Transcranial photobiomodulation therapy improves cognitive test scores in dogs with presumptive canine cognitive dysfunction: A case series of five dogs.

Background: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer's disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT) or transcranial laser therapy has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of tPBMT on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (>9-year-old) dogs with moderate (16-33) to severe (>33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient's head, three times per week for one month and two times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30- and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD.

Oral administration of an integrative supplement (CogniCaps®) improves cognitive scores in aging dogs with canine cognitive dysfunction for at least two months: An open-label investigation in 10 dogs.

Background: Canine cognitive dysfunction (CCD), the dog analog of human Alzheimer's disease (AD), is a progressive neurodegenerative condition that presents many treatment challenges. There are few effective drugs with acceptable side effects for AD/CCD, which has prompted investigation into non-drug options, collectively termed nutraceuticals. Nutraceutical supplements are conceptually divided into conventional (Western) and non-conventional (Eastern) ingredients. Many of these individual supplements have shown in vitro and/or in vivo efficacy in ameliorating neuronal damage in rodent models, and some have demonstrated positive effects on cognition in rodent models and clinical trials in dogs and humans with cognitive impairment. Aim: The purpose of this open-label clinical trial was to investigate the effect of an oral integrative (combination of conventional nutraceuticals and Chinese herbals) supplement (CogniCaps®) on cognitive scores when administered to aging dogs with CCD over a 2-month period. Methods: Ten aging (>9-year-old) dogs with moderate (16-33) cognitive scores were recruited and administered oral CogniCaps® for two months. No additional drugs or nutraceuticals directed at improving cognitive function were allowed during the study period. Baseline cognitive scores were compared with those procured at 30 and 60 days. Cognitive scores for baseline, 30- and 60-days post-treatment were compared. Results: Cognitive scores improved at 30 days (38% reduction) and 60 days (41% reduction) post-treatment (p = 0.002). Scores did not differ between 30- and 60-day assessments (p = 0.7). Conclusion: The results of this small preliminary study suggest that the integrative supplement CogniCaps® might improve cognitive scores in dogs with CCD within the first 30 days of administration and that this improvement is sustained at 60-day follow up.

Felbamate as an oral add-on therapy in six dogs with presumptive idiopathic epilepsy and generalized seizures resistant to drug therapy.

Background: Idiopathic or genetic epilepsy commonly affects dogs; affected dogs are often refractory to anti-seizure drug therapy. Felbamate is an anti-seizure drug with established pharmacokinetic and safety data for dogs, but little published evidence of efficacy for managing generalized seizures in this species. Aim: The purpose of this retrospective case series was to evaluate the clinical efficacy and tolerability of oral felbamate in six presumptive epileptic dogs experiencing generalized seizures. Methods: Medical records from six dogs with presumptive idiopathic/genetic epilepsy manifesting as generalized seizure activity, for which oral felbamate was used as an add-on treatment, were reviewed. The number of seizures recorded for the 3-month period immediately before instituting felbamate was recorded for each dog. Short-term (3 months) and long-term (6 months or greater) seizure frequency post-felbamate therapy was recorded for each dog and compared with baseline. Results: Overall, dogs experienced a reduction (82%) in seizures after adding felbamate in the short term, with 5/6 dogs (83%) classified as responders (50% or greater reduction in seizures) and 3/6 dogs (50%) attaining seizure-free status. Mean and median long-term follow-up times were 13 and 11 months, respectively (range: 6 to 23 months). Four of the 6 dogs (67%) remained drug responders at final follow-up, with an average seizure reduction of 98%, 2 of which remained seizure-free at 8 and 21 months. Two dogs (33%) experienced increased seizure activity during long-term follow-up (12 and 23 months) and were considered non-responders. The non-responder dogs had an average long-term seizure reduction of 33%. No dog experienced any obvious adverse effects associated with felbamate administration. However, one dog not included in the analysis because of insufficient (<3 month) post-felbamate follow-up, was weaned off felbamate because of suspected hepatotoxicity. Conclusion: Our small case series suggests that oral felbamate might show promise as an add-on drug for epileptic dogs experiencing generalized seizures resistant to drug therapy. These results warrant a more controlled, prospective investigation into felbamate as a therapeutic agent for canine epilepsy.

Transcranial photobiomodulation (laser) therapy for cognitive impairment: A review of molecular mechanisms and potential application to canine cognitive dysfunction (CCD).

Alzheimer's disease (AD) is a common degenerative brain disorder of aging people which shares many clinical and pathological features with canine cognitive dysfunction (CCD). CCD is considered a naturally occurring model of human AD. Transcranial photobiomodulation therapy (tPBMT), also known as transcranial laser therapy, entails delivering photons of near infrared to infrared light from the skin surface of the scalp to the underlying brain. Specific molecular cellular receptors, called chromophores, absorb this energy, and use it to initiate biological reactions with potential therapeutic benefit. Improvement in cognitive ability using tPBMT has been documented in rodent AD models and human clinical trials. The purposes of this review are to provide an overview of the suspected molecular mechanisms of action of tPBMT for the treatment of cognitive decline and to propose potential application of this treatment modality for dogs affected by CCD.

The scientific basis of acupuncture for veterinary pain management: A review based on relevant literature from the last two decades.

The practice of acupuncture is becoming increasingly popular in veterinary medicine, especially as a method of providing pain relief. Originally based on principles derived from centuries of observation, conventional scientific mechanisms of action for acupuncture as a pain-relieving modality have recently been elucidated. Acupuncture points allow access to multiple regions of the body via the peripheral nervous system and its connection with the central nervous system. Local, segmental (spinal), and suprasegmental (brain) effects of acupuncture involve enhanced release of pain-relieving endogenous substances (e.g., opioids) and mitigated release of pain-inducing substances (e.g., inflammatory cytokines). In addition, there is evidence that acupuncture can induce positive neurochemical and cytoarchitectural change in the central nervous system via the phenomenon of neuroplasticity. Electroacupuncture is considered the most effective type of acupuncture delivery, allowing for more potent and long-lasting pain relief than is achieved via other methods (e.g., dry needling). The purpose of this review article is to summarize the relevant scientific literature from the last two decades relating to the physiological mechanisms of action of acupuncture as a pain-relieving modality.

Periodontal disease is associated with cognitive dysfunction in aging dogs: A blinded prospective comparison of visual periodontal and cognitive questionnaire scores.

Background: Periodontal disease has been linked to the development of Alzheimer's disease in people. It is theorized that the chronic inflammatory condition characteristic of oral dysbiosis in patients with periodontal disease leads to disruption of the blood-brain barrier, cytotoxin- and pathogen-induced brain damage, and accumulation of neurotoxic ß-amyloid. In this inflammatory theory of Alzheimer's disease, ß-amyloid-a known antimicrobial protein-accumulates in response to oral pathogens. Canine cognitive dysfunction (CCD) is considered a naturally occurring animal model of human Alzheimer's disease. Like humans, periodontal disease is quite common in dogs; however, a link between periodontal disease and cognitive dysfunction has not been identified in this species. Aim: The purpose of this prospective investigation was to compare visual periodontal scores (from digital oral photographs) with numerical (0-54) cognitive assessment questionnaire forms in aging dogs with and without a clinical diagnosis of CCD. Methods: A visual analogue scale (0-4) was used to score the severity of periodontal disease in 21 aging dogs: 11 dogs with a clinical diagnosis of presumptive CCD and 10 dogs without a clinical history of cognitive decline. Individuals scoring the dental photographs were blinded to all case information, including cognitive assessment scores. Cognitive assessment scores were compared with periodontal disease scores for all dogs. Results: There was a significant (p < 0.05) association between periodontal and cognitive scores, with higher cognitive impairment scores being more likely in dogs with more severe periodontal disease and vice versa. No associations were identified between age and either periodontal disease or cognitive impairment. Conclusion: Although a cause-and-effect relationship between periodontal disease and cognitive impairment cannot be ascertained from this preliminary study, we established a link between these two disorders that warrants further investigation using more stringent criteria for evaluating both periodontal disease and cognitive dysfunction.

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs.

Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of N-methyl-D-aspartic (NMDA) receptors. Rodent models have shown the efficacy of ketamine (KET) in treating RSE, and its use has been reported in one canine case of RSE. Boluses of KET 5 mg/kg IV have become the preferred treatment for RSE in our hospital. A retrospective study was performed to evaluate and report our experience with KET IV bolus to treat prolonged and/or repeated seizure activity in cases of canine CS, SE, and RSE. A total of 15 dogs were retrieved, for 20 hospitalizations and 28 KET IV injections over 3 years. KET IV boluses were used 12 times for RSE (9 generalized seizures, 3 focal seizures) and KET terminated the episode of RSE 12/12 times (100%); however, seizures recurred 4/12 times (33%) within ≤6 h of KET IV bolus. When used for CS apart from episodes of RSE, KET IV bolus was associated with termination of the CS episode only 4/14 times (29%). Only 4/28 (14%) KET IV boluses were associated with adverse effects imputable only to the use of KET. One dog experienced a short, self-limited seizure activity during administration of KET IV, which was most likely related to a pre-mature use of KET IV (i.e., before GABAergic resistance and NMDA receptor overexpression had taken place). This study indicates that KET 5 mg/kg IV bolus may be successful for the treatment of RSE in dogs.

Canine cognitive dysfunction patients have reduced total hippocampal volume compared with aging control dogs: A comparative magnetic resonance imaging study.

Background: Hippocampal atrophy is a key pathologic and magnetic resonance imaging (MRI) feature of human Alzheimer's disease (AD). Hippocampal atrophy has not been documented via MRI in canine cognitive dysfunction (CCD), which is considered as the dog model of human AD. Aim: The purpose of this retrospective comparative volumetric MRI study was to compare total hippocampal volumes between successfully aging (control) dogs and dogs diagnosed with CCD. Methods: Mimics® software was used to derive total hippocampal volumes and total brain volumes from the MRI studies of 42 aging dogs (≥ 9 years): 16 dogs diagnosed with CCD and 26 successfully aging controls. Hippocampal volumes were normalized to total brain volume and these values were compared between groups using Mann-Whitney U tests. Results: Total hippocampal volume normalized to total brain volume was significantly less for CCD patients compared with control dogs (p = 0.04). Conclusion: The results of this study suggest that - similar to human AD - hippocampal atrophy is a pathological feature of CCD. This finding has potential importance for both investigating disease mechanisms related to dementia as well as future hippocampal-targeted therapies.

Canine Cognitive Dysfunction: Pathophysiology, Diagnosis, and Treatment.

Canine cognitive dysfunction (CCD) is the canine analog of human Alzheimer disease (AD). The pathophysiology of CCD/AD is multifaceted. CCD is common in aged (>8 years) dogs, affecting between 14% and 35% of the pet dog population. Apparent confusion, anxiety, disturbance of the sleep/wake cycle, and decreased interaction with owners are all common clinical signs of CCD. Although there is no cure for CCD, several proven effective therapeutic approaches are available for improving cognitive ability and maintaining a good quality of life; instituting such therapies early in the disease course is likely to have the greatest positive clinical effect.