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The Journal of Neuroscience, September 22, 2004, 24(38):8205-8213; doi:10.1523/JNEUROSCI.1339-04.2004

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

P. Dwight Tapp,^1,4 Christina T. Siwak,^2,5 Fu Qiang Gao,³ Jr-Yuan Chiou,⁴ Sandra E. Black,^1,2,3 Elizabeth Head,⁵ Bruce A. Muggenburg,⁶ Carl W. Cotman,⁵ Norton W. Milgram,^1,2 and Min-Ying Su⁴

¹Department of Psychology, ²Institute of Medical Science, ³Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Scarborough, Ontario M1C 1A4, Canada, ⁴Center for Functional Onco-Imaging, and ⁵Institute for Brain Aging and Dementia, University of California, Irvine, California 92697, and ⁶Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87115

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.

Key words: brain volume; frontal lobe; aging; beagle; MRI; amyloid

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Received April 8, 2004; revised July 19, 2004; accepted July 22, 2004.

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