1. Milgram , NW , Head , E , Weiner , E & Thomas , E ( 1994 ) Cognitive functions and aging in the dog: acquisition of non spatial visual tasks . Behav Neurosci 108 , 57 – 68 .

2. Ruehl , WW , Bruyette , DS , DePaoli , A , et al . ( 1995 ) Canine cognitive dysfunction as a model for human age-related cognitive decline, dementia and Alzheimer’s disease: clinical presentation, cognitive testing, pathology and response to l-deprenyl therapy . In Progress in Brain Research , pp. 217 – 225 [PM Yu, AA Boulton and F Tipton, editors]. Amsterdam : Elsevier Science .

3. Ruehl , WW & Hart , BL ( 1998 ) Canine cognitive dysfunction . In Psychopharmacology of Animal Behavior Disorders , pp. 283 – 304 [NH Dodman and L Shuster, editors]. Boston, MA : Blackwell Scientific .

4. Azkona , G , Garcia-Belenguer , S , Chacon , G , et al . ( 2009 ) Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs . J of Small Anim Pract 50 , 87 – 91 .

5. Neilson , JC , Hart , BL , Cliff , KD , et al . ( 2001 ) Prevalence of behavioural changes associated with age-related cognitive impairment in dogs . J Am Vet Med Assoc 218 , 1787 – 1791 .

6. Borras , D , Ferrer , I & Pumarola , M ( 1999 ) Age-related changes in the brain of the dog . Vet Path 36 , 202 – 211 .

7. Dimakopoulos , AC & Mayer , RJ ( 2002 ) Aspect of neurodegeneration in the canine brain . J Nutr 132 , 1579S – 1582S.

8. Pan , Y ( 2011 ) Enhancing brain functions in senior dogs: a new nutritional approach . Top Companion Anim Med 26 , 10 – 16 .

9. Su , MY , Head , E , Brooks , WM , et al . ( 1998 ) Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging . Neurobiol Aging 19 , 479 – 485 .

10. Su , MY , Tapp , PD , Vu , L , et al . ( 2005 ) A longitudinal study of brain morphometrics using serial magnetic resonance imaging analysis in a canine model of aging . Prog Neuropsychopharmacol Biol Psychiatry 29 , 389 – 397 .

11. Uchida , K , Nakayama , H & Goto , N ( 1991 ) Pathological studies on cerebral amyloid angiopathy, senile plaques and amyloid deposition in visceral organs in aged dogs . J Vet Med Sci 53 , 1037 – 1042 .

12. Pan , Y ( 2013 ) Cognitive dysfunction syndrome in dogs and cats . CAB Rev 8 , 1 – 10 .

13. Cole , GM , Ma , QL & Frautschy , SA ( 2009 ) Omega-3 fatty acids and dementia . Prostaglandins Leukot Essent Fatty Acids 81 , 213 – 221 .

14. Duron , E & Hanon , O ( 2008 ) Hypertension, cognitive decline and dementia . Arch Cardiovasc Dis 101 , 181 – 189 .

15. Jellinger , KA & Attems , J ( 2006 ) Prevalence and impact of cerebrovascular pathology in Alzheimer’s disease and Parkinsonism . Acta Neurol Scand 114 , 38 – 46 .

16. Markesbery , WR ( 1997 ) Oxidative stress hypothesis in Alzheimer’s disease . Free Radic Biol Med 23 , 134 – 147 .

17. Miller , JW , Green , R , Ramos , MI , et al . ( 2003 ) Homocysteine and cognitive function in the Sacramento Area. Latino Study on Aging . Am J Clin Nutr 78 , 441 – 447 .

18. Qiu , C , Winblad , B & Fratiglioni , L ( 2005 ) The age-dependent relation of blood pressure to cognitive function and dementia . Lancet Neurol 4 , 487 – 499 .

19. Selhub , J , Bagley , LC , Miller , J , et al . ( 2000 ) B vitamins, homocysteine, and neurocognitive function in the elderly . Am J Clin Nutr 71 , 614S – 620S .

20. Weninger , SC & Yankner , BA ( 2001 ) Inflammation and Alzheimer disease: the good, the bad, and the ugly . Nat Med 7 , 527 – 528 .

21. Taupin , P ( 2010 ) A dual activity of ROS and oxidative stress on adult neurogenesis and Alzheimer’s disease . Cent Nerv Syst Agents Med Chem 10 , 16 – 21 .

22. Ciubotaru , I , Lee , YS & Wander , RC ( 2003 ) Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglyceride to HDL-cholesterol ration in postmenopausal women on HRT . J Nutr Biochem 14 , 513 – 521 .

23. Wall , R , Ross , RP , Fitzgerald , GF , et al . ( 2010 ) Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids . Nutr Rev 68 , 280 – 289 .

24. Dong , JY , Qin , LQ , Zhang , Z , et al . ( 2011 ) Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials . Am Heart J 162 , 959 – 965 .

25. Yamada , K , Noda , Y , Nakayama , S , et al . ( 1995 ) Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain . Br J Pharmacol 115 , 852 – 858 .

26. Bryan , J , Calvaresi , E & Hughes , D ( 2002 ) Short-term folate, vitamin B-12, or vitamin B-6 supplementation slightly affects memory performance, but not mood in women of various ages . J Nutr 132 , 1345 – 1356 .

27. Smith , AD , Smith , SM , de Jager , CA , et al . ( 2010 ) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial . PLoS ONE 5 , e12244 .

28. Lee , CM , Jeong , DM , Kang , MH , et al . ( 2017 ) Correlation between serum homocysteine concentration and severity of mitral valve disease in dogs . Am J Vet Res 78 , 440 – 446 .

29. Rossi , S , Rossi , G , Giordano , A , et al . ( 2008 ) Homocysteine measurement by an enzymatic method and potential role of homocysteine as a biomarker in dogs . J Vet Diagn Invest 20 , 644 – 649 .

30. Frank , B & Gupta , S ( 2005 ) A review of antioxidants and Alzheimer’s disease . Ann Clin Psychiatry 17 , 269 – 286 .

31. Loef , M , Schrauzer , GN & Walach , H ( 2011 ) Selenium and Alzheimer’s disease: a systematic review . J Alzheimer’s Dis 26 , 81 – 104 .

32. Lynch , SM , Gaziano , JM & Frei , B ( 1996 ) Ascorbic acid and atherosclerotic cardiovascular disease . Subcell Biochem 25 , 331 – 367 .

33. Peluzio Mdo , C , Teixeira , TF , Oliveira , VP , et al . ( 2011 ) Grape extract and α-Tocopherol effect in cardiovascular disease model of Apo E -/- Mice . Acta Cir Bras 26 , 253 – 260 .

34. Pocernich , CB , Lange , ML , Sultana , R , et al . ( 2011 ) Nutritional approaches to modulate oxidative stress in Alzheimer’s disease . Curr Alzheimer Res 8 , 452 – 469 .

35. Schwenke , DC & Behr , SR ( 1998 ) Vitamin E combined with selenium inhibits atherosclerosis in hypercholesterolemic rabbits independently of effects on plasma cholesterol concentrations . Circ Res 83 , 366 – 377 .

36. Pan , Y , Araujo , JA , Burrows , J , et al . ( 2013 ) Cognitive enhancement in middle-aged and old cats with dietary supplementation with a nutrient blend containing fish oil, B vitamins, antioxidants and arginine . Br J Nutr 110 , 40 – 49 .

37. Milgram , NW , Adams , B , Callahan , H , et al . ( 1999 ) Landmark discrimination learning in the dog . Learn Mem 6 , 54 – 61 .

38. Milgram , NW , Head , E , Muggenburg , B , et al . ( 2002 ) Landmark discrimination learning in the dog: effects of age, an antioxidant fortified diet, and cognitive strategy . Neurosci Biobehav Rev 26 , 679 – 695 .

39. Milgram , NW , Araujo , JA , Hagen , TM , et al . ( 2007 ) Acetyl-L-carnitine and α-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests . FASEB J 21 , 3756 – 3762 .

40. Christie , LA , Studzinski , C , Araujo , J , et al . ( 2005 ) A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog . Prog Neuropsychopharmacol Biol Psychiatry 29 , 361 – 369 .

41. Chan , ADF , Nippak , P , Murphey , H , et al . ( 2002 ) Visuospatial impairments in aged canines (Canis familiaris): the role of cognitive-behavioral flexibility . Behav Neurosci 116 , 443 – 454 .

42. Milgram , NW , Zicker , SC , Head , E , et al . ( 2002 ) Dietary enrichment counteracts age-associated cognitive dysfunction in canines . Neurobiol Aging 23 , 737 – 745 .

43. Association of American Feed Control Official ( 2011 ) Official Publication . Atlanta, GA : AAFCO .

44. Evans , AM , DeHaven , CD , Barrett , T , Mitchell , M & Milgram , E ( 2009 ) Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems . Anal Chem 81 , 6656 – 6667 .

45. Sha , W , et al . ( 2010 ) Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline . FASEB J 24 , 2962 – 2975 .

46. Feart , C , Samieri , C & Barberger-Gateau , P ( 2010 ) Mediterranean diet and cognitive function in older adults . Curr Opin Clin Nutr Metab Care 13 , 14 – 18 .

47. Oulhaj , A , Jernerén , F , Refsum , H , et al . ( 2016 ) Omega-3 fatty acid status enhances the prevention of cognitive decline by b vitamins in mild cognitive impairment . J Alzeimers Dis 50 , 547 – 557 .

48. Kohli , P & Levy , BD ( 2009 ) Resolvins and protectins: mediating solutions to inflammation . Br J Pharmacol 158 , 960 – 971 .

49. Serhan , CN ( 2014 ) Pro-resolving lipid mediators are leads for resolution physiology . Nature 510 , 92 – 101 .

50. Weylandt , KH , Chiu , CY , Gomolka , B , et al . ( 2012 ) Omega-3 fatty acids and their lipid mediators: Towards an understanding of resolvin and protectin formation . Prostaglandins Other Lipid Mediat 97 , 73 – 82 .

51. De Jager , CA , Oulhaj , A , Jacoby , R , et al . ( 2011 ) Cognitive and clinical outcome of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial . Int J Geriatr Psychiatry 27 , 592 – 600 .

52. Manukhina , EB , Pshennikova , MG , Goryacheva , AV , et al . ( 2008 ) Role of nitric oxide in prevention of cognitive disorders in neurodegenerative brain injuries in rats . Bull Exp Biol Med 146 , 391 – 395 .

53. Ast , J , Jablecka , A , Bogdanski , P , et al . ( 2010 ) Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring . Med Sci Monit 16 , CR266 – CR271 .

54. Rajapakse , NW , De Miguel , C , Das , S , et al . ( 2008 ) Exogenous L-arginine ameliorates angiotensin II-induced hypertension and renal damage in rats . Hypertension 52 , 1084 – 1090 .

55. Yurko-Mauro , K , McCarthy , D , Rom , D , et al . ( 2010 ) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline . Alzheimers Dement 6 , 456 – 464 .

56. Jiang , LH , Shi , Y , Wang , LS & Yang , ZR ( 2009 ) The influence of orally administered docosahexaenoic acid on cognitive ability in aged mice . J Nutr Biochem 20 , 735 – 741 .

57. Harris , WS ( 2008 ) The omega-3 index as a risk factor for coronary heart disease . Am J Clin Nutr 87 , 1997S – 2002S .