Many morphological features which occur in brains of old dogs are similar to those observed in the brains of aged humans [34]. These changes, which are related to age, include cortical atrophy and increased ventricular spaces, morphological changes in meninges and choroid plexus, changes in cerebral and meningeal vasculature; it is also evident degraded protein accumulation and DNA damage [43 - 44.16]. Other lesions in dogs include inflammation of meninges, gliosis, amyloid deposits, degeneration of myelin in white matter and accumulation of oxidative stress products which have a close relationship with apoptotic processes. Apop‐ totic cell death has been described in brains from AD patients and in geriatric dogs affected with CDS. Neuronal death by apoptosis processes is related to amyloid accumulation, and according to various authors, may be the main responsible factor for age-related dementia [1]. These morphological changes are related to the characteristic signs of dementia in dogs [2,37, 41,42,45], therefore these has received much attention from researchers who have considered dog as a model for studying human neurodegenerative diseases [29].

In contrast, brains of patients with AD show neurofibrillary plaques and intra-neuronal formation of tau protein products. Tau protein normally is a essential constituent of cytoskeleton in neurons [46], however, in people with AD, protein is hyper-phosphorylat‐ ed, then it starts a process which induces formation of paired helical filaments which saturate the cytoplasm and induce destruction of microtubules and neurodegeneracion [47-49]. Neurofibrillary plaques are rare in other species and their presence is a major difference between CDS and AD, especially because dogs not develop these structures, because tau's protein sequence is different in dogs and human beings, it could affect formation of neurofibrillary plaques. However, recent studies suggest presence of imma‐ ture nascent plaques in brains of aged dogs [2,5].

### **6. Pathological lesions**

stress and accumulation of beta-amilode peptide (βA) as possible causal factors of clinical

βA peptide, which plays an important role in pathophysiology of canine dementia [2,8,25-26] and AD [2], generates its neurotoxic effects by intra-neuronal accumulation [6], hence, it induces degeneration of cholinergic neurons and it seems that quantity of accumulated βA is associated with severity of clinical signs [1,10, 23,25,27, 28]. Reactive oxygen species (ROS), which are recognized as inductors of oxidative stress, has been involved in presentation of CDS and other demential syndromes as AD. Oxidative stress induces its deleterious effects on neuronal cells and their effects are similar in dogs and older adults [2]. Mitochondria is the first organelle involved in production of ROS due to its aerobic metabolism [29], nevertheless, other sources could be also considerating as metabolic sources of ROS generation, such as peroxisomes and release of oxidants by neutrophils. Similarly, exogenous influence such as ionizing radiation, pollution and carcinogens, can contribute to production of free radicals in

According to some authors, oxidative damage is a key mechanism for development of diseases associated with age that cause cognitive dysfunction [31]. Brain is highly predisposing to suffer lesions induced by oxidative stress because it is common accumulation of oxidants substances and because it is probably that protective mechanisms, such as superoxide dismutase and vitamin E, can be less efficient to prevent alterations induced by oxidative stress [32], and thus FR could potentially damage neuronal function causing cell death [2]. Neuronal death leads to uncontrolled release of excitatory neurotransmitters such as acetylcholine, involved in practically all cognitive functions especially in the memory, dopamine, which is associated with control of movement (motor); norepinephrine, associated with wakefulness, attention and serotonin, which is related to mood and sleep control [23,24,33,34]. In this sense, it is possible suggest that neurochemical changes which occurring in brain of aged patients, are

Many morphological features which occur in brains of old dogs are similar to those observed in the brains of aged humans [34]. These changes, which are related to age, include cortical atrophy and increased ventricular spaces, morphological changes in meninges and choroid plexus, changes in cerebral and meningeal vasculature; it is also evident degraded protein accumulation and DNA damage [43 - 44.16]. Other lesions in dogs include inflammation of meninges, gliosis, amyloid deposits, degeneration of myelin in white matter and accumulation of oxidative stress products which have a close relationship with apoptotic processes. Apop‐ totic cell death has been described in brains from AD patients and in geriatric dogs affected with CDS. Neuronal death by apoptosis processes is related to amyloid accumulation, and according to various authors, may be the main responsible factor for age-related dementia [1]. These morphological changes are related to the characteristic signs of dementia in dogs [2,37, 41,42,45], therefore these has received much attention from researchers who have considered

the responsible of severity and clinical manifestation in patients with CDS.

dog as a model for studying human neurodegenerative diseases [29].

signs observed in CDS [2].

618 Neurodegenerative Diseases

mammalian systems [30].

**5. Pathological lesions**

Many morphological features which occur in brains of old dogs are similar to those observed in the brains of aged humans [25]. These changes, which are related to age, include cortical atrophy and increased ventricular spaces, morphological changes in meninges and choroid plexus, changes in cerebral and meningeal vasculature, it is also evident degraded protein accumulation and DNA damage [35, 36, 37]. Other lesions in dogs include inflammation of meninges, gliosis, amyloid deposits, degeneration of myelin in white matter and accumulation of oxidative stress products which have a close relationship with apoptotic processes. Apop‐ totic cell death has been described in brains from AD patients and in geriatric dogs affected with CDS. Neuronal death by apoptosis processes is related to amyloid accumulation, and according to various authors, may be the main responsible factor for age-related dementia [38]. These morphological changes are related to the characteristic signs of dementia in dogs [10,39,40,41,42], therefore these has received much attention from researchers who have considered dog as a model for studying human neurodegenerative diseases [2].

In contrast, brains of patients with AD show neurofibrillary plaques and intraneuronal formation of tau protein products. Tau protein normally is a essential constituent of cytoskeleton in neurons [43], however, in people with AD, protein is hyperphosphorylat‐ ed, then it starts a process which induces formation of paired helical filaments which saturate the cytoplasm and induce destruction of microtubules and neurdegeneracion [44, 45]. Neurofibrillary plaques are rare in other species and their presence is a major differ‐ ence between CDS and AD, especially because dogs not develop these structures, be‐ cause tau's protein sequence is different in dogs and human beings, it could affect formation of neurofibrillary plaques. However, recent studies suggest presence of immature nascent plaques in brains of aged dogs [10, 23].

Neurochemical changes such as low levels of dopamine, norepinephrine, serotonin, acetylcholine, choline acetyl-transferase and decreased number of D2 receptors, are characteristics that are commonly observed in CDS and AD [34]. However, there are disease-specific changes as decrease of muscarinic receptor number [46] and increase of activity of enzyme acetylcholinesterase, which are factors present only in AD [47]. In contrast, in affected dogs have been detected increased MAO activity and increased sensitivity to glutamate neurotransmitter, which is capable of initiating processes neurotox‐ icity [23]. However, the most consistent alteration in brains of dogs and humans with AD is βA peptide accumulation in hippocampus and frontal cortex (areas especially related cognitive behavioral changes) [10, 48]. In neuron, βA is initially concentrated in microdo‐ mains of plasma membrane in neurons of the prefrontal cortex and subsequently affects other brain regions such as the parietal and entorhinal cortices [49].

Although learning and memory are quite susceptible to decline with aging, it is necessary evaluating too the spatial memory (the ability to remember the location of food, for example) and the object recognition memory (the ability to recall objects seen with 10-120 seconds ahead) [10], because it is well accepted that these both two memory types are affected in neurodege‐ nerative processes, therefore several studies have developed scales that evaluate the spatial memory and the recognition abilities for indirect evaluation of dementia in dogs [52]. For example, it has been proposed a dementia evaluation index that discriminates between normal, pre-dementia and dementia states [17]. ARCAD scale (assessing cognitive and affective disorders associated with age), where dog's behavior is assessed indirectly through a ques‐ tionnaire applied to owner, in order to assess the deficit by a scale evaluation of 1 to 5 [53].

Cognitive Dysfunction Syndrome in Senior Dogs

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621

Although various tests have shown be able to diagnose the cognitive dysfunction syndrome, we must consider that the results obtained with each test, can vary according to the test, it is possible that cognitive skills, may have a different meaning on the outcome of the test [11.13]. Moreover, besides the possibility to compare results obtained in each test, it is necessary to correlate the results of behavior modifications in dogs examined with paraclinical test results, such as electroencephalography. This relationship could establish whether the test results are able to correlate disturbances in learning, memory and cognitive with disorders of brain circuits that are involved in CDS. It is possible that paraclinical tests can predict dysfunctional

Finally, it is worth mentioning that several cognitive domains that are affected during the CDS (language, memory, visuospatial skills) and observation of a sign, is not sufficient for begin‐ ning a treatment. However, the onset of cognitive impairment in some specific domain could be related into a worsening of other existing signs, therefore it is important following up clinical

In conclusion, to determine if a dog shows signs of cognitive dysfunction, the veterinarian must rely on information provided by the owner in the medical record, however, the design and implementation of a questionnaire, and possibly paraclinical tests, are necessary to detected signs of CDS during the early stages of development, especially if it comes from

Currently there are several therapeutic strategies that have been developed along different

One consequence of age-associated diseases in dogs is loss of memories acquired during professional or home training, therefore dog may lose its ability to perform simple tasks or to

animals that have previously had a high level of training [3].

studies in geriatric dogs affected by CDS.

**9. Behavioral type therapy**

**8. Therapeutic alternatives for the treatment of CDS**

brain diseases in dogs?

evaluations routinely [10].

### **7. Diagnosis**

Veterinarians commonly faced with behavioral disturbances in older dogs, however, although it is true that CDS may be the main responsible for these changes, it is also true that behavioral disturbances could be induced by other multifactorial causes [6,10,28]. Therefore, considering the variety and inspecificity of clinical signs associated with CDS, it is important to use clinical history for obtain patient-specific data, which ensures that owners had provided a complete list of all medical and behavioral signs observed in their pets. This information could provide a solid support in finding potential medical problems that may be responsible for the devel‐ opment or exacerbation of clinical signs [3], furthermore this information along with clinical and neurological examination, which can be developed using assessment tests cognitive, may let to veterinarian obtain an early diagnosis [23].

However, we must emphasize difficulty for obtaining accurate information, because in many cases information obtained from pet owners could be little objective, possibly leading to false diagnosis. Thus, shortage of reliable diagnostic tests to ensure presence or absence of disease, gives to early identification of clinical signs a crucial role in establishment of effective treat‐ ment, capable of improvement the quality of life of affected patients. In this sense, and according to some authors, the most effective way to detect the condition is through the routinely establishment of behavioral questionnaires in geriatric dogs [2.10]. These question‐ naires that ask to owners about your pet's behavior, which have been obtained from various researches [15.35], pretend classifying the behavior of affected patients. Within these cognitive evaluation questionnaires, neuropsychological tests are looking classify systematic cognitive impairment through methods such as modified apparatus of Wisconsin General Test (Uni‐ versity of Toronto), in which the dogs are rewarded for each correct answer they obtain. Overall, in this test the dogs have access to a removable tray containing three food wells built in, which can be covered to test visual learning and memory [50, 51].

These neurophysiological tests allow assessment objective and quantitative of deficits in learning and memory, without relying on questionnaires applied to owners. These evaluation tests look for three specific objectives: 1. Identification of non-subjective cognitive changes that are characteristic of aging in dogs, 2. Characterization of the neurobiological basis of decline in cognitive abilities due to aging, and 3. Preparation of potential interventions in order to eliminate or minimize the adverse effects on quality of life [2, 50, 51].

Although learning and memory are quite susceptible to decline with aging, it is necessary evaluating too the spatial memory (the ability to remember the location of food, for example) and the object recognition memory (the ability to recall objects seen with 10-120 seconds ahead) [10], because it is well accepted that these both two memory types are affected in neurodege‐ nerative processes, therefore several studies have developed scales that evaluate the spatial memory and the recognition abilities for indirect evaluation of dementia in dogs [52]. For example, it has been proposed a dementia evaluation index that discriminates between normal, pre-dementia and dementia states [17]. ARCAD scale (assessing cognitive and affective disorders associated with age), where dog's behavior is assessed indirectly through a ques‐ tionnaire applied to owner, in order to assess the deficit by a scale evaluation of 1 to 5 [53].

Although various tests have shown be able to diagnose the cognitive dysfunction syndrome, we must consider that the results obtained with each test, can vary according to the test, it is possible that cognitive skills, may have a different meaning on the outcome of the test [11.13]. Moreover, besides the possibility to compare results obtained in each test, it is necessary to correlate the results of behavior modifications in dogs examined with paraclinical test results, such as electroencephalography. This relationship could establish whether the test results are able to correlate disturbances in learning, memory and cognitive with disorders of brain circuits that are involved in CDS. It is possible that paraclinical tests can predict dysfunctional brain diseases in dogs?

Finally, it is worth mentioning that several cognitive domains that are affected during the CDS (language, memory, visuospatial skills) and observation of a sign, is not sufficient for begin‐ ning a treatment. However, the onset of cognitive impairment in some specific domain could be related into a worsening of other existing signs, therefore it is important following up clinical evaluations routinely [10].

In conclusion, to determine if a dog shows signs of cognitive dysfunction, the veterinarian must rely on information provided by the owner in the medical record, however, the design and implementation of a questionnaire, and possibly paraclinical tests, are necessary to detected signs of CDS during the early stages of development, especially if it comes from animals that have previously had a high level of training [3].

#### **8. Therapeutic alternatives for the treatment of CDS**

Currently there are several therapeutic strategies that have been developed along different studies in geriatric dogs affected by CDS.

### **9. Behavioral type therapy**

contrast, in affected dogs have been detected increased MAO activity and increased sensitivity to glutamate neurotransmitter, which is capable of initiating processes neurotox‐ icity [23]. However, the most consistent alteration in brains of dogs and humans with AD is βA peptide accumulation in hippocampus and frontal cortex (areas especially related cognitive behavioral changes) [10, 48]. In neuron, βA is initially concentrated in microdo‐ mains of plasma membrane in neurons of the prefrontal cortex and subsequently affects

Veterinarians commonly faced with behavioral disturbances in older dogs, however, although it is true that CDS may be the main responsible for these changes, it is also true that behavioral disturbances could be induced by other multifactorial causes [6,10,28]. Therefore, considering the variety and inspecificity of clinical signs associated with CDS, it is important to use clinical history for obtain patient-specific data, which ensures that owners had provided a complete list of all medical and behavioral signs observed in their pets. This information could provide a solid support in finding potential medical problems that may be responsible for the devel‐ opment or exacerbation of clinical signs [3], furthermore this information along with clinical and neurological examination, which can be developed using assessment tests cognitive, may

However, we must emphasize difficulty for obtaining accurate information, because in many cases information obtained from pet owners could be little objective, possibly leading to false diagnosis. Thus, shortage of reliable diagnostic tests to ensure presence or absence of disease, gives to early identification of clinical signs a crucial role in establishment of effective treat‐ ment, capable of improvement the quality of life of affected patients. In this sense, and according to some authors, the most effective way to detect the condition is through the routinely establishment of behavioral questionnaires in geriatric dogs [2.10]. These question‐ naires that ask to owners about your pet's behavior, which have been obtained from various researches [15.35], pretend classifying the behavior of affected patients. Within these cognitive evaluation questionnaires, neuropsychological tests are looking classify systematic cognitive impairment through methods such as modified apparatus of Wisconsin General Test (Uni‐ versity of Toronto), in which the dogs are rewarded for each correct answer they obtain. Overall, in this test the dogs have access to a removable tray containing three food wells built

These neurophysiological tests allow assessment objective and quantitative of deficits in learning and memory, without relying on questionnaires applied to owners. These evaluation tests look for three specific objectives: 1. Identification of non-subjective cognitive changes that are characteristic of aging in dogs, 2. Characterization of the neurobiological basis of decline in cognitive abilities due to aging, and 3. Preparation of potential interventions in order to

other brain regions such as the parietal and entorhinal cortices [49].

in, which can be covered to test visual learning and memory [50, 51].

eliminate or minimize the adverse effects on quality of life [2, 50, 51].

let to veterinarian obtain an early diagnosis [23].

**7. Diagnosis**

620 Neurodegenerative Diseases

One consequence of age-associated diseases in dogs is loss of memories acquired during professional or home training, therefore dog may lose its ability to perform simple tasks or to answer previously learned commands. Faced with this kind of behavioral changes, which may be observed in patients with CDS, the establishment of behavioral therapy, in the early stages of the disease, has been suggested as appropriate, when it is accompanied with additional therapeutic tools like drug treatment. Re-training dogs with cognitive dysfunction requires patience and it is necessary to use simple commands with a clear reward and it is important that re-training begins as soon as possible to prevent the development of unwanted behaviors in the dog [2.6].

and even humans, attributing this property to its antioxidant and anti-inflammatory capabil‐

Cognitive Dysfunction Syndrome in Senior Dogs

http://dx.doi.org/10.5772/54903

623

There are several compounds which have been described their antioxidant activity, among them we can mention the vitamins E and C, beta-carotene, selenium, L-carnitine and alpha lipoic acid, all them have shown to improve mitochondrial function and likely by some neuroprotective effect it is explains the improvement of memory. Similarly, some authors suggest that GingkoBiloba, besides possessing antioxidant effect, has a variety of properties such as anti-inflammatory, cerebral vasodilator, mitochondrial function enhancer and MAO enzyme inhibitor [3,13,60], therefore, it has been suggested that GingkoBiloba could reduce the severity of clinical symptoms observed in patients with CSD. Additionally, natural compounds of animal origin, such as propolis, which our research group studies its neuro‐ protective properties, currently are valued for their antioxidant and neuroprotective qualities [61], however, there are still no studies describing the positive effects of this compound on

Other group of compounds with ROS activity is composed of certain molecules classified as mitochondrial cofactors (acidolipoico, L-carnitine) which can potentiate the function of mitochondria, resulting in a lower production of ROS during aerobic respiration. Nutritional supplementation with these mitochondrial cofactors induces their cell acumulation where they restore mitochondrial efficiency and reduces oxidative damage to RNA [62]. It has also been suggested the use of mitochondrial cofactors along with antioxidants, in order to cause an

It is probably the best evidence of positive effect of dietary supplementation on cognitive impairment in dogs, was found after applying neuropsychological tests for a period exceeding two years. The study aimed to supplement diet of dogs with mitochondrial cofactors and antioxidants of broad spectrum to enhance antioxidant defenses and reduce ROS accumula‐ tion. Results indicated that these products slowed the age associated cognitive decline [3]. However, to develop a diet supplemented with antioxidants, it should be noted that the selection of components, the ranges of dosage and route of administration, vary considerably between species. Also, some antioxidants are absorbed more quickly than others, speciesspecific factors, metabolic differences due to inherent bioavailability: thus, different species may benefit from different types of antioxidants, but not all species may benefit from the same

Departamento de Ciencias para la Salud Animal, Facultad de Medicina Veterinaria y de

improvement in learning processes and memory, through a synergistic action [19].

ities [3,5,58].

CDS.

antioxidants [2].

**Author details**

Camilo Orozco Sanabria, Francisco Olea and Manuel Rojas

Zootecnia, Universidad Nacional de Colombia, Sede Bogota, Colombia

### **10. Pharmacological treatment alternatives**

Drug therapy is aimed, on the one hand, restoring neurotransmitter concentrations and, on other hand, preventing too rapid advancement of neurodegenerative process [54, 55]. Most treatments used for people affected with AD, have not yet been tested in dogs, nevertheless it is necessary perform clinical studies which be able to clarify which treatments work and which do not. However, there are some options available as selegiline, this was the first therapeutic agent approved by the FDA in 1998 for use in dogs [5.56], this is a selective irreversible inhibitor of the enzyme monoamine oxidase B (MAO B) which increases the concentration of dopamine in brain and it seems to prevent oxidative stress, therefore it could decrease neuronal death. The therapeutical efficacy of selegiline has been shown by studies that verify a decrease in the progression of degenerative changes in AD patients and a significant improvement in dogs with CDS [1]. Therefore, regulating the concentration of neurotransmitters has been consid‐ ered the main therapeutic alternative for treatment of CDS in dogs, nevertheless, it is possible that new studies could verify a major efficiency of other drugs, for example drugs with anticholinenterase activity or NMDA blockers drugs, which have been effective for treatment of AD, could be could be effective for dogs.

### **11. Nutritional therapies**

After recognizing the role of ROS (reactive oxygen species) in neurodegenerative diseases, some researchers have recommended reduce the amount of free radicals formed from exogenous influences or include in habitual diet nutritional supplements capable to scavenge ROS, nowadays it is well accepted which these supplements can maximize the benefits of psychopharmacological therapy, improving quality of life promoting positive changes in behavior of canines that suffering CDS [5, 57].

Within the beneficial effects attributed to the antioxidant products, could be considered potentiating of mitochondrial function during aging, which resulting in decreased production of ROS [2-3,8,58]. As a result of these effects, some authors have suggested that dogs suffering CDS, and have received a supplement of antioxidants in diet, show an improvement in cognitive ability [59]. Besides, a variety of studies have shown that intake of fruits and vegetables may decrease the risk of cognitive declines associated with age in rodents, dogs, and even humans, attributing this property to its antioxidant and anti-inflammatory capabil‐ ities [3,5,58].

There are several compounds which have been described their antioxidant activity, among them we can mention the vitamins E and C, beta-carotene, selenium, L-carnitine and alpha lipoic acid, all them have shown to improve mitochondrial function and likely by some neuroprotective effect it is explains the improvement of memory. Similarly, some authors suggest that GingkoBiloba, besides possessing antioxidant effect, has a variety of properties such as anti-inflammatory, cerebral vasodilator, mitochondrial function enhancer and MAO enzyme inhibitor [3,13,60], therefore, it has been suggested that GingkoBiloba could reduce the severity of clinical symptoms observed in patients with CSD. Additionally, natural compounds of animal origin, such as propolis, which our research group studies its neuro‐ protective properties, currently are valued for their antioxidant and neuroprotective qualities [61], however, there are still no studies describing the positive effects of this compound on CDS.

Other group of compounds with ROS activity is composed of certain molecules classified as mitochondrial cofactors (acidolipoico, L-carnitine) which can potentiate the function of mitochondria, resulting in a lower production of ROS during aerobic respiration. Nutritional supplementation with these mitochondrial cofactors induces their cell acumulation where they restore mitochondrial efficiency and reduces oxidative damage to RNA [62]. It has also been suggested the use of mitochondrial cofactors along with antioxidants, in order to cause an improvement in learning processes and memory, through a synergistic action [19].

It is probably the best evidence of positive effect of dietary supplementation on cognitive impairment in dogs, was found after applying neuropsychological tests for a period exceeding two years. The study aimed to supplement diet of dogs with mitochondrial cofactors and antioxidants of broad spectrum to enhance antioxidant defenses and reduce ROS accumula‐ tion. Results indicated that these products slowed the age associated cognitive decline [3]. However, to develop a diet supplemented with antioxidants, it should be noted that the selection of components, the ranges of dosage and route of administration, vary considerably between species. Also, some antioxidants are absorbed more quickly than others, speciesspecific factors, metabolic differences due to inherent bioavailability: thus, different species may benefit from different types of antioxidants, but not all species may benefit from the same antioxidants [2].

### **Author details**

answer previously learned commands. Faced with this kind of behavioral changes, which may be observed in patients with CDS, the establishment of behavioral therapy, in the early stages of the disease, has been suggested as appropriate, when it is accompanied with additional therapeutic tools like drug treatment. Re-training dogs with cognitive dysfunction requires patience and it is necessary to use simple commands with a clear reward and it is important that re-training begins as soon as possible to prevent the development of unwanted behaviors

Drug therapy is aimed, on the one hand, restoring neurotransmitter concentrations and, on other hand, preventing too rapid advancement of neurodegenerative process [54, 55]. Most treatments used for people affected with AD, have not yet been tested in dogs, nevertheless it is necessary perform clinical studies which be able to clarify which treatments work and which do not. However, there are some options available as selegiline, this was the first therapeutic agent approved by the FDA in 1998 for use in dogs [5.56], this is a selective irreversible inhibitor of the enzyme monoamine oxidase B (MAO B) which increases the concentration of dopamine in brain and it seems to prevent oxidative stress, therefore it could decrease neuronal death. The therapeutical efficacy of selegiline has been shown by studies that verify a decrease in the progression of degenerative changes in AD patients and a significant improvement in dogs with CDS [1]. Therefore, regulating the concentration of neurotransmitters has been consid‐ ered the main therapeutic alternative for treatment of CDS in dogs, nevertheless, it is possible that new studies could verify a major efficiency of other drugs, for example drugs with anticholinenterase activity or NMDA blockers drugs, which have been effective for treatment

After recognizing the role of ROS (reactive oxygen species) in neurodegenerative diseases, some researchers have recommended reduce the amount of free radicals formed from exogenous influences or include in habitual diet nutritional supplements capable to scavenge ROS, nowadays it is well accepted which these supplements can maximize the benefits of psychopharmacological therapy, improving quality of life promoting positive changes in

Within the beneficial effects attributed to the antioxidant products, could be considered potentiating of mitochondrial function during aging, which resulting in decreased production of ROS [2-3,8,58]. As a result of these effects, some authors have suggested that dogs suffering CDS, and have received a supplement of antioxidants in diet, show an improvement in cognitive ability [59]. Besides, a variety of studies have shown that intake of fruits and vegetables may decrease the risk of cognitive declines associated with age in rodents, dogs,

in the dog [2.6].

622 Neurodegenerative Diseases

**10. Pharmacological treatment alternatives**

of AD, could be could be effective for dogs.

behavior of canines that suffering CDS [5, 57].

**11. Nutritional therapies**

Camilo Orozco Sanabria, Francisco Olea and Manuel Rojas

Departamento de Ciencias para la Salud Animal, Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia, Sede Bogota, Colombia

#### **References**

[1] Neilson J, Hart B, Cliff K, Ruehl W. Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. JAVMA 2001; 218(11):1787-1791.

[14] Frank D. Cognitive dysfunction in dog. In: Hill's European Symposia on Canine Brain Ageing (en línea) 2002. (fecha de acceso 27 de mayo de 2009). URL disponible

Cognitive Dysfunction Syndrome in Senior Dogs

http://dx.doi.org/10.5772/54903

625

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624 Neurodegenerative Diseases

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### *Edited by Uday Kishore*

This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.

Photo by Ralwel / iStock

Neurodegenerative Diseases

Neurodegenerative Diseases