The goal of the studies proposed for supplemental funding is threefold: (1) to include a group of young dogs that have been receiving the same antioxidant enriched diet described in our original proposal; (2) to increase the sample size of old animals that are being assessed on newly developed cognitive tasks measuring spatial and object recognition memory and; (3) to develop and test the feasibility of detecting Abeta neuropathology that naturally develops in aging canine brain using an Abeta probe and PET scans. Our currently funded project is testing the hypotheses that reducing oxidative damage with a diet rich in antioxidants, and/or promoting neuron survival by providing an enriched environment will significantly enhance cognitive function in 36 aging dogs relative to 12 untreated controls. We will perform annual MRI studies to monitor the development of brain atrophy and cerebrovascular abnormalities in these dogs both as a function of age and in response to treatment. Sixteen young dogs are currently being studied at the University of Toronto using a parallel study design and is supported by another NIA R01 grant (AG12694 """"""""The Canine as an Animal Model of Human Aging""""""""). We seek funding to include these 16 young animals into the currently funded MRI study, which will provide us with a unique opportunity to obtain both treatment and comparison data in young animals. Another goal of the research at the University of Toronto is to study age-related memory decline and thus the second goal of this proposal is to obtain in vivo MRI measures that may provide support for the hypothesis that spatial memory declines more rapidly than object recognition memory. Thirty-six dogs will be studied during the next 4 years. A third goal of this proposal is to obtain supplemental funding to optimize methods to detect beta-amyloid (Abeta) in the canine brain using an Abeta-specific probe ([18F]FDDNP, developed by UCLA group) with PET (Positron Emission Tomography) scans. This exciting new area of research is particularly well suited for use in the canine model because dogs naturally deposit human-type Abeta in the brain with age. The in vitro and in vivo binding characteristics of this probe to Abeta within senile plaques have been demonstrated. A pilot study is proposed that will include 10 animals (8 aged and 2 young) to detect Abeta by PET and to compare in vivo data directly to post mortem Abeta loads determine using established immunocytochemistry and imaging protocols. Noninvasive imaging techniques may offer a means of detecting early signs of pathological aging and allows us the opportunity to monitor treatment efficacy in vivo.
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