Cognitive Dysfunction Syndrome (Dementia in Dogs and Cats)
CDS, Canine cognitive dysfunction (CCD / CCDS), Feline cognitive dysfunction (FCD), Dog dementia, Cat dementia, Senility / "just old age", Sundowning (night-time restlessness)
Cognitive dysfunction syndrome is dementia in pets. As some dogs and cats get older, the brain changes in ways that look a great deal like Alzheimer's disease in people, so a pet may seem lost in a familiar room, pace or cry at night, forget house training, or stop greeting you the way they always did. This is not your pet being naughty or stubborn, and it is far more common than the number of pets diagnosed with it. Many of the same signs also come from things that can be treated, such as joint pain, kidney disease, an overactive thyroid gland in cats, high blood pressure, or fading eyesight and hearing, so the first step is a proper check-up rather than assuming it is only old age.
What you might notice
- Getting lost or stuck in familiar places - standing in a corner, staring at a wall, or going to the hinge side of a door
- Pacing, restlessness or crying at night, and sleeping much more during the day (the day-night flip is often the first thing owners notice)
- Loud night-time yowling, which was the most commonly reported sign in cats with cognitive dysfunction (40% of FCD-positive cats in one survey)
- Accidents in the house, or a cat going outside the litter box, in a pet who was reliably clean for years
- Less interest in greeting you, being petted, or playing - or the opposite, becoming much clingier and more anxious about being left alone
- Forgetting routines, names or commands, or seeming not to hear or notice you
- Walking into things, hesitating at steps or kerbs, or bumping into furniture that has always been there
- Eating less, or standing at the bowl as though unsure what to do next
Standard of care
Work up and treat the mimics before treating the brain - in both species
Approved / guideline-backedEvery sign on the DISHAA list is also produced by something else in a senior pet. In cats the mandatory short list is osteoarthritic pain, chronic kidney disease, hyperthyroidism and systemic hypertension; hypertension in cats is usually secondary to CKD or hyperthyroidism, causes ocular, cardiac, renal and brain target-organ damage, and amlodipine besylate is the treatment of choice. In dogs the short list is pain, hypothyroidism, hyperadrenocorticism, hepatic disease, intracranial disease and sensory loss. This step is not a formality: it is the step most likely to change the pet's life, and skipping it is how a treatable disease gets labelled dementia. Order of operations for a pet with house-soiling: rule out pain, rule out urinary and GI disease, then consider cognitive decline, then treat as behaviour.
Named products: Amlodipine besylate is named by ISFM as the treatment of choice for feline hypertension. Telmisartan (Semintra, NADA 141-501) is FDA-approved with the verbatim indication "SEMINTRA is indicated for the control of systemic hypertension in cats." Methimazole-class antithyroid therapy, radioiodine and thyroidectomy are the feline hyperthyroidism options. No canine dose or product from this step transfers to cats.
2023 AAHA Senior Care Guidelines describe a systematic, evidence-guided assessment of healthy and unhealthy senior dogs and cats and explicitly address the client misconception that decline is unavoidable old age (dog and cat). 2021 AAFP Feline Senior Care Guidelines make blood pressure a minimum diagnostic in senior cats and treat pain as its own syndrome to be considered in every senior cat (cat). ISFM hypertension guidelines are a formal practice guideline (cat).
DOGS ONLY: selegiline hydrochloride (Anipryl) - the only FDA-approved drug for this disease in any species
Approved / guideline-backedLabel indication, verbatim from the FDA Freedom of Information Summary: "Anipryl tablets are indicated for the control of clinical signs associated with canine Cognitive Dysfunction Syndrome (CDS)." Recommended dosage, verbatim: "0.5 -1.0 mg/kg once daily, preferably administered in the morning. Initially, dogs should be dosed to the nearest whole tablet. Adjustments should then be made based on response and tolerance to the drug." Report the pivotal numbers honestly, because they are modest and the placebo response was large. In 199 client-owned dogs (181 evaluable at 4 weeks) randomised to placebo, 0.2 mg/kg or 1.0 mg/kg for the first 4 weeks, improvement at 1.0 mg/kg versus placebo was: sleep pattern 52.7% vs 16.7% (p = 0.001), activity 54.7% vs 28.6% (p = 0.012), house training 34.8% vs 26.3% (p = 0.030, and non-monotonic - the 0.2 mg/kg group scored 38.9%). Three of six domains did NOT reach significance: orientation 55.2% vs 35.5% (p = 0.098), responsiveness 52.1% vs 41.8% (p = 0.499), greeting 32.6% vs 25.0% (p = 0.584). FDA's own verbatim conclusion: "Anipryl administered at 1.0 mg/kg once daily was shown to provide safe and effective control of clinical signs associated with CDS in pet dogs. The onset, duration and magnitude of response varied with individual dogs." And the durability caveat, verbatim: "The duration of effect may be as short as 8 weeks in about 50% of the cases." A widely quoted 77.2% improvement figure at day 60 comes from an OPEN-LABEL, uncontrolled study of 641 dogs and must never be presented as a controlled efficacy result. Anipryl is prescription-only because, in FDA's words, "professional expertise is required for the diagnosis of clinical signs associated with cognitive dysfunction syndrome and for the monitoring of adverse events and response to therapy." Selegiline is NOT approved for cats and canine dosing must not be carried across.
Named products: Selegiline hydrochloride (Anipryl), NADA 141-080, sponsor Pfizer Inc., CDS indication approved 10 December 1998 as a supplement to the original 30 May 1997 approval; 2, 5, 10, 15 and 30 mg tablets; Rx. Selegiline is the levorotatory form of deprenyl HCl and acts as a monoamine oxidase B inhibitor, so a drug-interaction review is mandatory before co-prescribing - the pivotal trial specifically excluded dogs on "medications known to interact with Anipryl," and one trial dog on concurrent metronidazole, prednisone and trimethoprim-sulfa developed weakness, confusion, incoordination and seizure-like activity that resolved when all drugs were stopped.
FDA-approved indication supported by a placebo-controlled, multi-site, dose-ranging clinical field trial plus an open-label dose-confirmation trial (dog). The supporting open-label 641-dog study is uncontrolled and is Tier 3 evidence at best (dog).
DOGS: change the diet, do not just add a supplement - MCT-enriched therapeutic nutrition
Controlled trial in this speciesTwo lines of canine evidence support medium-chain triglyceride (MCT) enrichment. In client-owned dogs with CDS signs, 87 dogs were randomised into three arms of 29 (control, 6.5% MCT oil plus a brain protection blend, 9% MCT oil plus the blend) and fed for 90 days: all 6 categories of CDS signs improved significantly (p < 0.05) on the 6.5% MCT diet, and the honest comparator is that the control diet improved in 4 of 6 categories too. The 9% arm only improved in dogs that accepted the diet, which is a palatability warning as much as a dose finding. In colony aged Beagles, 8 months of a 5.5% MCT-supplemented diet produced significantly better performance on most of a cognitive test battery with elevated circulating beta-hydroxybutyrate, supporting the ketone-as-alternative-brain-fuel mechanism. The systematic review across 30 trials found that studies of enriched diets were of higher methodological quality than studies of supplements, that omega-3 fatty acids showed cognitive benefit especially at higher doses, that antioxidants from plant extracts and vitamins E and C alone were less effective but remain necessary to stabilise the omega-3s, and that SAMe, MCTs, homotaurine and apoaequorin "also showed promise." Owner behaviour runs the other way: in 394 owners of dogs with age-related behavioural change, 54% used dietary supplements (most commonly fish oil, 48%) but only 8% changed the base diet - a direct mismatch with where the evidence is stronger.
Named products: Not a drug. Therapeutic diets and supplements are not FDA-approved drugs and no diet may be marketed as treating or preventing dementia. Describe the nutrient composition (MCT percentage, omega-3 dose, B vitamins, antioxidants, arginine), not a disease claim.
One 90-day prospective double-blinded placebo-controlled clinical study in 87 client-owned dogs with CDS signs, industry-authored (Nestle Purina and CanCog); one 8-month controlled colony-Beagle cognitive-testing study, industry-authored; one systematic review of 30 trials appraised with a modified CAMARADES checklist (all dog).
CATS: nutritional support exists but the feline evidence is two trials, in healthy older cats, not in cats with diagnosed dementia
Early evidenceThe one identifiable feline intervention trial fed middle-aged and old cats (5.5 to 8.7 years) a base diet with or without a blend of antioxidants, arginine, B vitamins and fish oil, after assignment to cognitively equivalent groups on baseline testing. The supplemented cats performed significantly better on 3 of 4 cognitive test protocols (egocentric learning, discrimination and reversal learning, and acquisition of a spatial memory task). Two things must be said on the same page every time. First, these were middle-aged and old cats undergoing laboratory cognitive testing - not client-owned cats with a clinical diagnosis of FCD - so this is evidence for supporting brain ageing, not evidence for treating feline dementia. Second, the systematic review of 30 cognition trials in ageing pets found only 2 feline trials against 27 canine ones, so every feline cognitive-support claim PetSmartMeds makes is standing on canine data and must say so in the same sentence. There is no approved dietary or pharmaceutical intervention for cognitive dysfunction in cats anywhere in the world.
Named products: None approved. A 2010 review states plainly "the absence of any approved dietary or pharmaceutical interventions for cognitive dysfunction" in cats. Any pharmacological attempt in a cat is extra-label, is the prescribing veterinarian's decision, and must never be framed on a website as established care.
One controlled colony/laboratory cognitive-testing trial in cats, industry-authored (Nestle Purina), in cats without a clinical FCD diagnosis; plus a systematic review documenting that only 2 of 30 trials in the field were feline (cat).
Environmental management, enrichment and a predictable routine - the intervention with the best cost-to-benefit ratio
Controlled trial in this speciesPractical, specific, and free: keep furniture and litter-box positions unchanged; add night lighting along the route to water and the litter box or garden; swap to low-sided, larger litter boxes and add one on every floor for cats; add ramps or non-slip runners; feed, walk and settle at the same times each day; keep short, low-stress training or food-puzzle sessions going during the day to load the sleep-wake cycle in the right direction; block access to stairs, pools and gaps behind furniture where a disoriented pet gets stuck. In aged dogs, the combination of behavioural enrichment and an antioxidant-fortified diet raised temporal-cortex BDNF mRNA toward young-animal levels, while either intervention alone gave intermediate levels, and BDNF correlated positively with cognitive performance and inversely with cortical amyloid-beta - a mechanistic reason to pair enrichment with nutrition rather than choosing one. Be honest about ceiling effects: a 5-week structured group-training programme in 42 dogs with mild-to-moderate CCD did not move CADES scores at all ("CCD scores remained stable across all phases, suggesting no measurable cognitive changes"), so enrichment should be sold as function, safety and quality of life, not as reversal of dementia.
Named products: Not a drug intervention.
Controlled colony study with molecular endpoints in aged dogs (dog); guideline-level recommendation for environmental management of the senior pet (dog and cat); one 5-week prospective study of 42 dogs with mild-to-moderate CCD reporting no change in the cognitive score (dog, honest negative).
Treat comorbid pain - with species-correct drugs, never carried across species
Approved / guideline-backedPain is the most common confounder and the most common untreated cause of the behaviours owners report as dementia. In cats, the anti-nerve-growth-factor monoclonal antibody frunevetmab (Solensia) is FDA-approved to control OA pain, with honestly modest effect sizes in the pivotal RCT of 275 cats (number needed to treat 9 and standardised effect size 0.3 on the Client Specific Outcome Measures at day 56) and a disclosable adverse-event signal of skin disorders (32/182 treated vs 8/93 placebo) plus a published case series of five cats with moderate-to-severe pruritus and self-trauma after injection. Feline NSAID use must follow the 2024 ISFM/AAFP consensus: feline-specific drug, feline-specific dose, pre-prescription screening and attention to CKD, which is common in this age group. In dogs, the corresponding biologic is bedinvetmab (Librela, FDA-approved 5 May 2023) and the approved canine NSAIDs are carprofen, meloxicam, deracoxib and firocoxib plus grapiprant. No canine product or dose on this list may be used in a cat.
Named products: Cats: frunevetmab (Solensia), NADA 141-546, approved 13 January 2022, the first monoclonal antibody FDA-approved for any animal species; meloxicam and robenacoxib (Onsior) per label and geography - the US robenacoxib label is for postoperative pain and inflammation for a maximum of 3 days, not chronic OA. Dogs: bedinvetmab (Librela); carprofen, meloxicam, deracoxib, firocoxib, grapiprant. Never acetaminophen in a cat, at any dose, in any formulation.
FDA-approved indications in the respective species, with RCT support of modest effect size in cats; consensus guideline for long-term feline NSAID use (cat); FDA approval plus consensus pain guidelines in dogs (dog).
DOGS: S-adenosylmethionine (SAMe) as an adjunct, with its limits stated
Controlled trial in this speciesIn a double-blinded, placebo-controlled trial, 36 dogs older than 8 years with at least one month of cognitive dysfunction signs received SAMe tosylate 18 mg/kg (n = 17) or identical placebo (n = 19) for 2 months, with concurrent behavioural treatment forbidden. SAMe-treated dogs improved more than placebo in activity (57.1% vs 9.0% at 8 weeks, P < 0.003) and awareness (59.5% vs 21.4% at 8 weeks, P < 0.01), and the aggregate mental impairment score fell by more than 50% in 41.2% of SAMe dogs versus 15.8% of placebo dogs. The limits: n = 36, a 14-item owner questionnaire as the only outcome, 8 weeks of follow-up, and authorship from the manufacturer's medical department. The systematic review lists SAMe among supplements that "showed promise," which is the correct strength of claim. There is no feline SAMe cognition trial.
Named products: S-adenosylmethionine (SAMe) tosylate, marketed as a veterinary nutraceutical, not an approved drug. Do not present it as approved therapy.
One randomised, double-blinded, placebo-controlled trial, n = 36, owner-questionnaire outcome, industry-authored (dog). No feline data located.
Caregiver support, quality-of-life tracking and an explicit end-of-life plan
Approved / guideline-backedNight waking, vocalisation and house-soiling are the signs that break households, and caregiver burden is a legitimate clinical endpoint in this disease - the canine group-training study measured it alongside sleep and activity for exactly that reason. Set expectations at the first consultation: CDS is progressive, the goal is function and comfort rather than reversal, and treatments are judged over months, not days. The 2023 AAHA Senior Care Guidelines include palliative and hospice care and client education as part of senior care, and the 2021 AAFP feline guidelines address quality of life, budgets of care and euthanasia decision-making directly. Agreeing in advance on what a bad week looks like is kinder than deciding in a crisis at 3 a.m.
Guideline-level recommendation in both species; caregiver-burden instruments used as endpoints in a canine CCD study (dog and cat).
Emerging and not yet standard of care - senolytic plus NAD+ precursor, depot donepezil, faecal microbiota transplantation
Early evidenceThree canine signals exist and none of them changes practice yet. (1) Senolytic plus NAD+ precursor combination (LY-D6/2): 70 dogs with mild-to-moderate cognitive impairment randomised to placebo, low or full dose; a significant between-group difference in owner-reported CCDR score at the 3-month primary endpoint (p = 0.02), largest in the full-dose group. But there was NO difference on in-house cognitive testing and NO difference in accelerometer-measured activity, the authors state "All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation," and the intervention was a combination so nothing can be attributed to NAD+ alone. The trial used an ORAL product; injectable or nasal NAD+ at 500-1000 mg has no canine or feline data at any dose. (2) Long-acting intramuscular donepezil depot: 32 dogs randomised to high dose, low dose or control, with significant improvement in CCDR, CADES and DISHAA in the high-dose group at days 14 and 28 and lower serum neurofilament light chain in both treated groups at day 28; 28 days of follow-up, n = 32, pharmaceutical-company co-authorship, and no regulatory approval anywhere. (3) Faecal microbiota transplantation: 11 dogs, open-label, no control; only 6 dogs had complete 90-day DISHAA data, of whom 4 improved and 2 worsened. That is hypothesis-generating and nothing more. None of the three has any feline data.
Named products: LY-D6/2 (senolytic plus NAD+ precursor, investigational, oral); donepezil depot injection (investigational, not approved for animals in any jurisdiction); faecal microbiota transplant capsules (not an approved drug). None may be presented as treatment.
One randomised controlled trial with a positive owner-reported endpoint and negative objective endpoints (dog); one small randomised 28-day industry-affiliated trial (dog); one uncontrolled 11-dog pilot (dog). No feline data for any of them.
2023 AAHA Senior Care Guidelines for Dogs and Cats — American Animal Hospital Association (AAHA). Covers both species, which is why it is the governing document for this protocol. There is NO ACVIM, AAHA or ISFM/AAFP consensus guideline specific to cognitive dysfunction syndrome in either dogs or cats - we searched and it does not exist, so do not cite one. The closest species-specific companions are the 2021 AAFP Feline Senior Care Guidelines (PMID 34167339, DOI 10.1177/1098612X211021538), which name cognitive dysfunction syndrome, frailty and pain as senior-cat considerations and make blood pressure a minimum diagnostic; and, for the canine clinical algorithm, a 2026 peer-reviewed review rather than a guideline (Dondi M, et al. Evidence-Based Clinical Management of Canine Cognitive Dysfunction Syndrome. Animals (Basel). 2026;16(7):1114. PMID 41976093. DOI 10.3390/ani16071114).
How it is diagnosed
- Take a structured behavioural history first, ideally on a scored owner questionnaire - CADES or CCDR in dogs, and the DISHAA framework (disorientation, interaction changes, sleep-wake changes, house soiling, activity change, anxiety) to make sure all six domains are asked about. CDS is a clinical diagnosis of exclusion built on documented change over time, not a test result (Dondi M et al. Animals (Basel). 2026;16(7):1114. PMID 41976093. DOI 10.3390/ani16071114).
- Full physical and neurological examination including deliberate assessment of vision and hearing. Sensory decline reproduces disorientation, unresponsiveness and startle-aggression, and it is common in exactly the age group in question.
- Minimum database: CBC, serum biochemistry, urinalysis and indirect blood pressure. The 2021 AAFP Feline Senior Care Guidelines include blood pressure assessment as a minimum diagnostic procedure in both apparently healthy and ill senior cats (PMID 34167339, DOI 10.1177/1098612X211021538).
- Cats specifically: total T4, because apparent hyperthyroidism prevalence is 8.7% in cats 10 years and older and drives restlessness, vocalisation and night activity (PMID 25028466); and renal staging, because CKD prevalence was 50% in a randomly age-stratified feline cohort and 68.8% in cats recruited for degenerative joint disease studies (PMID 24217707, DOI 10.1177/1098612X13511446).
- Deliberate pain and orthopaedic assessment in both species, and especially in cats. In 100 cats aged 6 years and older, increased inappropriate elimination was significantly associated with osteoarthritis (P = 0.046), and cats with OA usually do not limp - an arthritic cat may simply be unable to climb into a high-sided litter box (PMID 20083417, DOI 10.1016/j.tvjl.2009.12.014).
- Dogs specifically: consider endocrine testing for hypothyroidism and hyperadrenocorticism, and hepatic evaluation, where the history or bloodwork points that way. The Anipryl field trial excluded dogs with concurrent debilitating disease or drugs that could affect behaviour precisely because these confound the assessment (FDA FOI Summary, NADA 141-080).
- Advanced imaging (MRI) where onset was rapid, progression is fast, signs are asymmetric or lateralising, or seizures are present - to exclude intracranial neoplasia and cerebrovascular disease. Fluid biomarkers are promising but not clinical tests: plasma neurofilament light chain correlated with CADES score (r = 0.41, p = 0.025) in 39 aging pet dogs and with inhibitory control performance (r = -0.7, p <= 0.001), and remains a research measure (PMID 35431246, DOI 10.3233/JAD-215562).
Where a biologic fits
Our own product, graded by the same rule
There is no controlled evidence that stem cell, exosome or peptide products improve cognitive dysfunction in dogs or cats: the only study that dosed dogs was an uncontrolled two-week pilot by the product's own manufacturer using owner questionnaires, nothing at all has been published in cats, and in a disease whose approved-drug trial recorded up to 42% improvement in the placebo group, that kind of study cannot tell benefit from expectation - so PetSmartMeds does not offer these products for dementia and instead puts its weight behind the work-up that finds treatable causes, FDA-approved selegiline in dogs, MCT-enriched nutrition, treating comorbid pain, and the home changes that keep an old pet safe.
What exists
Exactly one published study has given a cell or exosome product to dogs for cognitive change, and it cannot support an efficacy claim. Kim et al. 2025 gave human embryonic-stem-cell-derived MSCs to 21 geriatric small dogs and human ES-MSC-derived extracellular vesicles to another 21, assessed the Canine Cognitive Dysfunction Rating (CCDR) and Liverpool Osteoarthritis in Dogs (LOAD) owner questionnaires before and 2 weeks after treatment, and reported no notable side effects and improvement in both scores in both groups (Front Vet Sci 2025;12:1549870, PMID 40206251, DOI 10.3389/fvets.2025.1549870). The design defeats the conclusion: there was NO placebo arm, follow-up was 2 weeks, the outcomes were owner questionnaires - the single most placebo-susceptible endpoint class in veterinary medicine - six of nine authors were employed by the manufacturer (Daewoong Co., Ltd. / Daewoong Pet Corp.), and the source cells were human embryonic stem cells, a xenogeneic and regulatorily loaded material. The placebo problem is not theoretical here: in the Anipryl registrational trial the placebo group improved on 16.7% to 41.8% of the very domains at issue, so a single-arm 2-week questionnaire study in this disease would look positive whether or not anything was in the syringe. The only other relevant canine neurological data are from an experimentally induced demyelination model - a disease dogs do not get naturally - where both intrathecal stem cells and exosomes beat control on clinical, MRI and histological endpoints, and the cells outperformed the exosomes (PMID 38459498, DOI 10.1186/s12917-024-03920-4). A 2024 review of 45 companion-animal stem-cell studies from 2015-2023 lists canine cognitive dysfunction among the conditions in which stem cells have been evaluated, and in the same breath records that 22 of the 45 studies were open-label baseline-controlled and only 12 were randomised and controlled, "making overall study interpretation difficult" (PMID 38795363, DOI 10.1093/stmcls/sxae034). For peptides the answer is shorter: no peptide in the catalogue has controlled efficacy evidence in dogs, cats or horses for any indication, let alone this one; BPC-157 and TB-500 have essentially nothing in companion animals and TB-500 is FEI-banned; and Semax, Selank and Epitalon are human or Russian-registered nootropics with no located canine or feline pharmacokinetic, safety or efficacy data. The closest thing to a positive cognitive signal from an anti-ageing molecule in dogs is the oral senolytic plus NAD+ precursor combination (PMID 38811634), which improved an owner questionnaire at 3 months but moved neither in-clinic cognitive testing nor accelerometer activity, and which was a combination product - so it cannot be attributed to NAD+ and it does not license an injectable or nasal NAD+ product in either species.
What has not been shown
There is no placebo-controlled trial of any mesenchymal stromal cell product, any exosome or extracellular-vesicle product, or any peptide, for cognitive dysfunction syndrome in dogs or in cats. There is nothing at all in cats - not a controlled trial, not an uncontrolled series, not a case report located in this search. There are no pharmacokinetic, biodistribution or brain-penetration data for any of these products in dogs or cats, so there is no evidence any of them reaches the brain at a biologically active concentration. No cognitive, imaging, biomarker or neuropathological endpoint has ever been shown to change in a controlled fashion in either species with any of these modalities. Two further claims must never appear on a PetSmartMeds page. First, these products are not immune-invisible: Punzon et al. found that BOTH equine and canine MSCs raised antibody titres in dogs, so "immune-privileged" is not defensible, although safety in that study was nonetheless acceptable (Front Vet Sci 2023;10:1098029, PMID 37266387). Second, the existence of an authorised cell product is not transferable evidence: DogStem (EMA EMEA/V/C/005829) is authorised, uses EQUINE umbilical-cord MSCs in DOGS, and reported 51% of treated dogs versus 5% of placebo dogs meeting a force-plate gait endpoint at 8 weeks - that is OSTEOARTHRITIS, in the limbs, and it says nothing whatsoever about the brain. In the United States no animal cell or exosome product is FDA-approved; they are unapproved new animal drugs, and FDA CVM has enforced against conditioned media on exactly that basis.
Sources
- Kim 2025 - the only dog-dosed MSC/EV study for cognitive change; uncontrolled, 2 weeks, manufacturer-authored — Kim TY, Kim NH, Chae JA, et al. Evaluation of cognitive and mobility function in geriatric dogs following treatment with stem cell and stem cell extracellular vesicles derived from embryonic stem cells: a pilot study. Front Vet Sci. 2025;12:1549870. PMID 40206251 https://doi.org/10.3389/fvets.2025.1549870
- Punzon 2023 - both equine and canine MSCs raised antibody titres in dogs; "immune-privileged" is not defensible — Punzon E, et al. Front Vet Sci. 2023;10:1098029. PMID 37266387 https://doi.org/10.3389/fvets.2023.1098029
- Williams 2024 - review of 45 companion-animal stem-cell studies; 22 open-label, only 12 randomised controlled — Williams ZJ, Pezzanite LM, Chow L, Rockow M, Dow SW. Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023). Stem Cells. 2024;42(8):677-705. PMID 38795363 https://doi.org/10.1093/stmcls/sxae034
- Induced canine demyelination model - cells outperformed exosomes, and dogs do not get this disease naturally — Controlled intrathecal stem cell versus exosome comparison in an experimentally induced canine demyelination model. BMC Vet Res. 2024. PMID 38459498 https://doi.org/10.1186/s12917-024-03920-4
- Senolytic plus NAD+ precursor - positive owner questionnaire, negative objective endpoints, combination product, oral route — Simon KE, Russell K, Mondino A, et al. Sci Rep. 2024;14(1):12399. PMID 38811634 https://doi.org/10.1038/s41598-024-63031-w
- Anipryl FOI - the placebo-group improvement rates (16.7-41.8%) that make uncontrolled CDS studies uninterpretable — FDA Freedom of Information Summary, ANIPRYL (selegiline hydrochloride) Tablets, NADA 141-080, 10 December 1998 https://animaldrugsatfda.fda.gov/adafda/app/search/public/docume
- FDA CVM - cell-based products for animal use are new animal drugs requiring approval — FDA CVM Guidance for Industry #218, Cell-Based Products for Animal Use (June 2015); FDA, FDA's Role in Veterinary Regenerative Medicine https://www.fda.gov/animal-veterinary/cell-and-tissue-products-a
Tracking response
How you know whether it is working
Clinicians track this with Dogs: the CAnine DEmentia Scale (CADES), paired with the owner-performed sustained-gaze video test as a semi-objective companion measure. CADES beat the Canine Cognitive Dysfunction Rating scale (CCDR) head-to-head on convergent validity: in 39 dogs aged 9.3-15.3 years, CADES correlated with sustained attention duration (r = -0.47, p = 0.002), inhibitory control (r = -0.51, p = 0.002), a detour task (r = -0.43, p = 0.001) and plasma neurofilament light chain (r = 0.41, p = 0.025), while CCDR correlated only with inhibitory control (r = -0.46, p = 0.005). CADES has four severity strata (normal, mild, moderate, severe). The sustained-gaze test is the best owner-performed task in this literature: 20 dogs, owners recorded it at home in triplicate weekly for 3 weeks, 162 of 183 videos were acceptable, within-dog test-retest ICC 0.96, intra- and inter-observer ICC 0.99 and 0.96 for gaze duration, and gaze duration was significantly associated with CADES (p = 0.0026). Cats: no validated feline cognitive instrument was located. Track a structured sign-frequency log built on the signs recorded in MacQuiddy 2022 (vocalisation, disorientation, altered interaction, sleep-wake change, house-soiling) plus a night-vocalisation and litter-box diary, and label it on the page as an unvalidated care tool rather than a validated instrument..
Madari A, Farbakova J, Katina S, Smolek T, Novak P, et al. Assessment of severity and progression of canine cognitive dysfunction syndrome using the CAnine DEmentia Scale (CADES). Appl Anim Behav Sci. 2015;171:138-145. DOI 10.1016/j.applanim.2015.08.034 (verified via Crossref; not indexed in PubMed under that search); Fefer G, Panek WK, Khan MZ, et al. Use of Cognitive Testing, Questionnaires, and Plasma Biomarkers to Quantify Cognitive Impairment in an Aging Pet Dog Population. J Alzheimers Dis. 2022;87(3):1367-1378. PMID 35431246. DOI 10.3233/JAD-215562; Hoel JA, Templeton GB, Fefer G, et al. Sustained Gaze Is a Reliable In-home Test of Attention for Aging Pet Dogs. Front Vet Sci. 2021;8:819135. PMID 35004935. DOI 10.3389/fvets.2021.819135; Salvin HE, McGreevy PD, Sachdev PS, Valenzuela MJ. The canine cognitive dysfunction rating scale (CCDR). Vet J. 2011;188(3):331-336. DOI 10.1016/j.tvjl.2010.05.014; MacQuiddy B, Moreno J, Frank J, McGrath S. J Feline Med Surg. 2022;24(6):e131-e137. PMID 35536055. DOI 10.1177/1098612X221095680
Unresolved and blocking for implementation. CADES and CCDR item structures, scoring and licensing are unverified; no licence statement was located for either. DISHAA is a commercially distributed tool with unverified terms. The sustained-gaze video test is described in sufficient detail in an open-access paper (PMID 35004935) to implement, and the MacQuiddy feline sign list is open-access (PMID 35536055), so a compliant first release can be built from those two plus a plain-language owner diary while instrument licences are sorted out.
Suggested cadence: Quarterly, not monthly. CADES scores remained stable across all phases of a 5-week intervention study in 42 dogs with mild-to-moderate CCD ("CCD scores remained stable across all phases, suggesting no measurable cognitive changes"), so short check-in intervals produce survey fatigue and noise rather than signal (Taylor TL, et al. Geroscience. 2026. PMID 42126808. DOI 10.1007/s11357-026-02309-5). Layer faster, cheaper items on top of the quarterly score: a weekly sustained-gaze video in dogs, and a weekly tally of night-waking episodes and out-of-box eliminations in either species, since those are the items that drive caregiver burden and change soonest. Re-screen the medical mimics on the senior-care guideline schedule - blood pressure and renal values in both species, plus total T4 in cats - and reassess pain at every visit, not only when the owner reports limping. One rule is non-negotiable: an uncontrolled owner-reported time series will drift toward improvement whether or not a product works, so PetSmartMeds must never aggregate these check-ins and present them as evidence of product efficacy. The monitoring loop is a care tool for the patient in front of the veterinarian, not an evidence-generation engine.
Questions you can answer at home
- In the last week, how many nights did your pet wake you by pacing, crying or wandering? (write the number)
- In the last week, how many times did your pet have an accident indoors, or a cat go outside the litter box?
- Does your pet still come to greet you, and does it still respond to its name or to being petted - more, the same, or less than a month ago?
- Has your pet got stuck or seemed lost in the house, stood in a corner, or gone to the wrong side of a door?
- Is your pet eating and drinking normally, and finishing meals without standing at the bowl as if unsure?
- On a scale of 1 to 10, how hard has the last week been for you and your household? (this matters to us and we ask it on purpose)
- Dogs only: record the 30-second sustained-gaze video this week and upload it with your answers.
Build a profile for your pet
Tell us what you are dealing with and the site will show you only what applies.