Successful brain aging in dogs - DVM
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Successful brain aging in dogs
Contributions, causes of age-related cognitive changes in dogs.


DVM360 MAGAZINE


Shifts in oxygen and energy availability for the brain

Glucose is considered the common brain energy currency, but it is not stored. The stored form of glucose is glycogen. Glycogen is found mainly in astrocytes, and the amount of glycogen available is affected by glucose concentration and by neurotransmitter presence and function. During hypoglycemia, glycogen is converted to lactate via pyruvate (glucose > pyruvate > lactate). The lactate is then transferred to adjacent neurons. This conversion and transfer allow the neurons to use a source of aerobic fuel.

The use of lactate in hypoglycemic events can extend axon functions for 20 or more minutes — a long time for a neuron. Astrocytic glycogen is also converted to lactate during periods of intense neural activity, demonstrating the role of astrocytes as bankers of energy-conversion compounds. Most lactate used as an energy source is thought to come from glycogenic processes because lactate, itself, is too large a molecule to pass through the blood-brain barrier.

Ketone bodies and fatty acids have also been proposed as alternate energy sources because of their modulating effects on hypoglycemia. Beta-hydroxybutyrate (beta-OHB), in particular, may be useful for protecting hippocampal neurons from toxicity. In a placebo-controlled, double-blind study in people, mildly impaired patients with Alzheimer's disease who were supplemented with medium-chain triglycerides (MCTs) showed improvement in a number of cognitive test measures, and such improvement correlated with beta-OHB increases.1 Note that this result depended on the apolipoprotein E (APOE) genotype since only patients without an APOE-epsilon4 allele responded to acute elevation of beta-OHB.

The role for adequate provisioning of brain energy is not separate from that of protecting against beta-amyloid lesions. In a study of eight 9- to 11-year-old beagles (four control, four treatment), supplementation with MCT at a dosage of 2 g/kg/day resulted in improved mitochondrial function, which was most pronounced in the parietal lobe.2 Steady-state levels of amyloid precursor protein (APP) also decreased in the parietal lobe after short-term supplementation, leading to the conclusion that short-term MCT supplementation can improve brain energy metabolism and also decrease APP levels in old dogs.

Polyunsaturated fatty acids (PUFAs) may also play an interactive role in neuronal integrity and energy available to the brain. The long-chain PUFAs commonly shown to be involved in neuronal integrity and development of the nervous system include arachidonic acid (ARA), docosahexaenoic acid (DHA) and eicosahexanoic acid (EHA). All of these PUFAs are essential for early brain development. ARA is thought to maintain hippocampal cell membrane fluidity and protect cells in the hippocampus from oxidative stress.

DHA may encourage development stage-specific associational learning, although the data are mixed. Supplementation with DHA and EPA affects concentration of these substances in rat brains, but their distribution is not uniform. Diets deficient in alpha-linoleic acid especially cause decreases of DHA in the frontal cortex — the part of the brain responsible for complex learning and integration of information and executive function. In dogs, low DHA concentrations during gestation or lactation depress the retinal sensitivity of puppies, which can have profound and complex behavioral outcomes. The current data support the need for DHA for optimal neurologic development in puppies, and there are hints that it may improve both early and long-term cognitive abilities, but the data are scant.

Age-related cognitive decline in dogs may be associated with decreases in omega-3 PUFAs in the brain.3 Because MCTs increase fatty acid oxidation, they may increase omega-3 PUFAs in the brain via metabolism of adipose tissue. In a two-month study of eight beagles (four controls, four treatment) fed an MCT-enriched diet, enrichment was shown to result in increases in brain phospholipid and total lipid concentrations.

Conclusion

We and our dogs will age and die, but we do not have to go gently into that good night. Instead, by judicious and smart use of diet, medication and exercise as I will discuss in Part 2 of this article, we can extend quality of life for ourselves and for the dogs who love us.

Dr. Overall, faculty member at the University of Pennsylvania, has given hundreds of national and international presentations on behavioral medicine. She is a diplomate of the American College of Veterinary Behavior (ACVB) and is board certified by the Animal Behavior Society (ABS) as an Applied Animal Behaviorist.

References

1. Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 2004;25(3):311-314.

2. Studzinski CM, MacKay WA, Beckett TL, et al. Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-beta precursor protein (APP) levels in the aged dog. Brain Res 2008;1226:209-217.

3. Taha AY, Henderson ST, Burnham WM. Dietary enrichment with medium chain triglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs: implications for treating age-related cognitive decline. Neurochem Res 2009;34(9):1619-1625.


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