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Cognitive Dysfunction Syndrome A Disease of Canine and Feline Brain Aging

  • Veterinary Emergency and Specialty Center of New Mexico
  • InterVivo Solutions, Toronto, Canada

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
*, Jeff Nichol, DVM
Joseph A. Araujo, BSc
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.
North Toronto Animal Clinic, 99 Henderson Avenue, Thornhill, Ontario, Canada L3T 2K9;
CanCog Technologies Inc, 120 Carlton Street, Suite 204, Toronto, Ontario, Canada M5A 4K2;
Veterinary Emergency and Specialty Center of New Mexico, 4000 Montgomery Boulevard NE,
Albuquerque, NM 87109, USA;
InterVivo Solutions Inc, 120 Carlton Street, Suite 203, Toronto,
Ontario, Canada M5A 4K2;
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:
Vet Clin Small Anim 42 (2012) 749–768
0195-5616/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
• Cognitive dysfunction syndrome • Brain aging • Behavior • Canine • Feline
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
With increasing age, there is an increase in
reactive oxygen species leading to oxidative damage in dogs and likely cats.
Increases in monoamine oxidase B activity in dogs is reported, which may increase
catalysis of dopamine with subsequent increases in free radicals.
A decline in
cholinergic tone occurs in canine aging as evidenced by hypersensitivity to anticho-
linergics and decreased brain muscarinic receptor density.
Diminished cholinergic
function is also reported in cats.
Collectively, these alterations may contribute to
working memory deficits or CDS, as well as alterations in motor function and REM
9,10,20 –22
In aged dogs, cats, and humans, there are similarities in deposition of A
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.
Moreover, similar to humans, A
load is positively correlated with cognitive impairment in dogs.
By contrast,
cats demonstrate more diffuse A
plaques than either human or dog.
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.
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.
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
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.
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.
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.
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.
Also, brain amyloid
deposition is reported earliest at 8 to 9 years of age.
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.
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.
This impairment is analogous to the
diminished executive function observed in human aging, AD, and other species.
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).
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-
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.
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.
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.
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.
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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.
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
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.
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.
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.
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.
Additionally, senior pets may be less able to
cope with stress, which may make them more susceptible to changes in their
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
Signs: DISHAAL Age First Noticed Score 0–3
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
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
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/
Endocrine: hyperadrenocorticism/
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,
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
Abbreviation: REM, rapid eye movement.
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critical for both treatment selection and monitoring of behavioral and medical
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.
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.
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.
In another study of 102 dogs, 41% had
alterations in at least 1 category associated with CDS and 32% had alterations in 2
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.
Moreover, social interactions and
house training were the most impaired categories.
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.
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.
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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.
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,
5% 3%
Prevalences of owner reported signs in
senior dogs
Cognive dysfuncon
Separaon anxiety
Anxiety, Fears and Phobias
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).
This is analogous to human studies in which increased mental activity and physical
exercise have been found to delay the onset of dementia.
Environmental enrichment can have positive effects on behavioral health and
quality of life in pets and is likely to improve cognitive function.
Inconsistency in the
management of the senior pet’s environment (especially for cats) can cause stress
and negatively impact health and behavioral well-being.
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
2% 2%
Prevalences of owner reported signs in
senior cats
Cognive Dysfuncon
Fear / Aggression
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.
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.
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
0.2–1 mg/kg sid–bid 0.2–0.5 mg/kg sid–bid
0.1–1.0 mg/kg bid–tid 0.02–0.2 mg/kg sid–bid
0.025–0.2 mg/kg sid–tid 0.025–0.05 mg/kg sid–bid
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.
Use single dosing prior to sleep or anxiety-evoking event, up to maximum daily dosing for
control of ongoing anxiety.
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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
Selegiline is not licensed for use in cats but is used off label with
anecdotal reports of improvement in CDS-like signs.
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).
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.
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.
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.
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.
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.
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
One product (Senilife; CEVA Animal Health, Libourne, France) was
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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.
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.
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.
In a recent placebo-controlled trial, greater improvement in
activity and awareness was reported in the SAMe group after 8 weeks.
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
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
Flavonoids and carotenoids from
fruits and vegetables, vitamin E,
vitamin C, beta-carotene,
selenium, L-carnitine, alpha-lipoic
acid, omega 3 fatty acids
Purina One Vibrant
Maturity 7Senior
Medium chain triglycerides (from
coconut oil)
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
Feliway spray or diffuser for cats
As per label
Lavender Aromatherapy for dogs As per label
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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.
In laboratory aged dog and cat studies, SAMe
improved measures of executive function and possibly attention.
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.
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.
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.
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.
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
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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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... A síndrome da disfunção cognitiva canina (SDCC) é uma desordem neurodegenerativa que afeta cães idosos, resultando em declínio cognitivo progressivo (Landsberg et al., 2005;Studzinski et al., 2005;Osella et al., 2007). Os principais sinais da SDCC são desorientação, alterações no ciclo sono-vigília, diminuição da interação social e aumento da ansiedade (Landsberg et al., 2012;Fast et al., 2013). Devido à natureza inespecífica desses sinais, muitos tutores e veterinários não reconhecem a SDCC, levando ao subdiagnóstico (Neilson et al., 2001). ...
... Geralmente os tutores procuram pela consulta veterinária apenas quando as mudanças de comportamento se tornam problemáticas, como agressividade e desaprendizado (Landsberg et al., 2012). Essas alterações podem comprometer a qualidade de vida do cão até enfraquecer o relacionamento entre tutor e animal, levando à consideração da eutanásia (Dewey e Costa, 2017). ...
... Pantoja (2010) relatou 37,66% de casos sugestivos de SDCC em 77 cães com idade entre 8 e 17 anos, sendo o cão de 13 anos deste caso enquadrado nesse intervalo. Não há evidências de predisposição com base no porte ou sexo (Fast et al., 2013), embora a castração possa estar associada a uma maior predisposição devido à redução dos hormônios sexuais (Landsberg et al., 2012). Geralmente, os cães são considerados idosos aos 5 anos para raças grandes e gigantes e aos 7 anos para raças pequenas (Freitas et al., 2006). ...
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A expectativa de vida dos cães aumentou por conta dos avanços científicos da medicina veterinária e, consequentemente, as doenças neurodegenerativas relacionadas ao envelhecimento estão se tornando rotina clínica. A síndrome da disfunção cognitiva canina (SDCC) é considerada uma doença sem cura e o objetivo do tratamento se baseia em retardar o avanço dos sinais clínicos. Os principais sinais clínicos da SDCC são desorientação, alteração no ciclo sono-vigília, diminuição na interação social e aumento da ansiedade. Além do tratamento convencional, o uso da acupuntura vem se mostrando eficaz, melhorando a função cognitiva e trazendo qualidade de vida para os cães e tutores. No presente relato de caso, realizou-se o tratamento com acupuntura em um cão macho de 13 anos, da raça Schnauzer, com sinais de SDCC como desorientação e alteração na interação social. Foram utilizados os pontos Yin Tang, VG20, PC6, B23, E36 e R3, tendo como resultado a melhora dos sinais cognitivos. Como há escassez de dados na literatura sobre a terapia integrativa utilizando a acupuntura na síndrome da disfunção cognitiva, o objetivo do presente trabalho foi relatar um tratamento com acupuntura em um paciente canino idoso diagnosticado com SDCC.
... In addition, certain diets and DSs have also been shown to delay the onset of clinical signs in aging dogs [25,26]. The monoamine oxidase B inhibitor L-deprenyl (selegiline) [7,8] increases levels of catecholamines in the cortex and hippocampus and may provide neuroprotection against free radicals [27], improving the clinical signs of CCD. ...
... However, improving all clinical signs of CCD [7] with selegiline is not possible, nor is it effective in all dogs. High variability in results with selegiline has been described and some dogs do not improve their cognitive ability with its supplementation [27][28][29][30][31]. Propentofylline stimulates blood flow to the brain and other organs, such as the heart and skeletal muscles, and may therefore improve dullness, depression, and lethargy of elderly human patients [7]. Limited evidence exists to confirm the benefits of propentofylline on cognitive abilities in people [32] and none in dogs. ...
... Various studies describe the prevalence ranging from 14.2% to 68% in geriatric dogs [2][3][4]. As these patients can exhibit various clinical signs and behavioral changes such as disorientation, confusion, incontinence, altered activity, and changes in sleep-wake rhythms [5,6], the quality of life can be severely affected in dogs and their caretakers [7]. ...
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Simple Summary Canine cognitive dysfunction is considered the canine equivalent to human Alzheimer’s disease. It is a growing concern in veterinary medicine, as it affects many aged dogs. Dietary intervention with different diets and supplements may improve clinical signs and prevent further degeneration. Using an online questionnaire, we found that even though few owners were willing to change their dog’s main diet, many of them added supplements such as oils and vitamins. Consulting a veterinary surgeon when using dietary supplements is important as it allows for evidence-based recommendations to be made. Abstract Canine cognitive dysfunction (CCD) is becoming increasingly recognized in veterinary medicine, as dogs live longer and with CCD being highly prevalent among the elderly dog population. Various studies have shown that diet and dietary supplementation can positively influence the clinical signs of CCD, especially if given at an early stage. The aim of this study was to investigate owner use of dietary supplements (DSs) in dogs with age-related behavioral changes. An observational study based on an online questionnaire for owners of dogs with age-related behavioral changes was performed. Out of a total of 394 owners who completed the survey, after noticing age-related behavioral changes, over half of the dogs received DSs (54%), whereas only 8% reported changing their dog’s base diet. The most used DS was fish oil (48%). The use of DSs should be discussed with and monitored by veterinary surgeons since many geriatric patients have multi-morbidities, may have specific nutritional requirements and receive multi-faceted medications.
... Aging is commonly accompanied by deteriorations in a variety of behavioral and cognitive functions, which can lead to the development of neurodegenerative disorders that significantly impact an individuals' quality of life [1][2][3]. For example, aged dogs may develop pathological cognitive impairments, referred to as canine cognitive dysfunction syndrome (CCD) [31,32], which not only show high phenotypic similarity to cognitive symptoms in aged humans but also share some physiological characteristics suggesting similar neuropathological pathways [33]. The decline in the physical and cognitive functions in older dogs poses challenges not only for the dog but also for its owner. ...
... The last question in this part asked the owner if they think the dog is "old", i.e., if they see any signs of aging in the dog regardless of its actual age. Part 2, entitled "General behavior" consisted of 9 characteristics that were selected based on the CCD checklist of [31] and the results of a previous survey study as the characteristics that most strongly change with age [45]. Each characteristic was rated on a 1-10 scale, with only the extremes specified. ...
... Each characteristic was rated on a 1-10 scale, with only the extremes specified. Part 3, entitled "CCD symptoms", contained 5 questions selected from [31,45,46] to cover the main symptoms of the canine cognitive disorder syndrome. In these questions, the owners were asked to rate each symptom on a five-point frequency scale adapted from [46]. ...
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The twofold life expectancy difference between dog breeds predicts differential behavioral and cognitive aging patterns between short- and long-lived dogs. To investigate this prediction, we conducted a cross-sectional analysis using survey data from over 15,000 dogs. We examined the effect of expected lifespan and three related factors (body size, head shape, and purebred status) on the age trajectory of various behavioral characteristics and the prevalence of canine cognitive dysfunction (CCD). Our findings reveal that, although age-related decline in most behavioral characteristics began around 10.5 years of age, the proportion of dogs considered “old” by their owners began to increase uniformly around 6 years of age. From the investigated factors, only body size had a systematic, although not gradual, impact on the aging trajectories of all behavioral characteristics. Dogs weighing over 30 kg exhibited an earlier onset of decline by 2–3 years and a slower rate of decline compared to smaller dogs, probably as a byproduct of their faster age-related physical decline. Larger sized dogs also showed a lower prevalence of CCD risk in their oldest age group, whereas smaller-sized dogs, dolichocephalic breeds, and purebreds had a higher CCD risk prevalence. The identification of differential behavioral and cognitive aging trajectories across dog groups, and the observed associations between body size and the onset, rate, and degree of cognitive decline in dogs have significant translational implications for human aging research, providing valuable insights into the interplay between morphology, physiological ageing, and cognitive decline, and unravelling the trade-off between longevity and relative healthspan.
... 1 Klinicky jsou CDS i AD charakterizovány pomalu progresivními příznaky postižení mentálního statusu a demencí, patofyziologie zahrnuje onemocnění mozkových cév a ukládání beta amyloidu (Aβ protein). [2][3][4][5] Další patologické procesy přispívající k progresi nemoci zahrnují oxidativní poškození mozku, neuronální mitochondriální dysfunkci, narušený metabolismus glukózy a abnormální funkci mikroglií a astrocytů. [6][7][8][9][10] Prevalence CDS v populaci psů se pohybuje mezi 14-35 % a dramaticky narůstá s věkem (až 60-70 % psů nad 12-15 let věku vykazuje CDS). ...
... Mozek nevykazoval změny symetrie, tympanické buly byly vzdušné, nebyl přítomný žádný efekt masy, signál intraaxiálních struktur byl standardní a žádná oblast nevykazovala postkontrastní sycení (gadobutrol ve specialitě Gadovist 1,0 mmol/ml v dávce 0,1 mmol/kg, tzn. 1 ml pro toto i.v.), krční oblast byla bez abnormalit (obr. [2][3][4][5][6]. Mozkomíšní mok (CSF -cerebrospinal fluid) odebraný punkcí cisterna magna byl čirý s počtem mononukleárních buněk pod 5/μl (použita spinální jehla Spinocan ® 22 G. x 1½ in., 40 mm). ...
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Presented case report describes the twelve-year-old male crossbreed with chronic progressive motoric impairment, behavior changes and inappropriate voiding. Magnetic resonance imaging of the brain revealed cortical atrophy and the patient is monitored with cognitive dysfunction syndrome. Characteristics of this degenerative disease and recommended steps in affected patients are discussed.
... However, the formation of abnormally phosphorylated tau can lead to a gain-of-toxic function and characterize many neurodegenerative diseases [12]. Old cats may develop a syndrome known as Feline Cognitive Dysfunction (FCD) or feline dementia, in which behavioral and cognitive alterations emerge with age-related tau and Aβ deposition, and neurodegenerative changes (e.g., cerebral atrophy, neuronal loss, ventricular enlargement, vascular changes, etc.) [23,25,[29][30][31]. The main signs of FCD are summarized by the acronym DISHA: Disorientation, alterations in Interactions with owners, other pets, and the environment, Sleep-wake cycle disturbances, house soiling, and changes in Activity [25,[29][30][31]. ...
... Old cats may develop a syndrome known as Feline Cognitive Dysfunction (FCD) or feline dementia, in which behavioral and cognitive alterations emerge with age-related tau and Aβ deposition, and neurodegenerative changes (e.g., cerebral atrophy, neuronal loss, ventricular enlargement, vascular changes, etc.) [23,25,[29][30][31]. The main signs of FCD are summarized by the acronym DISHA: Disorientation, alterations in Interactions with owners, other pets, and the environment, Sleep-wake cycle disturbances, house soiling, and changes in Activity [25,[29][30][31]. Apart from the age-related tau pathology, no other feline tauopathies have been described. ...
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Simple Summary Tauopathies are a group of neurodegenerative diseases where a specific protein called tau accumulates and forms aggregates in neurons and glial cells. In humans, these diseases can be caused by only this protein (primary) or in combination with another one (secondary). Primary tauopathies are common in humans but rare in animals. We analyzed the development of tau pathology in 16 cats of different ages. A female cat showed progressive mental status and gait abnormalities over a six-year period. Brain imaging revealed a progressive shrinkage of the brain (atrophy). Due to a poor prognosis, the cat was euthanized at the age of ten years. Evaluation of the brain tissue showed significant loss of neurons in the parietal cortex and Purkinje cells in the cerebellum. Immunohistochemistry identified abnormal tau protein aggregates in neurons (referred to as pre-tangles) and oligodendrocytes (referred to as coiled bodies). Genetic testing did not reveal any known genetic alteration associated with this disease. None of the other 15 cats studied showed similar clinical signs or brain changes. This is the first reported case of primary tauopathy in an adult cat that presented the first neurological signs when she was four years old. Abstract Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology in 16 cats aged from 1 to 21 years with different clinical backgrounds. Interestingly, a 10-year-old female cat presented a six-year progressive history of mental status and gait abnormalities. The imaging study revealed generalized cortical atrophy. Due to the poor prognosis, the cat was euthanatized at the age of ten. Neuropathological lesions were characterized by massive neuronal loss with marked spongiosis and associated moderate reactive gliosis in the parietal cortex, being less severe in other areas of the cerebral cortex, and the loss of Purkinje cells of the cerebellum. Immunohistochemical methods revealed a 4R-tauopathy with granular pre-tangles in neurons and coiled bodies in oligodendrocytes. Deposits were recognized with several phospho-site antibodies (4Rtau, tau5, AT8, PFH, tau-P Thr181, tau-P-Ser 262, tau-P Ser 422) and associated with increased granular expression of active tau kinases (p38-P Thr180/Tyr182 and SAPK/JNK-P Thr138/Thr185). The genetic study revealed well-preserved coding regions of MAPT. No similar alterations related to tau pathology were found in the other 15 cats processed in parallel. To our knowledge, this is the first case reporting a primary 4R-tauopathy with severe cerebral and Purkinje cell degeneration in an adult cat with neurological signs starting at a young age.
... No entanto, essas patologias quando diagnosticadas precocemente, possibilitam o emprego de tratamentos paliativos que visam proporcionar, aumento da expectativa e da qualidade de vida, além de providenciar bem-estar ao animal durante o processo de envelhecimento (Osella et al., 2007). Este é o caso da Síndrome da Disfunção Cognitiva em Cães (SDCC), uma doença neurodegenerativa que, por desconhecimento do tutor ou dos médicos veterinários, tende a ser subdiagnosticada (Landsberg et al., 2012;Madari et al., 2015). ...
... A DISHAAL é uma ferramenta muito utilizada para auxiliar o tutor e o médico veterinário na identificação de possíveis alterações comportamentais associadas a SDDC (Landsberg et al., 2012 ...
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Com os avanços da medicina veterinária, melhorias na nutrição e maior cuidado dos tutores com seus animais, a perspectiva de vida dos cães está aumentando significativamente. No entanto, esse aumento na longevidade vem acompanhado pelo surgimento mais frequente de doenças relacionadas ao envelhecimento, sendo uma delas a Síndrome da Disfunção Cognitiva Canina (SDDC). Essa síndrome afeta cães idosos não apenas fisicamente, mas também cognitivamente. Trata-se de uma doença neurodegenerativa que se desenvolve gradualmente e, inicialmente, pode passar despercebida, muitas vezes sendo confundida com os processos naturais de envelhecimento. Seu diagnóstico é desafiador e complexo, dependendo de vários fatores, principalmente, envolvendo a exclusão de outras suspeitas clínicas comuns em animais idosos, além de uma minuciosa anamnese conduzida pelo médico veterinário, levando também em consideração informações fornecidas pelos tutores. Questionários que abordam aspectos comportamentais e cognitivos do animal podem ser muito úteis para direcionar o diagnóstico. Uma vez confirmado o diagnóstico, é importante iniciar imediatamente as medidas de tratamento visando o conforto e o bem-estar do animal. Estratégias de enriquecimento ambiental desempenham um papel essencial, envolvendo a introdução de objetos que estimulem a cognição do cão. Além disso, ajustes na alimentação são recomendados, incluindo a adição de vitaminas C e E, bem como ácidos graxos, ômega-3 e ômega-6 na dieta. Alguns medicamentos, como o revimax, também podem ser administrados como parte do tratamento. O objetivo do tratamento é prolongar e promover qualidade de vida ao animal, buscando retardar a progressão da síndrome, embora ela não tenha uma cura definitiva até o momento. É interessante notar que essa síndrome possui semelhanças com a Doença de Alzheimer em Humanos (DAH), sendo assim, estudos e pesquisas sobre essa doença podem contribuir para o desenvolvimento de abordagens mais eficazes visando o tratamento da SDDC.
Davila and colleagues cover methods and review findings regarding dog olfactory cognition. The chapter begins by introducing the topic of dog cognition. Specific aspects of dog olfactory cognition are explored. The authors review methods and procedures that investigate different aspects of olfaction and memory, including episodic memory, working memory, and long-term memory. Next, olfactory category and concept learning in dogs is reviewed followed by a discussion of the nature of olfactory representations in dogs, as well as studies that involve an olfactory search image. Finally, the last section reviews olfactory quantity judgments. The authors conclude by emphasizing the importance of dog cognition and suggesting a converging operation approach for future research.
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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
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.
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.
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.
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.
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