Spatial attention is improved in aged canines treated with a medical food cocktail

Alzheimer's & Dementia(2012)

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摘要
Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ). Our hypothesis is that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD, given that aged dogs naturally develop learning and memory impairments, human-type Aβ deposits, and oxidative damage in the brain. Nine aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechin gallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. We used a modified Wisconsin General Test apparatus for behavioral testing of the dogs for 10 or 12 trials/day, 5 days/week, with food rewards. Data acquisition was controlled using dedicated software (DOGMA). After a 1 month wash in, dogs were given a landmark discrimination task to measure spatial attention. For the first 2 months of treatment, we observed a gradual but nonsignificant improvement in attention in treated animals as they progressively solved the problem using increasing landmark distances (0, 5, 18, 14 cm from the center of the correct object to be displaced). After 3 months of treatment, 13 dogs completed a 20-day variable distance version of the task. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11) = 4.3, P = 0.001) and were more accurate across all distances (F(1,9) = 20.7, P = 0.001). Blood biochemical measures from treated dogs had reduced aspartate transaminase (AST) (t(15) = 3.5, P = 0.003) and creatinine phosphokinase (CPK) (t(15) = 2.93, P = 0.01), indicating no liver or muscle toxicity with consumption of the medical food cocktail. Brain Aβ remained unchanged in treated dogs and there appeared to be no change in gliosis. Our results indicate that this medical food cocktail may be beneficial for reducing or preventing symptoms associated with aging and AD.
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