ArticlePDF AvailableLiterature Review

Cognitive Dysfunction Syndrome A Disease of Canine and Feline Brain Aging

Authors:
  • Veterinary Emergency and Specialty Center of New Mexico

Abstract and Figures

Brain aging is a degenerative process manifest by impairment of cognitive function; although not all pets are affected at the same level, once cognitive decline begins it is generally a progressive disorder. Diagnosis of cognitive dysfunction syndrome (CDS) is based on recognition of behavioral signs and exclusion of other medical causes that might mimic CDS or complicate its diagnosis. Drugs, diets, and supplements are now available that might slow CDS progression by various mechanisms including reducing oxidative stress and inflammation or improving mitochondrial and neuronal function. Moreover, available therapeutics may provide some level of improvement in cognitive and clinical signs of CDS.
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Cognitive Dysfunction Syndrome
A Disease of Canine and Feline Brain Aging
Gary M. Landsberg, DVM
a,b,
*, Jeff Nichol, DVM
c
,
Joseph A. Araujo, BSc
b,d,e
INTRODUCTION
As pets age, behavior changes may be the first indication of declining health and
welfare. This is particularly true for some of the most common problems associated
with aging, such as pain, sensory decline, and cognitive dysfunction syndrome (CDS).
Early identification of these signs provides an opportunity for effective intervention.
GML is an employee of CanCog Technologies Inc. JAA is an employee of InterVivo Solutions Inc
and a consultant for CanCog Technologies Inc.
The authors have nothing else to disclose.
a
North Toronto Animal Clinic, 99 Henderson Avenue, Thornhill, Ontario, Canada L3T 2K9;
b
CanCog Technologies Inc, 120 Carlton Street, Suite 204, Toronto, Ontario, Canada M5A 4K2;
c
Veterinary Emergency and Specialty Center of New Mexico, 4000 Montgomery Boulevard NE,
Albuquerque, NM 87109, USA;
d
InterVivo Solutions Inc, 120 Carlton Street, Suite 203, Toronto,
Ontario, Canada M5A 4K2;
e
Department of Pharmacology and Toxicology, University of
Toronto, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8
* Corresponding author. North Toronto Animal Clinic, 99 Henderson Avenue, Thornhill, Ontario,
Canada L3T 2K9.
E-mail address: gmlandvm@aol.com
Vet Clin Small Anim 42 (2012) 749–768
http://dx.doi.org/10.1016/j.cvsm.2012.04.003 vetsmall.theclinics.com
0195-5616/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
KEYWORDS
• Cognitive dysfunction syndrome • Brain aging • Behavior • Canine • Feline
KEY POINTS
Brain aging is a degenerative process that for many dogs and cats ultimately progresses
to a loss of one or more cognitive domains or impairment of cognitive function.
Diagnosis of cognitive dysfunction syndrome (CDS) is based on recognition of behavioral
signs and exclusion of other medical conditions and drug side effects, which in some
cases can mimic or complicate CDS.
• Clinical categories include disorientation, alterations in social interactions, sleep-wake
cycles, elimination habits, and activity, as well as increasing anxiety. Deficits in learning
and memory have also been well documented.
Treatment is aimed at slowing the advancement of neuronal damage and cell death and
improving clinical signs. Drugs, diet, and supplements can be used alone or concurrently
to improve neurotransmission and reduce oxidative damage and inflammation.
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During veterinary visits, pet owners are likely to report serious behavioral changes,
but subtle signs, which may be indicative of declining health or cognition, often go
unreported. Family members therefore need assistance in both identifying and
reporting any change from normal behavior to their veterinarian. Similarly, clinicians
must be proactive in asking about behavioral signs.
The current article focuses on how CDS in dogs and cats parallels neurodegen-
erative disorders in humans, particularly Alzheimer disease (AD). The goal is to help
the practitioner develop a senior care program incorporating behavioral screening to
aid in both the recognition of behavior changes consistent with CDS and the
implementation of appropriate treatment strategies.
BRAIN AGING AND COGNITIVE DYSFUNCTION
Most mammals show age-related neuropathologic changes. In humans, the most
common neurodegenerative disorder is AD, which progressively impairs cognition,
behavior, and quality of life. It is increasingly evident that humans, dogs, and cats
demonstrate parallels in brain aging associated with cognitive dysfunction. In fact, the
aged dog and, to a lesser extent, the aged cat are spontaneous models of AD and
therefore can play a valuable role in testing putative AD therapeutics. Conversely, the
knowledge gained from studying AD is highly relevant for understanding brain aging
and cognitive dysfunction in companion animals.
Lessons Learned from AD Research
Modern medicine has increased the life span across many species, which in turn has
increased the incidence of neurodegenerative diseases, such as AD. In humans, AD
is generally characterized by initial decline in episodic memory followed by progres-
sive decline across multiple cognitive domains.
1
Ultimately this results in behavioral
changes that impair social function and eventually results in death. Classical
diagnosis of AD has relied on post-mortem confirmation of 2 hallmark pathologies:
the presence of senile plaques, which consist of extracellular deposits of fibrilized
amyloid-beta protein (A
), and neurofibrillary tangles, which consist of intracellular
paired helical fragments of cytoskeletal hyperphosphorylated tau protein.
2
However,
it is uncertain if either of these pathologic changes is a causal factor as several other
brain changes are documented, including neuronal loss; cortical atrophy including
atrophy of the hippocampus; alterations in neurochemical systems such as the
cholinergic, glutaminergic, dopaminergic, and GABAergic neurotransmitter systems;
and reduced neuronal and synaptic function.
3
Moreover, risk factors associated with
the development of AD include genetic, metabolic, and nutritional influences, which
may be equally relevant to pet aging.
Recent clinical and research criteria propose there are progressive stages of AD
from the preclinical stage (ie, prior to clinical signs) to mild cognitive impairment (MCI;
prodromal stage likely to proceed to AD) to a clinical diagnosis of AD based on
cognitive-behavioral status.
1
It is suggested that beta-amyloid deposition may occur
early in disease progression, followed by neuronal degeneration/synaptic dysfunction
(measured by biomarkers of tau pathology or functional imaging). Both of these
pathologies likely precede the clinically identifiable stage of MCI or AD in humans.
4
Therefore, clinical AD is now considered a late stage of disease progression, which
may explain the limited clinical success of therapeutic interventions (ie, initiated too
late in disease progression to improve outcome). Therefore, identification of current
and/or novel biomarkers predictive of AD progression will be essential for diagnostic
characterization of preclinical and prodromal AD stages and for assessing interven-
tions aimed at prevention or reversing progression of AD. It is theorized that AD risk
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factors, similar to high blood pressure or increased cholesterol in early diagnosis of
cardiovascular disease, will be identified and validated, permitting early intervention
and monitoring of disease progression.
Lessons Learned from Senior Dog and Cat Research
Most mammals show evidence of brain aging and consequential cognitive deficits.
5
CDS in companion animals parallels AD progression in several respects. For example,
not all aged dogs and cats show behavioral signs consistent with CDS, yet subclinical
alterations in cognitive function may be present, which might eventually progress to
CDS.
6
Therefore, it is prudent to commence treatment early. Understanding age-
related brain pathology and cognitive dysfunction is essential to fully appreciate the
potential value of using biomarkers and/or cognitive status in the future diagnosis and
treatment of CDS progression.
Effects of Aging on the Brains of Senior Dogs and Cats
In canine aging, frontal lobe volume decreases, ventricular size increases, and there
is evidence of meningeal calcification, demyelination, increased lipofuscin, increased
apoptic bodies, neuroaxonal degeneration, and reduced neurons.
7,8
In cats, age-
related pathologies include neuronal loss, cerebral atrophy, widening of sulci, and
increases in ventricular size.
9 –11
Perivascular changes, including microhemorrhage or
infarcts in periventricular vessels, are reported in senior dogs and cats, which may
contribute to signs of CDS.
7,9,12–15
With increasing age, there is an increase in
reactive oxygen species leading to oxidative damage in dogs and likely cats.
9,16
Increases in monoamine oxidase B activity in dogs is reported, which may increase
catalysis of dopamine with subsequent increases in free radicals.
17
A decline in
cholinergic tone occurs in canine aging as evidenced by hypersensitivity to anticho-
linergics and decreased brain muscarinic receptor density.
18
Diminished cholinergic
function is also reported in cats.
10,19
Collectively, these alterations may contribute to
working memory deficits or CDS, as well as alterations in motor function and REM
sleep.
9,10,20 –22
In aged dogs, cats, and humans, there are similarities in deposition of A
in
extracellular plaques and perivascular infiltrates; however, dense core plaques seen
in AD are not found in dogs or cats, suggesting canine and feline plaques are less
mature than those seen in AD.
9,12,14,15,23
Moreover, similar to humans, A
plaque
load is positively correlated with cognitive impairment in dogs.
13,14,24
By contrast,
cats demonstrate more diffuse A
plaques than either human or dog.
9,12,15,25,26
Neurofibrillary tangles are not consistently reported in either species; however,
hyperphosphorylated tau is reported in brains of aged dogs and cats, which might
represent pre-tangle pathology.
7,9,13,25,26
Overall, both dogs and cats show A
brain deposition and pre-tangle pathology
with increasing age similar to that seen in AD progression; however, these pathologies
do not achieve the severity seen in AD. Nonetheless, brain A
deposition may prove
to be relatively early predictive biomarker of CDS consistent with preclinical and/or
prodromal stages of AD.
4
Effects of Age on Cognitive Ability of Senior Dogs and Cats
In humans, cognition is composed of multiple cognitive domains that include not only
learning and memory but also executive function, language, psychomotor ability,
attention, and spatial abilities. In the laboratory, there are protocols to assess many
of these domains in dogs and cats. Age-related and domain-specific cognitive decline
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is found in both species, but there is individual variation such that not all subjects are
affected.
Using the delayed nonmatching to position (DNMP) memory task (Fig. 1), old dogs
can be separated into 3 groups— unimpaired, impaired, and severely impaired—
which may be analogous to the various stages of AD progression.
27,28
Aged dogs
with DNMP impairments also demonstrate altered sleep-wake cycles, increased
stereotypy, and decreased social contact with humans, which suggests a link
between cognitive impairment and behavioral changes consistent with CDS.
29
Importantly, DNMP impairments can be detected as early as 6 years of age in some
Fig. 1. The DNMP is a test of short-term visuospatial working memory.
27,30
The test consists of
2 phases. In the sample phase, the subject is required to displace an object placed over 1 of 3
possible locations on a food well (top); in this case the cat is required to displace block S
covering food reward in the well on cat’s right. The second stage (bottom) occurs after a
delay and the subject is presented with 2 objects identical to that used in the sample phase.
One object (marked with an X) is located in the same position as the sample object. The
correct object is located in one of the remaining 2 positions (the nonmatch), and if the subject
displaces the object, it can retrieve the food reward beneath. Initially, subjects are trained
using a 5-second delay between the phases, but when the cat learns the rule that the food
will always be found under the block in the nonmatch position, gradually longer delays can
be introduced to assess memory.
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dogs, which is consistent with early memory deficits in AD.
30
Also, brain amyloid
deposition is reported earliest at 8 to 9 years of age.
23
Collectively, this suggests that
memory impairment is an early consequence of canine aging that can precede both
clinically relevant behavioral changes and amyloid deposition.
When dogs are repetitively rewarded for approaching 1 of 2 objects that differ
substantially (ie, simple object discrimination learning), by contrast, no age effects on
learning are evident.
31
However, if the reward contingencies are reversed after
learning a simple object discrimination problem such that the dog must learn to
respond to the object that previously was not rewarded in the original learning task
(reversal learning), aged dogs require significantly more trials to learn to respond to
the newly rewarded object than young dogs.
31,32
This impairment is analogous to the
diminished executive function observed in human aging, AD, and other species.
32
On
the other hand, age-related learning deficits are apparent when complex discrimina-
tion learning is assessed (eg, objects more similar or more objects), which may be
related to age-related deficits in attention (Fig. 2).
33
Previous studies have identified eyeblink conditioning deficits in aged cats, and a
holeboard task revealed age effects on working memory, but not on spatial learn-
ing.
34,35
Age-related cognitive impairments are also seen in cats when feline adap-
tations of canine tests are used (see Figs. 1 and 2). Like dogs, cats demonstrate
reversal learning and DNMP impairments with increasing age.
36
While there are
insufficient data to determine age-of-onset of these impairments, reversal learning
impairments were evident in 7.7- to 9-year-old cats compared to 2- to 3.8-year-old
cats, suggesting that cognitive deficits precede clinical signs.
37
Similarly, while aged
cats demonstrate neuropathologic brain changes similar to those reported in aged
humans and dogs, the effect of neuropathologic changes on cognition have not been
thoroughly investigated in the cat.
9,26
Overall, both dogs and cats demonstrate
age-dependent and domain-specific cognitive decline consistent with those reported
in aged humans.
Fig. 2. In the attention task, the dog must select the correct object (covering a food reward),
which is presented concurrently with either 1, 2, or 3 incorrect objects (distracters). Studies
have demonstrated that performance declines and latency increases with increased distracter
number, consistent with a test that assesses selective attention.
33
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Do Dogs and Cats Get AD?
Dogs and cats show both neuropathologic and cognitive changes that share many
attributes of human aging and AD progression. However, late-stage AD progression
is associated with impairment in most, if not all, cognitive domains. By contrast, dogs
and cats do not show such extensive cognitive impairments (eg, ability to eat is
retained), which suggests that the disease progression in pets is more comparable to
earlier stages of AD progression. Consistent with this view, aged dogs show declining
CSF levels of A
42, increased CSF levels of phospho-tau, and atrophy of the
hippocampus, all of which are biomarkers being investigated as early diagnostic
predictors of AD.
8,38,39
Future research better characterizing the longitudinal interac-
tion among neuropathologic, cognitive, and behavioral changes in aging dogs and
cats will be essential in better determining if and how CDS overlaps with AD
progression.
COGNITIVE DYSFUNCTION SYNDROME
Clinical Signs of CDS
Classic signs of CDS are summarized by the acronym DISHA, which refers to
disorientation; alterations in interactions with owners, other pets, and the environ-
ment; sleep-wake cycle disturbances; housesoiling; and changes in activity.
40
Although a decline in activity might be reported, laboratory studies suggest that
increased locomotor activity and decreased immobile time are associated with
greater cognitive impairment.
29,41
In addition, signs of fear, phobias, and anxiety,
which are commonly reported by owners of senior pets, may be analogous to the
finding of agitation and anxiety in humans with AD and might also be considered a
component of CDS (Table 1).
42– 46
Finally, memory deficits, which are some of the first
recognizable signs of cognitive impairment in humans, have been identified early in
the process of brain aging in both dogs and cats.
30,36
Therefore, learning or memory
deficits in aged dogs and cats would also be a sign of CDS. However, these are
difficult to recognize except perhaps in dogs that have been trained to a high level of
performance (eg, service dogs, dogs trained for detection tasks) or by highly
perceptive owners. For clinical signs of CDS, see the questionnaire in Table 1.
Differentiating Medical and Behavioral Problems from CDS
The determination of either a primary behavioral diagnosis or CDS must first be
approached by excluding medical causes (Table 2). In the senior pet, this can be
particularly challenging because with increasing age, there is an increased likelihood
of concomitant medical conditions. Potential behavioral effects of medications must
also be considered, especially those known to impact behavior. For example, steroids
can increase drinking, appetite, and panting and are also associated with behavioral
signs including nervousness, restlessness, irritable aggression, startling, food guard-
ing, avoidance, and increased barking.
47
Additionally, senior pets may be less able to
cope with stress, which may make them more susceptible to changes in their
environment.
Thus behavioral signs in the senior pet can be due to medical or behavioral causes,
cognitive dysfunction, or a combination thereof. For example, disruption of night time
sleep in senior pets may be due to CDS, sensory dysfunction, or medical conditions
that present with pain, polyuria, or hypertension, as well as alterations in the owner’s
schedule or home environment. Once problems arise, experience (ie, learning) further
influences whether the behavior is likely to be repeated. In establishing a diagnosis of
CDS, the clinician must be aware that the characteristic behavioral signs overlap with
those of many medical and behavioral disorders.
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Table 1
CDS checklist
1
Signs: DISHAAL Age First Noticed Score 0–3
a
D: Disorientation/Confusion—Awareness—Spatial orientation
Gets stuck or cannot get around objects
Stares blankly at walls or floor
Decreased recognition of familiar people/pets
Goes to wrong side of door; walks into door/walls
Drops food/cannot find
Decreased response to auditory or visual stimuli
Increased reactivity to auditory or visual stimuli (barking)
I: Interactions—Social Relationships
Decreased interest in petting/avoids contact
Decreased greeting behavior
In need of constant contact, overdependent, “clingy”
Altered relationships other petsless social/irritable/aggressive
Altered relationships with peopleless social/irritable/aggressive
S: Sleep–Wake Cycles; Reversed Day/Night Schedule
Restless sleep/waking at nights
Increased daytime sleep
H: Housesoiling (Learning and Memory)
Indoor elimination at sites previously trained
Decrease/loss of signaling
Goes outdoors, then returns indoors and eliminates
Elimination in crate or sleeping area
A: Activity—Increased/Repetitive
Pacing/wanders aimlessly
Snaps at air/licks air
Licking owners/household objects
Increased appetite (eats quicker or more food)
A: Activity—Apathy/Depressed
Decreased interest in food/treats
Decreased exploration/activity/play
Decreased self-care (hygiene)
A: Anxiety
Vocalization, restlessness/agitation
Anxiety, fear/phobia to auditory or visual stimuli
Anxiety, fear/phobia of places (surfaces, locations)
Anxiety/fear of people
Separation anxiety
L: Learning and Memory—Work, Tasks, Commands
Decreased ability to perform learned tasks, commands
Decreased responsiveness to familiar commands and tricks
Inability/slow to learn new tasks
a
Score: 0 none; 1 mild; 2 moderate; 3 severe.
Adapted from Landsberg GM, Hunthausen W, Ackerman L. The effects of aging on the behavior of
senior pets. Handbook of behavior problems of the dog and cat. 2nd edition. Philadelphia: WB
Saunders; 2003. p. 273; with permission.
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The practitioner will need to consider physical examination findings (including
neurologic, sensory, and pain assessment) along with medical and behavioral signs to
select the appropriate diagnostic tests required to reveal the causes and contributing
factors of a patient’s signs. Identifying all influences on specific behavioral signs is
Table 2
Medical causes of behavioral signs
Medical Condition/Medical
Presentation Examples of Behavioral Signs
Neurologic: central (intracranial/
extracranial) particularly if
affecting forebrain, limbic/
temporal and hypothalamic;
REM sleep disorders
Altered awareness, response to stimuli, loss of learned
behaviours, housesoiling, disorientation, confusion,
altered activity levels, temporal disorientation,
vocalization, change in temperament (fear,
anxiety), altered appetite, altered sleep cycles,
interrupted sleep
Partial seizures: temporal lobe
epilepsy
Repetitive behaviors, self-traumatic disorders,
chomping, staring, alterations in temperament (eg,
intermittent states of fear or aggression), tremors,
shaking, interrupted sleep
Sensory dysfunction Altered response to stimuli, confusion, disorientation,
irritability/aggression, vocalization, house soiling,
altered sleep cycles
Endocrine: feline hyperthyroidism Irritability, aggression, urine marking, decreased or
increased activity, night waking
Endocrine: canine hypothyroidism Lethargy, decreased response to stimuli, irritability/
aggression
Endocrine: hyperadrenocorticism/
hypoadrenocorticism
Lethargy, house soiling, altered appetite, decreased
activity, anxiety
Endocrine: insulinoma, diabetes Altered emotional state, irritability/aggression,
anxiety, lethargy, house soiling, altered appetite
Endocrine: functional ovarian and
testicular tumors
Increased androgen-induced behaviors. Males:
aggression, roaming, marking, sexual attraction,
mounting. Females: nesting or possessive aggression
of objects.
Metabolic disorders: hepatic/renal Signs associated with organ affected: may be anxiety,
irritability, aggression, altered sleep, house soiling,
mental dullness, decreased activity, restlessness,
increase sleep, confusion
Pain Altered response to stimuli, decreased activity,
restless/unsettled, vocalization, house soiling,
aggression/irritability, self-trauma, waking at night
Peripheral neuropathy Self-mutilation, irritability/aggression, circling,
hyperesthesia
Gastrointestinal Licking, polyphagia, pica, coprophagia, fecal house
soiling, wind sucking, tongue rolling, unsettled
sleep, restlessness
Urogenital House soiling (urine), polydypsia, waking at night
Dermatologic Psychogenic alopecia (cats), acral lick dermatitis
(dogs), nail biting, hyperesthesia, other self-trauma
(chewing/biting/sucking/scratching)
Abbreviation: REM, rapid eye movement.
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critical for both treatment selection and monitoring of behavioral and medical
disorders.
Effects of Stress on Health and Mental Well-Being
Stress is an altered state of homeostasis that can be caused by physical or emotional
factors that trigger psychological, behavioral, endocrine, and immune effects. Acute
and chronic stress can also impact both health and behavior.
48 –50
In addition, senior
pets, especially those with medical or behavioral issues, may be more affected by
stress and less able to adapt to change. Owners should pay particular attention to
their pet‘s emotional and behavioral state as well as its appetite, sleep, and
elimination to evaluate the role of stress. While enrichment can help maintain both
physical and mental health, changes in the elderly pet’s household or schedule should
be made slowly. Natural products or drugs may also be indicated (discussed later).
Prevalence of Behavioral Signs in Senior Pets
Spontaneously reported behavior problems
A number of studies have examined the prevalence of spontaneously reported
behavioral signs in senior pets referred to behavioral specialists.
44,45
In 2 canine
studies, behavioral complaints related to aggression, or fear and anxiety, were most
prevalent. In a similar senior cat study, most displayed signs of marking or soiling;
however, cases of aggression, vocalization, and restlessness were also serious
enough to solicit referral.
50
To further examine the distribution of problems reported by owners of senior dogs
and cats, the Veterinary Information Network (VIN) database was searched for
behavior problems of 50 senior dogs (aged 9 –17) and 100 senior cats (aged 12–22
years). Of dogs, 62% had signs consistent with CDS, but most demonstrated anxiety,
night waking, and vocalization. In the 100 feline cases reviewed, the most common
complaints were related to vocalization, especially at night, and soiling. Figs. 3 and 4
summarize the distribution of behavioral signs most commonly reported by owners of
senior pets across studies.
Solicited reports of behavior problems
Since many of the most common behavioral signs in senior pets go unreported, a
more proactive approach is required to establish their prevalence. In 1 study of dogs
aged 11 to 16, 28% of 11-to 12-year-old dogs and 68% of 15- to 16-year-old dogs
showed at least 1 sign consistent with CDS.
51
In another study of 102 dogs, 41% had
alterations in at least 1 category associated with CDS and 32% had alterations in 2
categories.
52
In a more recent study, females and neutered males were significantly
more affected than intact males with both prevalence and severity increasing with
age, which is consistent with previous reports.
46,53
Moreover, social interactions and
house training were the most impaired categories.
46
In a recent epidemiologic study using an internet survey format of 497 dogs ranging
in age from 8 to 19 years, the prevalence of CDS was 5% in 10- to 12-year-old dogs,
23.3% in dogs 12- to 14-year-old dogs, and 41% in dogs older than 14, with an
overall prevalence of 14.2%. However, only 1.9% of cases had a veterinary diagnosis
of CDS.
54
In 1 study of aged cats presented to veterinary clinics for routine annual
care, 28% of 95 cats aged 11 to 15 and 50% of 46 cats older than 15 years were
diagnosed with possible CDS.
37
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Importance of Client Education and Screening in the Veterinary Clinic
The data presented above indicate several important findings. First, behavioral signs
related to anxiety, vocalization, night waking, soiling in cats, and aggression in dogs
are more often spontaneously reported to veterinarians, which is likely related to the
impact of these behaviors on the owner. Second, behavioral changes consistent with
CDS are reported less frequently but are present in a significant proportion of the
population. Third, the prevalence of behavioral signs consistent with CDS increases
with age. Finally, because CDS is likely underdiagnosed when solicited reporting is
not used, proactive monitoring and assessment of behavioral signs should be
components of every veterinary visit involving senior pets. Veterinarians and their staff
must inform clients of the health and welfare consequences if these problems are
untreated. Handouts and web links on senior care and cognitive dysfunction
syndrome can be used to further educate owners. Questionnaires are particularly
effective for quick and comprehensive screening. Several are available for screening,
including Table 1, a scoring system known as age-related cognitive and affective
disorders, and a recently published 13-point data-based assessment tool.
40,54
THERAPEUTIC OPTIONS FOR PETS WITH CDS
Behavioral Support and Environmental Enrichment in the Management of CDS
Canine studies have shown that mental stimulation is an essential component in
maintaining quality of life and that continued enrichment in the form of training, play,
45%
29%
17%
15%
8%
5% 3%
3%
Prevalences of owner reported signs in
senior dogs
Aggression
Cognive dysfuncon
Separaon anxiety
Anxiety, Fears and Phobias
Vocalizaon
Compulsive
Destrucve
Soiling
Fig. 3. Fears and phobias (includes generalized anxiety), compulsive includes repetitive and
stereotypic behavior; cognitive dysfunction includes disorientation, wandering, waking and
anxious at night. Behavior signs were combined from 3 studies: a Spanish study of 270 dogs
older than age 7 that were presented for behavior problems, 103 dogs referred to a
veterinary behaviorist, and a search of the Veterinary Information Network (VIN) of 50 dogs
aged 9 to 17 years.
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exercise, and novel toys can help to maintain cognitive function (ie, use it or lose it).
55
This is analogous to human studies in which increased mental activity and physical
exercise have been found to delay the onset of dementia.
56,57
Environmental enrichment can have positive effects on behavioral health and
quality of life in pets and is likely to improve cognitive function.
58
Inconsistency in the
management of the senior pet’s environment (especially for cats) can cause stress
and negatively impact health and behavioral well-being.
40,50
As sensory, motor, and
cognitive function decline, new odor, tactile, and/or sound cues may help the pet
better cope with its environment. Dogs with increased urine frequency may need
more frequent trips outdoors or even the addition of an indoor toilet area. Ramps and
physical support devices may be necessary to address mobility issues. For cats,
inappropriate elimination may be improved by providing more litter boxes with lower
sides and nonslip ramps.
Enrichment should focus on positive social interactions as well as new and varied
opportunities for exploration, climbing, perching, hunt-and-chase games, and other
stimulating ways to obtain food and treats. Food toys that require pushing, lifting,
dropping, batting, pawing, or rolling to release food help older dogs and cats to
remain active and alert (Fig. 5). By scattering favored food, treats, or catnip in different
locations, pets can learn to hunt, search, and retrieve.
Maintenance of a day-night cycle by opening blinds and providing outdoor
activities (where practical) to provide daylight during the day and reducing exposure
to artificial light at night may be considered. Increased daytime enrichment with
several quality interactive sessions, food toys, outdoor exercise (if appropriate), and
a final interactive play session prior to bed may help encourage better sleep.
Drug Therapy for CDS
CDS cannot be cured at present, but deterioration may be slowed and clinical signs
improved. Assuming concomitant medical and behavior problems are being controlled,
various drugs (Table 3) may be considered to improve cognitive function or control
clinical signs. For each pet, the clinician must weigh potential risks against potential
benefits.
48%
36%
35%
11%
2% 2%
Prevalences of owner reported signs in
senior cats
Soiling
Vocalizaon
Cognive Dysfuncon
Syndrome
Fear / Aggression
Overgrooming
Clingy
Fig. 4. Soiling includes marking, cognitive dysfunction includes disorientation, restless,
wandering and night waking, and fear/aggression (includes fear and hiding). Behavior signs
were combined from a VIN data search of 100 cats aged 12 to 22 years and 83 from 3 different
behavior referral practices.
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Selegiline (Anipryl; Pfizer Animal Health, New York, NY, USA) is a selective and
irreversible inhibitor of monoamine oxidase B.
59
It may enhance dopamine and other
catecholamines in the cortex and hippocampus and has been shown both in the
laboratory and clinic to improve signs consistent with CDS in dogs.
59,61
Selegiline
Fig. 5. A food manipulation toy, the Kong Wobbler (Kong Company, Golden, CO, USA). This
toy is filled with food pieces and treats that are delivered through the opening as the dog
learns to tip the toy.
Table 3
Doses for drugs for behavior therapy of senior pets
Dog Cat
Selegiline (CDS) 0.5–1 mg/kg sid in am 0.5–1 mg/kg sid in am
Propentofylline (CDS) 2.5–5 mg/kg bid ¼ of a 50 mg tablet daily
Oxazepam
a
0.2–1 mg/kg sid–bid 0.2–0.5 mg/kg sid–bid
Clonazepam
a
0.1–1.0 mg/kg bid–tid 0.02–0.2 mg/kg sid–bid
Lorazepam
a
0.025–0.2 mg/kg sid–tid 0.025–0.05 mg/kg sid–bid
Diphenhydramine
a
2–4 mg/kg 1–4 mg/kg
Fluoxetine 1.0–2.0 mg/kg sid 0.5–1.5 mg/kg sid
Paroxetine 0.5–2 mg/kg 0.5–1.5 mg/kg
Sertraline 1–5 mg/kg sid or divided bid 0.5–1.5 mg/kg sid
Buspirone 0.5–2.0 mg/kg sid–tid 0.5–1 mg/kg bid
Trazodone 2–5 mg/kg (up to 8–10) prn–tid Not determined
Phenobarbital 2.5–5 mg/kg bid 2.5 mg/kg bid
Memantine 0.3–1 mg/kg sid Not determined
Gabapentin 10–30 mg/kg q 8–12 h 5–10 mg/kg q 12 h
Abbreviation: sid, once daily.
a
Use single dosing prior to sleep or anxiety-evoking event, up to maximum daily dosing for
control of ongoing anxiety.
760 Landsberg et al
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also may be neuroprotective possibly by reducing free radical production and/or
increasing enzymes that scavenge free radicals such as superoxide dismutase and
catalase.
59,60
Selegiline is not licensed for use in cats but is used off label with
anecdotal reports of improvement in CDS-like signs.
62
Selegiline may require 2 weeks
or longer before clinical improvement is seen, should not be used concurrently with
other monoamine oxidase inhibitors (eg, amitraz), and should be avoided, or used
cautiously, with drugs that may enhance serotonin transmission (such as selective
serotonin reuptake inhibitors, tricyclic antidepressants, buspirone, trazodone, trama-
dol, and dextromethorphan).
Propentofylline (Vivitonin; Merck Animal Health, Milton Keyes, UK) is licensed in
some European countries for the treatment of dullness, lethargy, and depressed
demeanor in old dogs. Propentofylline may increase blood flow to the heart, skeletal
muscles, and brain and may have neuroprotective properties due to inhibiting the
uptake of adenosine and blocking phosphodiesterase. Propentofylline has been
anecdotally used in cats, but there is no clinical evidence of efficacy.
Drugs thought to enhance the noradrenergic system, such as adrafinil and modafinil,
might be useful in older dogs to improve alertness and help maintain normal sleep-wake
cycles (by increasing daytime exploration and activity).
63,64
However, dose and efficacy
in dogs are not well established. Newer treatment strategies include the N-methyl-D-
aspartate receptor antagonist memantine or hormone replacement therapy, but evidence
is currently lacking to make appropriate suggestions for treatment.
65
In canine and feline CDS, as well as in AD, there is evidence of cholinergic
decline (see earlier). Because the elderly are particularly susceptible to anticho-
linergic drugs, it is prudent to consider therapies with less anticholinergic effects.
Drugs and natural products that enhance cholinergic transmission might have
potential benefits for improving signs of CDS, but more research is required to
select appropriate drugs and doses.
66
Nutritional and Dietary Therapy for CDS
Nutritional and dietary interventions (Table 4) can improve antioxidant defense
thereby reducing the negative effects of free radicals. A senior diet (Canine b/d, Hills
Pet Nutrition, Topeka, KS, USA) for dogs improves signs and slows the progress of
cognitive decline.
67– 69
The diet improved performance on a number of cognitive tasks
when compared to a nonsupplemented diet as early as to 2 to 8 weeks after the onset
of therapy. However, the combined effect of the supplemented diet and environmen-
tal enrichment provided the greatest benefit and, when started prior to the onset of
behavioral signs, may extend cognitive health.
67
Another strategy is a diet containing medium-chain triglycerides (MCTs), which are
converted to ketone bodies by the liver. Since a decline in cerebral glucose
metabolism and reduced energy metabolism are associated with cognitive decline,
MCT-induced ketone bodies provide an alternate energy source that can be used by
the brain. When compared to control, the diet (Purina One Vibrant Maturity 7
Formula; Nestlé Purina PetCare, St Louis, MO, USA) significantly improved perfor-
mance on several cognitive tasks.
70
Supplementation with MCTs also improves
mitochondrial function, increases polyunsaturated fatty acids in the brain, and
decreases amyloid precursor protein in the parietal cortex of aged dogs.
71,72
Supplementation with MCTs is also approved as a medical dietary supplement for AD
patients. Cognitive diets for cats have not yet been developed.
A number of clinical trials have shown improvements in signs associated with CDS
in dogs using dietary supplements containing phosphatidylserine, a membrane
phospholipid.
73,74
One product (Senilife; CEVA Animal Health, Libourne, France) was
761
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tested in aged dogs using a cross-over design in which DNMP memory performance
was improved after 60 days of treatment with Senilife.
75
Although labeled for use in
cats, efficacy studies are not published.
Another product containing phosphatidylserine (Activait; Vet Plus Ltd, Lytham St.
Annes, UK) demonstrated significant improvement over placebo on signs of disori-
entation, social interactions, and house soiling in dogs.
74
A feline version of Activait,
with no alpha-lipoic acid, is also available but has not been tested in clinical trials.
Another available supplement for cognitive health (Novifit; Virbac Animal Health, Ft
Worth, TX, USA) contains S-adenosyl-L-methionine (SAMe) tosylate, which is found in
all living cells and is formed from methionine and adenosine triphosphate. SAMe may
help to maintain cell membrane fluidity, receptor function, and the turnover of
monoamine transmitters, as well as increase the production of the endogenous
antioxidant glutathione.
76
In a recent placebo-controlled trial, greater improvement in
activity and awareness was reported in the SAMe group after 8 weeks.
77
Since SAMe
might increase central serotonin levels, caution should be used when combining with
Table 4
Ingredients and doses of natural therapeutics for senior pets
Ingredients Dose
Senilife Phosphatidylserine, Gingko biloba,
vitamin B6 (pyridoxine),
vitamin E, resveratrol
Dogs and cats (see label)
Activait Phosphatidylserine, omega-3 fatty
acids, vitamins E and C,
L-carnitine, alpha-lipoic acid,
coenzyme Q, selenium
Separate dog and cat products
Activait Cat Note: no alpha-lipoic acid in feline
version
See label
Novifit S-Adenosyl-L-methionine-tosylate
disulfate (SAMe)
Dog: 10–20 mg/kg sid
Cat: 100 mg sid
Neutricks Apoaequorin Dogs: 1 tablet per 18 kg
Prescription diet b/d
Canine aging and
alertness
Flavonoids and carotenoids from
fruits and vegetables, vitamin E,
vitamin C, beta-carotene,
selenium, L-carnitine, alpha-lipoic
acid, omega 3 fatty acids
Dogs
Purina One Vibrant
Maturity 7Senior
Medium chain triglycerides (from
coconut oil)
Dogs
Melatonin Endogenous-based peptide Dogs: 3–9 mg
Cats: 1.5–6 mg
Anxitane Suntheanine Dogs: 2.5–5 mg/kg bid
Cats: 25 mg bid
Harmonease Magnolia and phellodendron Dogs: up to 22 kg ½ tablet daily;
22 kg 1 tablet daily
Cats: N/A
Zylkene Alpha-casozepine Dogs: 15–30 mg/kg/d
Cats: 15 mg/kg/d
Pheromones Adaptil collar, diffuser, or spray for
dogs
Feliway spray or diffuser for cats
As per label
Lavender Aromatherapy for dogs As per label
762 Landsberg et al
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other drugs that might increase serotonin. On the other hand, SAMe has been used
in human patients to enhance the effects of serotonin reuptake inhibitors in the
treatment of depressive disorders.
78
In laboratory aged dog and cat studies, SAMe
improved measures of executive function and possibly attention.
79,80
In cats, these
effects were mainly evident in the least cognitively impaired subjects, suggesting that
supplementation with SAMe early in disease progression, rather than in more severely
impaired subjects, should be most beneficial.
80
Apoaequorin (Neutricks; Quincy Animal Health, Madison, WI, USA), recently
released in the United States, improved learning and attention in laboratory trials
compared to both placebo and selegiline.
81
Apaoequorin is a calcium buffering
protein that has been postulated to provide neuroprotection in aging and conse-
quently have positive effects on signs of brain aging.
Last, curcumin, an antioxidant, antiamyloid, and antiinflammatory compound found
in the turmeric and catechin spices, is postulated to be helpful.
82
Adjunctive Therapies for Anxiety and Night Waking
Because behavioral signs associated with anxiety and night waking are highly
prevalent in senior pets and greatly impact the owner-pet bond, it is prudent for the
practitioner to rapidly address them. Drugs and natural remedies that help reduce
anxiety and aid in reestablishing normal sleep-wake cycles can also be of benefit in
senior pets alone or in conjunction with drugs for CDS (see Tables 3 and 4).
Melatonin is best given to dogs 30 minutes before bedtime. Diphenhydramine,
phenobarbital, or trazodone can also promote sedation. For the dog or cat that has
difficulty settling at night but then sleeps well, situational use of anxiolytics can be
helpful. Benzodiazepines have rapid onset, are generally short acting, and have
sedative effects at the higher end of the recommended dosage range. In pets where
liver function is compromised, clonazepam, lorazepam, or oxazepam is recom-
mended because they have no active metabolites. Since pain may contribute to
unsettled sleep or night waking, gabapentin can be added both as an adjunctive
therapy for pain management and for its behavioral calming effects.
For senior pets with generalized anxiety, noise phobias, or separation anxiety,
buspirone or selective serotonin reuptake inhibitors like fluoxetine (Reconcile; Elanco,
Greenfield, IN, USA) and sertraline may be considered because of their low risk of side
effects. Paroxetine and tricyclic antidepressants have varying degrees of anticholin-
ergic effects and therefore should not be a first-choice therapeutic. However, these
drugs should not be used concurrently with selegiline.
Natural compounds that may reduce anxiety and help pets settle at night include
suntheanine (Anxitane; Virbac Animal Health, Ft Worth, TX, USA), honokiol and
berberine extracts (Harmonease; VPL, Phoenix, AZ, USA), alpha casozepine (Zylkene;
Vetoquinol Canada, Lavaltrie, PQ, Canada), pheromones (Adaptil and Feliway; CEVA
Animal Health, Libourne, France), and lavender essential oils.
40
SUMMARY
CDS is an underdiagnosed behavioral problem that affects a substantial number of
aged pets. Because changes in behavior are often early indicators of medical or
behavior problems in senior pets, the veterinarian faces the challenge of ruling out the
influence of medical problems, sleep disturbances, anxiety, concurrent medications,
and pain before a diagnosis of CDS can be made. While there are several options for
treatment of CDS, many therapeutics have not been adequately tested. Moreover,
early intervention is likely to be most beneficial. As we learn more about biomarkers
of brain aging, objective tests for identifying pets likely to progress to CDS may be
763
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developed. In the meantime, a proactive approach for early identification and
monitoring of behavioral signs is essential for establishing a diagnosis and monitoring
treatment success.
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768 Landsberg et al
... Aged dogs develop both neuropathology and cognitive decline paralleling several aspects of Alzheimer's disease that likely contribute to the behavioral signs associated with canine cognitive dysfunction syndrome (CDS) (1)(2)(3)(4)(5)(6)(7)(8). Some of the neuropathological similarities include reduced brain volume, neuronal loss, impaired neurogenesis, and amyloid beta deposition (9), the latter of which has been shown to positively correlate with level of cognitive impairment (10). ...
... Both frontal cortex amyloid deposition and brain atrophy are negatively correlated with performance on the DNMP and reversal learning tasks, suggesting that frontal cortex neuropathology is linked to cognitive deficits in these domains (15,16). In pet dogs, the sequalae of these neurodegenerative processes can result in behavioral changes that may lead to a diagnosis of CDS (1)(2)(3)(4)(5)(6)17). Importantly, we have previously demonstrated that age-related cognitive decline in dogs precedes behavioral changes such as alterations in sleep-wake patterns, interaction with humans, and environmental attention (1,3). ...
... In pet dogs, the sequalae of these neurodegenerative processes can result in behavioral changes that may lead to a diagnosis of CDS (1)(2)(3)(4)(5)(6)17). Importantly, we have previously demonstrated that age-related cognitive decline in dogs precedes behavioral changes such as alterations in sleep-wake patterns, interaction with humans, and environmental attention (1,3). ...
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Canine cognitive dysfunction syndrome (CDS) is a disorder found in senior dogs that is typically defined by the development of specific behavioral signs which are attributed to pathological brain aging and no other medical causes. One way of objectively characterizing CDS is with the use of validated neuropsychological test batteries in aged Beagle dogs, which are a natural model of this condition. This study used a series of neuropsychological tests to evaluate the effectiveness of supplementation with a novel lipid extract containing porcine brain-derived sphingolipids (Biosfeen®) and docosahexaenoic acid (DHA) for attenuating cognitive deficits in aged Beagles. Two groups (n = 12), balanced for baseline cognitive test performance, received a daily oral dose of either test supplement, or placebo over a 6-month treatment phase. Cognitive function was evaluated using the following tasks: delayed non-matching to position (DNMP), selective attention, discrimination learning retention, discrimination reversal learning, and spatial discrimination acquisition and reversal learning. The effect of the supplement on brain metabolism using magnetic resonance spectroscopy (MRS) was also examined. A significant decline (p = 0.02) in DNMP performance was seen in placebo-treated dogs, but not in dogs receiving the supplement, suggesting attenuation of working memory performance decline. Compared to placebo, the supplemented group also demonstrated significantly improved (p = 0.01) performance on the most difficult pattern of the spatial discrimination task and on reversal learning of the same pattern (p = 0.01), potentially reflecting improved spatial recognition and executive function, respectively. MRS revealed a significant increase (p = 0.048) in frontal lobe glutamate and glutamine in the treatment group compared to placebo, indicating a physiological change which may be attributed to the supplement. Decreased levels of glutamate and glutamine have been correlated with cognitive decline, suggesting the observed increase in these metabolites might be linked to the positive cognitive effects found in the present study. Results of this study suggest the novel lipid extract may be beneficial for counteracting age-dependent deficits in Beagle dogs and supports further investigation into its use for treatment of CDS. Additionally, due to parallels between canine and human aging, these results might also have applicability for the use of the supplement in human cognitive health.
... The management of clinical symptoms through drugs, diet, and supplements decreases the progression of cognitive disorders by various mechanisms, including a reduction in oxidative stress and inflammation, or improved mitochondrial and neuronal function [3,4]. ...
... linked with neuroinflammatory diseases would help diagnosis and improve treatment response rates. The management of clinical symptoms through drugs, diet, and supplements decreases the progression of cognitive disorders by various mechanisms, including a reduction in oxidative stress and inflammation, or improved mitochondrial and neuronal function [3,4]. ...
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Increasing evidence links chronic neurodegenerative diseases with neuroinflammation; it is known that neuroprotective agents are capable of modulating the inflammatory processes, that occur with the onset of neurodegeneration pathologies. Here, with the intention of providing a means for active compounds’ screening, a dysregulation of neuronal inflammatory marker genes was induced and subjected to neuroprotective active principles, with the aim of selecting a set of inflammatory marker genes linked to neurodegenerative diseases. Considering the important role of microglia in neurodegeneration, a murine co-culture of hippocampal cells and inflamed microglia cells was set up. The evaluation of differentially expressed genes and subsequent in silico analysis showed the main dysregulated genes in both cells and the principal inflammatory processes involved in the model. Among the identified genes, a well-defined set was chosen, selecting those in which a role in human neurodegenerative progression in vivo was already defined in literature, matched with the rate of prediction derived from the Principal Component Analysis (PCA) of in vitro treatment-affected genes variation. The obtained panel of dysregulated target genes, including Cxcl9 (Chemokine (C-X-C motif) ligand 9), C4b (Complement Component 4B), Stc1 (Stanniocalcin 1), Abcb1a (ATP Binding Cassette Subfamily B Member 1), Hp (Haptoglobin) and Adm (Adrenomedullin), can be considered an in vitro tool to select old and new active compounds directed to neuroinflammation.
... We suspect that the age of the dog played a role, because no dog older than 8 years reached the criteria. It is well documented that cognitive abilities drastically reduce after 8 years of age 65 , and this may be why we could not train older dogs in this difficult task. Furthermore, the dogs used in this experiment were laboratory dogs kept in a kennel and were not familiar with training for visual discrimination, and the learning the task was challenging for them. ...
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In humans, contrasting emotional states can lead to a broadening or narrowing of attentional scope. Whether this is also the case in animals has yet to be investigated. If confirmed, measurement of attentional scope has potential as a novel cognitive method of welfare assessment. In this study, we therefore aimed to investigate a test of attentional scope as a measure of emotional state in animals. We did this by inducing four putatively different emotional states in dogs (N = 10), varying in valence (positive, negative) and arousal (high, low), in two different reward contexts (food rewards in Experiment 1, social rewards in Experiment 2) and then assessing dogs’ behavioural responses in a test of attentional scope. We also recorded heart rate variability (HRV) parameters as additional confirmatory affective indicators. In Experiment 1, the dogs showed a narrowing of attentional scope after the induction of both positively valenced emotional states. That dogs were in a positive state was supported by the reduced Standard Deviation of normal-to-normal R-R intervals (SDNN) and the reduced Low Frequency (LF) and Very Low Frequency (VLF) HRV. In Experiment 2, when responses to social rewards were examined, we did not detect any statistically significant differences in attentional scope between the emotional states, but dogs had a slightly narrow attentional scope in the negatively valenced emotional states. The LF tended to be reduced in the high arousal positive treatment. In conclusion, our study provides the first indication that emotional states can also alter attentional scope in animals. The results justify further investigation of this approach for use in animal welfare assessment, although additional studies are needed to refine predictions.
... Additionally, Fourtillan et al., 2002 presented a study on beagle dogs with melatonin synthetic analogs suggesting that insomnia may be treated by administering hypnotic acetyl metabolites of melatonin or their synthetic analogs [138]. Some authors have recommended melatonin doses of 3-9 mg for dogs and 1.5-6 mg for cats to improve cognitive dysfunction syndrome, sleep-wake disturbances, and anxiety in older pets [139][140][141]. In a clinical study with 14 dogs on sleep behavior disorders, melatonin treatment showed uneven results. ...
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The use of nutraceuticals or functional ingredients is increasingly widespread in human food; their use is also widespread in animal feed. These natural compounds generally come from plant materials and comprise a wide range of substances of a very diverse chemical nature. In animals, these compounds, so-called phytogenics, are used to obtain improvements in feed production/stability and also as functional components with repercussions on animal health. Along with polyphenols, isoprenoid compounds represent a family of substances with wide applications in therapy and pet nutrition. Essential oils (EOs) are a group of complex substances with fat-soluble nature that are widely used. Melatonin is an indolic amine present in all living with amphiphilic nature. In this work, we present a review of the most relevant phytogenics (polyphenol, isoprenoid, and alkaloid compounds), their characteristics, and possible uses as nutraceuticals in dogs, with special emphasis on EOs and their regulatory aspects, applied in foods and topically. Additionally, a presentation of the importance of the use of melatonin in dogs is developed, giving physiological and practical aspects about its use in dog feeding and also in topical application, with examples and future projections. This review points to the combination of EOs and melatonin in food supplements and in the topical application as an innovative product and shows excellent perspectives aimed at addressing dysfunctions in pets, such as the treatment of stress and anxiety, sleep disorders, alopecia, and hair growth problems, among others.
... Unfortunately, at this time, it is not possible to cure CCD, but certain therapies can slow the progression of cognitive decline and improve quality of life of the patients (Campbell et al., 2001;Pero et al., 2019;Pop et al., 2010;Zakosek Pipan et al., 2021). An early diagnosis is ideal because therapeutic impact is greater if initiated early in disease course (Landsberg et al., 2012;Osella et al., 2007). Owner-based questionnaires are the most employed diagnostic tools; though, they represent a subjective and indirect evaluation of the disease and their diagnostic sensitivity and specificity has not been evaluated against the gold standard for diagnosis, histopathology (Madari et al., 2015;Rofina et al., 2006;Salvin et al., 2011;Schütt et al., 2015). ...
Article
Canine cognitive dysfunction (CCD) is a highly prevalent neurodegenerative disease considered the canine analog of early Alzheimer's disease (AD). Unfortunately, CCD cannot be cured. However, early therapeutic interventions can slow the progression of cognitive decline and improve quality of life of the patients; therefore, early diagnosis is ideal. In humans, electroencephalogram (EEG) findings specific to AD have been described, and some of them have successfully detect early stages of the disease. In this study we characterized the EEG correlates of CCD, and we compared them with the EEGs of healthy aging dogs and dogs at risk of developing CCD. EEG recordings were performed in 25 senior dogs during wakefulness. Dogs were categorized in normal, at risk of CCD or with CCD according to their score in the Rofina questionnaire. We demonstrated that, quantitative EEG can detect differences between normal dogs and dogs with CCD. Dogs with CCD experience a reduction in beta and gamma interhemispheric coherence, and higher Joint Lempel Ziv complexity. Dogs at risk of developing CCD, had higher alpha power and interhemispheric coherence, making these features potential markers of early stages of the disease. These results demonstrate that quantitative EEG analysis could aid the diagnosis of CCD, and reinforce the CCD as a translational model of early AD.
... In addition, an accelerometer has been used in humans for gait examination [12]- [15] as well as for the analysis of circadian rhythms [16], [17], and sensors have been used to observe and monitor lameness in horses for the past few years [18]- [21]. An accelerometer has been used to monitor various activities in dogs [22]- [26], types of activity [27], cognitive issues, and lameness recognition [28]- [30]. Wearable sensors combining embedded systems with acceleration and gyro sensors have been established for activity recognition and are used in everyday life and sports activities. ...
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Among pets, dogs are very famous in the whole world. The owners of dogs are very cautious about the well-being of dogs. The well-being of dogs can be ensured by continuous monitoring of their activities. Studies related to activity detection have gained much popularity due to the significant progress in sensor technology during the last few years. Automatic monitoring of pet applications includes real-time monitoring systems and surveillance which detect the pets with high accuracy using the latest pet activity classification techniques. The revolution in the domain of technology has allowed us to obtain better results using conventional techniques. Convolutional neural networks (CNNs) 1D recently become a cutting-edge approach for signal processing-based systems such as patient-individual ECG categorization, sensor-based health monitoring systems, and anomaly identification in manufacturing areas. Adaptive and compact 1D models have several advantages over their conventional 2D counterparts. A limited dataset is sufficient to train a 1D CNN efficiently while 2D CNNs require a plethora of data for training. Its architecture is not very complicated, so it is suitable for real-time detection of activities. The main goal of this study is to develop a state-of-the-art system that can detect and classify the activities based on sensors’ data (accelerometer, and gyroscope. We proposed a 1D CNN-based system for pet activity detection. The objective of this study was to recognize ten pet activities such as walking, sitting, down, staying, eating, sideway, jumping, running, shaking, and nose work respectively, using wearable sensor devices based on deep learning technique. The data collection procedure for this study was conducted with 10 dogs of different breeds, sex (male=7, female = 3), age (age = 4±3), and sizes (small, medium, large) in a healthy environment. After collecting the data, the following steps, namely data synchronization, and data preprocessing were considered to remove the irrelevant data from the dataset. To overcome imbalanced problems in the dataset we used the class-weight technique. Subsequently, we applied 1D CNN algorithm using the class-weight technique. The model with the class-weight technique showed 99.70% training accuracy and 96.85% validation accuracy. The 1D CNN approach will be helpful for real-time monitoring of activities and for tracing the behavior of dogs.
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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.
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The prolonged lifespan of companion dogs has resulted in increased behavioural and physical challenges linked to old age. The development of behavioural tests to identify and monitor age‑related differences has begun. However, standardised testing requires validation. The present study aimed to assess external validity, interobserver reliability, and test–retest reliability of an indoor test battery for the rapid assessment of age‑related behavioural differences in dogs. Two experimenters tested young dogs (N = 20, mean age ± SD = 2.7 ± 0.4 years) and old dogs (N = 18, mean age ± SD = 11.8 ± 1.3 years) in the test battery once and then again after two weeks. Our results found external validity for two subtests out of six. On both test occasions, old dogs committed more errors than young dogs in a memory subtest and showed more object avoidance when encountering a novel object. Interobserver reliability and test–retest reliability was high. We conclude that the Memory and Novel object subtests are valid and reliable for monitoring age‑related memory performance and object neophobic differences in dogs.
Article
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.
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A large number of aged dogs and cats demonstrate behavioral signs consistent with a clinical diagnosis of cognitive dysfunction syndrome (CDS), which likely is a consequence of pathological brain aging. Identification of treatments that prevent, halt, or reverse CDS, therefore, represents an unmet need in senior animal veterinary care. NOVIFIT Tablets are an S-adenosylmethio-nine (SAMe) tosylate supplement currently marketed for improving cognitive health of aged dogs and cats. SAMe is an endogenous metabolite involved in several biochemical pathways, and is deficient in humans with Alzheimer's disease. The current study examined the efficacy of NOVIFIT tablets on cognitive performance enhancement in cognitive domains impaired in canine and feline aging. In the first study, aged dogs initially balanced for memory performance were divided into NOVIFIT tablet and placebo groups and tested on both the same memory task and an object discrimination learning and reversal learning task. No treatment effects on memory performance were found, but the NOVIFIT tablets-treated dogs did not show a significant increase in reversal learning errors compared to learning errors seen both under placebo and in previous aging studies, suggesting NOVIFIT tablets
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As dogs age, behavior problems often emerge, but owners may not tell you about them unless you ask. Here's how you can identify and treat these behavioral abnormalities.
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Aging is associated with behavioral and cognitive changes in all mammals. Unlike most clinical presentations, changes associated with aging do not always reflect an underlying pathology and therefore baselines for normality can be difficult to establish. Using data from a large cross-sectional survey of older dog owners, we aimed to identify normative behavioral changes associated with “successful aging” in dogs, and the rate of deterioration that could be expected over a 6-month period. Binary logistic regression identified significant age group effects from 18 items (difference in reported item incidence across age group: 4.5%-30.3%, P < 0.001-0.038). Significant age group effects on the percentage of dogs deteriorating over the preceding 6 months were evident in 21 items (difference in item deterioration across age group: 3.5%-25.7%, P < 0.001-0.033). The modal frequency of problem behaviors and abnormal ingestive or locomotory items was found to be low and the effect on memory and learning was minimal. Despite this, more than half of the items were reported to have shown a greater than 10% incidence of deterioration. In particular, activity and play levels, response to commands, and fears and phobias showed considerable deterioration. These findings represent the first steps toward the development of baseline values for normal behavioral changes in “successfully aging” dogs.
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Glucocorticoids are widely used in veterinary medicine and their physical side effects are well-known; however, the effects on dog behavior linked to their role in the stress response and effects on mood have not been reported in previously published data. In this article, retrospective owner reports of the behavioral changes in dogs during corticosteroid therapy in a series of cases have been described so as to generate items for future use in a controlled structured questionnaire. The perceptions of behavioral changes in dogs during corticosteroid therapy were investigated through semi-structured open interviews of the owners of 31 dogs of different breeds, genders, and ages. All dogs had received corticosteroid therapies in the past 6 months. In all, 18 dogs had been administered methylprednisolone (dose range, 0.2-1 mg/kg), 8 were administered prednisolone (dose range, 0.2-1 mg/kg), and 5 were administered dexamethasone (dose range, 0.01-0.3). Methylprednisolone and prednisolone were used for dermatological conditions, and dexamethasone was used for orthopedic conditions. Owners were asked to describe their dog’s behaviors both on and off corticosteroid therapy. Interviews were ceased when answers became repetitive with no new reported behavioral change (interview to redundancy). In all, 11 owners reported behavioral changes in their dogs; 9 dogs were reported to show more than one behavioral change. Six dogs reportedly showed nervousness and/or restlessness, 3 showed an increase in startle responses, 3 showed food guarding, 2 showed a decrease in their activity level, 3 showed an increase in avoidance responses, 4 showed irritable aggression, and 2 dogs increased barking. Semi-structured interviews can be useful preliminary tools for the identification of areas of future investigation, and the outcomes of the interviews reported in this article will be used in further quantitative research, to investigate more rigorously the possible relationship between these signs and corticosteroid use in dogs.
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.