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Prevalence of behavioral changes associated with age-related cognitive impairment in dogs

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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.
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T
hanks to improvements in nutrition, medical care,
and protection from accidental death, many com-
panion dogs live well into their elderly stages of life. As
of 1996, 14% (7.3 million) of all dogs in the United
States were 11 years of age or older.
1
A longer life span
brings with it age-related degenerative changes in a
number of organ systems, including those of the car-
diovascular, musculoskeletal, visual, auditory, renal,
and endocrine systems. The brain also undergoes
degenerative changes with age, resulting in noticeable
impairment of memory and learning in dogs.
2,3
The
growing interest in understanding the nature and
prevalence of signs of dysfunction in dogs related to
impairment of memory and learning was enhanced by
the recent approval of the dopaminergic and neuropro-
tective drug selegiline hydrochloride
a
by the FDA
Center for Veterinary Medicine for treatment of cogni-
tive dysfunction syndrome in dogs.
4
Because signs such as disorientation in the home,
disturbance of house training, and reduced recognition
of family members involve deficits in memory and
learning, the terms cognitive dysfunction and cognitive
impairment have been introduced into the literature
dealing with aging dogs to refer to these behavioral
changes.
2,3,5
Animal cognition usually refers to complex
learned associations where the animal makes respons-
es that appear to reflect abstractions from previously
learned material; that is, a new response is made that
was not the result of prior direct reinforcement.
6,7
Although such cognitive function would be difficult to
assess clinically in companion dogs, this species, like
many mammalian and avian species studied,
6,7
is
undoubtedly capable of cognitive behavior. Loss of ori-
entation in the home or yard, impaired recognition of
family members, and loss of house training, although
not necessarily manifestations of impairment in cogni-
tive behavior, do reflect impairment of memory and
learning and would be logically linked with impair-
ment of cognitive function.
Use of the terms cognitive dysfunction or cogni-
tive impairment is predicated on the assumption that
these changes reflect neuronal, neurotransmitter, meta-
bolic, cerebrovascular, or biochemical degenerative
changes in the brain and are not primarily a reflection
of dysfunction in other organ systems.
2,3
Aged dogs
have been known for some time to accumulate β-amy-
loid deposits in the hippocampus and frontal cortex
(areas especially involved in changes in cognitive
behavior),
8,9
and results of recent research indicate that
the deposits are similar to the primitive or early stage
β-amyloid plaques in the brains of human Alzheimer’s
patients.
10,11
In humans with Alzheimer’s disease, the
plaques mature into discrete plaques that result in neu-
ronal cell death.
12,13
Results of laboratory research on
aging Beagles suggest that the degree of β-amyloid
JAVMA, Vol 218, No. 11, June 1, 2001 Scientific Reports: Original Study 1787
SMALL ANIMALS
Prevalence of behavioral changes associated
with age-related cognitive impairment in dogs
Jacqueline C. Neilson, DVM, DACVB; Benjamin L. Hart, DVM, PhD, DACVB; Kelly D. Cliff, DVM;
William W. Ruehl,
DVM, PhD, DACVP
Objective—To determine the prevalence of age-relat-
ed behavioral changes, namely impairment, in a ran-
domly chosen population of dogs.
Design—Age-stratified cohort study.
Animals—97 spayed female and 83 castrated male
dogs that were 11 to 16 years old.
Procedure—Data on possible impairment in 4 behav-
ioral 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 2 signs of dysfunction within a cate-
gory. Dogs with impairment in 1 category were consid-
ered mildly impaired and those with impairment in 2
categories were considered severely impaired.
Results—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 1 cate-
gory was 28% (22/80), of which 10% (8/80) had
impairment in 2 behavioral categories. Of 15- to 16-
year-old dogs, 68% (23/34) had impairment in 1 cat-
egory, of which 35% (12/34) had impairments in 2
categories. There were no significant effects of body
weight on the prevalence of signs of dysfunction in
the behavioral categories.
Conclusions and Clinical Relevance—Data collect-
ed provide estimates of the prevalence of various
degrees of age-related behavioral changes associated
with cognitive dysfunction in dogs. Age-related behav-
ioral changes may be useful indicators for medical
intervention for dogs with signs of cognitive impair-
ment. (
J Am Vet Med Assoc
2001;218:1787–1791)
From the Animal Behavior Clinic, 809 SE Powell, Portland, OR
97202 (Neilson); and the Behavior Service, Veterinary Medical
Teaching Hospital (Hart), and the Department of Anatomy,
Physiology, and Cell Biology (Cliff), School of Veterinary
Medicine, University of California, Davis, CA 95616; and 13868
Skyline Blvd, Woodside, CA 94062 (Ruehl).
Supported in part by Friskies PetCare Residency Program in Clinical
Animal Behavior at the University of California, Davis, the UC
Davis Center for Companion Animal Health, and Deprenyl Animal
Health, Overland Park, Kan.
The authors thank Dr. David Bruyette for technical assistance and
Dr. Neil Willits for statistical assistance.
Address correspondence to Dr. Hart.
deposition corresponds to degree of impairment in
learning complex tasks.
14,15
Neuropathologic and
behavioral changes described in some aging dogs are
similar to behavioral changes in humans with demen-
tia and suggest that canine dementia can serve as a
model for human dementia.
5
A further link between age-related behavioral
changes in dogs and of humans with signs of
Alzheimer’s disease was profiled in 2 double-blind con-
trolled studies with the drug selegiline, 1 revealing a
slowing in the progression of degenerative changes in
human Alzheimer’s patients,
16
and the other revealing a
significant improvement in aged dogs with cognitive
dysfunction syndrome.
4
Although dogs can be expected to have some aging
of behavioral function, it could be that only a propor-
tion of dogs at any age will have cerebral degeneration
of the magnitude sufficient to cause severe impair-
ments in memory and learning. Owners of older dogs
may describe a variety of behavioral changes, and
results of preliminary work indicated that aside from a
reduction in activity, the signs could generally be
grouped into the following 4 categories
2,3
: orientation
in the immediate environment, social interactions with
human family members, house training, and the sleep-
wake cycle. Changes in the sleep-wake cycle are per-
haps the most difficult to relate to deficits in memory
or learning. However, the sleep-wake cycle is disturbed
in humans with Alzheimer’s, possibly as a reflection of
disruption of the circadian rhythm.
13,17
The purpose of the study presented here was to
assess the age-related prevalence of behavioral changes
in a randomly selected population of aging dogs receiv-
ing veterinary care. In addition to the behavioral
changes, information was collected on visual and hear-
ing impairment. It is known that dogs of larger body size
physically age more rapidly than dogs of smaller body
size.
18
Thus, we also set out to determine whether there
was a correspondence between body weight and the age
of onset of signs of failing learning and memory.
Materials and Methods
Selection of dogs—Dogs included in our study were
receiving veterinary care and were chosen from the database
of clients of the Veterinary Medical Teaching Hospital at the
University of California, Davis. A computer program was
used to randomly generate lists of case numbers of dogs that
fell into targeted age groups.
Data collection—The hospital records were reviewed by
a trained screener. Clients were then contacted by the screen-
er to obtain information about whether their dogs were still
alive and the willingness of the caregiver to participate in the
study. Information was also sought about the existence of
medical problems not apparent from the hospital record and a
convenient time for a veterinary behaviorist (JCN) to call. The
owner was then sent an information sheet about possible
behavioral and physical changes in aging dogs, and approxi-
mately 2 weeks later, the behaviorist contacted the owner to
conduct a structured telephone interview of approximately 30
minutes. An outside consultant on telephone interview tech-
niques contributed to development of the interview methods
to avoid biasing the responses of the interviewee.
Information was recorded on prepared data forms and
organized onto a spreadsheet. Data collection forms dealt
with the following 4 categories of behaviors: orientation in
the home or yard, social interactions with human family
members, house training, and the sleep-wake cycle. Prior to
asking about signs of dysfunction in each category, there was
an open-ended question for recording responses from each
owner about signs displayed by their dogs. Following the
open-ended question, the interviewer then asked about spe-
cific changes known to develop in older dogs associated with
each category if these signs had not been previously men-
tioned by the owner. The initial part of the interview con-
tained distractors to intentionally evoke comments of “no
change” from the owner so they would not expect that ques-
tions should be answered in the affirmative.
During the interview, 3 to 4 specific questions were used
that addressed signs of dysfunction in each behavioral cate-
gory. The criterion for impairment in a category was that
dogs had 2 distinct signs in that category that were not
observed when they were younger (ie, 5 to 8 years of age). A
dog had impairment in orientation if it had 2 of the fol-
lowing signs: staring into space, getting lost in the house or
yard, getting stuck in corners, standing at the wrong door or
wrong part of the door to go out, and any other sign that was
logically attributable to disorientation. A dog had impair-
ment in social interaction if it had 2 of the following signs:
decrease in greeting owners, decrease in soliciting attention
from the owners, and a change (increase or decrease) in fol-
lowing owners around the house. A dog had impairment in
house training if it had the following 2 signs: started to uri-
nate or defecate in the house with no other behavioral or
medical explanation discernible such as urinary incontinence
or separation anxiety, and a decrease in signaling to go out or
a decrease in use of a dog door. If a dog was strictly an out-
door dog or never house trained, so that learned house train-
ing could not be evaluated, the dog was not included in our
study. A dog had impairment in the sleep-wake cycle if it had
2 of the following signs: regularly waking up the owner at
night by pacing or vocalizing, sleeping less at night, and
sleeping noticeably more during the day.
Evaluation system—To have impairment in a category, a
dog had to have the signs of dysfunction in that category 1
time a week continuously for at least the previous month. The
system was considered conservative. For example, it may be rea-
sonable to assume that a dog had disorientation if it regularly
stared into space, but a dog was not considered to have impair-
ment in orientation unless there was 1 other marker of disori-
entation. Owners were asked about visual impairment and hear-
ing impairment that was not noticeable earlier in the dogs life,
and this information was considered during evaluation.
Owners were also asked about behavioral problems such
as recent onset of separation anxiety, fears of inanimate stim-
uli, and aggression. If these problems could account for
behavioral findings, the dog was not considered to have
impairment in the related category.
The primary analysis dealt with each of the 4 behavioral
categories. It was determined whether each dog had impair-
ment in 0, 1, and 2 categories. Dogs with impairment in
1 category were arbitrarily considered to have mild impair-
ment, whereas dogs with impairment in 2 categories were
arbitrarily considered to have severe impairment.
Other methods of designating severity of impairment
were considered, such as giving more weight to impairment
in some categories than others (eg, requiring disorientation
for a classification of severe impairment). Analysis of pilot
data, however, revealed that the prevalence of dogs in each
age group with impairments was not affected by whether data
were weighted or not.
Statistical analysis—Analyses of changes in the propor-
tion of dogs with impairments in the various categories as well
1788 Scientific Reports: Original Study JAVMA, Vol 218, No. 11, June 1, 2001
SMALL ANIMALS
as visual and hearing impairment across age groups included
not only the possibility of sex differences but also the possibil-
ity of interaction between sex and age, which would compli-
cate an analysis of the progression of signs of dysfunction
across the age groups. The significance of such interactions
was examined by logistic regression. Examination of age
effects, after suppressing sex as a factor, was done with the
Fisher exact test. The analysis of the degree of impairment as
a function of body weight involved the possibility of interac-
tion between body weight and age, which was also addressed
by logistic regression. The effect of weight alone was examined
after ruling out the age by weight interaction. Significance for
all analyses was set at P < 0.05, using a 2-tailed t-test.
Results
Dogs—Data were obtained on 180 dogs, compris-
ing 83 castrated males and 97 spayed females and rep-
resenting 3 age groups, namely, 11 to 12 (n = 80), 13 to
14 (66), and 15 to 16 (34) years old. These were dogs
for which there was no evidence in the hospital record
that could provide an explanation for behavioral
changes that could be attributed to dysfunction in 1
organ system other than the CNS.
Data were available for a somewhat larger number of
dogs in the younger age groups than in the oldest group.
Of the 11- to 12-year-old dogs, 56% (45/80) were females
that were spayed at a mean age of 2.9 (± 2.6) years, and
44% (35/80) were males that were castrated at a mean
age of 3.6 (± 3.1) years. Of the 13- to 14-year-old dogs,
53% (35/66) were females that were spayed at a mean age
of 2.7 (± 2.6) years, and 47% (31/66) were males that
were castrated at a mean age of 5.3 (± 4.1) years. Of the
15- to 16-year-old dogs, 50% (17/34) were females that
were spayed at a mean age of 2.3 (± 2.6) years, and 50%
(17/34) were males that were castrated at a mean age of
6.3 (± 4.2) years. Therefore, the percentage of each sex in
each of 3 age groups was approximately the same.
Overall, females were spayed at a mean age of 2.7 (± 2.6)
years, and males were castrated at a mean age of 4.8
(± 3.8) years. Mean elapsed time from the last hospital
visit indicated on the hospital record and the data-collec-
tion telephone call was 20.6 (± 22.5) months.
There was not a significant effect of age by sex
interaction on the 4 categories and the 3 degrees of
impairment represented by impairment in 1 or 2
categories (P values ranged from 0.26 to 0.85). To
determine possible sex differences in proportion of
dogs with impairments in the various categories and
degrees of impairment, age groups were combined (Fig
1). Castrated male dogs were significantly more likely
have impairment in orientation than spayed female
dogs (P = 0.03). In the other 3 categories and 3 degrees
of impairment, there were no significant sex differ-
ences (P values ranged from 0.06 to 0.35).
Age-related prevalence of impairment in behav-
ioral categories—Because there were no significant sex
by age interactions, subsequent analyses used com-
bined data from female and male dogs across age groups
(Fig 2). There was a progressive and significant age-
related prevalence of dogs with impairment in each cat-
egory and proportion of dogs with impairments in 1
and 2 categories (P values ranged from 0.001 to
0.004). The proportion of dogs with impairment in just
1 category was not expected to be significantly different
between age groups, because further impairment with
advancing age would be expressed as impairment in 2
categories. The percentage of 11- to 12-year-old dogs
with impairment in 1 category was 28% (22/80), of
which 10% (8/80) had impairment in 2 categories.
Among 15- to 16-year-old dogs, 68% (23/34) had
impairment in 1 category, of which 35% (12/34) had
impairments in 2 categories. There was no indication
of a chronologic progression of impairment such that
dogs would have impairment in any particular category
prior to developing impairment in other categories.
Impairment of vision and hearing—Visual and
hearing impairment was described by the owner and
not necessarily evaluated by a veterinarian. There were
no sex by age interactions for visual or hearing impair-
ment (P = 0.39 and 0.45, respectively). Combining
data from males and females for further analysis
revealed a significant age-related increase in prevalence
of visual and hearing impairment (P = 0.03 and P <
0.001, respectively). Visual impairment progressed
JAVMA, Vol 218, No. 11, June 1, 2001 Scientific Reports: Original Study 1789
SMALL ANIMALS
Figure 1—Percentage of male castrated (MC; n = 83) and
female spayed (FS; 97) dogs that had impairments in each of 4
behavioral categories and in 1 category, 2 categories, and 1
category.
a,b
Different letters within a set of bar graphs (ie, 2 bars)
indicate a significant difference (
P
< 0.05) between sexes.
Figure 2—Percentage of 11- to 12-year-old (n = 80), 13- to 14-
year-old (66), and 15- to 16-year-old (34) dogs that had impair-
ments in each of 4 behavioral categories and in 1 category, 2
categories, and 1 category.
a,b
Different letters within a set of
bar graphs indicate significant differences (
P
< 0.05) among age
groups.
from 41% (33/80) of 11- to 12-year-old dogs to 68%
(23/34) of 15- to 16-year-old dogs. Hearing impair-
ment progressed from 48% (38/80) of 11- to 12-year-
old dogs to > 97% (33/34) of 15- to 16-year-old dogs.
Body weight and signs of dysfunction—The issue
of body weight and predisposition for behavioral
impairment was addressed by testing for interactions
between age and weight for dogs with impairment in
2 categories. The interaction was not significant, and
the analysis conducted without the age by weight inter-
action revealed no significant weight effect (P = 0.36).
Discussion
Our cross-sectional analysis of data from dogs
ranging in age from 11 to 16 years provides information
on the prevalence of age-related behavioral changes
associated with cognitive dysfunction. These signs were
the result of impairment in the behavioral categories of
orientation in the house and yard, social interactions
with human family members, house training, and the
sleep-wake cycle. Impairment in 1 category was arbi-
trarily designated as mild impairment, and impairment
in 2 categories was designated as severe impairment.
As discussed, signs of dysfunction in all the behavioral
categories except the sleep-wake cycle can be related, at
least in part, to disturbances of learning and memory.
Although the behavioral patterns affected may not rep-
resent cognitive function as studied by animal behav-
iorists or neuroscientists, the changes in dogs corre-
spond with neuropathologic changes, especially the
deposition of diffuse β-amyloid plaques,
14,15
and share
similarities with Alzheimers disease in humans, which
is also characterized by β-amyloid deposition.
12,13,17
Behavioral impairments in some dogs in our study
may have actually been a reflection of an organ system
abnormality (other than brain degeneration). More
likely, perhaps, is the possibility that hypothyroidism,
arthritis, and cardiovascular disease may have intensi-
fied some signs that also reflected loss of memory and
learning. In fact, most old dogs have 1 major organ
system disorder, so it would be unusual to find a 15- to
16-year-old dog with impairment in 2 behavioral cat-
egories without any substantial impairment in any
nonbrain organ system. Data from the clinical trial
with selegiline,
4
involving 199 dogs that had an exten-
sive physical examination with a routine neurologic
examination, hematologic analysis, blood biochemical
analysis (including T
4
analysis), and urinalysis to rule
out medical disorders as causal factors in the signs of
cognitive dysfunction, provided evidence that the signs
of dysfunction in the categories of orientation, social
interaction, house training, and sleep-wake cycle were
not typically a consequence of a medical disorder
(other than brain degeneration). We believe that our
demographic study is a fair approximation of the age-
related prevalence of the signs associated with cogni-
tive dysfunction in dogs.
Further confirmation of the legitimacy of our
demographic study as a guide to age-related prevalence
of this syndrome comes from the longitudinal study
19
from this institution focusing on the short-term pro-
gression of impairment in a subset of dogs of our study
presented here. Results of that study indicate that
almost all dogs that initially had impairment in a cate-
gory continued to have impairment in the category,
and many progressed to a more severe degree of
impairment, because they developed impairment in 1
additional category during a subsequent 6- to 18-
month period. If the signs used to define impairments
in our study presented here had reflected disturbances
in the environment, interactions with the owner, or
transient medical problems, rather than age-related
pathologic changes in the brain, one would expect a
reversal in many of the signs, and this would have
invalidated the particular behavioral measures used.
Results from the longitudinal study
19
also indicate
that the onset of visual impairment, hearing impair-
ment, or both accounted for only a small proportion of
dogs that developed disorientation during the same
period. Thus, although some disorientation developed
or was intensified by visual or hearing impairment,
most instances of disorientation were independent of
impairment in these organ systems.
In this study, 23% (22/80 of 11- to 12-year olds
and 68% (23/34) of 15- to 16-year-olds had impair-
ment in 1 category. Ten percent (8/80) of 11- to 12-
year-olds and 35% (12/34) of 15- to 16-year-olds had
impairment that was designated as severe in 2 cate-
gories. The only significant difference between male
and female dogs was a higher proportion of castrated
male than spayed female dogs with impairment in ori-
entation. Visual and hearing impairment also increased
with age; 68% (23/34) of 15- to 16-year-old dogs had
visual impairment, and 97% (33/34) had hearing
impairment. The age-related increase in impairment in
dogs for all behavioral categories was significant, as
was the increase in impairment in visual and hearing
function with advancing age.
Although it is established that dogs of large body
size die at a younger age, presumably as a function of
more rapid aging in the cardiovascular, musculoskele-
tal, and endocrine systems,
18
findings of our study sug-
gest that the processes in the brain responsible for age-
related behavioral changes do not progress more rapid-
ly in larger dogs. At any given age, small dogs are as
likely to have impairment in 2 categories as large
dogs. This means that because small dogs often live
longer, one would predict they would be more likely to
have signs associated with cognitive dysfunction dur-
ing their lifetime than dogs of larger body size.
If impairment in 1 category is an indication for
medical intervention, results of our study indicate that
almost 30% of dogs 11 to 12 years of age would be can-
didates for such treatment, as would about 70% of dogs
15 to 16 years of age. On the assumption that dogs often
progress in severity of signs of impairment in behavioral
categories with advancing age, some clinicians may wish
to recommend treatment when a dog has 1 sign of dys-
function in a behavioral category, as long as an extensive
medical evaluation precludes an organ system disorder
as the causal factor (other than brain degeneration). It
should also be emphasized that there are undoubtedly
other behavioral changes associated with aging that
were not included in our study, which could be used as
indications for medical interventions.
1790 Scientific Reports: Original Study JAVMA, Vol 218, No. 11, June 1, 2001
SMALL ANIMALS
a
Anipryl, Pfizer Animal Health, Exton, Pa.
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... 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). The prevalence of CCDS is high in aging dogs. ...
... The prevalence of CCDS is high in aging dogs. 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). ...
... 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). ...
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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.
... 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. ...
... 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. ...
... Just like in humans, some senior dogs eventually develop cognitive impairment or cognitive dysfunction syndrome (CDS). 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 [12][13][14][15][16]. About 27.5% of old dogs from 11 to 12 years of age developed mild to severe cognitive impairment and the incidence was 67% for dogs between 15 to 16 years of age [13]. ...
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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.
... Although questionnaires have the inherent ability to grade clinical signs, with the resulting scores being a useful method to monitor CDS progression, single itemized clinical signs within the D.I.S.H.A. five categories were originally used [66,67]. MCI was then diagnosed if clinical signs fell under a single category, while signs within two or more categories were indicative of CDS [66]. ...
... MCI was then diagnosed if clinical signs fell under a single category, while signs within two or more categories were indicative of CDS [66]. Using this two-level diagnostic classification, MCI was detected in 13% to 28% of dogs aged 8-12 years [67] as well as 41% to 68% of dogs 13 years old and over [24,66,68]. 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. ...
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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.
... 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). ...
Chapter
These proceedings contain oral and poster presentations from various experts on animal behaviour and animal welfare in veterinary medicine presented at the conference.
... 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. ...
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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.
... The domestic dog has been suggested a number of times as a suitable model of AD, both in natural and genetically modified form [220][221][222][223]. Aged dogs develop a dementialike syndrome called canine cognitive dysfunction (CCD), which has been suggested to be the canine counterpart to AD [180,224,225]. The presence of CCD symptoms has been in more than a quarter of dogs in the 11-12 age range, and nearly 70% in dogs 15-16 [226]. Dogs are the only animal outside humans where cognitive impairment in older age has been reasonably well characterised, and at least three standardised tests exist for assessing CCD [227][228][229]. ...
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Alzheimer’s disease (AD) is one of the looming health crises of the near future. Increasing lifespans and better medical treatment for other conditions mean that the prevalence of this disease is expected to triple by 2050. The impact of AD includes both the large toll on individuals and their families as well as a large financial cost to society. So far, we have no way to prevent, slow, or cure the disease. Current medications can only alleviate some of the symptoms temporarily. Many animal models of AD have been created, with the first transgenic mouse model in 1995. Mouse models have been beset by challenges, and no mouse model fully captures the symptomatology of AD without multiple genetic mutations and/or transgenes, some of which have never been implicated in human AD. Over 25 years later, many mouse models have been given an AD-like disease and then ‘cured’ in the lab, only for the treatments to fail in clinical trials. This review argues that small animal models are insufficient for modelling complex disorders such as AD. In order to find effective treatments for AD, we need to create large animal models with brains and lifespan that are closer to humans, and underlying genetics that already predispose them to AD-like phenotypes.
... 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). ...
Article
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.
... 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 . ...
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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.
... Pathological cognitive declines become markedly more common in this age category. Neilson and colleagues evaluated signs of cognitive impairment in dogs aged 11-12, 13-14, and 15-16 years and found that dogs aged 15 and 16 years had a much greater incidence of cognitive impairment compared with both other age groups (49). 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). ...
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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.
Article
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.
Article
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.
Article
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.
Article
It is well known that β-amyloid accumulates abnormally in Alzheimer's disease; however, β-amyloid's relationship to cognitive dysfunction has not been clearly established and is often confounded by the presence of neurofibrillary tangles. We used canines to investigate the relationship between β-amyloid accumulation and cognitive function in an animal model of aging lacking neurofibrillary tangles. The performance of 20 canines (11 purebred beagles and 9 mongrels) on a battery of six cognitive tasks was measured. These tasks included Reward Approach and Object Approach learning, as well as Discrimination, Reversal, Object Recognition, and Spatial learning and memory. Aged canines were impaired on some tasks but not others. β-Amyloid-immunopositive plaques were found in many of the older animals. Plaques were all of the diffuse subtype and many contained intact neurons detected with double-labeling for neurofilaments. No neurofibrillary tangles were detected. β-Amyloid was also associated with the processes of many neurons and with blood vessels. Using computerized image analysis, we quantified the area occupied by β-amyloid in entorhinal cortex, frontal cortex, and cerebellum. Controlling for age-related increases in β-amyloid, we observed that increased β-amyloid deposition is strongly associated with deficits on Discrimination learning (r= .80), Reversal learning (r= .65), and Spatial learning (r= .54) but not the other tasks. There were a few differences between breeds which are discussed in the text. Overall, these data suggest that β-amyloid deposition may be a contributing factor to age-related cognitive dysfunction prior to the onset of neurofibrillary tangle formation.
Article
Amyloid angiopathy with cerebral hemorrhage and senile plaques was found in the brain of aged dogs. In all 9 cases examined, 13 to 19 years old, 6 males and 3 females, amyloid deposits were observed mostly in the wall of cerebral arterioles and capillaries showed hyaline degeneration. The accumulation of amyloid fibrils measuring about 10 nm in diameter was seen in the cerebral vessel wall by electron microscopy. The cerebral hemorrhage was observed in 6 of 9 dogs and 2 of them showed massive hemorrhage. The hemorrhagic foci were sometimes closely contact with the vessels involved in amyloid angiopathy. In addition, senile plaques being classified into 2 types were found in the cerebral cortex of 3 dogs. The first type was characterized by the accumulation of degenerative neurites and often contained granular argyrophilic material. The second type had a well-defined amyloid core with neuritic halo. Amyloid deposits were also found in or around intestinal vessel walls of 3 dogs. The amyloid deposited in the cerebral vessels, senile plaques and intestinal vessels showed characteristic green birefringence under the polarized light even after potassium permanganate treatment.
Article
The protein beta-amyloid is said to be central to the disease process of Alzheimer's disease (AD). Several groups have developed transgenic models that overexpress the amyloid precursor protein or beta-amyloid and then develop AD-like neuropathology. Another report suggests that beta-amyloid accumulation in old dogs correlates with cognitive impairment. However, many other researchers argue that beta-amyloid deposition in senile plaques is a secondary event because plaque numbers in man do not correlate well with cognition. We set out to analyse this conumdrum in man. We selected 16 mild to severely demented AD cases on the basis of mini-mental state exam scores (MMSE; n = 16). We also included 4 controls who represented the upper range of cognitive ability. We used a computer-based image analysis of cross-sectional area of the brain occupied by beta-amyloid immunopositive deposition. We used this technique in preference to conventional methods of manual plaque counts and found a strong relation between beta-amyloid load in entorhinal cortex and cognition measured on various scales (r = -0.93 versus the Blessed IMC). Our study suggests that the size of cortical area affected by beta-amyloid deposition is an important factor in the clinical manifestation of dementia, and lends support to the possibility that beta-amyloid is central to the aetiology of AD.
Article
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.