Chapter 35: Cognitive Dysfunction in Dogs References


Adams B, Chan A, Callahan H, et al. Use of a delayed non-matching to position task to model age-dependent cognitive decline in the dog. Behavioural Brain Research 2000; 108: 47-56.

Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proceedings of the National Academy of Sciences of the United States of America 1993; 90: 7915-7922.

Anderson AJ, Ruehl WW, Fleischmann LK, et al. DNA damage and apoptosis in the aged canine brain: Relationship to Abeta deposition in the absence of neuritic pathology. Progress in Neuropsychopharmacology and Biological Psychiatry 2000; 24: 787-799.

Araujo JA, Landsberg GM, Miolo A. Assessment of the effects of a phosphatidylserine-containing neutraceutical on visuospatial memory of aged dogs: Neuropsychological testing. Journal of Veterinary Pharmacology and Therapeutics 2006; 29(s1): 205-206.

Araujo JA, Studzinski CM, Head E, et al. Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging. AGE 2005; 27: 27-37.

Araujo JA, Studzinski CM, Milgram NW. Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging. Progress in Neuropsychopharmacology and Biological Psychiatry 2005a; 29(3): 411-422.

Arnold O, Saletu B, Anderer P, et al. Double-blind, placebo-controlled pharmacodynamic studies with a neutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. European Neuropsychopharmacology 2005; 15: 533-543.

AVMA. Overview of the 2002 household pet survey. 2002 U.S. Pet Ownership and Demographics Sourcebook. American Veterinary Medical Association, Schaumburg, IL, 2002.

Bain MJ, Hart BL, Cliff KD, et al. Predicting behavioral changes associated with age-related cognitive impairment in dogs. Journal of the American Veterinary Medical Association 2001; 218: 1792-1795.

Beckman KB, Ames BN. The free radical theory of aging matures. Physiological Reviews 1998; 78: 547-581.

Borras D, Ferrer I, Pumarola M. Age-related changes in the brain of the dog. Veterinary Pathology 1999; 36: 202-211.

Callahan H, Ikeda-Douglas C, Head E, et al. Development of a protocol for studying object recognition memory in the dog. Progress in Neuropsychopharmacology and Biological Psychiatry 2000; 24: 693-707.

Carillo M-C, Ivy GO, Milgram NW, et al. Deprenyl increases activity of superoxide dismutase. Life Science 1994; 54: 1483-1489.

Cena F, Colangeli R, Fassola F, et al. Effect of a combination of phosphatidylserine, Gingko biloba, vitamin E and pyridoxine on clinical signs of brain ageing: A pilot multicentric study. Proceedings of the European College of Veterinary Behavioral MedicineCompanion Animals 2005; 2: 127-135.

Chan AD, Nippak PM, Murphey H, et al. Visuospatial impairments in aged canines (Canis familiaris): The role of cognitive-behavioral flexibility. Behavioral Neuroscience 2002; 116: 443-454.

Chapman BL, Voith VL. Behavioral problems in old dogs: 26 cases (1984-1987). Journal of the American Veterinary Medical Association 1990; 196: 944-946.

Christie LA, Studzinski CM, Araujo JA, et al. A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog. Progress in Neuropsychopharmacology and Biological Psychiatry 2005; 29: 361-369.

Colle MA, Hauw JJ, Crespeau F, et al. Vascular and parenchymal Abeta deposition in the aging dog: Correlation with behavior. Neurobiology of Aging 2000; 21: 695-704.

Cottrell DA, Turnbull DM. Mitochondria and ageing. Current Opinion in Clinical Nutrition and Metabolic Care 2000; 3: 473-478.

Cummings BJ, Head E, Afagh AJ, et al. Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine. Neurobiology of Learning and Memory 1996; 66: 11-23.

Czasch S, Paul S, Baumgartner W. A comparison of immunohistochemical and silver staining methods for the detection of diffuse plaques in the aged canine brain. Neurobiology of Aging 2006; 27: 293-305.

de Rivera C, Boutet I, Zicker SC, et al. A novel method for assessing contrast sensitivity in the beagle dog is sensitive to age and an antioxidant enriched food. Progress in Neuropsychopharmacology and Biological Psychiatry 2005; 29: 379-387.

De Ruvo C, Amodio R, Algeri S, et al. Nutritional antioxidants as antidegenerative agents. International Journal of Developmental Neuroscience 2000; 18: 359-366.

Dehasse J. Senile dementia in dogs and cats. 50 Congresso Nazionale Multisala SCIVAC, Brussels, Belgium, 2005.

Dodd CE, Zicker SC, Jewell DE, et al. Can a fortified food affect behavioral manifestations of age-related cognitive decline in dogs? Veterinary Medicine 2003; 98: 396-408.

Epstein M, Kuehn NF, Landsberg G, et al. AAHA Senior Care Guidelines for Dogs and Cats. Journal of the American Animal Hospital Association 2005; 41: 81-91.

Gelbmann CM, Muller WE. Chronic treatment with phosphatidylserine restores muscarinic cholinergic receptor deficits in the aged mouse brain. Neurobiological Aging 1992; 13: 45-50.

Harman D. Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology 1956; 11: 298-300.

Head E, Callahan H, Muggenburg BA, et al. Visual-discrimination learning ability and beta-amyloid accumulation in the dog. Neurobiology of Aging 1998; 19: 415-425.

Head E, Liu J, Hagen TM, et al. Oxidative damage increases with age in a canine model of human brain aging. Journal of Neurochemistry 2002; 82: 375-381.

Head E, McCleary R, Hahn FF, et al. Region-specific age at onset of beta-amyloid in dogs. Neurobiology of Aging 2000; 21: 89-96.

Head E, Zicker SC. Neutraceuticals, aging, and cognitive dysfunction. Veterinary Clinics of North America: Small Animal Practice 2004; 34: 217-228.

Heath SE, Barabas S, Craze PG. Nutritional supplementation in cases of cognitive dysfunction; results of a clinical trial. Applied Animal Behavior Science 2007; 105: 284-296.

Heinonen EH, Lammintausta R. A review of the pharmacology of selegiline. Acta Neurology Scandinavia 1991; 84 (Suppl. 136): 44-59.

Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmaceutical Research 1999; 40: 211-225.

Hou Y, White RG, Bobik M, et al. Distribution of beta-amyloid in the canine brain. Neuroreport 1997; 8: 1009-1012.

Ikeda-Douglas CJ, Zicker SC, Estrada J, et al. Prior experience, antioxidants, and mitochondrial cofactors improve cognitive function in aged beagles. Veterinary Therapeutics 2004; 5: 5-16.

Johnstone EM, Chaney MO, Norris FH, et al. Conservation of the sequence of the Alzheimer’s disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis. Brain Research. Molecular Brain Research 1991; 10: 299-305.

Kapl D, Rudolphi KA. New pharmacological aspects in the neurologic profile of propentofylline (Karsivan) Vet Tierarztl Prax Augs Kleintiere Heimtiere 1998; 26: 317-321.

Khan E. An examination of the blood-brain barrier in health and disease. British Journal of Nursing 2005; 14: 509-513.

Kiatipattanasakul W, Nakamura S, Kuroki K, et al. Immunohistochemical detection of anti-oxidative stress enzymes in the dog brain. Neuropathology 1997; 17: 307-312.

Knoll J. L-Deprenyl (selegiline)A catecholaminergic activity enhancer (CAE) substance acting in the brain. Pharmacology and Toxicology 1998; 82: 57-66.

Landsberg G, Araujo JA. Behavior problems in geriatric pets. Veterinary Clinics of North America: Small Animal Practice 2005; 35: 675-698.

Landsberg G, Hunthausen W, Ackerman L. The effects of aging on behavior in senior pets. Handbook of Behavior Problems of the Dog and Cat. Edinburgh, Scotland: Elsevier Health Sciences, 2003.

Milgram NW, Adams B, Callahan H, et al. Landmark discrimination learning in the dog. Learning & Memory 1999; 6: 54-61.

Milgram NW, Head E, Weiner E, et al. Cognitive functions and aging in the dog: Acquisition of nonspatial visual tasks. Behavioral Neuroscience 1994; 108: 57-68.

Milgram NW, Head E, Zicker SC, et al. Learning ability in aged beagle dogs is preserved by behavioral enrichment and dietary fortification: A two-year longitudinal study. Neurobiology of Aging 2005; 26: 77-90.

Milgram NW, Head E, Zicker SC, et al. Long-term treatment with antioxidants and a program of behavioral enrichment reduces age-dependent impairment in discrimination and reversal learning in beagle dogs. Experimental Gerontology 2004; 39: 753-765.

Milgram NW, Ivy GO, Head E, et al. The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog. Neurochemistry Research 1993; 18: 1211-1219.

Milgram NW, Zicker SC, Head E, et al. Dietary enrichment counteracts age-associated cognitive dysfunction in canines. Neurobiology of Aging 2002; 23: 737-745.

Morita T, Mizutani Y, Sawada M, et al. Immunohistochemical and ultrastructural findings related to the blood-brain barrier in the blood vessels of the cerebral white matter in aged dogs. Journal of Comparative Pathology 2005; 133: 14-22.

Neilson JC, Hart BL, Cliff KD, et al. Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. Journal of the American Veterinary Medical Association 2001; 218: 1787-1791.

Osella MC, Re G, Odore R, et al. Canine cognitive dysfunction: Prevalence, clinical signs and treatment with a neutraceutical. Applied Animal Behavior Science 2007; 105: 297-310.

Penaliggon J. The use of nicergoline in the reversal of behavioural changes due to aging in dogs: A multicentre clinical field trial. Proceedings on the International Conference of Behavioral Medicine. UFAW: Herts, UK 1991; 1: 37-41.

Pfizer Animal Health Senior Dog CDS Checklist at www.cdsindogs.com/cds_checklist.asp.

Pocernich CB, La Fontaine M, Butterfield DA. In-vivo glutathione elevation protects free radical-induced protein oxidation in rat brain. Neurochemistry International 2000; 36: 185-191.

Pop V, Head E, Muggenberg BA, et al. Secretase activity as a function of age, antioxidant diet and/or behavioral enrichment in canine parietal cortex. Program No. 662.8. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online.

Pop V, Head E, Nistsor M, et al. Reduced beta-amyloid deposition with long-term antioxidant diet treatment in aged canines. Program No. 525.4. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.

Prior R, D’Urso D, Frank R, et al. Loss of vessel wall viability in cerebral amyloid angiopathy. Neuroreport 1996; 7: 562-564.

Pugliese M, Geloso MC, Carrasco JL, et al. Canine cognitive deficit correlates with diffuse plaque maturation and S100beta (-) astrocytosis but not with insulin cerebrospinal fluid level. Acta Neuropathologica (Berlin) 2006a; 111: 519-528.

Pugliese M, Mascort J, Mahy N, et al. Diffuse beta-amyloid plaques and hyperphosphorylated tau are unrelated processes in aged dogs with behavioral deficits. Acta Neuropathologica (Berlin) 2006; 112: 175-183.

Rofina JE, Singh K, Skoumalova-Vesela A, et al. Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine. Amyloid 2004; 11: 90-100.

Ruehl WW, Bruyette DS, DePaoli A, et al. 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. Progress in Brain Research 1995; 106: 217-225.

Russell MJ, Bobik M, White RG, et al. Age-specific onset of beta-amyloid in beagle brains. Neurobiology of Aging 1996; 17: 269-273.

Russell MJ, White R, Patel E, et al. Familial influence on plaque formation in the beagle brain. NeuroReport 1992; 3: 1093-1096.

Selkoe DJ. The genetics and molecular pathology of Alzheimer’s disease: Roles of amyloid and the presenilins. Neurologic Clinics 2000; 18: 903-922.

Siwak CT, Tapp PD, Head E, et al. Chronic antioxidant and mitochondrial cofactor administration improves discrimination learning in aged but not young dogs. Progress in Neuropsychopharmacology and Biological Psychiatry 2005; 29: 461-469.

Siwak CT, Tapp PD, Milgram NW. Effect of age and level of cognitive function on spontaneous and exploratory behaviors in the beagle dog. Learning and Memory 2001; 8: 317-325.

Siwak CT, Tapp PD, Zicker SC, et al. Locomotor activity rhythms in dogs vary with age and cognitive status. Behavioral Neuroscience 2003; 117: 813-824.

Su MY, Head E, Brooks WM, et al. Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging. Neurobiology of Aging 1998; 19: 479-485.

Su MY, Pop V, Vu L, et al. Enhanced MRI and the correlation of blood-brain-barrier permeability with beta-amyloid angiopathy assessed by immunohistochemical staining. Program No. 32. International Society for Magnetic Resonance in Medicine, Seattle, Washington, 2006.

Su MY, Tapp PD, Vu L, et al. A longitudinal study of brain morphometrics using serial magnetic resonance imaging analysis in a canine model of aging. Progress in Neuropsychopharmacology and Biological Psychiatry 2005; 29: 389-397.

Tapp PD, Siwak CT, Estrada J, et al. Effects of age on measures of complex working memory span in the beagle dog (Canis familiaris) using two versions of a spatial list learning paradigm. Learning and Memory 2003a; 10: 148-160.

Tapp PD, Siwak CT, Estrada J, et al. Size and reversal learning in the beagle dog as a measure of executive function and inhibitory control in aging. Learning and Memory 2003; 10: 64-73.

Tapp PD, Siwak CT, Gao FQ, et al. Frontal lobe volume, function, and beta-amyloid pathology in a canine model of aging. Journal of Neuroscience 2004; 24: 8205-8213.

Tapp PD, Siwak CT, Head E, et al. Concept abstraction in the aging dog: Development of a protocol using successive discrimination and size concept tasks. Behavioural Brain Research 2004a; 153: 199-210.

Vannucchi MG, Casamenti F, Pepeu G. Decrease of acetylcholine release from cortical slices in aged rats: Investigations into its reversal by phosphatidylserine. Journal of Neurochemistry 1990; 55: 819-825.

Zicker SC. Cognitive and behavioral assessment in dogs and pet food market applications. Progress in Neuropsychopharmacology and Biological Psychiatry 2005; 29: 455-459.



Box 35-1 Bibliography

Brellou G, Vlemmas I, Lekkas S, et al. Immunohistochemical investigation of amyloid beta-protein (Abeta) in the brain of aged cats. Histology and Histopathology 2005; 20: 725-731.

Cummings BJ, Satou T, Head E, et al. Diffuse plaques contain C-terminal A beta 42 and not A beta 40: Evidence from cats and dogs. Neurobiology of Aging 1996; 17: 653-659.

Head E, Moffat K, Das P, et al. Beta-amyloid deposition and tau phosphorylation in clinically characterized aged cats. Neurobiology of Aging 2005; 26: 749-763.

Hill’s Pet Nutrition, Inc., Omnibus Study on Aging Pets. U.S. Marketing Research Summary, 2000.

Landsberg G, Araujo JA. Behavior problems in geriatric pets. Veterinary Clinics of North America: Small Animal Practice 2005; 35: 675-698.

Landsberg G, Hunthausen W, Ackerman L. The effects of aging on behavior in senior pets. Handbook of Behavior Problems of the Dog and Cat. Edinburgh, Scotland: Elsevier Health Sciences, 2003.

Landsberg G. The most common behavior problems in older dogs. Veterinary Medicine 1995; 90: 16-24.

Moffat K, Landsberg G. An investigation into the prevalence of clinical signs of cognitive dysfunction syndrome (CDS) in cats. Journal of the American Animal Hospital Association 2003; 39: 512.

Nakamura S, Nakayama H, Kiatipattanasakul W, et al. Senile plaques in very aged cats. Acta Neuropathologica (Berlin) 1996; 91: 437-439.



Box 35-2 Bibliography

Araujo JA, Milgram NW. A novel cognitive palatability assessment protocol for dogs. Journal of Animal Science 2004; 82: 2200-2206.

Milgram NW, Head E, Weiner E, et al. Cognitive functions and aging in the dog: Acquisition of nonspatial visual tasks. Behavioral Neuroscience 1994; 108: 57-68.



Box 35-3 Bibliography

Adams B, Chan A, Callahan H, et al. Use of a delayed non-matching to position task to model age-dependent cognitive decline in the dog. Behavioural Brain Research 2000; 108: 47-56.

Cummings BJ, Head E, Afagh AJ, et al. Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine. Neurobiology of Learning and Memory 1996; 66: 11-23.

Cummings BJ, Head E, Ruehl W, et al. The canine as an animal model of human aging and dementia. Neurobiology of Aging 1996; 17: 259-268.

Head E, Callahan H, Muggenburg BA, et al. Visual-discrimination learning ability and beta-amyloid accumulation in the dog. Neurobiology of Aging 1998; 19: 415-425.

Head E, Mehta R, Hartley J, et al. Spatial learning and memory as a function of age in the dog. Behavioral Neuroscience 1995; 109: 851-858.

Milgram NW, Head E, Weiner E, et al. Cognitive functions and aging in the dog: Acquisition of nonspatial visual tasks. Behavioral Neuroscience 1994; 108: 57-68.

Su MY, Head E, Brooks WM, et al. Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging. Neurobiology of Aging 1998; 19: 479-485.

Tapp PD, Siwak CT, Gao FQ, et al. Frontal lobe volume, function, and beta-amyloid pathology in a canine model of aging. Journal of Neuroscience 2004; 24: 8205-8213.