Cognitive dysfunction in aging dogs and cats: diagnosis and management perspectives

Abstract

Importance

Cognitive dysfunction syndrome (CDS) is an age-related neurodegenerative disorder increasingly recognized in dogs and cats because of their longer lifespans and stronger human–animal bonds. Behavioral changes, disorientation, and altered sleep–wake cycles reduce quality of life and complicate management.

Observations

Recent research highlights the utility of behavioral tools, such as the Canine Dementia Scale, Canine Cognitive Assessment Scale, and Canine Cognitive Dysfunction Rating Scale, for early detection and monitoring. Blood biomarkers, particularly neurofilament light chain and glial fibrillary acidic protein, show strong associations with disease severity and progression in dogs, highlighting diagnostic and prognostic potential, though standardization remains limited. Nutritional interventions supported by reviews suggest benefits from medium-chain triglycerides, omega-3 fatty acids, and S-adenosyl methionine, while outcomes for antioxidant combinations vary with dose and study quality. Environmental enrichment and structured activities enhance resilience, and when combined with dietary strategies, they produce synergistic benefits on cognition and neuropathology. However, variations in diagnostic criteria, small sample sizes, and inconsistent outcome measures hinder comparability across studies, challenges more pronounced in feline CDS owing to scarce evidence.

Conclusions and Relevance

By consolidating behavioral, biomarker, nutritional, and environmental evidence, this review provides a clear multimodal framework for diagnosis and management of CDS in companion animals. The findings highlight substantial progress in canine medicine and the urgent need for validated feline-specific tools and longitudinal, standardized trials. Advancing CDS research improves veterinary care and strengthens its translational value as a spontaneous model for human dementia.

INTRODUCTION

Cognitive dysfunction syndrome (CDS) is a progressive neurodegenerative disorder that affects aging dogs and cats. The disorder is characterized by disorientation, altered social interactions, house-soiling, and disturbances in the sleep–wake cycle. These behavioral changes significantly impair the quality of life and strain the human–animal bond as described elsewhere [1,2]. The prevalence of CDS increases with age, affecting 14%–35% of dogs over eight years and up to 70% beyond 15 years [3,4,5,6]. In addition to age-related neurodegeneration, recent studies suggest that certain medical conditions, such as idiopathic epilepsy, Cushing’s syndrome, and periodontal disease, may exacerbate cognitive decline or increase the risk of early-onset CDS in dogs [7,8,9]. In contrast, CDS is likely underrecognized in cats because of the vague clinical signs and a lack of validated diagnostic tools [2,10].

Neuropathological features of CDS, such as β-amyloid (Aβ) accumulation, tau hyperphosphorylation, oxidative damage, and chronic neuroinflammation, closely mirror those in Alzheimer’s disease (AD) [11,12,13,14]. These parallels, which are particularly evident in aged dogs, position CDS as a spontaneous model for human dementia research [13,15]. Nevertheless, ante-mortem diagnosis is largely reliant on behavioral assessments because no biomarker has been validated for routine clinical application.

Validated tools, such as the Canine Dementia Scale (CADES), Canine Cognitive Assessment Scale (CCAS), and Canine Cognitive Dysfunction Rating Scale (CCDR), have enhanced the early recognition and staging of CDS in dogs, allowing clinicians to track disease progression more systematically [16,17,18,19]. Observational studies suggest that the timely identification and supportive interventions may prolong survival and preserve the quality of life [4,20]. In contrast, consistent disease characterization in cats is limited by the absence of a validated feline-specific scoring system [2,10,21].

Recent research has explored several candidate biomarkers for the earlier and more objective diagnosis of CDS. The neurofilament light chain (NfL), indicative of axonal damage, and glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, correlate with the severity of cognitive decline in dogs [22,23]. The plasma and cerebrospinal fluid Aβ42 levels have also been investigated, but the findings are inconsistent, and validated reference intervals are lacking [24]. Feline biomarker studies, however, are still needed for diagnostic validation.

Nutritional and environmental strategies are increasingly recognized as essential components of a multimodal approach to CDS management. Diets enriched with medium-chain triglycerides (MCTs), omega-3 fatty acids, and S-adenosylmethionine (SAMe) have been associated with improved cognitive outcomes, potentially via enhanced neuronal metabolism and reduced oxidative stress [25,26]. In parallel, environmental enrichment—including structured play, training exercises, and problem-solving activities—has been shown to support neuroplasticity and cognitive resilience in aging dogs [27,28]. When combined, dietary and environmental interventions may produce additive benefits, reducing Aβ accumulation and improving learning and memory [27,28]. Nevertheless, variability in study design, small sample sizes, and species differences limit broader application, particularly in feline CDS, where controlled studies are scarce.

This review summarizes the current evidence on the diagnosis of CDS in aging dogs and cats, integrating behavioral assessment tools with biomarker evaluation, and on management strategies, focusing on nutritional interventions and evidence-based environmental enrichment. Unlike previous reviews that focused mainly on canine CDS or emphasized clinical features while giving limited attention to emerging biomarker and management data, this review provides an integrated synthesis across behavioral, pathological, and interventional domains. It further identifies key knowledge gaps and outlines priorities for future research to improve clinical care and enhance the translational value of CDS.

METHODS

A comprehensive literature search was conducted to identify peer-reviewed studies on CDS in aging dogs and cats. Searches were performed in PubMed, Scopus, and Web of Science for studies published up to July 2025. The search terms included the following: cognitive dysfunction syndrome, canine/feline cognitive dysfunction, behavioral assessment, biomarkers (e.g., NfL, GFAP), dietary intervention, nutraceuticals, and environmental enrichment. In addition, reference lists of relevant articles were screened manually to identify eligible studies.

Eligible studies focused on naturally occurring CDS in dogs or cats and included descriptions of the clinical features, behavioral assessment tools, biomarkers, or nutritional and environmental interventions. Only studies published in English in peer-reviewed journals were included. The eligible study types encompassed observational studies, clinical trials, and experimental interventions specifically addressing CDS. Case reports, conference abstracts, studies involving unrelated experimental models, or those focused on other neurological disorders without clear relevance to cognitive impairment were excluded.

The titles and abstracts were screened to remove duplicates and irrelevant publications, and full texts of eligible studies were reviewed. The strength and consistency of the evidence were qualitatively assessed based on the study design, sample size, and methodological clarity. The findings were narratively synthesized and organized into two main thematic sections: 1) diagnosis and characterization, encompassing clinical features and pathophysiology, behavioral assessment tools, and biomarker evaluation; and 2) management strategies, focusing on nutritional interventions and evidence-based environmental enrichment.

OBSERVATIONS

The literature increasingly recognizes CDS as a significant age-related neurodegenerative disorder in companion animals. Since the early 2000s, research has expanded the understanding of CDS in terms of the clinical signs, neuropathology, and management, but the quality of evidence remains variable. Most available data are derived from canine studies, providing valuable insights into epidemiology and Alzheimer-like pathology, whereas feline research in CDS is limited, often based on small-scale surveys, and lacking standardized diagnostic approaches.

Validated behavioral tools have improved early recognition and staging in dogs, while biomarkers, such as NfL and GFAP, show promise for objective assessment. Nutritional and environmental strategies, including antioxidant-enriched diets and behavioral enrichment, have shown potential benefits. Nevertheless, heterogeneity in the study design and small sample sizes restrict the strength of current recommendations, particularly for cats.

The following sections summarize the key findings organized into two thematic areas: 1) diagnosis, including clinical features, behavioral assessments, and biomarker evaluation; and 2) management perspectives, encompassing nutritional interventions and evidence-based environmental enrichment, while highlighting knowledge gaps and directions for future research.

Diagnosis

Accurate diagnosis of CDS requires a comprehensive evaluation of clinical features, standardized behavioral assessments, and objective biomarker measurements.

Clinical features and pathophysiology

CDS in aging dogs and cats is characterized by progressive behavioral and cognitive changes that interfere with daily activities. In dogs, disorientation, altered social interactions, house-soiling, disrupted sleep–wake cycles, anxiety-like behaviors, and increased nighttime restlessness have frequently been reported [1,4,20,29]. Recent polysomnographic research further supports this finding, suggesting that a reduced REM sleep duration is associated with cognitive impairment in aging dogs [30]. Feline cognitive decline is less apparent clinically because the behavioral changes are often subtle and mistaken for other geriatric conditions. Nevertheless, increased nocturnal vocalization, altered social interactions, and inappropriate elimination are emerging as potential indicators in survey-based studies [1,10,21,31]. Table 1 lists the major clinical signs reported in both species to provide a comparative overview. In addition to behavioral abnormalities, certain physical signs, such as gait disturbances, postural asymmetry, and head tilt, have also been described in dogs with CDS, suggesting broader neurological involvement [32].

Table 1. Clinical features and neuropathological findings of CDS in dogs and cats.

Species	Common clinical signs	Prevalence	Neuropathology	Notable differences
Dogs	Disorientation, altered social interaction, house-soiling, sleep–wake disruption, anxiety-like behaviors, repetitive/restless behaviors, decreased activity, aimless wandering	14%–35% (> 8 years), up to 68%–70% (> 15 years)	Aβ deposition (prefrontal cortex, hippocampus), occasional tau pathology, oxidative stress, astrocytosis and microgliosis, lipofuscin and ubiquitin inclusions	Region-specific and consistent Aβ deposition, considered a reliable model for human Alzheimer’s disease
Cats	Nocturnal vocalization, altered social interaction, litter box avoidance, subtle disorientation, decreased grooming, appetite changes, irritability	Up to 33% (11–14 years), > 50% (≥ 15 years), up to 88% (16–19 years)a	Aβ deposits, cortical atrophy, rare tauopathy, neuroinflammation not well characterized	Less tau pathology, limited oxidative/inflammatory data, diagnosis mainly based on owner-reported behavioral changes

CDS, cognitive dysfunction syndrome; Aβ, β-amyloid.

^aPrevalence in cats is based on owner-reported behavioral changes suggestive of cognitive dysfunction, not confirmed diagnoses.

The prevalence of CDS increases markedly with age, affecting a substantial proportion of senior dogs, whereas epidemiological data in cats remain limited and based mainly on small-scale observational surveys [3,4,10,20,21]. This under-recognition in cats is compounded by the absence of validated feline-specific diagnostic tools and the nonspecific nature of behavioral signs.

Neuropathological investigations reveal substantial parallels between CDS and AD. Progressive Aβ deposition, including cerebral amyloid angiopathy, has been described consistently in aging dogs [12,13,14,15]. Region-specific accumulation in the prefrontal cortex and hippocampus correlates with cognitive decline in some studies [12,33,34,35], but not all findings are consistent [13,15]. Hyperphosphorylated tau and neurofibrillary tangles, characteristic of AD, are rare in dogs, but a limited tau-related pathology has been documented [13,33]. Additional histological findings, such as lipofuscin accumulation and ubiquitin-positive intraneuronal inclusions, suggest altered protein homeostasis as a contributing mechanism [12].

Oxidative stress and mitochondrial dysfunction have been recognized as the key drivers of neuronal injury [26,36]. Increased oxidative damage markers have been observed in canine brains, supporting chronic oxidative stress as a factor in disease progression [12,26]. Chronic neuroinflammation, reflected by activated microglia and astrocytosis, is evident in dogs and less consistently in cats [10,13]. Species differences are notable. Beagles exhibit predictable age-related cognitive decline with early Aβ deposition [14,33], whereas feline neuropathological data remain sparse. Aβ deposits and cortical atrophy have been described in aging cats, but tauopathy appears rare, suggesting species-specific differences in the pathogenesis of the disease [10].

Behavioral assessment tools

Behavioral assessments remain the primary method for diagnosing and monitoring CDS in dogs because no definitive ante-mortem diagnostic test is currently available [14,37]. CCDR was the first validated questionnaire specifically designed for home-based evaluations, showing high reliability and sensitivity in detecting age-related cognitive decline [16,38]. The subsequent development of the CADES improved clinical utility by stratifying affected dogs into normal, mild, moderate, and severe stages. This stratification has facilitated the longitudinal monitoring of disease progression and treatment response [17,39]. More recently, the CCAS has been validated for clinical and research use, particularly for identifying mild cognitive impairment, a prodromal stage of CDS (Table 2) [18,19].

Table 2. Behavioral assessment tools for diagnosing and monitoring cognitive dysfunction in dogs and cats.

Assessment tool	Species	Key features	Staging ability	Prognostic utility	Limitations
CCDR	Dogs	Owner-based questionnaire; validated for home use	Limited (binary or mild staging only)	Baseline scores predict survival and progression	Subjective; influenced by owner perception
CADES	Dogs	Stages: normal, mild, moderate, severe	Excellent (multi-stage: mild to severe)	Higher scores linked to shorter survival and faster decline	Subjective bias; environmental influences
CCAS	Dogs	Detects MCI; clinical and research use	Good (MCI detection)	Limited prognostic validation	Validation in diverse populations is limited
Adapted canine tools	Cats	Modified CCDR or survey-based questionnaires	Not validated	None	No feline-specific validated tools; underdiagnosis common

CCDR, Canine Cognitive Dysfunction Rating Scale; CADES, Canine Dementia Scale; CCAS, Canine Cognitive Assessment Scale; MCI, mild cognitive impairment.

Long-term observational studies using these tools have provided important insights into disease progression and prognosis [17]. Higher baseline CCDR and CADES scores have been associated with shorter survival times and more rapid cognitive deterioration, underscoring their prognostic value [16,17]. In addition, some studies have combined behavioral assessments with observations of physical signs such as postural abnormalities or gait changes [40,41]. These findings support the use of behavioral tools to evaluate the relationship between behavioral changes and disease severity [40,42]. Recent research also suggests that combining structured behavioral questionnaires with owner-reported physical changes may improve the early recognition of CDS [39,40,41].

Despite these diagnostic advances, several limitations remain. Behavioral scoring is inherently subjective and may be influenced by owner perception, environmental factors, and concurrent medical conditions [1,39,43,44]. The lack of species-specific assessment tools for cats further limits the early detection of feline CDS [45,46]. Surveys have shown that behavioral changes in older cats, including increased nocturnal vocalization, altered social interactions, and inappropriate elimination, are often misinterpreted as normal aging rather than the signs of cognitive decline [2,10,45]. Although some canine-based questionnaires have been adapted for feline use, their diagnostic accuracy remains unvalidated. Moreover, no consensus exists regarding the staging criteria or cutoff thresholds in cats [2,45,46].

Behavioral assessment tools are indispensable for diagnosing CDS, tracking its progression, and evaluating treatment efficacy. Nevertheless, their diagnostic precision requires further refinement and validation to enhance both clinical utility and prognostic value, especially in feline patients.

Biomarker evaluation

Biomarkers are being increasingly explored as objective tools to support the diagnosis and monitoring of CDS, particularly in dogs, whereas feline applications have been largely unexplored [43]. These biomarkers provide valuable insights into the underlying neuropathology and may facilitate earlier detection compared to behavioral assessment alone.

Among the most studied biomarkers in canine CDS, NfL has become a promising indicator of axonal degeneration [47]. Elevated serum and plasma NfL concentrations have been significantly associated with greater cognitive impairment in dogs [22,48]. Moreover, higher baseline NfL levels have been linked to accelerated cognitive decline and reduced survival times in longitudinal studies, highlighting its prognostic potential [22,23,48]. Similarly, GFAP, which reflects astrocytic activation and neuroinflammation, has been reported to increase in dogs with CDS [22]. Preliminary data suggest that the GFAP levels may increase even during the early stages of cognitive decline. Table 3 lists the key biomarkers and their characteristics.

Table 3. Investigated biomarkers in CDS: evidence in dogs and knowledge gaps in cats.

Biomarker	Pathological target	Clinical relevance	Key findings in dogs	Status in cats
NfL	Axonal degeneration	Diagnostic and prognostic	Elevated levels correlate with severity and shorter survival	Not studied
GFAP	Astrocytic activation, neuroinflammation	Early neuroinflammation marker	Increased in early cognitive decline	Not studied
Aβ42 (CSF, plasma)	Amyloid deposition	Reflects cerebral amyloid burden	Decreased CSF/plasma Aβ42 with increased brain deposition; inconsistent correlation with clinical scores	Anecdotal findings; no validated data
Oxidative stress markers (protein carbonyls, lipid peroxidation)	Oxidative injury	Pathogenesis and treatment monitoring	Elevated in CDS; reduced with antioxidant intervention	Not studied
Proteomics-based panels	Multiple pathways (acute-phase proteins, complement, lipid metabolism)	Exploratory diagnostic panels	Identified altered apolipoproteins and inflammatory components	No data

CDS, cognitive dysfunction syndrome; NfL, neurofilament light chain; GFAP, glial fibrillary acidic protein; Aβ, β-amyloid; CSF, cerebrospinal fluid.

Amyloid-related biomarkers have also been studied extensively [24,33,49,50]. Decreased cerebrospinal fluid (CSF) and plasma concentrations of Aβ42 are typically interpreted as indicators of increased Aβ deposition in the canine brain, mirroring the findings in human AD [24,49]. Region-specific amyloid accumulation, particularly in the prefrontal cortex and hippocampus, has been correlated with elevated CADES and CCDR scores, suggesting a link between the amyloid burden and behavioral changes [33,35,50]. Nevertheless, the results remain inconsistent across studies. Some studies failed to demonstrate a consistent association between the Aβ42 levels and clinical severity, likely due to methodological differences, limited sample sizes, and heterogeneous disease stages [24,49]. In addition, the absence of defined reference ranges and the ethical and practical limitations of repeated CSF sampling restrict the routine clinical use of amyloid biomarkers [24,49,50,51].

Other biochemical markers, particularly those reflecting oxidative stress and mitochondrial dysfunction, have been investigated in relation to cognitive impairment [14,52]. Increased levels of protein carbonyls and lipid peroxidation products have been observed in aged dogs with CDS, which often correlate with the histopathological evidence of neuronal injury [52,53]. The findings from an experimental study in aged Beagles showed that dietary antioxidants and mitochondrial cofactors may mitigate the oxidative damage and enhance cognitive performance [54].

Interestingly, recent proteomics-based analyses have identified alterations in acute-phase proteins, complement cascade components, and apolipoproteins related to lipid metabolism in dogs with CDS [55]. Phochantachinda et al. [55] suggested that a multi-marker panel could improve diagnostic precision and offer insights into disease heterogeneity. On the other hand, variability in assay techniques, small cohort sizes, and the absence of standardized cutoff values currently limit reproducibility and clinical translation.

In cats, biomarker research remains scarce and largely anecdotal, with no validated diagnostic thresholds currently available [45,56]. Therefore, large-scale, longitudinal studies are required before these biomarkers can be incorporated into routine clinical assessments in veterinary practice.

Management perspectives

Management perspectives focus on slowing cognitive decline and improving quality of life through targeted nutritional interventions and structured environmental enrichment. Key nutritional and environmental interventions are summarized in Table 4.

Table 4. Nutritional and environmental interventions for cognitive dysfunction in aging dogs and cats.

Intervention	Key mechanism	Evidence in dogs	Evidence in cats	Limitations
MCTs	Provide ketone bodies as an alternative neuronal energy source; enhance mitochondrial metabolism	Improved learning, memory, and behavioral scores in clinical trials	No controlled trials	Optimal dose and long-term safety are unclear
Omega-3 fatty acids	Anti-inflammatory and neuroprotective effects	Associated with cognitive improvement and reduced Aβ accumulation	Suggested benefit based on reviews	No clinical trials
SAMe	Antioxidant and methylation support	Modest improvement in aged dogs	Suggested benefit: no trials	Species-specific dosing not established
Antioxidant-enriched diets (vitamins E, C, L-carnitine, alpha-lipoic acid)	Reduce oxidative damage and Aβ accumulation	Improved learning and memory, especially when combined with enrichment	No trials	Heterogeneous protocols; variable outcomes
Environmental enrichment	Enhances synaptic plasticity, cognitive resilience	Structured play, problem-solving, and novel stimuli delay decline; additive with antioxidant diets	Recommended; no controlled trials	No standardized protocols in veterinary practice

MCT, medium-chain triglyceride; SAMe, S-adenosylmethionine; Aβ, β-amyloid.

Nutritional interventions

Nutritional strategies are the most extensively studied non-pharmacological approaches for the management of CDS in dogs and, to a lesser extent, in cats [1,45,57]. Diets enriched with MCTs, omega-3 fatty acids, and SAMe have been repeatedly associated with cognitive benefits, likely by enhancing neuronal metabolism and reducing oxidative stress [58,59,60,61,62]. Experimental studies in aged dogs have shown that MCT supplementation can provide alternative energy substrates to the brain through ketone body production, thereby supporting neuronal function in the setting of impaired glucose utilization [58,61,63]. Similarly, omega-3 fatty acids, particularly docosahexaenoic acid, contribute to membrane stability and synaptic plasticity, while SAMe has demonstrated neuroprotective effects through its role in methylation and antioxidant pathways [58,61,62].

In addition to these individual nutrients, antioxidant-enriched diets have attracted substantial interest. Formulations containing vitamins E and C, lipoic acid, and carnitine, often combined with natural sources such as fruits and vegetables, have been shown to improve learning and memory performance in aged dogs [26,27,57,62]. Longitudinal studies reported that such antioxidant diets not only reduced oxidative damage but also supported mitochondrial homeostasis and improved overall cognitive performance [54]. Importantly, the beneficial effects were sometimes amplified when nutritional strategies were combined with behavioral enrichment, highlighting the value of multimodal interventions [27].

Nevertheless, results across trials have not always been consistent. Variability in study design, sample size, nutrient formulation, and treatment duration contributes to conflicting findings. For example, while several studies observed reduced Aβ accumulation in dogs receiving antioxidant supplementation [26,27], other trials showed cognitive improvements independent of amyloid pathology, suggesting multiple mechanisms of action [54]. Moreover, although canine studies provide a strong translational model, evidence in cats is sparse. Dietary interventions such as commercially available nutraceutical formulations (e.g., containing antioxidants, phosphatidylserine, or polyunsaturated fatty acids) are marketed for feline use, but controlled clinical data remain limited [45,58,59,62].

Taken together, dietary interventions represent a cornerstone of CDS management. While no single nutrient or supplement provides a definitive solution, the collective body of evidence supports the role of targeted nutritional modification in slowing cognitive decline. Continued research is needed to establish standardized formulations, optimal dosages, and feline-specific protocols, but the current findings justify the inclusion of dietary strategies as an essential component of multimodal management in aging companion animals.

Environmental enrichment

Environmental enrichment represents a complementary, though historically less emphasized, management strategy for CDS. It encompasses physical activity, social interaction, and cognitive stimulation, all of which aim to enhance engagement with the environment and preserve neuronal function. The rationale for enrichment is grounded in evidence from both human and animal aging studies, which consistently demonstrate that stimulating environments can enhance neuroplasticity and mitigate cognitive decline [1,27,64]. In dogs, enrichment protocols have included regular exercise, increased social contact, exposure to novel toys, and structured cognitive tasks such as puzzle feeders or discrimination learning exercises. These interventions not only improve daily activity and welfare but also contribute to measurable neurobiological changes [27,65,66].

Experimental work in aged beagles has shown that enrichment reduces hippocampal neuron loss and preserves neuronal populations in vulnerable brain regions [66]. Other studies demonstrated that enrichment enhances neurogenesis and increases brain-derived neurotrophic factor (BDNF) availability, thereby supporting synaptic resilience [27,64]. Importantly, when enrichment was combined with antioxidant diets, the cognitive benefits were additive, with significant improvements in learning, memory, and neuropathological outcomes compared to either intervention alone [27,54]. This synergy underscores the importance of incorporating environmental strategies alongside dietary management.

Beyond laboratory studies, practical enrichment strategies have been proposed for clinical application in both dogs and cats. In cats, environmental interventions focus on ensuring easy access to essential resources (food, water, litter boxes), reducing stress through the use of pheromones, and introducing structured play or exploration opportunities [45]. Problem-solving devices such as puzzle feeders, especially when presented at variable intervals, have been shown to maintain motivation and engagement while preventing habituation [65,67]. These approaches align with the concept of cognitive enrichment, which emphasizes opportunities for learning and problem-solving as a means of sustaining brain health [1,45].

Despite its promise, enrichment research faces challenges. Controlled trials in client-owned animals are relatively scarce, and outcome measures vary across studies, limiting comparability [1,45,54]. Moreover, implementation in clinical practice requires adaptation to individual household environments and owner compliance. Nonetheless, the accumulating evidence indicates that environmental enrichment plays a significant role in maintaining cognitive function and quality of life in aging companion animals. By addressing behavioral, social, and environmental dimensions, enrichment strategies provide a vital complement to dietary management, reinforcing the need for multimodal approaches to CDS care.

DISCUSSION

CDS is increasingly being recognized as a spontaneous age-related neurodegenerative disorder in dogs, with comparatively fewer studies addressing feline cases. This review specifically aimed to integrate current knowledge on the diagnosis (behavioral assessments and biomarkers) and management perspectives (nutritional and environmental interventions) for CDS in aging dogs and cats, thereby providing a clear and structured overview for both clinical application and comparative research. Compared to previous reviews, this study strengthens the current evidence across behavioral, pathological, and interventional domains, highlighting both progress and persistent gaps in veterinary and comparative dementia research.

Despite the growing interest, the scientific evidence for CDS, particularly in cats, remains uneven [68,69]. Although canine CDS has been studied for more than two decades, with the accumulating data on epidemiology, neuropathology, and interventional outcomes, feline studies are comparatively rare and often limited to owner surveys or postmortem observations [1,14]. This disparity restricts the development of standardized diagnostic frameworks and therapeutic recommendations for cats [1,2,45,68,69]. Such gaps are consistently observed across diagnostic, biomarker, and interventional domains.

Behavioral assessments remain the cornerstone of clinical diagnosis and disease monitoring, particularly in the absence of definitive ante-mortem tests [1,14]. In dogs, validated instruments, such as CCDR, CADES, and CCAS, have improved early recognition, staging, and prognostic assessment [16,17,18,19]. Nevertheless, their reliance on caregiver reports introduces subjectivity, and their performance may be influenced by environmental and comorbid factors [19,43]. In particular, comorbid sensory impairments, such as age-related hearing loss, may confound behavioral assessments because they can mimic or exacerbate the signs of cognitive decline [70]. In cats, no standardized or validated tools exist, and many behavioral signs are subtle or mistaken for normal aging [2,10,21]. These limitations underscore the urgent need to develop species-specific diagnostic instruments—ideally integrating behavioral and objective indicators—to improve the clinical accuracy and early detection, particularly in feline practice.

Biomarkers offer promise for supporting a CDS diagnosis and monitoring, with NfL and GFAP showing particular potential in dogs [22,48]. Elevated serum NfL levels are associated with greater cognitive impairment, faster progression, and shorter survival, suggesting diagnostic and prognostic value [22,48,70]. Similarly, GFAP may reflect neuroinflammatory activity in the early disease stages, but its clinical utility remains to be validated in larger canine cohorts [22,71]. On the other hand, these markers have been fully validated for routine clinical use because of the methodological variability and lack of standardized thresholds. Amyloid-based biomarkers, such as Aβ42, have also shown relevance in canine studies but are limited by inconsistencies across protocols and restricted applicability in live patients [13,20,72,73,74]. Thus far, published research investigating the biomarkers in feline CDS is lacking, in contrast to the growing literature in dogs. Establishing feline-specific biomarker profiles through standardized methodologies and longitudinal data is essential for clinical application and comparative research. Thus, although it may be due to species differences, new diagnostic criteria or evaluation systems may be needed in the future for diagnosing CDS in cats, unlike in dogs.

Nutritional interventions are practical, low-risk strategies to support cognitive function [25,26,27,28,54,58,59,62,63,64,65,66]. Among the dietary strategies, MCTs have the most robust evidence, improving behavioral outcomes in controlled canine studies [58,60,61,62,63]. Antioxidant-enriched diets and nutraceutical combinations, such as those containing omega-3 fatty acids, SAMe, and mitochondrial cofactors, have also shown beneficial effects, particularly when implemented early and maintained for the long term [26,27,28,62]. These nutritional approaches enhance neuronal metabolism, reduce oxidative damage, and provide alternative energy substrates, thereby delaying disease progression. Environmental enrichment represents an equally important non-pharmacological strategy that independently contributes to cognitive resilience. Structured play, training exercises, interactive problem-solving, and exposure to novel stimuli have been shown to promote neuroplasticity and preserve neuronal function [44,60,64,65,66,67]. Experimental work in aged dogs further demonstrates that enrichment reduces hippocampal neuron loss and enhances BDNF activity [64,66], supporting synaptic health and learning capacity. Beyond laboratory findings, clinical recommendations emphasize tailoring enrichment programs to individual animals, including interactive play and owner–pet engagement, to maximize quality of life. When nutritional and environmental interventions are combined, their effects appear synergistic, producing greater improvements in learning, memory, and neuropathological outcomes compared to either approach alone [27,54,60,64]. This multimodal framework underscores the importance of integrating complementary strategies for long-term management of CDS in aging companion animals.

Although not the primary focus of this review, emerging pharmacological approaches, such as cholinesterase inhibitors, are also being evaluated to mitigate cognitive decline, particularly in canine studies. A novel butyrylcholinesterase inhibitor showed behavioral improvement in affected dogs in a recent experimental study [75]. Furthermore, recent comprehensive reviews have outlined a range of diagnostic and therapeutic advances for CDS, highlighting the need for multimodal and individualized treatment approaches [76]. Nevertheless, robust studies evaluating these strategies in cats are virtually non-existent, and current feline recommendations are extrapolated mainly from canine evidence or based on anecdotal reports. Thus, tailored interventions must be developed and validated with species-specific considerations.

Beyond its veterinary relevance, CDS offers significant comparative value as a spontaneous model of human dementia, particularly AD. Aged dogs naturally develop neuropathological changes, such as Aβ deposition, tau hyperphosphorylation, oxidative injury, and chronic neuroinflammation, all of which closely resemble the abnormalities observed in AD patients [11,12,13,14,15,56]. Clinically, dogs with CDS show disorientation, altered social interactions, and sleep–wake disturbances, paralleling the behavioral manifestations of human dementia [1,2,43]. These similarities underscore the translational potential of CDS for investigating disease mechanisms and testing therapeutic interventions in a real-world setting, which distinguishes it from induced rodent models. However, challenges remain, including limited feline data, variability in diagnostic approaches, and the absence of standardized outcome measures across species. Addressing these gaps will be critical to strengthen the comparative utility of CDS, thereby advancing both veterinary management and human dementia research.

This review highlights the importance of a multimodal and species-appropriate framework for managing CDS in companion animals. Although progress has been substantial in canine medicine, clinical translation remains constrained by the limitations in diagnostic objectivity and the paucity of feline-specific research. Future studies should prioritize the development of validated behavioral instruments for cats, the refinement and clinical validation of biomarker panels, and standardized protocols for nutritional and environmental interventions. Therefore, longitudinal, large-scale trials with harmonized outcome measures will be critical to establishing evidence-based guidelines. Bridging species gaps and enhancing diagnostic precision will improve the welfare of aging companion animals and enhance the translational utility of CDS as a spontaneous model for human AD.