the prefrontal cortex are impaired by age more consistently and earlier in the dog (Tapp et al 2003a(Tapp et al , b, 2004a. Further, the frontal lobes selectively atrophy in aged dogs prior to overall brain atrophy (Tapp et al 2004a). This pattern of frontal lobe-based deficits is consistent with humans, where frontal lobe volume is correlated with impairment in executive function (GunningDixon and Raz 2003) and is highly sensitive to age (Jernigan et al 2001;Resnick et al 2000).…”

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

“…Aged canines show reduced cerebral volume, cortical atrophy and ventricular widening by in vivo magnetic resonance imaging [103,110,111]. The aging canine also shows impairments in visuospatial working memory and executive function [36,102,108].…”

Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines

“…Cortical atrophy and increased ventricular volume are observed in the aged dog brain (Su et al 1998;Tapp et al 2004;Kimotsuki et al 2005) and may underlie some of the cognitive impairments observed in old dogs. In particular, atrophy in frontal regions may contribute to executive dysfunction .…”