Survey of risk factors and frequency of clinical signs observed with feline cognitive dysfunction syndrome

Abstract

Objectives

The aims of this study were to distribute a survey to cat owners to identify common clinical signs of feline cognitive dysfunction (FCD) and to evaluate for potential risk factors.

Methods

A questionnaire was developed and adapted based on previously validated canine cognitive dysfunction questionnaires. This questionnaire was distributed to 4342 cat owners who had presented to Colorado State University Veterinary Teaching Hospital between 2015 and 2020. Cats aged ⩾8 years with signs of cognitive dysfunction and no underlying medical conditions were classified as the FCD-positive group. Cats aged ⩾8 years with no signs of cognitive dysfunction were classified as the FCD-negative control group. Chi-square or Fisher’s exact tests were used to determine associations between categorical variables and a P value <0.05 was considered indicative of evidence of association.

Results

A total of 615 completed survey responses were recorded, which was a response rate of 14.2%. Among those, 80 (13%) cats were identified as the FCD-positive group and 114 (18.5%) were identified as the FCD-negative control group. The most common clinical sign in the FCD-positive group was inappropriate vocalization (32/80, 40.0%). The only variable determined to have an association with the FCD group (positive or negative), with a P value of 0.033, was the environmental setting. Cats living in a rural environment (FCD-positive or -negative) had the largest contribution to the χ² statistic.

Conclusion and relevance

The observed number of FCD-positive cats living in a rural community was less than the expected value based on the χ² tests. This is suggestive of an association between living in a rural environment and a reduced chance of cognitive dysfunction. There are many factors such as air pollution, social interactions and environmental enrichment that need to be studied further to determine how they relate to FCD as this could not be concluded from this study.

Introduction

Thanks to advances in veterinary medicine and nutrition, the population of elderly cats is growing. According to a 2016 US survey of pet owners performed by the American Veterinary Medical Association, 19% of the cat population (~10 million) were aged 11 years or older. ¹ This warrants the need for a better understanding of disorders related to aging, such as cognitive dysfunction.

Cognitive dysfunction syndrome (CDS), like Alzheimer’s disease in humans, is a progressive, neurodegenerative disease that leads to behavioral changes and cognitive decline. ² Approximately 28% of cats aged 11–14 years, and 50% of cats aged 15 years or older, were found to show behavior changes unattributed to underlying disease.^3,4 Behavior changes attributed to CDS in cats can be represented by the acronym VISHDAAL: vocalization, alterations in interactions, changes in sleep-wake cycle, house soiling, disorientation, alterations in activity levels, anxiety, and learning and memory. ⁵ Unfortunately, it is common for subtle changes in behavior to go unreported as they are thought to be part of the normal aging process; therefore, client education and thorough historical investigation is important. In a survey of pet owners, 75% reported signs of CDS when specifically asked, but only 12% volunteered this information. ⁶

Vascular insufficiency leading to hypoxia, oxidative damage and compromised cerebrovascular blood flow have all been implicated as potential causes for neurodegeneration in feline cognitive dysfunction (FCD). ⁵ Many of the neuropathological changes described in both humans and canines with cognitive decline have been sparsely described in the aging feline population. Changes identified in the aging feline brain include brain atrophy, neuronal loss, vascular and perivascular changes, amyloid beta (Aβ) deposition and tau hyperphosphorylation.^3,5,7 The two classical features most discussed in humans with Alzheimer’s disease are Aβ deposition and the accumulation of hyperphosphorylated tau leading to neurofibrillary tangles. In the few published papers available, the Aβ plaques observed in cats are not as well developed or circumscribed as those found in humans with Alzheimer’s disease. ⁸ Furthermore, the soluble Aβ1-40 species, which is deposited following Aβ1-42 in canines and humans and is thought to represent older deposits of Aβ in plaques, has not yet been observed in the aging feline brain. ⁹ The Aβ deposition in aged cats more closely resembles the plaque accumulation exhibited in non-demented elderly humans. ⁹ Additionally, the extent of Aβ deposition in cats does not seem to correlate with severity of cognitive dysfunction. While the onset of cognitive decline is more commonly noted in cats aged >10 years, there are certain neuropathological changes that have been seen in cats as young as 6–8 years of age.^9–14 The extent of these pathologies in cats is less pronounced than those seen in humans and, to date, have not been directly linked to FCD. However, it is important to note the scarcity of published literature describing FCD.

As FCD is thought to be an ante-mortem diagnosis of exclusion, it is necessary to first rule out other underlying medical conditions (ie, osteoarthritis, hypertension, hyperthyroidism, etc) by performing physical examinations (including orthopedic and neurologic examinations) and minimum database diagnostics. Advanced imaging, such as MRI of the brain, may be warranted in some cases to rule out intracranial disease. However, physical evaluation and certain diagnostics are often difficult to perform in cats due to stress elicited by a clinical setting, making the initial assessment challenging. Furthermore, unlike dogs, there is not a validated questionnaire available for cats, further contributing to the diagnostic dilemma.

While canine CDS has been well described with several clinical assessment tools and treatment studies, there is a lack of research regarding FCD. If we are to truly understand and gain more insight into FCD, we must establish an effective screening tool to identify those elderly cats that are potentially affected, as well as recognize risk factors that may contribute to disease development. To create a validated owner questionnaire, it is important to understand the most common clinical signs that afflict cats suffering from cognitive impairment. The first aim of this study was to distribute a questionnaire for cat owners to identify common signs of FCD. Further investigation of the potential environmental, social and emotional risk factors is necessary to help cat owners implement lifestyle changes that could slow progression or even prevent cognitive impairment. Therefore, the second aim of this study was to evaluate for potential risk factors for cats that develop FCD.

Materials and methods

Questionnaire

By adapting validated canine questionnaires to fit feline patients, a questionnaire was created using Qualtrics software (see the ‘FCD questionnaire’ in the supplementary material). The purpose of the questionnaire was to identify cats with signs of FCD, preferably without any known underlying conditions, and to determine associated risk factors. Risk factors previously identified in humans and dogs, such as environment, lifestyle (other pets, children and amount of time spent indoors/outdoors) and diet/nutrition, were explored through this questionnaire. Once created, the questionnaire was evaluated by a focus group that provided feedback incorporated into the final version. The questions were formatted as both closed and open-ended, understanding the advantages and disadvantages of each as described by Boynton et al. ¹⁵ The final questionnaire consisted of 29 questions.

Participants

Participants for the online survey were identified by performing a medical record search of cats (all ages) that had presented to Colorado State University Veterinary Teaching Hospital (CSU VTH) between 2015 and 2020. An email was sent using Qualtrics software to 4342 cat owners requesting their participation in our survey. The survey was made available between 31 August 2020 and 5 October 2020. A total of 615 anonymous surveys were completed and included in the analysis.

Data recording and analysis

Data were reviewed from completed surveys. The data were exported from Qualtrics to a Microsoft Excel spreadsheet. Responses were divided into three groups (Table 1): (1) cats with no underlying medical conditions that had at least one behavior consistent with FCD; (2) cats with underlying medical conditions that had at least one behavior consistent with FCD; and (3) cats with no behaviors consistent with FCD with or without underlying medical conditions. While those cats that were in group 2 still could have signs attributable to FCD, they were excluded from analysis because they had underlying medical conditions that, due to the nature of the study, could not be ruled out as a cause for their signs. Groups 1 and 3 were further divided based on age of the cats (a: cats aged ⩾8 years, b: cats aged <8 years) with group 1a being our suspected FCD-positive group and group 3a being our age-matched negative control group. An explanation for the age cutoff can be found in the discussion. Comparisons were made between groups based on the behaviors observed, number of children and other pets in the household, body condition score (thin, average or overweight as assessed by the owner), lifestyle (amount of time spent indoors/outdoors), environment (rural, suburban or urban setting) and diet/nutrition. Among the group 1a cats (young with one FCD behavior) and group 1b cats (aged with one FCD behavior), the percentage of each behavior sign exhibited in these two groups was recorded. Chi-square or Fisher’s exact tests were used to determine associations between the FCD groups (negative or positive) and different assessed risk factors. A P value <0.05 was considered significant.

Table 1.

Definition of each group and the number of cats per group out of the number of completed surveys

Groups	Surveyed cats in each group/completed surveys (n/n)	Cats in this group (%)
Group 1a (FCD positive): cats with no underlying medical conditions that had at least one behavior consistent with FCD (aged ⩾8 years)	80/615	13
Group 1b: cats with no underlying medical conditions that had at least one behavior consistent with FCD (aged <8 years)	63/615	10.2
Group 2: cats with underlying medical conditions that had at least one behavior consistent with FCD	271/615	44.1
Group 3a (FCD negative): cats with no behaviors consistent with FCD with or without underlying medical conditions (aged ⩾8 years)	114/615	18.5
Group 3b: cats with no behaviors consistent with FCD with or without underlying medical conditions (aged <8 years)	87/615	14.2

FCD = feline cognitive dysfunction

Results

The completed response rate for the questionnaire was 14.2% (615/4342). Of the completed surveys, 414 cats were reported to have at least one behavior change in the past 6 months consistent with FCD. Among these cats, 271 had underlying medical conditions that could not be ruled out as the cause for their behavior changes and were classified into group 2. The remaining cats were divided into groups as described previously (Table 1).

Among the FCD-positive cats, 45.0% (36/80) came from a one-cat household compared with 35.9% (41/114) of the FCD-negative cats (Figure 1a). When considering the number of cats per household (1 or 2+) vs FCD group (positive or negative), the χ² P value was 0.205 (df = 2). Nearly all the FCD-positive (90.0%) and FCD-negative (88.6%) cats spent >75% of their time indoors (Figure 1b). When considering where cats spent most of their time (indoors, outdoors, equal time in both) vs FCD group (positive or negative), the Fisher’s exact P value was 0.949 (df = 2). Most of the cats were reported to be of average body condition equating to 58.8% (47/80) of the FCD-positive cats and 57.9% (66/114) of the FCD-negative cats. Approximately 11.3% (9/80) of the FCD-positive cats and 20.2% (23/114) of the FCD-negative cats were considered to be obese (Figure 1c). Considering body condition score (thin, average, overweight) vs FCD group (positive or negative), the χ² P value was 0.175 (df = 2). The majority of cats in both groups lived in a suburban setting with 66.3% (53/80) of FCD-positive cats and 54.4% (62/114) of FCD-negative cats. Interestingly, 29.8% (34/114) of the FCD-negative cats lived in a rural setting compared with 13.8% (11/80) of the FCD-positive cats (Figure 1d). Considering the environmental setting (rural, suburban, urban) vs FCD group (positive or negative), the χ² P value was 0.033 (df = 2). The percentage of cats that lived in a household with at least one child aged less than 12 years was 16.3% (13/80) for FCD-positive cats and 8.8% (10/114) for FCD-negative cats (Figure 1e). When considering the presence or absence of children in the household vs FCD group (positive or negative), the χ² P value was 0.113 (df = 2). Nearly 51% (58/114) of the FCD-negative cats and 47.6% (38/80) of the FCD-positive cats lived with at least one dog (Figure 1f). When considering the presence or absence of dogs in the household vs FCD group (positive or negative), the χ² P value was 0.644 (df = 2).

Figure 1.

(a–f) Comparison of the environmental and lifestyle backgrounds of the 80 feline cognitive dysfunction (FCD)-positive and 114 FCD-negative cats (aged ⩾8 years): (a) cats per household; (b) where they spend >75% of their time; (c) body condition scores; (d) the communities in which they live; (e) children per household; (f) dogs per household

The only variable determined to have an association with the FCD group (positive or negative), with a P value of 0.033, was the environmental setting. Cats (FCD-negative or -positive) living in a rural environment had the largest contribution to the χ² statistic compared with those living in a suburban or urban setting. The number of observed FCD-positive cats living in a rural setting compared with the expected value were 11 and 18.6, respectively (Table 2).

Table 2.

Evaluation of the association between environmental setting and feline cognitive dysfunction (FCD) group (positive or negative cats aged ⩾8 years) using the χ² test (degrees of freedom = 2, χ² = 6.8285, P = 0.0329)

		Rural	Suburban	Urban	Total observed
FCD-positive (group 1a)	Observed Expected χ2 contribution	11 18.6 3.0773	53 47.4 0.6559	16 14 0.2794	80
FCD-negative (group 3a)	Observed Expected χ2 contribution	34 26.4 2.1595	62 67.6 0.4603	18 20 0.1961	114
Total observed		45	115	34	194

Of the completed surveys, 53.6% (330/615) did not answer the questions regarding diet. Of the diet responses (285/615), 96.8% (276/285) were fed a strictly commercial diet with one cat fed a homemade diet, three cats fed a strictly raw diet and five cats fed a mix of commercial and raw food diet.

When comparing group 1a and group 1b (Table 3), the most commonly reported behavior sign for each group was inappropriate vocalization (40.0%, 32/80) and restlessness at night (30.1%, 19/63), respectively. Disorientation was more commonly reported in the FCD-positive cats (18.7%) compared with the younger group 1b cats (3.2%). Changes in sleep patterns were also much less commonly reported in the younger group 1b cats (1.6%) compared with the FCD-positive cats (12.5%).

Table 3.

Frequency of behavior signs reported (%) among feline cognitive dysfunction (FCD)-positive cats (aged ⩾8 years; group 1a) and group 1b cats (aged <8 years) in which all cats had at least one behavior sign reported

Behavior signs	Group 1a (n = 80)	Group 1b (n = 63)
Aggression	28.7	17.5
Anxiety	17.5	19.0
Behavior changes	21.2	11.0
Disorientation	18.7	3.2
Excessive grooming	13.7	11.1
Hiding	21.3	22.2
House soiling	26.3	17.5
Inappropriate vocalization	40.0	20.6
Increased/decreased attention seeking	28.8	22.2
Increased/decreased interest in play	7.5	17.5
Changes in sleep patterns	12.5	1.6
Restlessness at night	31.3	30.2

Discussion

FCD is a neurodegenerative disorder of aging cats that, due to lack of research in the field, is still poorly understood. Since the purposes of this study were to identify common clinical signs and potential risk factors associated with FCD, the FCD-positive group (group 1a) and FCD-negative group (group 3a) were evaluated. Cats in groups 1 and 3 were further divided based on whether they were aged <8 years or ⩾8 years. Previous studies have reported signs of cognitive dysfunction in cats aged >10 years, but characteristic neuropathological changes have been discovered in cats as early as 6–8 years of age.^9–14 Based on the described neuropathological changes in those cats aged 6–8 years, it is postulated that cats aged <10 years can be affected by FCD. Therefore, for this report, a cutoff of 8 years of age was used to define FCD-positive cats. The reported FCD-positive cats (13%) were likely undercounted, as group 2 cats had behaviors that could be attributed to FCD but their underlying medical conditions could not be ruled out as a cause for their signs (Table 1). While the survey created for this study was a good starting point, further work is needed to develop a more appropriate questionnaire that addresses the limitations mentioned later in the discussion. This new questionnaire should be paired with an in-depth clinical evaluation and targeted diagnostics to determine if cats have FCD.

The most common behavior sign noted in the FCD-positive cats was inappropriate vocalization (40%). In a study evaluating prevalence of behavioral changes in 100 elderly cats aged 12–22 years, the most common behavior change, reported in 61% of the surveyed population, was also increased vocalization. ⁷ Increased vocalization may have many underlying causes such as disorientation, attention seeking, pain and/or resource seeking.^5,16 In a recent survey, owners of cats with diagnosed FCD reported that the main cause of increased vocalization was disorientation (40.5%) or attention seeking (40.5%) with most owners (64.8%) suspecting more than one underlying cause. ¹⁶ Therefore, further investigation is required to determine the true underlying cause of inappropriate vocalization so that treatment may be implemented.

Across the globe, more than 90% of the population is breathing air that does not meet World Health Organization standards. ¹⁷ One study measured global cognitive function in adult humans utilizing a mini-mental state examination (MMSE) and found that residents in an urban area had significantly lower cognition scores compared with residents in rural areas. ¹⁸ In the current study, 86.3% (69/80) of the FCD-positive cats lived in suburban or urban areas and 13.8% (11/80) lived in rural areas. Interestingly, 29.8% (34/114) of the FCD-negative cats lived in rural areas with 54.4% (62/114) living in suburban areas and 15.8% (18/114) living in urban areas. There were less FCD positive cats living in a rural setting than expected based on the χ² tests. This suggests that there is an association between cats living in a rural community and a reduced chance of cognitive dysfunction. Even with this evidence of association, a direct correlation with air pollution is unable to be determined based on the current data. Further studies are required to explore this as a possible risk factor for FCD.

Obesity has also been identified as a risk factor in humans with cognitive impairment. Owing to the variability in size of dogs based on breed, a relationship between weight and canine cognitive dysfunction has yet to be identified. ¹⁹ In one study evaluating 1.3 million people worldwide, it was found that a higher body mass index at mid-life was correlated with a higher risk of developing dementia later in life. ²⁰ In the current study, only 11.3% of the FCD-positive cats were reported to be obese compared with 20.2% of the FCD-negative cats. It is common for owners to underestimate their pet’s body condition score, which makes it difficult to trust the results in this case. Assessment of obesity as a risk factor for FCD would be more accurate with a veterinary evaluation of the patient.

It has been postulated that engaging in activities requiring physical exercise throughout life to stimulate the cognitive pathways may promote neuroprotection and prevent age-related cognitive decline. ²¹ In cats, this may be accomplished by providing environmental enrichment and interacting with owners, children or other pets in the household. In the current study, there were no clear differences between the FCD-positive cats and the FCD-negative cats when comparing the number of cats in the household, number of children or dogs in the household or the indoor/outdoor status of the cat. However, the quality of the outdoor activities in these cats could not be fully assessed, which means subtle differences between the groups could have been overlooked. Although environmental enrichment has been implemented in dogs with CDS to slow progression of disease, once clinical signs of FCD arise, any change to their environment can cause stress, which may in turn have a negative effect. ²² Further research is needed to determine the role physical activity and mental stimulation have in the development of FCD.

The limitations of this study are largely attributed to the method used to conduct the survey. As this was a voluntary online survey, the time it takes to complete the survey was kept between 5 and 10 mins to maximize the response rate; however, this limited the number of questions that could be asked. Information about the cats surveyed did not include sex, breed or reproductive status, which has been explored in dogs as potential risk factors. For those that did respond, a large number only answered the first few questions, which did not include any questions regarding behavior, environment or medical history. Unfortunately, there was no analyzable data from these responses. Some responders had difficulty recalling medical history information, which made it difficult to categorize them into groups. Another factor that was not assessed within this survey was how long the owner had owned the cat. This would greatly impact the question regarding behaviors seen in the past 6 months if they had not owned the cat for that amount of time. The survey was emailed to cat owners who had presented to the CSU VTH within the previous 5 years. Based on the title and description of the survey, a portion of owners may not have participated in the study because they felt their cat did not have behavior changes consistent with FCD. Therefore, the prevalence of FCD could not be derived based on the survey population. Responses to open-ended questions regarding medical history, diet/nutrition and more, varied greatly, making direct comparisons challenging. Reviewing veterinary electronic medical records would have substantially increased the power of this study. Given that neuropathological evaluation of the brain is necessary to make a definitive diagnosis, the FCD-positive cats reported in this study were considered a presumptive diagnosis. Post-mortem brain tissue analysis would be necessary for confirmation. In summary, the limitations of this study included a finite number of questions, owners’ willingness to complete the survey, owners’ understanding of the questions, interpretation of open-ended questions and the accuracy of the responses.

Future longitudinal studies, in which the survey results are compared with characteristic pathological changes, including neuroinflammation and accumulation of misfolded proteins (Aβ and neurofibrillary tangles), would be critical for validating the survey, as well as further studying the aging process in cats. ²³ Targeted neuropathological analysis, using immunohistochemistry, of the feline brain, to demonstrate an increase in Aβ and phosphorylated tau protein, as well as neuroinflammation, such as activated astrocytes, would be necessary for understanding the disease course in domestic cats.^24–27

Conclusions

The survey was completed by 615 cat owners and identified 80 cats aged ⩾8 years that exhibited at least one behavior sign consistent with FCD, without concurrent medical conditions. The most common clinical sign reported was inappropriate vocalization, which is consistent with a previous report. ⁷ The number of observed FCD-positive cats living in a rural environment was less than the expected value, which suggests an association between living in a rural environment and a reduced chance of cognitive dysfunction. A direct correlation to air pollution cannot be made based on the current data. More studies are needed to further elucidate the risk factors associated with cognitive decline in the senior feline population.