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jtitle_s:("Age (dorer)")
1.  Amyloid-modifying therapies for Alzheimer’s disease: therapeutic progress and its implications 
Age  2010;32(3):365-384.
Alzheimer’s disease (AD) is the most prevalent form of dementia, affecting an estimated 4.8 million people in North America. For the past decade, the amyloid cascade hypothesis has dominated the field of AD research. This theory posits that the deposition of amyloid-beta protein (Aβ) in the brain is the key pathologic event in AD, which induces a series of neuropathological changes that manifest as cognitive decline and eventual dementia. Based on this theory, interventions that reduce Aβ burden in the brain would be expected to alleviate both the neuropathological changes and dementia, which characterize AD. Several diverse pharmacological strategies have been developed to accomplish this. These include inhibiting the formation of Aβ, preventing the aggregation of Aβ into insoluble aggregates, preventing the entry of Aβ into the brain from the periphery and enhancing the clearance of Aβ from the central nervous system. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials; however, several trials are currently underway. This article provides a review of the status of amyloid-modifying therapies and the implications for the amyloid cascade hypothesis.
doi:10.1007/s11357-010-9142-z
PMCID: PMC2926857  PMID: 20640545
Beta-amyloid; Amyloid cascade hypothesis; Alzheimer’s disease; Vaccination; Secretase; Cognition
2.  Age and distraction are determinants of performance on a novel visual search task in aged Beagle dogs 
Age  2011;34(1):67-73.
Aging has been shown to disrupt performance on tasks that require intact visual search and discrimination abilities in human studies. The goal of the present study was to determine if canines show age-related decline in their ability to perform a novel simultaneous visual search task. Three groups of canines were included: a young group (N = 10; 3 to 4.5 years), an old group (N = 10; 8 to 9.5 years), and a senior group (N = 8; 11 to 15.3 years). Subjects were first tested for their ability to learn a simple two-choice discrimination task, followed by the visual search task. Attentional demands in the task were manipulated by varying the number of distracter items; dogs received an equal number of trials with either zero, one, two, or three distracters. Performance on the two-choice discrimination task varied with age, with senior canines making significantly more errors than the young. Performance accuracy on the visual search task also varied with age; senior animals were significantly impaired compared to both the young and old, and old canines were intermediate in performance between young and senior. Accuracy decreased significantly with added distracters in all age groups. These results suggest that aging impairs the ability of canines to discriminate between task-relevant and -irrelevant stimuli. This is likely to be derived from impairments in cognitive domains such as visual memory and learning and selective attention.
doi:10.1007/s11357-011-9219-3
PMCID: PMC3260365  PMID: 21336566
Aging; Canine; Attention; Distraction; Visual learning
3.  Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging 
Age  2005;27(1):27-37.
The present review focuses on the utility of a canine model in evaluating nutritional interventions for age-related cognitive dysfunction. Aged dogs demonstrate progressive cognitive decline with concurrent amyloid-beta pathology that parallels the pathology observed in aging humans. Dogs, therefore, provide a natural model of human pathological aging. We have and are in the process of evaluating several nutritional-based interventions aimed at preventing cognitive decline and brain aging. In a three-year longitudinal study, we examined the effects of a diet enriched with antioxidants and mitochondrial cofactors on several measures of cognition and brain aging. Compared to controls, aged dogs on the enriched diet demonstrated both short- and long-term cognitive benefits, as well decreased deposition of amyloid-beta protein. The diet also reduced behavioral signs associated with canine Cognitive Dysfunction Syndrome when assessed in veterinary clinical trials. We also have preliminary evidence suggesting a beneficial effect of a proprietary blend of docosahexaenoic acid and phospholipids on both cognitive and physiological measures. Collectively, our data indicate (1) that the dog, either in the laboratory or in the clinic, provides an important tool for assessing nutritional interventions and (2) that combination interventions aimed at several mechanisms of pathological aging may prove more effective than single nutritive components in human trials.
doi:10.1007/s11357-005-4001-z
PMCID: PMC3456092  PMID: 23598601
aging; Alzheimer’s disease; antioxidants; brain pathology; canine model; cognitive dysfunction; docosahexaenoic acid; mitochondrial cofactors; nutritional interventions; phospholipids

Results 1-3 (3)