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Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs: PAPER
Abstract
The aim of this study was to describe the prevalence and severity of behavioural changes associated with age and their relationship to risk factors such as sex, reproductive status, bodyweight and age.
A cross-sectional study design was chosen. A total of 325 geriatric dogs were included. Owners of dogs older than nine years were interviewed by a veterinary behaviourist. Structured phone interviews were used to gather information about four behavioural categories related to cognitive impairment: sleep/wake cycles, social interaction, learning and house training and signs of disorientation.
Signs of cognitive impairment showed a prevalence of 22.5 per cent in geriatric dogs. Sex and age emerged as significant predictor variables. Females and neutered dogs were significantly more affected than males and entire dogs, respectively. Prevalence and severity increased with age. Although weight was not a statistically significant predictor variable, smaller animals had greater odds of showing age-related cognitive impairment. The most impaired behavioural categories were social interaction and house training.
Age-related behavioural changes should be considered by practicing veterinarians because of their relative high prevalence among geriatric dogs, especially in females.
... Animals 2023, 13, 2203 2 of 15 dogs over 10 years of age [2] to 22.5% in dogs over 9 years of age [3] to as high as 74% in dogs over 7 years of age [4]. Age is a major risk factor for the increasing prevalence and severity of CCDS [2,3,5]. The authors observed that over a period of 24 months, 33% of dogs over eight years of age with normal cognitive function progressed to mild cognitive impairment (MCI), and 22% with MCI progressed to severe cognitive impairment [6]. ...
... (1) Demographic information about the dog-breed, weight, height, age, body condition score (BCS), and how recently it had been examined by a veterinarian; (2) Assessment of the dog's cognitive health-CCAS scale [25] comprising 17 items which assessed six domains of behaviour (disorientation, sleep-wake cycles, social interactions, learning and memory, activity level, and anxiety). The scale utilises a four-point Likert scale; never (0), once a month (1), once a week (2), almost every day (3), reporting behaviour over the previous six months. If a participant was unsure how to respond, they were asked to select 'Never' as opposed to leaving it blank as directed by the original CCAS; (3) An assessment of the subject's general health-37 questions regarding behaviours that reflect the pathology of different body systems, hereafter referred to as 'general health questions (GHQs),' and 12 questions regarding diagnoses made by a veterinarian in the preceding year, hereafter referred to as 'diagnoses questions' (see Supplementary Information). ...
... Further large-scale, prospective, longitudinal studies are required to investigate the impact of co-variables (such as neuter status, age at neutering, exposure to environmental factors, and physical activity) on the relationship between physical health and cognitive decline and establish the nature of their interaction. There is high variability in the prevalence of CCDS reported in the literature [2,3,5,[7][8][9], which may partly be due to differences in study designs and the scales used, but it is also possible that such differences could be indicative of other confounding factors such as undetected medical conditions (e.g., pain). Given the lack of specificity of behavioural change to underlying causes, it is possible that changes due to disease processes other than cognitive impairment, such as pain, could lead to higher scores on the CCAS. ...
Canine cognitive dysfunction syndrome (CCDS) is a progressive age-related neurodegenerative disorder in dogs. Minimal research has been performed to investigate how clinical signs may be impacted by other medical conditions. A cross-sectional study was performed using the Canine Cognitive Assessment Scale (CCAS) to evaluate cognitive impairment as reported by owners. Owner-reported health-related measures included behaviour changes, the body condition score, and veterinary diagnoses of disease. The responses from 804 dogs in the last 25% of their expected lifespan were analysed. Factors were identified in the owner-reported behavioural signs of disease representing pathologies in four body systems: musculoskeletal-neurological, digestive, metabolic, and dermatological, with the items comprising these factors also compiled into a cumulative measure of health. The results showed a strong correlation between the CCAS score and both the musculoskeletal-neurological factor and the overall cumulative measure of health. Moderate correlations between the CCAS score and the digestive factor and metabolic factor were also observed. The correlation between the dermatological factor and the CCAS score was weak. This study highlights the need to screen dogs for concurrent diseases when using scales to assess cognitive impairment and to monitor dogs who have health conditions, particularly those that are painful, for the onset of cognitive impairment.
... Na pesquisa, as características mais afetadas foram: a alteração do ritmo dia/noite (87%), desorientação (32%), perda de memória (10%) e o comportamento errático/sem rumo (42%), o que condiz com relatos de autores, pois os cães com disfunção cognitiva demonstram comportamentos compulsivos, mudanças no padrão do sono e deixam de se relacionar com tutores ou membros da família. Geralmente são essas categorias as mais compatíveis com os primeiros sinais da disfunção cognitiva, e resultados similares são encontrados na literatura por outros pesquisadores (Azkona et al., 2009;González-Martínez et al., 2012), que em seus estudos os sinais mais descritos foram alteração no sono/vigília e interação socioambiental. Em relação ao ritmo dia/noite, 87% dos cães geriátricos de 12 a 19 anos tiveram alterações nesta categoria, sendo dados corroborativos com estudos anteriores, onde problemas no ciclo do sono são reclamações constantes dos proprietários (Fast et al., 2013). ...
... Estes dados corroboram a literatura existente, na qual a memória é significativamente afetada em cães com SDCC (Osella et al., 2007;Salvin et al., 2010). Isso acontece, devido ao acúmulo da proteína beta-amiloide sob a forma de placas senis, principalmente no hipocampo e córtex frontal (na região intraneuronal e regiões sinápticas) provocando a degeneração dos neurônios colinérgicos (Azkona et al., 2009;Ervin & Appleton, 2013). Nesta fase observam-se alterações na memória (Cotman et al., 2002). ...
... O aparecimento de lesões corticais generalizadas e localizadas (no córtex pré-frontal) levam ao desenvolvimento de sinais como mudanças de "personalidade", confusão e falha na interpretação correta da informação sensorial. Estas lesões podem suceder no aparecimento de manifestações como olhar para o vazio ou para objetos inanimados (Azkona et al., 2009). Com o avançar da idade, ocorre um aumento na prevalência dessas alterações, entre as quais, maior irritabilidade ou agressividade (Osella et al., 2007;Pineda et al., 2014). ...
Elderly dogs are prone to acquire numerous diseases over the years, with geriatrics as a field of medicine being important. It is visible the emotional bond that owners have with their dogs, consequently, generating a greater concern with the life expectancy of their animals. Cognitive changes are commonly seen in aging, with Canine Cognitive Dysfunction Syndrome being an example. Canine Cognitive Dysfunction Syndrome is a neurodegenerative disease and neurodegeneration starts over six years old (depending on the size of the dog), and may show specific clinical signs of cognitive decline. However, with the lack of knowledge, the owners are not aware that such a disease may affect their pet, thinking that any clinical sign associated with aging is normal. The definitive diagnosis is histopathological and the diagnosis of exclusion is made by means of imaging tests, CSF analysis, laboratory tests and the increment of questionnaires. Symptom control, on the other hand, is defined by using specific medications, environmental enrichment, among other aspects, all associated with an increase in the patient's longevity and delay in the evolution of the disease. Therefore, the objective of the present work is to identify signs of senile cognitive changes in dogs. A questionnaire was made available to owners of dogs over six years of age, with five symptoms highlighted in the literature to analyze the signs presented with those of the Canine Cognitive Dysfunction Syndrome. The animals were separated into two age groups, one from six to eleven years old and the other from twelve to nineteen years old, and then the Chi-Square test was used to reveal whether there is significance between the increase in signs with advancing age, using P
... CDS can manifest itself through behavioral changes, decreased learning ability and memory, decreased response to stimuli and confusion. The acronym DISHAA is frequently used to describe the main behavioral changes associated with CDS and it refers to disorientation, altered social interactions with people or other pets, altered sleep-wake cycles, house soiling and loss of other learned behaviors, altered activity levels and increasing anxiety [2][3][4][5][6][7][8]. According to several studies, the prevalence of CDS is high, ranging from 14.2% to 68% [3,5,9] and, both the prevalence [9] and severity of symptoms increase with age [3]. ...
... The acronym DISHAA is frequently used to describe the main behavioral changes associated with CDS and it refers to disorientation, altered social interactions with people or other pets, altered sleep-wake cycles, house soiling and loss of other learned behaviors, altered activity levels and increasing anxiety [2][3][4][5][6][7][8]. According to several studies, the prevalence of CDS is high, ranging from 14.2% to 68% [3,5,9] and, both the prevalence [9] and severity of symptoms increase with age [3]. ...
... For a method to be practical, it has to be easy and quick to perform [12]. In the last years, a variety of scales to diagnose, evaluate and determine the prevalence of CDS in dogs have been created [3][4][5]8,13,14]. The information of those tools is based on the dog's owners' responses. ...
Cognitive dysfunction syndrome is the most common cause of cognitive decline in aged dogs. Early diagnosis is crucial because the sooner treatment is implemented, the greater the chance of slowing the progression of the disease. Assessment tools to assess cognitive decline may differ depending on the environment in which the dogs live. The aims of this study were threefold, first, to describe two feasible methods to evaluate cognitive impairment in aged dogs living in different environments: (i) a Canine Cognitive Assessment Scale (CCAS) for dogs living in a home environment and (ii) a practical cognitive test (PCT) potentially useful for dogs not living in a home environment (NHE); second, to assess the effect of age on the outcome of both tools and, finally, to compare the results of the CCAS with those of the PCT. Both methods were found to be practical to perform. Age was found to significantly predict the score obtained by the CCAS (p = 0.0011) and the outcome of the PCT (p = 0.009). However, the reversal phase from the PCT did not significantly predict the outcomes of the CCAS (p = 0.97). Taken together, these findings suggest that the CCAS is a practical method to evaluate age related cognitive changes in owned dogs. The fact that the PCT has not been proven to be related with the CCAS calls into question the use of the PCT as a sensitive tool to assess cognitive impairment. Further studies in this field are suggested.
... Just like in humans, senior dogs can be classified into successful agers, mild cognitive impairment, and severe cognitive impairment called cognitive dysfunction syndrome (CDS) [9,10]. With increased longevity in dogs, higher incidence of CDS has been reported in senior dogs [11][12][13]. Clinical symptoms in dogs with CDS include disorientation, reduced social interaction, increased anxiety, disrupted sleep/wake cycle, change in activity, and loss of house training [13][14][15][16]. Since the aging-induced neurodegenerative process is gradual and irreversible, more efforts should be made to develop solutions that are able to slow down brain aging and brain atrophy [17,18] and an optimal nutritional solution should be able to both enhance cognitive function and reduce the irreversible brain atrophy. ...
... Another study reported that changes in social interaction (37.7%) and loss of house training (37.7%) were the most common signs, followed by disrupted sleep/wake cycle (20.2%) and disorientation (16.4%) in dogs with CDS [11]. CDS adversely affects the quality of life of both dogs and their owners. ...
... Gender appears to be a significant risk factor for AD in people and the incidence of AD in females is almost twice of that in male subjects [70]. Similarly, the incidence of CDS in female dogs was more than twice that in male dogs [11]. Menopause is associated with increased risk of AD in people [71,72]. ...
Due to a difference in genetics, environmental factors, and nutrition, just like in people, dogs age at different rates. Brain aging in people and dogs share similar morphological changes including irreversible cortical atrophy, cerebral amyloid angiopathy, and ventricular enlargement. Due to severe and irreversible brain atrophy, some aging dogs develop cognitive dysfunction syndrome (CDS), which is equivalent to dementia or Alzheimer’s disease (AD) in people. The risk factors and causes of CDS in dogs have not been fully investigated, but age, gender, oxidative stress, and deficiency of sex hormones appears to be associated with increased risk of accelerated brain aging and CDS in dogs. Both AD and CDS are incurable diseases at this moment, therefore more efforts should be focused on preventing or reducing brain atrophy and minimizing the risk of AD in people and CDS in dogs. Since brain atrophy leads to irreversible cognitive decline and dementia, an optimal nutritional solution should be able to not only enhance cognitive function during aging but also reduce irreversible brain atrophy. Up to now, only one nutritional intervention has demonstrated both cognition-enhancing benefits and atrophy-reducing benefits.
... Cognitive dysfunction syndrome (CDS) is a major condition affecting senior dogs (1,2) that has parallels to human dementia. Both CDS in dogs and Alzheimer's disease (AD) in humans share similar neuropathological changes including severe cortical atrophy, cerebral amyloid angiopathy and ventricular enlargement (3)(4)(5). ...
... Dogs with CDS present with clinical signs in a number of behavioral domains including disorientation, altered social interactions, sleep/wake disturbances, house soiling, anxiety and activity, which may be referred to by the acronym DISHAA (1,2,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Therefore, for this clinical study we used a questionnaire (35) that incorporated all 6 DISHAA categories (Supplementary Table 1), including questions from all previously validated questionnaires to have a complete and sensitive screening tool for identifying dogs that had levels ranging from mild to severe (27,(36)(37)(38)(39). ...
... This is in comparison to the control diet in which disorientation and social interactions did not improve significantly. As pet owners are particularly sensitive to changes in social interactions, it is perhaps not surprising that they are the most frequently reported signs in mild cognitive decline and amongst the most commonly reported signs (1,27). Additionally, signs of disorientation are indicative of more advanced stages of dementia and amongst the most common signs in severe CDS (1,27,28,36). ...
These proceedings contain oral and poster presentations from various experts on animal behaviour and animal welfare in veterinary medicine presented at the conference.
... There was no significant difference in mean age between groups (control group mean 11.63 years ± 2.36 and CS group mean 11.73 years ± 2.29; P = 0.27); in sex (both groups with 79% females and 21% males; P = 1.00), and in reproductive status (both groups with 89.5% neutered and 10.5% unneutered animals; P = 1.00). This matching procedure was important because dogs, just like most mammals, have aging-related neuropathologic disorders, which hinder cognitive function, making age a risk factor for diseases that coexist with cognitive and behavioral dysfunctions such as Alzheimer's disease (AD) in humans and its equivalent in dogs -CD ( Azkona et al., 2009 ;Landsberg et al., 2012 ). Apart from age, Azkona et al. (2009) reported that being female, similarly to what has been observed for AD in women, and neutering, are risk factors for the development of cognitive disorders, demonstrating in their study a higher incidence of cognitive dysfunction in bitches. ...
... This matching procedure was important because dogs, just like most mammals, have aging-related neuropathologic disorders, which hinder cognitive function, making age a risk factor for diseases that coexist with cognitive and behavioral dysfunctions such as Alzheimer's disease (AD) in humans and its equivalent in dogs -CD ( Azkona et al., 2009 ;Landsberg et al., 2012 ). Apart from age, Azkona et al. (2009) reported that being female, similarly to what has been observed for AD in women, and neutering, are risk factors for the development of cognitive disorders, demonstrating in their study a higher incidence of cognitive dysfunction in bitches. Interestingly, neutered dogs had a twice as high risk to develop CD compared to the unneutered ones. ...
... A higher score for cognitive impairment in dogs with hypercortisolism corroborates the finding in humans, since NOCS affects mainly spayed female ( Pöppl et al., 2016 ;Carotenuto et al., 2019 ). Hence, the population at risk for developing CS is similar to the population at greater risk for developing CD, as pointed out by Azkona et al. (2009) . ...
Hypercortisolism has been associated with impairment of cognitive function in humans with Cushing's syndrome (CS), but there are currently no studies looking into this effect in dogs with CS. The present study evaluated the pattern of cognitive deficits and behavioral changes in dogs with naturally-occurring CS (NOCS). A previously published questionnaire (DISHA - disorientation, changes in interactive behavior, sleep-wake cycle disturbances, house-soiling, and changes in activity) was used to assess cognitive dysfunction (CD) in dogs with recently diagnosed CS, and in age-, sex-, and gonadal status-matched dogs (1:2), according to their owners’ perception. The questionnaire consisted of 32 multiple-choice questions, scored 0 to 96. The higher the score, the higher the severity of CD. The questionnaire included eight categories of behavioral signs, namely: disorientation, social interactions, sleep-wake cycles, house-soiling, compulsive behaviors, depressive behaviors, anxiety, and memory and learning. Of the 57 dogs assessed in the study, 19 were included in the CS group and 38 in the control group. Exclusion criteria for the control group were animals suspected of having CS, chronic glucocorticoid therapy, or glucocorticoid exposure in the past month. Dogs with CS exhibited a higher final score (Wilcoxon test) of cognitive dysfunction (W = 149, p = 0.001), especially, higher memory dysfunction (W = 96, p = 0.01), compulsive behaviors (W = 93, p = 0.04), depressive behaviors (W = 86, p = 0.03), and anxiety (W = 117, p=0.001). There was no correlation between age and CD score in dogs with NOCS (r = 0.32, p = 0.465) and neither control dogs (r = 0.18, p = 0.051). Results suggest hypercortisolism may accelerate neurodegenerative process, thus resulting in more intense behavioral and cognitive changes than those observed in age-matched dogs without CS.
... (46). An interview study of owners of dogs aged older than 9 years classified dogs into three unlabeled age groups (9-11, 12-14, and 15-17 years) and found that each group showed a greater incidence of cognitive impairment than the previous (47). However, there were no dogs with "severe" cognitive impairments in the 9-11 age group compared with 3.3% aged 12-14 years classified as "severe" and 14.3% of the 15-17-yearold population. ...
... In accepting that dogs should be considered "Mature adults" when aged between 2 and 6 years, it is suggested here that dogs aged 7-11 years could be considered "Senior, " whereas dogs aged 12+ years be considered "Geriatric" based upon the greater incidence of cognitive impairments in dogs of that age (13,40,46,47) and the greater likelihood of death past the age of 12 years (3,48). For studies of senior dogs where finer detail is desired, the senior period between 7 and 11 years of age could be split into Early-senior (7-9 years) and Late-senior (10-11 years), as significant differences have been found between dogs in these age groups (7,43,46). ...
... In a group of Japanese dogs of various breeds, the physical signs of canine cognitive dysfunction, a behavioral syndrome affecting old dogs, increased steadily from the age of 10 years, whereas confirmed diagnoses of canine cognitive dysfunction increase sharply from 15 years of age (8). Severe cognitive impairments have also been found more commonly in dogs aged 15-17 years, with 47.6% of dogs in this age group showing some signs of cognitive impairment (47). ...
Behavioral development is a lifelong process where cognitive traits such as learning and memory may be expected to take quadratic or linear trajectories. It is common practice for operational purposes to reduce study subjects into chronological categories when conducting research. However, there are no agreed-upon thresholds for this practice, and the lack of standardization may hinder comparison between studies of normative and pathological aging. In this perspective review, chronological categories have been identified that can be considered to represent normative cognitive and neurological aging in domestic family dogs. These categories work to capture age-related developmental trajectories for the majority of dog breeds. It is encouraged that researchers studying cognition and behavior, pathological cognitive deficits, or welfare of dogs across age categories utilize the categories presented here to best enable comparison between studies. The proposed groups could also support education programs informing owners of what behavioral changes to expect in their dog as they age, but they cannot be used to reflect health-based needs associated with breed-specific morbidity. The use of the age categories proposed here highlights significant welfare issues for breeds with the shortest average lifespans (e.g., the Great Dane). Studies show no evidence of an increased rate of behavioral or cognitive aging in short-lived breeds, and the shortest-lived breeds are most likely to die when classified by the proposed categories as Mature Adults. Adoption of these chronological categories in future research would aid comparison between studies and identification of non-normative age-related pathologies.
... In addition, there is no definitive antemortem test for CCD, and a diagnosis is typically made through a combination of physical examination, behavioural observation, and exclusion of other conditions (Fefer et al., 2022). Consequently, the prevalence of CCD is unclear, although studies have estimated rates of around 25% of dogs aged between 8 and 12 years, increasing to 70% of dogs over 15 years (Azkona et al., 2009;Neilson et al., 2001;Salvin et al., 2010). Breed does not seem to be a risk factor for the disease (Salvin et al., 2010), however as smaller dogs tend to live longer than larger ones clinical signs of CCD are more often observed in smaller dogs (Schmidt et al., 2015). ...
... Canine Cognitive Dysfunction is characterised by behavioural signs such as changes in social interactions, disorientation in familiar environments, changes in sleep-wake cycles, deficits in learning, memory and toilet training, and changes in anxiety and activity levels (Madari et al., 2015). Affect is not always seen equally across these domains, with one area often being more impacted than another (Azkona et al., 2009;Fast et al., 2013). The exact physiology of CCD is still not fully understood, however signs consistent with the disease include an accumulation of amyloid-beta plaques in the brain (Schütt et al., 2015;Urfer et al., 2021), brain atrophy (Head, 2011), neurofibrillary tangles of the peptide tau (Mihevc and Majdic, 2019), oxidative stress (Rofina et al., 2006), and chronic inflammation (Ozawa et al., 2016). ...
... Em relação ao gênero e o status reprodutivo, possui uma maior prevalência em fêmeas e animais castrados, tanto machos como fêmeas, portanto, estudos sugerem que a influência hormonal do estrogênio ou da testosterona podem auxiliar na prevenção das disfunções cognitivas, pelo fato destes hormônios, por mecanismos ainda não elucidados, atuarem como protetores neurais, reduzindo o acúmulo de proteínas β-amiloide no tecido neuronal (Azkona et al., 2009). Segundo Azkona et al. (2009) não há uma predisposição relacionada a raça e porte de animais, no entanto, animais de porte grande e gigante podem apresentar maior predisposição devido a susceptibilidade ao envelhecimento precoce e alguns autores afirmam que cães da raça Beagle possuem maior susceptibilidade e prevalência para a síndrome. ...
... Em relação ao gênero e o status reprodutivo, possui uma maior prevalência em fêmeas e animais castrados, tanto machos como fêmeas, portanto, estudos sugerem que a influência hormonal do estrogênio ou da testosterona podem auxiliar na prevenção das disfunções cognitivas, pelo fato destes hormônios, por mecanismos ainda não elucidados, atuarem como protetores neurais, reduzindo o acúmulo de proteínas β-amiloide no tecido neuronal (Azkona et al., 2009). Segundo Azkona et al. (2009) não há uma predisposição relacionada a raça e porte de animais, no entanto, animais de porte grande e gigante podem apresentar maior predisposição devido a susceptibilidade ao envelhecimento precoce e alguns autores afirmam que cães da raça Beagle possuem maior susceptibilidade e prevalência para a síndrome. A SDDC se assemelha muito a fase inicial da DAH, caracterizada pela presença de uma grande quantidade de radicais livres, acúmulo de proteínas, perda de células neurais e da função cerebral. ...
Com os avanços da medicina veterinária, melhorias na nutrição e maior cuidado dos tutores com seus animais, a perspectiva de vida dos cães está aumentando significativamente. No entanto, esse aumento na longevidade vem acompanhado pelo surgimento mais frequente de doenças relacionadas ao envelhecimento, sendo uma delas a Síndrome da Disfunção Cognitiva Canina (SDDC). Essa síndrome afeta cães idosos não apenas fisicamente, mas também cognitivamente. Trata-se de uma doença neurodegenerativa que se desenvolve gradualmente e, inicialmente, pode passar despercebida, muitas vezes sendo confundida com os processos naturais de envelhecimento. Seu diagnóstico é desafiador e complexo, dependendo de vários fatores, principalmente, envolvendo a exclusão de outras suspeitas clínicas comuns em animais idosos, além de uma minuciosa anamnese conduzida pelo médico veterinário, levando também em consideração informações fornecidas pelos tutores. Questionários que abordam aspectos comportamentais e cognitivos do animal podem ser muito úteis para direcionar o diagnóstico. Uma vez confirmado o diagnóstico, é importante iniciar imediatamente as medidas de tratamento visando o conforto e o bem-estar do animal. Estratégias de enriquecimento ambiental desempenham um papel essencial, envolvendo a introdução de objetos que estimulem a cognição do cão. Além disso, ajustes na alimentação são recomendados, incluindo a adição de vitaminas C e E, bem como ácidos graxos, ômega-3 e ômega-6 na dieta. Alguns medicamentos, como o revimax, também podem ser administrados como parte do tratamento. O objetivo do tratamento é prolongar e promover qualidade de vida ao animal, buscando retardar a progressão da síndrome, embora ela não tenha uma cura definitiva até o momento. É interessante notar que essa síndrome possui semelhanças com a Doença de Alzheimer em Humanos (DAH), sendo assim, estudos e pesquisas sobre essa doença podem contribuir para o desenvolvimento de abordagens mais eficazes visando o tratamento da SDDC.
... 11 Generally, studies agree that around a quarter of dogs aged between 8 and 12 years and 70% of dogs over 15 years may have CCD. [12][13][14] Pet ownership is widely regarded as good for our physical and psycho-emotional health, motivating us to take better care of ourselves. 15 However, little is known about the experience of owners when the burden of caring for the dog becomes greater than the purported benefits of ownership. ...
... The overall prevalence of dogs with CCD in this study was 75%, comparable to that reported by Osella et al. 25 (73%) using a similar guardian self-report survey methodology. However, the current results are higher than those reported by researchers providing participants with an information sheet describing the possible behavioural and physical changes in ageing dogs, with 64% of the 8-12-year-old age group having some level of CCD in this study compared to the 25% reported by Azkona et al. 13 and 28% reported by Neilson et al. 12 In the 15 years or older age group, the difference was also stark, with 97% in this study compared to 70% in Neilson et al.'s paper. 12 These differences are likely due to differences in the measures used to score CCD and cohort effects. ...
Background:
Canine cognitive dysfunction (CCD) is a neurodegenerative disease that is difficult to diagnose, as its clinical signs are similar to those of other age-related conditions. The experience of caring for a senior dog with or without CCD is not well described.
Methods:
Data were collected via an online survey. Using a mixed methods design, the level of CCD and burden of care were measured using validated tools, and open-ended questions gathered qualitative data. A general linear model showed the factors associated with guardian burden of care.
Results:
Sixteen percent of guardians experienced a clinically significant burden of care. Factors associated with burden of care included severity of CCD, sleep location, guardian employment, household size, dog age, guardian age and the dog taking medication. Few dogs with CCD were prescribed CCD medications to ameliorate clinical signs. Euthanasia, strong attachment mitigating burden and the complexities of caregiving were themes presented by guardians.
Limitations:
Measures are based on self-reports and as such the usual limitations apply.
Conclusions:
The burden of caring for an older dog is greater if they have CCD. More attention to the treatment of senior dogs, including medications to reduce clinical signs of CCD, could improve the welfare of older dogs and decrease the clinical burden experienced by guardians.
... They become restless, depressed, withdrawn, and lose basic functioning abilities in their final years (severe stage 3 54,58 ). Cognitive aging has also been reported in diverse nonhuman animal species and includes memory loss, decreased attention span, reduced performance on spatial tasks, anxiety, locomotor disabilities, as well as changes in vocalizing 46,48,[59][60][61][62][63][64][65][66][67][68][69][70][71] . ...
... If behavioral and cognitive deficits sufficiently impact daily activities, companion animals can be diagnosed with cognitive dysfunction syndrome (CDS) 64 . Among client-owned pets, the prevalence of CDS may be as high as 22% in geriatric dogs 60,63 and 50% in geriatric cats 189,190 . These studies further report that CDS is likely underdiagnosed, so the prevalence of age- 100 120 140 Pongo pygmaeus Gorilla gorilla Pan paniscus Homo sapiens 80 Pan troglodytes 5 ...
Alzheimer’s disease (AD) is characterized by brain plaques, tangles, and cognitive impairment. AD is one of the most common age-related dementias in humans. Progress in characterizing AD and other age-related disorders is hindered by a perceived dearth of animal models that naturally reproduce diseases observed in humans. Mice and nonhuman primates are model systems used to understand human diseases. Still, these model systems lack many of the biological characteristics of Alzheimer-like diseases (e.g., plaques, tangles) as they grow older. In contrast, companion animal models (cats and dogs) age in ways that resemble humans. Both companion animal models and humans show evidence of brain atrophy, plaques, and tangles, as well as cognitive decline with age. We embrace a One Health perspective, which recognizes that the health of humans is connected to those of animals, and we illustrate how such a perspective can work synergistically to enhance human and animal health. A comparative biology perspective is ideally suited to integrate insights across veterinary and human medical disciplines and solve long-standing problems in aging.
... This suggests that long-term gonadal steroid deprival could eventually have detrimental effects on GnRH neuronal function and, because brain GnRH release plays a vital role in controlling mental and sensory abilities (Manfredi-Lozano et al., 2022), it may accelerate cognitive decline (Karlamangla et al., 2017;Santoro et al., 2021), as suggested by preclinical findings in mice (Anckaerts et al., 2019;Kara et al., 2021;Manfredi-Lozano et al., 2022), and may thus be a risk factor for dementia. In dogs, there is some evidence suggesting that gonadectomy increases the risk of cognitive dysfunction in both sexes (Azkona et al., 2009), and increases the speed of progression from mild to more severe cognitive impairment in male dogs (Hart, 2001). From the preclinical and clinical data obtained in mice and in men (Manfredi-Lozano et al., 2022), respectively, it could be expected that the implantation of a programmable minipump releasing one pulse every 2-3 h to mimic the GnRH/LH secretory pattern during the luteal phase in bitches (Concannon, 2012;Kooistra et al., 1999), or in males (Enright et al., 2010), protects cognitive functions in these pets by stimulating neocortical GnRHR expressing neurons at a physiological pace and hence compensate the potential exhaustion of GnRH neuronal function induced by longterm gonadectomy . ...
... Patients with Alzheimer's disease also show olfactory deficits, as in the case of other neurodegenerative diseases (Doty, 2012). In resonance with the previous section, gonadectomized dogs appear to be more likely to show signs of CDD than intact dogs (Azkona et al., 2009;Hart, 2001). This, together with the fact that the human literature suggests that men receiving androgen deprivation therapy, that is GnRH agonists, for prostate cancer, may be prone to accelerated cognitive decline and have a higher risk of developing dementia and Alzheimer's disease than controls (Cherrier & Higano, 2020;Sharifi et al., 2005), it could be hypothesized that altered brain GnRH signalling may play, at least in part, a role in this process. ...
Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for the activation and maintenance of the function of the hypothalamic-pituitary-gonadal (HPG) axis, which controls the onset of puberty and fertility. Two provocative recent studies suggest that, in addition to control reproduction, the neurons in the brain that produce GnRH are also involved in the control postnatal brain maturation, odor discrimination and adult cognition. Long-acting GnRH antagonists and agonists are commonly used to control fertility and behavior in veterinary medicine, primarily in males. This review puts into perspective the potential risks of these androgen deprivation therapies and immunization on olfactory and cognitive performances and well-aging in domestic animals, including pets. We will also discuss the results reporting beneficial effects of pharmacological interventions restoring physiological GnRH levels on olfactory and cognitive alterations in preclinical models of Alzheimer's disease, which shares many pathophysiological and behavioral hallmarks with canine cognitive dysfunction. These novel findings raise the intriguing possibility that pulsatile GnRH therapy holds therapeutic potential for the management of this behavioral syndrome affecting older dogs.
... Clinical signs of this decline appear to be related to learning and memory deficits, loss of spatial awareness, altered social interactions, and disrupted sleeping patterns [4][5][6] . Further, the presentation of human AD and CCD share certain neuropathological features such as amyloid-β plaque deposition 2,[7][8][9][10] . ...
... A wide range of structured interviews and theory-driven scales for evaluating CCD have been developed within the last 20 years 4,[12][13][14] . Studies of these scales have shown a correspondingly wide range of prevalence estimates that nonetheless appear to indicate an increased prevalence of cognitive impairment as a dog ages 7,14,15 . In order to gain a better understanding of CCD in aging dogs, researchers recently have developed assessment tools that are able to distinguish cognitively impaired aged dogs from those who are experiencing healthy aging 11,14 . ...
Canine cognitive dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP) (n = 15,019). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and receiver operating curve (ROC) analysis. When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.
... Clinical signs of this decline appear to be related to learning and memory deficits, loss of spatial awareness, altered social interactions, and disrupted sleeping patterns 4,5,6 . Further, the presentation of human AD and CCD share certain neuropathological features such as amyloid-β plaque deposition 2,7,8,9,10 . ...
... A wide range of structured interviews and theory-driven scales for evaluating CCD have been developed within the last 20 years 4,12,13,14 . Studies of these scales have shown a correspondingly wide range of prevalence estimates that nonetheless appear to indicate an increased prevalence of cognitive impairment as a dog ages 7,14,15 . In order to gain a better understanding of CCD in aging dogs, researchers recently have developed assessment tools that are able to distinguish cognitively impaired aged dogs from those who are experiencing healthy aging 11,14 . ...
Canine Cognitive Dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and Receiver Operating Curve (ROC) analysis.
When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.
... Canine Cognitive Dysfunction Syndrome (CCDS) is a syndrome of progressive deterioration in cognition associated with amyloid deposition and cortical atrophy and it is considered the canine analog to Alzheimer's Disease in humans (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The symptoms associated with CCDS fall into the following domains: disorientation, social interaction changes, sleep/wake cycle alterations, house soiling, activity changes, anxiety, and deficits in learning and memory (4,5,(8)(9)(10)15). ...
... One study estimated a prevalence of 14.2-22.5% in animals 8 years and older (4), while another reported that 23% of dogs 11-12 years old and 68% of dogs 15-16 years old had at least 1 sign consistent with CCDS (15). Several studies have reported a dramatic increase in prevalence associated with increased age of dogs (7,10,15). However, while there are numerous studies documenting owner reported signs, studies aimed at quantifying behavioral and cognitive changes using specific validated testing are currently lacking (12,16,17). ...
Canine Cognitive Dysfunction Syndrome (CCDS) is a syndrome of progressive cognitive decline comparable to Alzheimer's Disease. The sustained gaze test captures attention loss associated with CCDS in laboratory settings, and adapting the sustained gaze test for use by owners at home could greatly increase the data generated on CCDS. We hypothesized that it would be feasible for owners to perform the sustained gaze test at home, and that results would be reliable over repeated trials. Training materials were developed and dog owners underwent training and performed the test in triplicate at weekly intervals for 3 weeks. Gaze videos and a CAnine DEmentia Scale (CADES) questionnaire were submitted each week. Videos were examined for inclusion and duration of gaze was recorded. One observer repeated video assessments twice, 1 week apart; five different observers assessed videos once. Outcome measures included the relationship between CADES and gaze duration, test-retest reliability of owner-performed sustained gaze testing, and intra- and inter-rater reliability. Twenty dogs aged 7–15.5 years completed testing. The majority of videos were acceptable (162/183). Within dog test-retest reliability was excellent (ICC = 0.96). Intra- and interobserver reliability for determining video validity for inclusion were substantial ( k = 0.76 and 0.78, respectively); for duration of gaze these were excellent (ICC = 0.99 and 0.96, respectively). Gaze duration was significantly associated with CADES ( p = 0.0026). We conclude that owners can perform the sustained gaze test at home and that data generated are reliable and correlate to CADES, a validated measure of dementia.
... Age-related degenerative illnesses such as canine cognitive dysfunction (CCD) are becoming more relevant for veterinary medicine, as a result of pets' longer life expectancies [1]. Various studies describe the prevalence ranging from 14.2% to 68% in geriatric dogs [2][3][4]. As these patients can exhibit various clinical signs and behavioral changes such as disorientation, confusion, incontinence, altered activity, and changes in sleep-wake rhythms [5,6], the quality of life can be severely affected in dogs and their caretakers [7]. ...
Simple Summary
Canine cognitive dysfunction is considered the canine equivalent to human Alzheimer’s disease. It is a growing concern in veterinary medicine, as it affects many aged dogs. Dietary intervention with different diets and supplements may improve clinical signs and prevent further degeneration. Using an online questionnaire, we found that even though few owners were willing to change their dog’s main diet, many of them added supplements such as oils and vitamins. Consulting a veterinary surgeon when using dietary supplements is important as it allows for evidence-based recommendations to be made.
Abstract
Canine cognitive dysfunction (CCD) is becoming increasingly recognized in veterinary medicine, as dogs live longer and with CCD being highly prevalent among the elderly dog population. Various studies have shown that diet and dietary supplementation can positively influence the clinical signs of CCD, especially if given at an early stage. The aim of this study was to investigate owner use of dietary supplements (DSs) in dogs with age-related behavioral changes. An observational study based on an online questionnaire for owners of dogs with age-related behavioral changes was performed. Out of a total of 394 owners who completed the survey, after noticing age-related behavioral changes, over half of the dogs received DSs (54%), whereas only 8% reported changing their dog’s base diet. The most used DS was fish oil (48%). The use of DSs should be discussed with and monitored by veterinary surgeons since many geriatric patients have multi-morbidities, may have specific nutritional requirements and receive multi-faceted medications.
... [6][7][8][9][10] Prevalence CDS v populaci psů se pohybuje mezi 14-35 % a dramaticky narůstá s věkem (až 60-70 % psů nad 12-15 let věku vykazuje CDS). [11][12][13] AD je pro lidskou populaci devastujícím onemocněním, aktuálně se celosvětově odhaduje 50 milionů případů s předpokladem trojnásobku v roce 2050. 14 CDS podle odhadů postihuje 30 milionů psů v USA a 15 milionů jedinců v Evropě. ...
Presented case report describes the twelve-year-old male crossbreed with chronic progressive motoric impairment, behavior changes and inappropriate voiding. Magnetic resonance imaging of the brain revealed cortical atrophy and the patient is monitored with cognitive dysfunction syndrome. Characteristics of this degenerative disease and recommended steps in affected patients are discussed.
... Aging is a natural and inevitable process that affects all living organisms including pets. As pets age, they become increasingly susceptible to various age-related diseases, such as cognitive dysfunction syndrome (CDS) [30,31], cardiac dysfunction [32], and other disorders. These diseases can significantly impact the quality of life of pets. ...
Stem cell therapy is an attractive treatment for diseases in companion animals that cannot be treated by conventional veterinary medicine practices. The unique properties of stem cells, particularly the ability to differentiate into specific cell types, makes them a focal point in regenerative medicine treatments. Stem cell transplantation, especially using mesenchymal stem cells, has been proposed as a means to treat a wide range of injuries and ailments, resulting in tissue regeneration or repair. This review aims to summarize the veterinary use of stem cells for treating age-related and joint diseases, which are common conditions in pets. While additional research is necessary and certain limitations exist, the potential of stem cell therapy for companion animals is immense.
... Studying aging dogs with and without canine cognitive dysfunction (CCD) syndrome shows promise for a better understanding of human age-related neurodegeneration. Canine cognitive dysfunction is considered an age-related disease, with the prevalence ranging from 14-35% of the senior canine population, exponentially increasing with age (Neilson et al., 2001;Azkona et al., 2009;Salvin et al., 2010). In a two-year longitudinal study of 51 dogs over the age of 8 years, 33% of dogs with normal cognitive status progressed to mild cognitive impairment and 22% of dogs with mild cognitive impairment progressed to CCD 10.3389/fnagi.2023.1128521 ...
Canine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimer’s disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Aβ 1-42 ). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Aβ 1-42 and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Aβ 1-42 like their aged, matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD.
... Apart from normal aging changes, dogs can develop pathologic cognitive dysfunction, often referred to as Canine Cognitive Dysfunction Syndrome (CCDS). Dogs with this condition generally present with multiple behavioral changes including disorientation, changes to social interactions, altered sleep/wake cycle, house-soiling, changes in activity, worsening memory, deficiency in learning, and increased anxiety (4)(5)(6)(7)(8)(9)(10)(11). Previous research has demonstrated that owners also note a decline in vision, hearing, and olfaction in older dogs (12,13). ...
Introduction
The aim of this study was to evaluate the engagement of aging dogs with a cognitively challenging and potentially frustrating task (the impossible task). Based on previous observations, we predicted that dogs showing signs of cognitive impairment in other cognitive tests and owner-completed questionnaires would show reduced engagement with the task.
Methods
In this task, dogs were shown a piece of food in a clear container that they could not open; time spent interacting with the container and the experimenter was measured. While the impossible task has not been used as a measure of frustration, the parameters of the test design creates a potential frustrate state, making this assessment appropriate. Thirty-two dogs enrolled in a longitudinal aging study participated in the study. Owners were asked to complete two cognitive dysfunction screening questionnaires (Canine Dementia Scale [CADES] and Canine Cognitive Dysfunction Rating Scale [CCDR]) as well a questionnaire assessing general frustration. Dogs participated in multiple measures of cognitive function as well the impossible task.
Results
Latency to disengage from the impossible task was faster for dogs with higher total (more impaired) CADES ( p = 0.02) and total CCDR ( p = 0.04) scores. Latency to disengage also correlated with decreased performance in cognitive tests observing social cues ( p = 0.01), working memory ( p ≤ 0.001), spatial reasoning and reversal learning ( p = 0.02), and sustained attention ( p = 0.02).
Discussion
The high correlation with several cognitive measures and the ease of administration of this test makes it a useful tool in evaluating canine cognitive dysfunction syndrome, however it is unclear if increased frustration or other cognitive processes are contributing to the observed changes.
... In addition, all dogs included in this study exhibited changes that are commonly observed in aged dogs, such as graying of hair and tooth wear (Pati et al., 2015). It is still important to note that many authors agree that cognitive impairment is more common from this age onward (e.g., 9 years old) (Salvin et al., 2011;González-Martínez et al., 2013;Stylianaki et al., 2020), and Azkona et al. (2009) also demonstrated that 22.5% of dogs older than 9 years exhibited cognitive impairments. Furthermore, the mean ages were higher in the BC group, and a positive correlation between age and questionnaire score was found, which is consistent the fact that cognitive alterations are related to advanced age in dogs. ...
The aim of this study was to evaluate the performance of older dogs in a food-searching task and analyze whether cognitive decline may influence the responses of these patients. Twenty-six dogs over 9 years of age were included, and among these, 10 dogs exhibited behavioral changes (BC group). Sixteen dogs were used as controls. The dog owners were asked to complete a questionnaire to assess the behavioral changes associated with cognitive dysfunction syndrome (CDS), and after clinical evaluations, the dogs were presented with a bowl containing 5 meat-flavored snacks at the bottom and covered with twelve equal-sized balls. The food-searching task was considered to be complete when a dog located and/or ingested the 5 snacks within three minutes. According to the performance of individual dogs in the task, the tester assigned a score ranging from 0-4. The mean ages and questionnaire scores were higher in the BC group (15.50 ± 1.72 years old, P = 0.0004 and 36.50 ± 16.75, P < 0.001) than in the control group (11.94 ± 2.77 years old and 1.94 ± 1.84). For most dogs in the BC group, the questionnaire scores indicated moderate or severe CDS. In the control group, 43.75% of dogs completed the food-searching task, while no dogs in the BC group were able to complete the task. The mean task score was higher in the BC group (3.40 ± 0.97, P = 0.042), which indicated worse performance for the task compared to the control group (2.31 ± 1.40). The behavioral changes were directly related to the dogs' advanced ages, and cognitive dysfunction compromised their performance in the food-searching task.
... Moreover, large animals have the potential to be naturalistic disease models of human brain diseases that can benefit from clinical veterinary studies. For example, dogs (Canis familiaris) present common behavioral problems such as anxiety, compulsive disorders, or age-related cognitive dysfunction (Azkona et al., 2009;Overall, 2000). In the same way, the study of neurodegenerative diseases may benefit from studies in aged large mammals (Danek et al., 2017;Eaton and Wishart, 2017;Emborg and Kordower, 2002;Moreno-Gonzalez and Soto, 2012;Ruple et al., 2022). ...
Animal models play a pivotal role in translational neuroscience but recurrent problems in data collection, analyses , and interpretation, lack of biomarkers, and a tendency to over-reliance on mice have marred neuroscience progress, leading to one of the highest attrition rates in drug translation. Global initiatives to improve reproducibility and model selection are being implemented. Notwithstanding, mice are still the preferred animal species to model human brain disorders even when the translation has been shown to be limited. Non-human primates are better positioned to provide relevant translational information because of their higher brain complexity and homology to humans. Among others, lack of resources and formal training, strict legislation, and ethical issues may impede broad access to large animals. We propose that instead of increasingly restrictive legislation, more resources for training, education, husbandry, and data sharing are urgently needed. The creation of multidisciplinary teams, in which veterinarians need to play a key role, would be critical to improve translational efficiency. Furthermore, it is not usually acknowledged by researchers and regulators the value of comparative studies in lower species, that are instrumental in toxicology, target identification, and mechanistic studies. Overall, we highlight here the need for a conceptual shift in neuroscience research and policies to reach the patients.
... 11 The prevalence of cognitive dysfunction syndrome was reported to be 22.5% in dogs older than 9 years and 68% in 15−16 years old dogs. 12,13 The incidence of brain tumours in adult dogs has been reported to be 2.8%-4.5%, with gliomas representing 36%-70% of primary brain tumours in dogs. ...
Background:
Detailed analysis of archived brain tissue is fundamental to advancing the understanding of neurological disease. The development of the UK Brain Bank Network (UBBN) has provided an invaluable resource to facilitate such research in the human medical field. Similar resources are needed in veterinary medicine. However, collection and archiving of companion animal brain tissue is a potentially sensitive area for pet owners and veterinary professionals.
Methods:
Using an online survey, we aimed to study pet owners' perceptions of brain banking. The survey included information on respondents, their views on organ donation, the UBBN and the Royal Veterinary College's Companion Animal Brain Bank (RVC CABB).
Results:
In total 185 respondents were included. The use of brain tissue from pets for research was supported by 87% of respondents, and 66% of respondents felt that they were highly likely or likely to donate their pet's brain tissue to a CABB. Furthermore, 94% felt that more information on tissue banking in companion animals should be readily available.
Conclusions:
We found that the perceptions of companion animal brain banking were positive in our respondents. Open dialogue and clear information provision on the process and benefits of the CABB could enhance awareness and thus facilitate brain donation for translational research.
... For example, while large dogs have shorter life spans and appear to age faster than smaller dogs in some respects, studies of ageassociated cognitive dysfunction are mixed, with some indicating earlier onset in larger dogs and others finding no such association. 53,62,63 This variability suggests a common set of mechanisms underlying aging that is modified in expression in each individual by both intrinsic and environmental factors. While teasing out these factors is an interesting and productive research challenge, drawing a bright line between healthy and unhealthy aging isn't critical from a clinical perspective. ...
Aging is the single most important cause of disease, disability, and death in adult dogs. Contrary to the common view of aging as a mysterious and inevitable natural event, it is more usefully understood as a set of complex but comprehensible biological processes that are highly conserved across species. Although the phenotypic expression of these processes is variable, there are consistent patterns both within and between species.
The purpose of this feature is to describe the patterns currently recognized in the physical and behavioral manifestations of aging in the dog and how these impact the health and welfare of companion dogs and their human caregivers. Important gaps in our knowledge of the canine aging phenotype will be identified, and current research efforts to better characterize aging in the dog will be discussed. This will help set the context for future efforts to develop clinical assessments and treatments to mitigate the negative impact of aging on dogs and humans.
... To our knowledge, there has been no related behavioral research but the studies of Gunn-Moore et al. (2018) and Stylianaki et al. (2019), provide evidence for potential cognitive decline in dolphins. Furthermore, cognitive aging has been documented in other species such as common marmosets (Callithrix jacchus, Sadoun et al. 2019), rhesus monkeys (Macaca mulatta, Herndon et al. 1997), chimpanzee (Pan troglodytes, Hopkins et al. 2021) and domesticated species (Azkona et al. 2009;Bellows et al. 2016). Hence, research on long-term cognitive functions in dolphins should be considered for future direction of cognitive studies. ...
Alliance formation plays a crucial part in male dolphins’ lives. These partnerships may last for decades or even for a lifetime; thus, partner choice and the maintenance of these relationships are both considered key components of alliance formation. In our previous investigations, pairs of adult male dolphins showed a high success rate in cooperative manipulation of a cognitive enrichment device. Here, we introduced two novel cognitive enrichment devices to the group of five dolphins, facilitating simultaneous actions for not only pairs, but for three or even four dolphins. The devices were made of PVC tubes, fittings and caps equipped with rope handles, creating a three-way (T-shape) and a four-way (TT-shape) device. The devices were filled with fish and ice and were designed to be opened by simultaneous pull of the handles. Both devices were tested in 12 trials (each lasted for 15 min), separately. Only one of the caps could be opened, the others were affixed with the position of the openable cap counter-balanced over the trials. Although the dolphins received no training regarding the manipulation of the devices, they were successful in cooperatively opening the three-way devices in 10/12 of trials (70% by two and 30% by three dolphins) and the four-way devices also in 10/12 trials (50% by two, 40% by three and 10% by four dolphins). The dolphins interacted with the devices during the entire testing time, and this was mostly spent in cooperative play (77% and 56% of the test duration with the three-way and four-way device, respectively). The majority of the cooperative play was observed between one particular pair of dolphins that was temporarily associated with a third or sometimes even with a fourth dolphin. These findings demonstrate the first successful use of multi-partner cooperative enrichment devices, providing information on the social organisation of a male dolphin group.
... Females were significantly more affected than males, as prevalence and severity increased with age. This study's hypothesis was that hormonal and/or genetic factors may influence the development of cognitive signals in elderly female dogs, as well as women with AD [52]. ...
Episodic memory, in humans, is the memory most affected by age-related deterioration or the constitution of neurodegenerative pathologies, such as Alzheimer's disease. However, it is unknown whether this relationship is also present in nonhuman animals. Since studies in birds, rats, primates, and dogs have been shown to have episodic-like memory, more studies aiming to improve the present understanding of this relationship in nonhuman animals are important to aid the development of new translational models for neurodegenerative disorders. Knowing that dogs (Canis familiaris) represent a promising experimental model for neurodegenerative disorders, a memory retrieval test was conducted with 90 clinically healthy domestic dogs of different ages, both sexes, and distinct breeds, for the purpose of evaluating episodic-like memory. The present study adapted a test that corroborates episodic memory requirements through incidental codification of experienced events. We performed a test with two exposure phases, with different characteristics between them, so that in the third phase it was necessary to integrate previous experiences in order to achieve success in the test. In our study, it was possible to verify the decline of episodic memory in elderly dogs, even clinically healthy, regardless of the dogs' sex and size. This episodic-like memory decline observed in elderly dogs may be related to the physiological process of aging or preclinical pathological manifestation of cognitive impairment, similar as reported in humans. More studies should be carried out evaluating episodic-like memory in dogs with suspected of canine cognitive dysfunction syndrome in order to better understand the physiological and pathological behavior of this type of memory in canine species.
... On the other hand, dogs diagnosed with CDS ranged from 10% (up to 12 years of age) to 61% (13 years old and over) [24,69], with Osella [68] reporting that 33% of the evaluated elderly dog population was affected by this syndrome. It must be mentioned, however, that different authors reported lower data, with cumulative (MCI and CDS) prevalence ranging from 14% [29,70] to 22.5% [71]. ...
Canine and feline cognitive dysfunction syndrome is a common neurodegenerative disorder of old age and a natural model of human Alzheimer’s disease. With the unavoidable expanding life expectancy, an increasing number of small animals will be affected. Although there is no cure, early detection and intervention are vitally important to delay cognitive decline. Knowledge of cellular and molecular mechanisms underlying disease onset and progression is an equally decisive factor for developing effective approaches. Uncontrolled neuroinflammation, orchestrated in the central nervous system mainly by astrocytes, microglia, and resident mast cells, is currently acknowledged as a hallmark of neurodegeneration. This has prompted scientists to find a way to rebalance the altered crosstalk between these cells. In this context, great emphasis has been given to the role played by the expanded endocannabinoid system, i.e., endocannabinoidome, because of its prominent role in physiological and pathological neuroinflammation. Within the endocannabinoidome, great attention has been paid to palmitoylethanolamide due to its safe and pro-homeostatic effects. The availability of new ultramicronized formulations highly improved the oral bioavailability of palmitoylethanolamide, paving the way to its dietary use. Ultramicronized palmitoylethanolamide has been repeatedly tested in animal models of age-related neurodegeneration with promising results. Data accumulated so far suggest that supplementation with ultramicronized palmitoylethanolamide helps to accomplish successful brain aging.
... Our main goal here was to test how ageing affects the dogs' separation related behaviour with a repeated separation test, in a longitudinal study. We have very little knowledge about the different aspects of age-related changes in separation behaviours, and how dogs' arousal level is coded in occurrences of NLP and spectral noise (Azkona et al., 2009;Neilson et al., 2001;Osella et al., 2007;Salvin et al., 2010). Some authors in cross-sectional studies (Marx et al., 2021;Mongillo et al., 2013) have addressed age effects on separation behaviour, but it is important to support these findings in repeated, longitudinal studies, as these have the potential to indicate the direct effects of ageing (Salthouse, 2019). ...
Separation related problems (SRP) caused by distress associated with separation from the preferred member of the social group, can be characterised by their symptoms e.g., excessive vocalisation. In dogs’ separation whines, nonlinear phenomena (NLP) (abrupt changes in the resonance of the vocal folds) might occur, which could be adaptive in communicating aroused inner states. Previously, using a separation test we found that more dogs that were classified as having SRP by their owner have NLP in their whines than nonaffected dogs and that NLP ratio increases with age, which suggests that separation stress might intensify with age.
We repeated the separation test 21.19 ± 9.37 months later with 32 dogs from the previous study to investigate longitudinally how separation behaviour and vocalisations change with age. Beside behaviour, we measured the acoustic structure of the whines (jitter - small-scale irregularity of the pitch, entropy - vocal harshness, call length, pitch (f0) related parameters, and the spectral components) and calculated the NLP ratio. We formed clusters based on the dogs’ behaviour changes from the first test to the second, to see individual ageing patterns. Finally, we compared the dogs’ behaviour and the acoustic structure of their whines in the two occasions.
We found that dogs could be clustered by the changes in their separation behaviour. 41 % of the dogs were stable over time, 38 % improved, and 16 % showed an increase in their separation behaviours. 3 % switched from barking to whining. Interestingly, SRP dogs were stable, some of them even showed improvement in their separation behaviour. On the contrary, we also found that SRP dogs tended to have an increased NLP ratio with age from test 1 to test 2 (p = 0.09), showed less escape-related behaviour (p = 0.01), but tended to spend more time passively whining at the door through which the owner left the room (p = 0.05), than non-SRP dogs.
The behavioural and vocal results suggest elevated stress levels in SRP dogs with age, although they did not decline but mostly stayed stable in their separation behaviour, confirming that there could be a connection between SRP status, age, and NLP. However, together with the results of the clustering that showed that there are different patterns in dogs’ separation behaviour, we emphasise the importance of individual level longitudinal investigations in order to facilitate the early diagnosis of SRP and to provide a solid basis for the development of individualised treatment plan for SRP dogs.
... Ook voor teven die na de leeftijd van één jaar geovariectomiseerd werden, bleef het risico groter dan bij intacte teven. Daarnaast blijkt dat cognitieve disfunctie, een aandoening die vooral oude, vrouwelijke honden treft, mogelijk vaker gezien wordt na gonadectomie; dit zowel bij de reu als de teef (Azkona et al., 2009). ...
In recent years, gonadectomy in dogs has become the subject of growing criticism. Novel studies have demonstrated that this type of surgery can have negative effects on the dog's health, effects that at first sight cannot be linked to the removal of the gonads or the absence of sex steroids. In this review, the literature on the long term-health effects of gonadectomy in dogs is described. The most important medical indication for ovariectomy in a bitch is lowering the risk of pyometra and mammary tumors, diseases which arc prevalent in intact bitches. Spaying is often done in young bitches because of the protective effect it has on the development of mammary tumors. However, recent research has shown that orthopedical problems and some non-genital tumors are more prevalent in dogs after gonadectomy, especially if spayed before puberty. Results of these studies also show a major impact of the breed of the dog, hence a general advice for the dog population is not feasible. Veterinarians have to evolve towards a patient-specific advice in this matter.
... Aging also significantly impacts visual attention [22][23][24][25][26][27][28][29][30][31] . A generalised slowing of information processing provides an explanation for an overall age-related decline in cognition 25 . ...
Forming eye contact is important in dog–human communication. In this study we measured what factors affect dogs’ propensity for forming eye contact with an experimenter. We investigated the effect of [1] cephalic index (head shape’s metric, indicator of higher visual acuity at the centre of the visual field), [2] breed function (visual cooperativeness), [3] age and [4] playfulness with strangers in 125 companion dogs. Cephalic index was measured individually and analysed as a continuous variable. Results showed that [1] dogs with a higher cephalic index (shorter head) established eye contact faster. Since cephalic index is highly variable even within a breed, using artificial head shape groups or breed average cephalic index values is not recommended. [2] Breed function also affected dogs’ performance: cooperative breeds and mongrels established eye contact faster than dogs from non-cooperative breeds. [3] Younger dogs formed eye contact faster than older ones. [4] More playful dogs formed eye contact faster. Our results suggest that several factors affect dogs’ interspecific attention, and therefore their visual communication ability.
... For example, researchers have found that, like humans, dogs experience declines in EF as they age (Cepeda et al. 2001;Mongillo et al. 2013;Tapp et al. 2003;Wallis et al. 2014Wallis et al. , 2016. Researchers have also found canine analogs of attentional deficit hyperactivity disorder (ADHD; Vás et al. 2007) and Alzheimer's disease (canine cognitive dysfunction; Azkona et al. 2009;Landsberg et al. 2003Landsberg et al. , 2012Ruehl et al. 1995). Such research provides a starting point in developing methods of testing various cognitive abilities, as well as the efficacy of interventions, such as those aiming to reduce age-related cognitive decline Milgram 2003;Milgram et al. 2002Milgram et al. , 2005. ...
... A prevalência de cães que apresentavam sinais clínicos sugestivos da SDCC no presente estudo (22,38% -15/67) está dentro dos valores encontrados por Azkona et al. (2009) de 22,5%, Heath et al. (2007 de 20 -30% e por Bain et al. (2001) de 22% em cães com idade entre 11 e 14 anos. Quanto maior a idade dos cães, mais alterações comportamentais (Neilson et al., 2001), visto que os idosos demonstram um declínio cognitivo dependente da idade e de afecções cerebrais existentes (Faraco, 2013). ...
O alto nível de relação entre humanos e animais de companhia intensificou a preocupação de alguns tutores com as desordens relacionadas ao envelhecimento. Durante a velhice, além de mudanças fisiológicas, alterações patológicas como a Síndrome da Disfunção Cognitiva Canina (SDCC) são comuns. Essa doença é caracterizada por processos degenerativos que culminam em perda gradual da função cognitiva, sendo frequentemente confundida com o processo natural de envelhecimento. Neste contexto, objetivou-se avaliar a ação de um suplemento nutricional à base de aminoácidos, prebióticos e ácidos graxos para cães idosos na evolução clínica da SDCC. Foram avaliados 67 cães em idade sênior (> 7 anos) para positividade aos sinais clínicos da SDCC. Posteriormente, os animais positivos (n=15 / 22%) foram alocados em dois grupos experimentais, controle (C) e tratamento (T- utilização do suplemento nutricional). Observou-se melhora, relatada pelos tutores, de sinais clínicos associados à SDCC em 80% dos animais tratados, no entanto mais estudos são necessários para elucidar o efeito de suplementos nutricionais na regressão da sintomatologia clínica de cães com sinais clínicos sugestivos da doença.
... In particular, transgenic rodent models, which harbor mutations causing the rare familial early-onset AD, fail to fully recapitulate the complex human AD phenotype (Babcock et al., 2015;Weishaupt et al., 2018). The prevalence of CCD has been estimated to be 14%e22% in dogs older than 8 years and more than 50% in dogs older than 15 years (Osella et al., 2007;Azkona et al., 2009;Salvin et al., 2010). As with sporadic AD, age is a major risk factor for developing CCD (Adams et al., 2000;Murphy et al., 2002;Schütt et al., 2018). ...
Cattle constitute one of the most commercially important livestock species. They are a significant source of nutrition as well has had great economic importance. Through thousands of years of selective breeding humans have shaped cattle into these multipurpose species that are adapted to various environments around the globe. In the past decade, the sequencing of the cattle genome has paved the way for genetic enhancement of existing breeds to increase productivity and sustainability. More recently, developments in genome editing technologies and pluripotent stem cell culture can now be combined to achieve highly commercial goals for the livestock industry. In this chapter, we discuss the basics of these cutting-edge technologies and their applications in cattle. We focus on bovine iPSCs (biPSCs) as they can be generated in theory from any individual long after their genetic value has been proven, and their phenotypic characteristics validated and regardless of their fecundity status. Furthermore, we discuss the various genome editors and how these novel tools can be used for the genetic improvement of cattle.
... In dogs, the diagnosis of canine cognitive dysfunction syndrome is based on behavioral signs and exclusion of other medical conditions [24]. Further, it is known clinically that the prevalence and severity of canine cognitive dysfunction increases with the age [25]. Different publications have studied that dogs affected by progressive cognitive impairment share certain histopathological changes including alterations related to the structure of certain proteins as in Alzheimer disease: neuronal loss, astrocytosis, amyloid-β deposition and rarely neurofibrillary tangles [26,27]. ...
Background
Aquaporin-4 (AQP4) is in growing recognition as potential marker for cancer progression, differentiation and therapeutic intervention. No information is available about AQP4 expression in the normal canine brain. The aim of this histopathological study is to confirm the presence of AQP4 by immunohistochemistry technique in a group of non-pathological canine brains and to describe its expression and distribution across the brain.
Results
Twelve non-pathological canine brains of various ages (ranging from 21 days to 17 years) and breeds were included in the study. Immunohistochemical expression of AQP4 was analyzed using formalin-fixed paraffin-embedded brain tissue sections. The findings were correlated between AQP4 expressing cells and astrocytes using glial fibrillary acidic protein (GFAP). AQP4 expression was more marked in the astrocyte foot processes of subpial, perivascular and periventricular surfaces in all specimens. The majority of the canine brain sections (9/12) presented with an AQP4 predilection for white matter tracts. Interestingly, the two youngest dogs (21 days and 3 months old) were characterized by diffuse AQP4 labelling in both grey and white matter tracts. This result may suggest that brain development and ageing may play a role in the AQP4 distribution throughout the canine brain.
Conclusions
This is the first study to describe immunohistochemical distribution of AQP4 in normal canine brains. The AQP4 expression and distribution in non-pathological canine brains was comparable to other species. Larger studies are needed to substantiate the influence of breed and ageing on AQP4 expression in the normal canine brain.
... Many studies have documented that senior dogs may experience canine cognitive dysfunction syndrome (CCDS), also known as "canine dementia." In these dogs, we usually notice behavioral changes that are described in short by the acronym DISHA [Disorientation, altered social Interactions, altered Sleep-wake cycles, House soiling and loss of other learned behaviors, altered Activity levels and increasing Anxiety; (4)(5)(6)(7)(8)], as well as neuropathological changes in the brain. CCDS is observed mainly in large-breed dogs over 8 years of age showing slow onset of behavioral and cognitive changes. ...
Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder in senior dogs that is mainly associated with decreased ability to learn and respond to stimuli. It is commonly under-diagnosed because behavioral changes are often attributed to the natural process of aging. In the present study, we used for the first time a comprehensive approach enabling early diagnosis of canine patients with mild cognitive disorders (MiCI). We included CAnine DEmentia Scale (CADES) questionnaires, biochemical parameters, and biomarkers in blood serum, and correlated them with post-mortem histopathological changes. The CADES questionnaires enabled us to identify MiCI dogs developing changes mainly in domains corresponding to social interaction and spatial orientation, which seems to be crucial for delineating early cognitive disorders. Biochemical analyses in these dogs showed slightly elevated liver enzyme parameters (AST and ALT) and significantly decreased sodium and chloride levels in blood serum. Furthermore, we describe for the first time a significant increase of neurofilament light chain (NFL) in blood serum of MiCI dogs, compared to normal aging seniors and young controls, but no changes in TAU protein and amyloid-β (Aβ42) peptide levels. In canine brains with cognitive impairment, amyloid plaques of mainly diffuse and dense types were detected. Furthermore, activated microglia with amoeboid body and dystrophic processes occurred, in some cases with spheroidal and bulbous swellings. On the other hand, no TAU pathology or neurofibrillary tangles were detected. These results suggest that a combination of CADES questionnaire mainly with CNS injury biomarker (NFL) and with biochemical parameters (ALT, AST, Na, and Cl) in blood serum may predict CCDS in senior dogs.
... dental disease, obesity, cognitive dysfunction, osteoarthritis, heart failure, survival). For example, prevalence estimates of canine cognitive dysfunction syndrome (CDS) in dogs > 8 years of age range from 14 to 60% [41][42][43][44]. Conservatively, assuming a CDS prevalence of 14% at age 8 years, we estimate having 80% power to detect OR> 1.50 for variables that 20-30% of controls are exposed to (Additional file 3). ...
Abstract Background Despite extensive research, many questions remain unanswered about common problems that impact dog welfare, particularly where there are multiple contributing factors that can occur months or years before the problem becomes apparent. The Generation Pup study is the first longitudinal study of dogs that recruits pure- and mixed-breed puppies, aiming to investigate the relative influence of environmental and genetic factors on a range of health and behaviour outcomes, (including separation related behaviour, aggression to familiar/unfamiliar people or dogs and obesity). This paper describes the study protocol in detail. Methods Prior to commencing recruitment of puppies, the study infrastructure was developed, and subject specialists were consulted to inform data collection methodology. Questionnaire content and timepoint(s) for data collection for outcomes and potential predictors were chosen with the aim of providing the best opportunity of achieving the aims of the study, subject to time and funding constraints. Recruitment of puppies (
... Such assessments may help to clarify the relationships between age-related cognitive deficits, behavioral changes, and neurological changes in pet dogs. Used in combination with physiological tests and questionnaires, cognitive assessments may also aid in the diagnosis of CDS (Wallis et al. 2016), thereby facilitating veterinary care for millions of pet dogs (for prevalence estimates, see Azkona et al. 2009;Salvin 2010). Moreover, physicians use a number of tools to diagnose AD including behavioral questionnaires, psychometric assessments, physiological assays, and neurological imaging. ...
Assessments for spatial working memory (SWM) in pet dogs that can detect age-related cognitive deficits in a single session may aid in diagnosing canine dementia and may facilitate translational research on Alzheimer’s disease in humans. Adaptive testing procedures are widely used in single-session assessments for humans with diverse cognitive abilities. In this study, we designed and deployed two up-down staircase assessments for SWM in which 26 pet dogs were required to recall the location of a treat hidden behind one of two identical boxes following delays of variable length. In the first experiment, performance tended to decline with age but few dogs completed the test (n = 10). However, all of the dogs that participated in the second experiment (n = 24) completed the assessment and provided reliable evidence of learning and retaining the task. Delay length and age significantly predicted performance supporting the validity of this assessment. The relationships between age and performance were described by inverted U-shaped functions as both old and young dogs displayed deficits in weighted cumulative-scores and trial-by-trial performance. Thus, SWM in pet dogs may develop until midlife and decline thereafter. Exploratory analyses of non-mnemonic fixation strategies, sustained engagement, inhibitory control, and potential improvements for future SWM assessments which adopt this paradigm are also discussed.
Introduction
In humans, gait speed is a crucial component in geriatric evaluation since decreasing speed can be a harbinger of cognitive decline and dementia. Aging companion dogs can suffer from age-related mobility impairment, cognitive decline and dementia known as canine cognitive dysfunction syndrome. We hypothesized that there would be an association between gait speed and cognition in aging dogs.
Methods
We measured gait speed on and off leash in 46 adult and 49 senior dogs. Cognitive performance in senior dogs was assessed by means of the Canine Dementia Scale and a battery of cognitive tests.
Results
We demonstrated that dogs' food-motivated gait speed off leash is correlated with fractional lifespan and cognitive performance in dogs, particularly in the domains of attention and working memory.
Discussion
Food-motivated gait speed off leash represents a relatively easy variable to measure in clinical settings. Moreover, it proves to be a more effective indicator of age-related deterioration and cognitive decline than gait speed on leash.
The popularity of dogs has been increasing owing to factors such as the physical and mental health benefits associated with raising them. While owners care about their dogs’ health and welfare, it is difficult for them to assess these, and frequent veterinary checkups represent a growing financial burden. In this study, we propose a behavior-based video summarization and visualization system for monitoring a dog’s behavioral patterns to help assess its health and welfare. The system proceeds in four modules: (1) a video data collection and preprocessing module; (2) an object detection-based module for retrieving image sequences where the dog is alone and cropping them to reduce background noise; (3) a dog behavior recognition module using two-stream EfficientNetV2 to extract appearance and motion features from the cropped images and their respective optical flow, followed by a long short-term memory (LSTM) model to recognize the dog’s behaviors; and (4) a summarization and visualization module to provide effective visual summaries of the dog’s location and behavior information to help assess and understand its health and welfare. The experimental results show that the system achieved an average F1 score of 0.955 for behavior recognition, with an execution time allowing real-time processing, while the summarization and visualization results demonstrate how the system can help owners assess and understand their dog’s health and welfare.
Canine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimers disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Amyloid beta 1-42). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Amyloid beta 1-42 and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines is seen. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Amyloid beta1-42 like their aged matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD
Introdução. A esterilização de cães é um dos tratamentos mais realizados na rotina cirúrgica da medicina veterinária, recebendo indicação em casos que envolvam controle populacional, distúrbios comportamentais e doenças no sistema reprodutor. Apesar de muitas vezes ser necessária, a retirada das gônadas ocasiona alterações endócrinas que reduzem significantemente os níveis hormonais. A ciência já sabe que níveis séricos baixos de testosterona reduz a proteção que a mesma exerce sobre o sistema nervoso central, e que a queda de estrogênio compromete os índices de neurotransmissores, crescimento neuronal, formação de sinapses, ação antioxidante e regulação da homeostase do cálcio. Objetivo. Identificar, através de revisão de literatura, a possível correlação entre o desenvolvimento de déficit cognitivo e a castração de cães. Método. Trata-se de uma revisão de literatura nas bases de dados Google Scholar, Pubmed, Scientific Electronic Libray Online e Portal Periódicos CAPES, com seleção de artigos, livros, dissertações e teses entre janeiro de 1990 a janeiro de 2019 por meio de palavras-chaves, tais quais gonadectomia, déficit cognitivo em cães, hormônios sexuais etc. Foram utilizados 55 trabalhos para elaboração da base científica, sendo considerado todos os idiomas e os que não fugissem ao tema central da pesquisa. Resultados. Mediante a leitura, observamos que quando se fala em cognição animal os hormônios sexuais têm papel real e fundamental para o funcionamento do cérebro canino. Conclusão. Portanto, constata-se que a metodologia atual de esterilização canina poderá trazer sequelas significativas aos cães, sendo recomendado a utilização de outros métodos contraceptivos que preservem a produção hormonal.
Objectives
The aim of this study was to investigate the potential risk factors involved in the development of presumptive advanced canine cognitive dysfunction (pACCD).
Materials and methods
A questionnaire was developed to identify dogs with presumptive canine cognitive dysfunction (CCD) based on an adapted Canine Dementia Scale and to evaluate for potential risk factors among the presumptive advanced cognitive dysfunction group. The questionnaire was distributed to 7,574 owners of dogs (≥8 years of age) who presented to the CSU VTH between 2017 and 2020. Dogs were classified into four groups based on the Canine Dementia Scale score (normal, mild, moderate, and severe cognitive impairment) and two subgroups for the cognitively impaired groups based on the presence or absence of underlying medical conditions. Comparisons between normal and presumptive advanced cognitively impaired groups, with and without underlying medical conditions, were made against various risk factors. Chi-square tests and logistic regression analysis were used to determine associations between categorical variables and a p -value of <0.05 was considered indicative of evidence of association.
Results
The completed response rate for the questionnaire was 14.2% (1,079/7,574). Among those, 231 dogs were classified as having presumptive advanced cognitive dysfunction. The prevalence of presumptive advanced cognitive dysfunction in the included age groups was 8.1% in ages 8 to <11 years, 18.8% in ages 11 to <13 years, 45.3% in ages 13 to <15 years, 67.3% in ages 15 to <17 years, and 80% in ages >17 years. Dogs with a thin body condition score had the largest contribution to the chi-square statistic. Based on the logistic regression model, both age ( p < 0.001) and BCS ( p = 0.0057) are associated with presumptive ACCD.
Conclusion and relevance
The chi-square test and logistic regression analysis both suggested an association between a thin body condition and an increased chance of cognitive decline. However, it is difficult to determine if the thin BCS in this group could be secondary to another confounding factor. The prevalence of cognitive dysfunction rapidly increased with age in this study. These findings warrant continued studies including veterinary evaluations to explore risk factors of canine dementia.
Veterinary science or veterinary medicine is a diverse and significant field. Concerned not only with the diagnosis and treatment of domestic animals and livestock, but it also places focus upon zoonotic diseases, the development and effectiveness of potential vaccines and the possibility of transmission of veterinary medication or viruses into animal food products. Electrochemiluminescence (ECL) is a powerful analytical technique, which despite its significant intrinsic benefits has not seen enormous adoption into the wider analytical chemical community. In contrast, the veterinary science sector has reaped the merit of ECL as far back as the late 90’s and continue to benefit from development of the technique a further three decades later. ECL offers the superb sensitivity, low running costs, rapid results and high reliability required within the veterinary science sector, as such its employment in this area shouldn’t be surprising. To this end this article aims to summarise the standing of ECL within the veterinary science field, in an attempt increase the awareness of its successful employment within this area to the electro-analytical and wider analytical chemistry communities. Where it is hope veterinary science will gain recognition as possible end user targets for academic and industrial electrochemical researchers.
As the most phenotypically diverse mammalian species that shares human environments and access to sophisticated healthcare, domestic dogs have unique potential to inform our understanding of the determinants of aging. Here we outline key concepts in the study of aging and illustrate the value of research with dogs, which can improve dog health and support translational discoveries. We consider similarities and differences in aging and age-related diseases in dogs and humans and summarize key advances in our understanding of genetic and environmental risk factors for morbidity and mortality in dogs. We address health outcomes ranging from cancer to cognitive function and highlight emerging research opportunities from large-scale cohort studies in companion dogs. We conclude that studying aging in dogs could overcome many limitations of laboratory models, most notably, the ability to assess how aging-associated pathways influence aging in real-world environments similar to those experienced by humans.
Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Objective:
To assess the effects of a 4-week group class specifically created for dogs ≥ 8 years old (senior dogs) on the development and progression of signs consistent with cognitive dysfunction syndrome (CDS).
Animals:
86 dogs with or without signs of CDS at the time of study enrollment.
Procedures:
Dog owners completed a proprietary CDS survey at baseline and then 3, 6, and 12 months after completion of the baseline survey. Twenty owners with their dogs attended 4 weekly 50-minute classes that were specifically developed for senior dogs, addressed common behavior problems for these dogs, and included training and enrichment activities. Survey results were compared between class and nonclass groups and within groups at 3, 6, and 12 months.
Results:
The association between age and CDS score was significant, such that older dogs had signs consistent with a higher degree of impairment. Cognitive dysfunction syndrome scores for dogs that attended the class did not significantly differ at 12 months, compared with scores at 3 months, whereas the CDS scores for dogs that did not attend the class were significantly increased at 12 months, compared with scores at 3 months.
Conclusions and clinical relevance:
Signs of CDS developed or worsened as dogs aged. Participation in the senior dog class mitigated the progression of signs of CDS and may improve a senior dog's quality of life.
Neurologic conditions represent some of the most confusing, challenging, and frustrating cases to treat. Because of this, it is not surprising that many pet owners turn to alternative therapies, including cannabis, to treat their pets. This chapter provides information on the use of cannabinoid compounds for the treatment or management of common neurologic diseases and disorders of dogs and cats.
Senior dogs and cats commonly present to veterinary clinics for wellness examinations and for illness. Nutritional needs change in healthy elder pets compared with the young adult life stage. Veterinary health care teams must provide nutritional assessments and individual recommendations, recognizing there is no defined nutrient profile for seniors. Individual variation prevents a one-size-fits-all approach. Advancing age places pets at risk for developing medical conditions. Early detection can lead to earlier nutritional intervention to support recovery, health, and quality of life. However, comorbidities may present a nutritional conundrum, requiring prioritization of problems and nutritional triage to balance needs.
The effect of breed and body weight on longevity in the pet dog was analyzed, and a method was developed to standardize the chronological age of dogs in terms of physiological time, using human year equivalents. Mortality data from 23,535 pet dogs were obtained from a computerized data base of North American veterinary teaching hospitals, and the median age at death was determined for pure and mixed breed dogs of different body weight. Body size in the dog was inversely related to longevity. Within each body weight category, the median age at death was lower for pure breed dogs compared with mixed breed dogs. The difference between the standardized physiological ages of mixed breed dogs of the same chronological age in the smallest and largest body weight categories varied from 8 to > 15 years, and between large and small pure breed dogs, the disparity was even greater. Laboratory research to explore the biological basis for these breed and body weight specific differences in life span among dogs may provide additional clues to genetic factors influencing senescence.
Although many age-related changes have been described in the nervous system of different species, few authors have specifically studied the topic. Knowledge of such changes is essential to veterinary pathologists, who must distinguish the lesions of specific pathologic processes from those arising as a result of normal aging. The brains of 20 old dogs, ranging in age from 8 to 18 years, were compared with those of 10 young dogs using routine staining techniques (hematoxilin and eosin, periodic acid-Schiff), special staining techniques (periodic acid-methenamine silver stain), and immunohistochemical techniques to detect glial fibrillary acid protein, neurofilaments, ubiquitin, and beta-amyloid. Changes affected meninges and choroid plexuses, meningeal and parenchymal vessels, neurons, and glial cells. Of special interest was the presence of polyglucosan bodies, cerebrovascular amyloid deposition, senile plaques, and ubiquitinated bodies. Some of the age-related changes found, particularly lipofuscin, polyglucosan bodies, and beta-amyloid protein deposition, may play a role in the pathogenesis of the canine cognitive dysfunction syndrome. The dog could be used as a natural animal model for the study of normal aging and human neurodegenerative diseases.
Recent changes in veterinary medicine have required quantitative epidemiological techniques for designing field surveys, identifying risk factors for multifactorial diseases, and assessing diagnostic tests. Several relevant techniques are brought together in the package of veterinary epidemiological computer software, WIN EPISCOPE 2.0, described in this paper. It is based on Microsoft Windows and includes modules for the design and analysis of field surveys, control campaigns and observational studies, and a simple mathematical model. It provides comprehensive 'Help' screens and should therefore be useful not only in field investigations but also for teaching veterinary epidemiology.
To monitor the progression of age-related behavioral changes in dogs during a period of 6 to 18 months and to determine whether signs of dysfunction in any of 4 behavioral categories can be used to predict further impairment.
Age-stratified cohort study.
63 spayed female and 47 castrated male dogs 11 to 14 years of age.
Data were collected from randomly selected dog owners who were interviewed by telephone twice at a 12- to 18-month interval; data were included if the dog had lived > or = 6 months between interviews. The interview focused on signs of impairment in the following behavioral categories: orientation in the home and yard, social interactions with human family members, house training, and the sleep-wake cycle. Dogs were determined to have impairment in 0 behavioral categories (on the basis of < or = 1 sign for each category), impairment in 1 category (> or = 2 signs of dysfunction in that category), or impairment in > or = 2 categories.
Between interviews, 22% (16/73) of dogs that did not have impairment in a category at the time of the first interview developed impairment in that category by the time of the second interview. Forty-eight percent (13/27) of dogs that had impairment in 1 category at the time of the first interview developed impairment in > or = 2 categories by the time of the second interview and were significantly more likely to develop impairment in > or = 2 categories, compared with dogs that initially had impairment in 0 categories. Dogs with 1 sign of dysfunction in orientation were significantly more likely to develop impairment in that category, compared with dogs that had 0 signs of dysfunction in orientation.
Age-related behavioral changes in dogs are progressive. Clinicians should consider trying to predict which dogs are most likely to become progressively impaired during the subsequent 6 to 18 months.
To determine the prevalence of age-related behavioral changes, namely impairment, in a randomly chosen population of dogs.
Age-stratified cohort study.
97 spayed female and 83 castrated male dogs that were 11 to 16 years old.
Data on possible impairment in 4 behavioral categories (ie, orientation in the home and yard, social interaction, house training, and sleep-wake cycle) linked to cognitive dysfunction were obtained from dog owners, using a structured telephone interview. Hospital records of dogs had been screened to exclude dogs with dysfunction in organ systems that may cause behavioral changes. Dogs with behavioral impairment were those with > or = 2 signs of dysfunction within a category. Dogs with impairment in 1 category were considered mildly impaired and those with impairment in > or =2 categories were considered severely impaired.
Age by sex interactions for dogs with impairment in any category were not significant, and, therefore, data on castrated males and spayed females were pooled for analyses across ages. The prevalence of age-related progressive impairment was significant in all categories. The percentage of 11- to 12-year-old dogs with impairment in > or = 1 category was 28% (22/80), of which 10% (8/80) had impairment in > or = 2 behavioral categories. Of 15- to 16-year-old dogs, 68% (23/34) had impairment in > or =1 category, of which 35% (12/34) had impairments in > or = 2 categories. There were no significant effects of body weight on the prevalence of signs of dysfunction in the behavioral categories.
Data collected provide estimates of the prevalence of various degrees of age-related behavioral changes associated with cognitive dysfunction in dogs. Age-related behavioral changes may be useful indicators for medical intervention for dogs with signs of cognitive impairment.
To determine whether gonadectomy predisposes dogs to development of age-related behavioral changes linked to cognitive impairment.
Cohort study.
29 sexually intact male dogs, 63 spayed female dogs, and 47 castrated male dogs 11 to 14 years old.
Information on possible impairments in 4 behavioral categories linked to cognitive impairment (orientation in the home and yard, social interactions, house training, and sleep-wake cycle) was obtained from owners of the dogs by use of a structured telephone interview format. A second interview was performed 12 to 18 months after the initial interview, and differences in responses were evaluated.
Sexually intact male dogs were significantly less likely than neutered dogs to progress from mild impairment (i.e., impairment in 1 category) to severe impairment (i.e., impairment in > or = 2 categories) during the time between the first and second interviews. This difference was not attributable to differences in ages of the dogs, duration of follow-up, or the owners' perceptions of the dogs' overall health.
Results suggest that the presence of circulating testosterone in aging sexually intact male dogs may slow the progression of cognitive impairment, at least among dogs that already have signs of mild impairment. Estrogens would be expected to have a similar protective role in sexually intact female dogs; unfortunately, too few sexually intact female dogs were available for inclusion in the study to test this hypothesis. There may be a need to evaluate possible methods for counteracting the effects of loss of sex hormones in gonadectomized dogs.
Circulating testosterone (T) levels have behavioral and neurological effects in both human and nonhuman species. Both T concentrations and neuropsychological function decrease substantially with age in men. The purpose of this prospective, longitudinal study was to investigate the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.
We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the dorsolateral prefrontal cortex (dlPFC) in ovariectomized (OVX) female rhesus monkeys, and that E induces a corresponding increase in spine density in layer III dlPFC pyramidal neurons. We have now investigated the effects of the same E treatment in young adult females. In contrast to the results for aged monkeys, E treatment failed to enhance dlPFC-dependent task performance relative to vehicle control values (group young OVX+Veh) but nonetheless led to a robust increase in spine density. This response was accompanied by a decline in dendritic length, however, such that the total number of spines per neuron was equivalent in young OVX+Veh and OVX+E groups. Robust effects of chronological age, independent of ovarian hormone status, were also observed, comprising significant age-related declines in dendritic length and spine density, with a preferential decrease in small spines in the aged groups. Notably, the spine effects were partially reversed by cyclic E administration, although young OVX+Veh monkeys still had a higher complement of small spines than did aged E treated monkeys. In summary, layer III pyramidal neurons in the dlPFC are sensitive to ovarian hormone status in both young and aged monkeys, but these effects are not entirely equivalent across age groups. The results also suggest that the cognitive benefit of E treatment in aged monkeys is mediated by enabling synaptic plasticity through a cyclical increase in small, highly plastic dendritic spines in the primate dlPFC.
• aging
• estradiol
• hormone
• neocortex
• plasticity
This chapter discusses the utility of the dog as a model of brain aging. The procedural learning task, designed to assess skill acquisition in the dog, consists of two learning phases: reward-approach and object-approach learning. Aged dogs raised as pets, having diverse and varied life experiences, perform as well as or better than young dogs. Object recognition learning, the ability to classify and register the identity of objects, is examined using a delayed nonmatching to sample (DNMS) paradigm. The correct response for the dog is to choose the novel stimulus. The location of the novel stimulus is randomized across trials, and different stimuli selected from a large pool of objects are used for each trial. One of the most consistent cognitive deficits in old dogs is the ability to acquire and use spatial information. In humans, spatial learning impairments are a common feature of aging and become more severe in neurodegenerative disorders.
This chapter explores the potential of the canine as a model of human age-related cognitive decline (ARCD), dementia, and Alzheimer's disease (AD). It also discuss a number of studies that indicate that some people with dementia and dogs with cognitive dysfunction respond to therapy with the monoamine oxidase inhibitor, 1-deprenyl (selegiline HCl). Results indicate that elderly pet dogs exhibit multiple behavioral or cognitive problems indicative of cognitive dysfunction, which in some canine patients are sufficiently severe to disrupt the dog's function as an adequate pet. In some affected pet dogs, the change in behavior was found to be due to the presence of systemic, non-neurological disease; however, in numerous cases, no such general medical condition was identified, suggesting that the behavioral or cognitive dysfunction may be due to brain pathology. Studies indicate that some cognitive deficits, but not others, are correlated with age and with amyloid accumulation. Screening tests might be developed to predict amyloid accumulation and/or response to therapy in pet dogs. If so, this information might be extrapolated to cognitively impaired people. The dogs in the study presented in the chapter responded quite favorably to once-daily therapy with 0.5 mg/kg 1-deprenyl. Similarly, human patients with dementia of the Alzheimer's type have responded to 1-deprenyl therapy.
Canine cognitive dysfunction (CCD) is a clinical condition, which impacts significantly on the lives of elderly dogs and their owners. It is hypothesised that nutritional supplementation can be used in the management of the condition and this trial was designed to investigate the therapeutic effects of a specific supplement when compared to a placebo. The trial was conducted in a clinical context and involved 20 UK veterinary practices, giving geographical spread across the country. The duration of the trial was 56 days, including a baseline period of 7 days and a post trial period of 7 days. There was a significant difference between the treated and the placebo groups in relation to improvement in their scores for disorientation, changes in interaction and house soiling behaviour at day 21, day 28 and day 42. These results support the clinical practice of nutritional supplementation as a valuable component of the therapeutic approach in cases of canine cognitive dysfunction.
The behavior of 25 dogs was indirectly assessed by a formal questionnaire (evaluation of Age-Related Cognitive and Affective Disorders—ARCAD), filled out by the owner. The density of diffuse and vascular deposits was evaluated using four anti-Aβ peptide antibodies, in four temporal areas. Parenchymal, diffuse deposits of Aβ42 peptide were found in all aged animals but one. They were Congo red negative and were not immunostained by the anti-Aβ40 antibody, contrary to the vascular deposits. The densities of vascular and parenchymal deposits were not correlated. The ARCAD score was correlated with age, density of Aβ parenchymal and vascular deposits, and with the number of areas containing deposits (extension index). Multivariate analysis showed that the age and the extension index explained most of the variance. Congo red positivity (indicating that the Aβ peptide has the characteristics of an amyloid substance) is limited in the dog to the vascular wall and is associated, as in man, with the deposition of the Aβ 1–40 isoform. Parenchymal Aβ deposition seems to be a common correlate of behavioral problems in aging dogs.
Recent reports have suggested that β-amyloid (Aβ) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length Aβ423 fragments (i.e., Aβ forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both Aβ423 and Aβ40 (Aβ forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential Aβ deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of Aβ immunoreactive plaques, using antibodies to Aβ1–17, Aβ17–24, Aβ1–28, Aβ40, and Aβ42. We report that plaques within the canine and feline brain are immunopositive for Aβ42 but not Aβ40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within Aβ1–17, Aβ17–24, and Aβ1–28. In all species examined, vascular deposits were immunopositive for both Aβ40 and Aβ42. In the human brain, diffuse plaques were preferentially Aβ42 immunopositive, while neuritic plaques and vascular deposits were both Aβ40 and Aβ42 immunopositive. However, not all neuritic plaques contain Aβ40 epitopes.
Cognitive dysfunction syndrome (CDS) is a progressive neurodegenerative disorder of senior dogs. Since age-related behavioural changes may be useful indicators for early diagnosis and treatment, the first purpose of the present study was to investigate the prevalence of clinical signs of CDS in a general population of aged dogs. The second aim was to evaluate the use of a neuroprotective nutraceutical (Senilife®, Innovet Italia srl, Rubano, Italy) using an open-label clinical pilot trial.Dogs were recruited from a geriatric population not referred for behavioural consultations. A questionnaire with a checklist of behaviours was filled out to evaluate behavioural items grouped in the following categories: disorientation (D), socio-environmental interaction (I), sleep–wake cycles (S), house soiling (H), general activity (A)—(DISHA). Each owner was asked to rate the frequency of the behavioural signs: never, rarely, often, or always.One hundred and twenty-four dogs were assessed in the first survey; 22 of the 124 dogs tested in the survey were ruled out based on exclusion criteria (clinically and/or sensory severe impairment), 42 dogs had alterations in one category and 33 dogs had signs in 2 or more categories. Consequently 75 dogs had signs consistent with CDS.Among this population eight dogs affected by CDS were enrolled for the second step of the project, an open-label clinical pilot trial with the neuroprotective nutraceutical Senilife®. Senilife® contains 25mg phosphatidylserine, 50mg of standardized Ginkgo biloba extract, 33.5mg/d-alpha tocopherol and 20.5mg pyridoxine per capsule and is dosed at one capsule per 5kg body weight. The investigator asked the owners to rate the frequency of behaviours referring to DISHA using a four point frequency scale (never, rarely, often, always). Post-treatment, the owners were asked to evaluate all the signs in each category on a five point scale (much better, slightly better, the same, slightly worse, much worse). At the time of the first visit (V0) the owners were briefed verbally about the procedure; no behavioural advice was given throughout the study time and whenever appropriate therapy with Senilife® (was started. At V0, V1 (28±3 days), V2 (56±3 days) and V3 (84±3 days) a control visit was performed and the owners were interviewed. Dogs treated with Senilife® showed a highly significant difference at V3 compared to V0 (p
Objectives:
Recent studies have suggested that estrogen may improve cognitive function or prevent cognitive decline in older women. Little research has been conducted on exogenous or endogenous sex hormones and cognition in older men, yet it has been hypothesized that testosterone, either directly or by conversion to estrogens, may improve cognitive function. We investigated whether serum level of testosterone and estradiol is associated with cognition in older community-dwelling men.
Design:
A cross-sectional study.
Setting:
Population-based listings in the Monongahela Valley near Pittsburgh, Pennsylvania.
Participants:
Three hundred ten men (mean age +/- standard deviation = 73.0 +/- 7.1) who were part of a cohort study.
Measurements:
We measured cognitive function using the Mini-Mental State Examination (MMSE), Trails B, and Digit Symbol. Sex hormone levels were determined by radioimmunoassay from serum obtained at the time of cognitive testing and analyzed by tertile.
Results:
No consistent association between total testosterone level and cognitive test scores was observed. However, men with high bioavailable (loosely protein-bound) testosterone had better cognitive test scores on all three tests (P < or =.001). Total estradiol levels were associated with worse cognitive scores on Digit Symbol (P <.001) and Trails B (P =.002), but bioavailable estradiol levels were not associated with cognitive function. Level of sex hormone binding globulin (SHBG) was negatively associated with cognitive scores on all three tests (P < or =.001). After adjusting for age and education, the statistical significance lessened for bioavailable testosterone (MMSE, P =.086; Digit Symbol, P =.047; Trails B, P =.076) and became nonsignificant for SHBG (all cognitive tests P>.10).
Conclusions:
Our findings support the hypothesis that higher levels of bioavailable testosterone, but not of bioavailable estradiol, are associated with better cognitive function in older men. In addition, bioavailable measures of testosterone may better reflect hormone levels available to the brain and thus be more closely associated with central nervous system outcomes such as cognition. Future studies, especially randomized trials, should be undertaken to determine whether testosterone may protect against cognitive decline in older men.
Among 26 dogs greater than or equal to 10 years old, the most frequent owner complaints relating to behavioral problems were destructive behavior in the house (n = 10), inappropriate urination or defecation in the house (n = 10), and excessive vocalization (n = 7). The most frequent behavioral diagnoses were separation anxiety (n = 13) and breakdown of housetraining (n = 6). Most of the behavioral problems in the 26 dogs began after the dogs reached the age of 10 years, and most of the dogs had been owned for many years without having behavioral problems. Few behavioral problems in old dogs had a medical basis. Most cases of inappropriate urination or defecation in the house were not related to urinary or fecal incontinence, but were exacerbated by problems such as degenerative joint disease and renal disease. Behavioral therapy is appropriate for behavioral problems in old dogs, and, taking into account an old dog's health and physical limitations, techniques used are the same as for younger dogs.
We characterized eight aged beagles (maintained from birth in a laboratory colony) and one black Labrador using Bielschowsky's, thioflavine S, and Congo red staining, and antibodies to the beta-amyloid peptide, dystrophic neurites, and other plaque components. All plaques within these canine brains were of the diffuse subtype and were neither thioflavine S- nor Congo red-positive. The majority of plaques in the entorhinal cortex contained numerous neurons within them while plaques in the dentate gyrus did not. beta-Amyloid immunoreactivity was also present within select neurons and neuronal processes and was detected as a diffuse linear zone corresponding to the terminal fields of the perforant path. There was no significant correlation between extent of beta-amyloid accumulation and neuron number in entorhinal cortex. Neither tau-1, PHF-1, nor SMI-31-immunostaining revealed dystrophic fibers, confirming the classification of these plaques as diffuse. Canine plaques did not appear to contain bFGF- or HS-positive immunostaining. This may explain why neuritic involvement was not detected within these canine plaques. It is possible that the beta-amyloid within the canine brain has a unique primary structure or may not be in an assembly state that adversely affects neurons.
The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning, memory and other cognitive functions. Canines develop extensive beta-amyloid deposition within neurons and their synaptic fields, which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular changes, dilation of the ventricles, and cytoskeletal changes. Neurofibrillary tangles (NFTs) are not present in the aged canine. Thus, the aged canine brain provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported by behavioral data. We have found that the extent of beta-amyloid deposition correlates with a decline in select measures of cognitive function. These data provide the first evidence of a correlation between beta-amyloid accumulation and cognitive decline in the absence of NFTs. We summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropathology similar to that observed in aged humans; (b) Veterinarians have observed that many canines exhibit a clinical syndrome of age-related cognitive dysfunction; (c) Aged canines are deficient on a variety of neuropsychological tests of cognitive function; (d) The level of beta-amyloid accumulation correlates with cognitive dysfunction in the canine. These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation.
Brains from 41 aged canines (> or = 10 years of age) were examined immunohistochemically to characterize the laminar distribution and age-related progression of beta-amyloid (A beta) in frontal cortex. We classified the A beta patterns into four distinct types. Type I was characterized by small, faint deposits of A beta in deep cortical layers. Type II consisted of diffuse deposits of A beta mainly in layers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dense plaques throughout all layers of cortex. We compared the A beta distribution pattern between the Old canines (10-15 years, n = 22) and the Very Old canines (> 15 years, n = 19). The Old group primarily had negative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (P < 0.05). We suggest that A beta deposition in canine frontal cortex is a progressive age-related process beginning with diffuse deposits in the deep cortical layers followed by the development of deposits in outer layers. In support of this hypothesis, the deeper layer diffuse plaques in the Very Old group of dogs also contain the largest proportion of beta-amyloid with an isomerized aspartic acid residue at position 7, indicating that these deposits had been present for some time. We also observed fiber-like A beta immunoreactivity within regions of diffuse A beta deposits. These fibers appeared to be degenerating neurites, which were negative for hyperphosphorylated tau. Therefore, these fibers may represent a very early form of neuritic change that precede tau hyperphosphorylation or develop by an alternative pathway.
Young, middle-aged, and old beagle dogs were tested on several visual-discrimination tasks: reward- and object-approach learning, object discrimination and reversal, long-term retention of a reversal problem, and a size-discrimination task. Beta-amyloid accumulation in the entorhinal, prefrontal, parietal, and occipital cortices was quantified using immunohistochemical and imaging techniques at the conclusion of cognitive testing. Middle-aged and old dogs were impaired in size-discrimination learning. In each task, a subset of aged dogs was impaired relative to age-matched peers. Beta-amyloid accumulation was age-dependent. However, not all middle-aged and old dogs showed beta-amyloid accumulation in the entorhinal cortex. The error scores from dogs tested with a nonpreferred object during visual discrimination learning and from reversal learning were correlated with beta-amyloid in the prefrontal but not entorhinal cortex. Size-discrimination and reward and object-approach learning error scores were correlated with beta-amyloid accumulation in the entorhinal but not prefrontal cortex. The results of these studies support an association between cognitive test and the location and extent of beta-amyloid pathology.
The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59-89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the "World" Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable testosterone with the "World" test; and total estradiol with the Trail-Making Test. All associations were relatively weak but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.
Although several studies have suggested that hormone replacement therapy lowers the risk of AD among postmenopausal women, few studies have evaluated the relationship of endogenous estrogen levels and AD. The current study investigated whether serum estrone and estradiol levels were related to the presence of AD among postmenopausal women not currently taking hormone replacement therapy.
Using a case-control design, we examined an ethnically diverse sample of postmenopausal women who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 50) and nondemented controls (n = 93). All women were participants in a study of aging and dementia and were seen consecutively between August 1997 and October 1998.
Patients with AD had lower estradiol (F[1,141] = 8.3, p = 0.005) levels than did normal controls. Patients also had lower estrone levels; however, this comparison did not quite meet significance criteria (F[1,141] = 3.6, p = 0.06). Compared to estradiol levels >20 pg/mL, women with AD were four to six times more likely to have levels <20 pg/mL after adjusting for age, years of education, presence of an APOE-epsilon4 allele, ethnicity, and body mass index. There were no significant differences in frequency of AD among women within different quartiles of estrone after adjusting for potential confounds.
The results of this preliminary case-control study suggest that estradiol levels may decline significantly in women in whom AD develops.
Previous studies have found no association between serum concentrations of total oestradiol and cognitive function, but these measurements may not reflect concentrations of hormone available to the brain. We tested the hypothesis that concentrations of non-protein-bound (free) and loosely bound (bioavailable) sex hormones are associated with cognitive function in older women.
We measured cognitive performance with a modified mini mental status examination (mMMSE) at baseline (1986-88) and 6 years later in 425 women (65 years or older). Concentrations of non-protein-bound and bioavailable oestradiol and total and non-protein-bound testosterone were measured by RIA in serum samples taken at baseline.
Initial cognitive scores did not differ by tertile of non-protein-bound oestradiol, bioavailable oestradiol, or testosterone. Cognitive impairment (a decrease of 3 points or more in mMMSE score) occurred in five (5%) of 94 women in the high tertile for non-protein-bound oestradiol and in 17 (16%) of 106 in the low tertile (odds ratio 0.3 [95% CI 0.1-0.8]). After adjustment for age, years of education, body-mass index, current oestrogen use, history of surgical menopause, and baseline mMMSE score, the odds ratio was 0.3 (0.1-0.9). The results were similar for bioavailable oestradiol (five [5%] vs 15 [15%]; adjusted odds ratio 0.3 [0.1-1.0]). There was no association between risk of cognitive impairment and serum testosterone.
Women with high serum concentrations of non-protein-bound and bioavailable oestradiol, but not testosterone, were less likely to develop cognitive impairment than women with low concentrations. This finding supports the hypothesis that higher concentrations of endogenous oestrogens prevent cognitive decline.
1. Aged dogs display many of the cognitive impairments associated with aging and dementia. 2. Aged dogs, like humans, display a wide range of individual variability in cognitive functioning (i.e., different cognitive functions decline at different rates in aged dogs). 3. Different categories of aged canines can be identified on the basis of neuropsychological test performance, and these categories can be used to model different subgroups of aged humans (i.e., dementia, mild cognitive impairment and successful aging). 4. Additional research is required to further validate the dog as a model of human cognitive aging and dementia.
Relatively few studies have investigated the relationship between endogenous sex steroid levels and cognition in older people and the reported results have been inconsistent. A number of experimental hormone replacement studies have suggested that estrogen replacement in older women enhances cognition, especially verbal memory. In contrast, little research has been done focusing on men. In the current study the association between endogenous sex steroids (estradiol and testosterone) and cognition was investigated in 38 healthy older women (mean age 68 years) and 30 healthy older men (mean age 69 years). Five cognitive tests measuring verbal memory, spatial memory, verbal fluency, mental rotation, and susceptibility to interference were administered. Results revealed that in women higher estradiol levels as well as testosterone levels were associated with better verbal memory (paired associates and estradiol; r =.38, P < 0.05; paired associates and testosterone; r =.33, P < 0.05;). Moreover estradiol, but not testosterone was associated with less susceptibility to interference (Stroop color word test; r = -0.34, P < 0.05). In men the only significant association was a negative correlation between testosterone and verbal fluency (r = -0.38, P < 0.05). The associations observed in this small study support the notion that estradiol is protecting verbal memory and possibly also frontal lobe mediated functions in older women. In contrast to the positive findings in women endogenous sex steroids do not appear to be closely linked to better cognition in older men.
The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition.
The effects of long-term treatment with both antioxidants and a program of behavioral enrichment were studied as part of a longitudinal investigation of cognitive aging in beagle dogs. Baseline performance on a battery of cognitive tests was used to assign 48 aged dogs (9-12 years) into four cognitively equivalent groups, of 12 animals per group: Group CC (control food-control environment), group CE (control food-enriched environment); Group AC (antioxidant fortified food-control environment); Group AE (fortified food-enriched environment). We also tested a group of young dogs fed the control food and a second group fed the fortified food. Both groups of young dogs received a program of behavioral enrichment. To evaluate the effects of the interventions on cognition after 1 year, the dogs were tested on a size discrimination learning task and subsequently on a size discrimination reversal learning task. Both tasks showed age-sensitivity, with old dogs performing more poorly than young dogs. Both tasks were also improved by both the fortified food and the behavioral enrichment. However, in both instances the treatment effects largely reflected improved performance in the combined treatment group. These results suggest that the effectiveness of antioxidants in attenuating age-dependent cognitive decline is dependent on behavioral and environmental experience.
For the past 15 years we have investigated the aged beagle dog as a model for human aging and dementia. We have shown that dogs develop cognitive deficits and neuropathology seen in human aging and dementia. These similarities increase the likelihood that the model will be able to accurately predict the efficacy of Alzheimer's disease (AD) treatments as well as detect therapeutics with limited or no efficacy. Better predictive validity of cognitive-enhancing therapeutics (CETs) could lead to enormous cost savings by reducing the number of failed human clinical trials and also may reduce the likelihood of negative outcomes such as those recently observed in the AN-1792 clinical trials. The current review assesses the pharmacological validity of the canine model of human aging and dementia. We tested the efficacy of (1) CP-118,954 and phenserine, two acetylcholinesterase inhibitors, (2) an ampakine, (3) selegiline hydrochloride, two drugs that have failed human AD trials, and (4) adrafinil, a putative CET. Our research demonstrates that dogs not only develop isomorphic changes in human cognition and brain pathology, but also accurately predict the efficacy of known AD treatments and the absence or limited efficacy of treatments that failed clinical trials. These findings collectively support the utilization of the dog model as a preclinical screen for identifying novel CETs for both age-associated memory disorder and dementia.
With increasing age, dogs develop a form of neurodegenerative disease which has many similarities to age related cognitive impairment and Alzheimer's disease in humans. A decline in learning and memory can be demonstrated in dogs beginning as young as 7 years of age using a variety of neuropsychological tests. However, clinical cases of cognitive dysfunction syndrome are seldom identified until the age of 11 years or older. This is likely due to the fact that the owners are relying on clinical observations such as house-soiling, sleep-wake cycles and disorientation, rather than tests of learning and memory. On the other hand, dogs that are trained to more exacting tasks such as guide dogs for the visually impaired, or bomb detection and agility trained dogs might be noticed to have a decline in performance at a much earlier age. Through the use of standardized neuropsychological testing protocols, a number of drugs, natural products and supplement formulations have been developed for use in dogs with cognitive dysfunction and, in some cases clinical trials have validated their efficacy. Furthermore, the testing of products currently licensed and in the pipeline for the treatment of cognitive decline and Alzheimer's in humans, may provide additional therapeutic agents for the treatment of senior dogs, as well as provide insight as to the potential for the efficacy of these compounds in humans. This review will examine those products that are now marketed along with some that might be considered for use in senior dogs with cognitive dysfunction as well as the research that has been used to validate the efficacy (or lack thereof) of these compounds.