A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer's Disease

Article type: Research Article

Authors: Head, Elizabeth^{a; b; *} | Murphey, Heather L.^a | Dowling, Amy L.S.^a | McCarty, Katie L.^a | Bethel, Samuel R.^a | Nitz, Jonathan A.^a | Pleiss, Melanie^a | Vanrooyen, Jenna^a | Grossheim, Mike^a | Smiley, Jeffery R.^c | Murphy, M. Paul^{a; d} | Beckett, Tina L.^a | Pagani, Dieter^e | Bresch, Frederick^f | Hendrix, Curt^g

Affiliations: [a] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [b] Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA | [c] Division of Laboratory Animal Resources, University of Kentucky, Lexington, KY, USA | [d] Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA | [e] dP and Associates, Georgetown, ON, Canada | [f] Metacog Testing Systems, New Westminster, BC, Canada | [g] Akeso Health Sciences, West Lake Village, CA, USA

Correspondence: [*] Correspondence to: Elizabeth Head, MA, PhD, Department of Molecular and Biomedical Pharmacology, Sanders Brown Center on Aging, University of Kentucky, 800 South Limestone Street, Lexington, KY 40536-0230, USA. Tel.: +1 859 257 1412 ext. 481; Fax: +1 859 323 2866; E-mail: Elizabeth.Head@uky.edu.

Abstract: Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of amyloid-β (Aβ) plaques. We hypothesized 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. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits, and oxidative damage in the brain. Thus, 9 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% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. 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), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and cerebrospinal fluid Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD.

Keywords: Alzheimer's disease, amyloid-β, cognition, dog, inflammation, oxidative damage, spatial attention

DOI: 10.3233/JAD-2012-120937

Journal: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1029-1042, 2012