Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.
Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies.
Cotman
Carl W
CW
Institute for Brain Aging and Dementia, University of California, 1226 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, USA. cwcotman@uci.edu
Head
Elizabeth
E
Muggenburg
Bruce A
BA
Zicker
S
S
Milgram
Norton W
NW
D000375:Aging / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000178:diet therapy* / Q000378:metabolism*; D004032:Diet; D004285:Dogs
D000975:Antioxidants