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

被引:21
|
作者
Head, Elizabeth [1 ]
Murphey, Heather L.
Dowling, Amy L. S.
McCarty, Katie L.
Bethel, Samuel R.
Nitz, Jonathan A.
Pleiss, Melanie
Vanrooyen, Jenna
Grossheim, Mike
Smiley, Jeffery R. [2 ]
Murphy, M. Paul [3 ]
Beckett, Tina L.
Pagani, Dieter [4 ]
Bresch, Frederick [5 ]
Hendrix, Curt [6 ]
机构
[1] Univ Kentucky, Dept Mol & Biomed Pharmacol, Sanders Brown Ctr Aging, Lexington, KY 40536 USA
[2] Univ Kentucky, Div Lab Anim Resources, Lexington, KY USA
[3] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY USA
[4] dP & Associates, Georgetown, ON, Canada
[5] Metacog Testing Syst, New Westminster, BC, Canada
[6] Akeso Hlth Sci, W Lake Village, CA USA
关键词
Alzheimer's disease; amyloid-beta; cognition; dog; inflammation; oxidative damage; spatial attention; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA-PROTEIN; LONG-TERM TREATMENT; BEHAVIORAL ENRICHMENT; AGED CANINES; IN-VIVO; OXIDATIVE DAMAGE; BRAIN PROTEINS; BEAGLE DOGS; CURCUMIN;
D O I
10.3233/JAD-2012-120937
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
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 amyloid-beta (A beta) 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 A beta 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 A beta 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.
引用
收藏
页码:1029 / 1042
页数:14
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