Diagnosis of CCD
Although CCD is highly prevalent the disease is severely under-diagnosed, affecting a growing population of aged dogs. The diagnosis of CCD is a diagnosis of elimination. The illness exacerbating symptoms, commonly also observed in CCD, must be excluded, such as brain tumors, hypertension, other neurological conditions, metabolic and hormonal imbalances, etc. Screening and diagnosis of CCD is primarily based on observation of clinical signs which are summarized by the acronym DISHAA [Disorientation, altered social Interactions, altered Sleep–wake cycles, House soiling and loss of other learned behaviors, altered Activity levels and increasing Anxiety (Ruehl et al., 1995; Neilson et al., 2001; Azkona et al., 2009; Rosado et al., 2012; Fast et al., 2013b; Madari et al., 2015)]. Sleeping during the day and restless at night, decreased interaction, disorientation at home and anxiety are common symptoms (Fast et al., 2013b).
The diagnosis depends largely on the owners and the veterinarians to observe and diagnose the disease, which is in most cases overlooked and symptoms attributed to the aging of dogs. To facilitate the detection of CCD, veterinarians can use a screening questionnaire that includes a list of possible signs. Several questionnaires are available and based on the scores the stage of dog’s cognitive decline can be identified (Colle et al., 2000; Neilson et al., 2001; Osella et al., 2007; Azkona et al., 2009; Golini et al., 2009; Salvin et al., 2011; Landsberg et al., 2012; Rosado et al., 2012; Fast et al., 2013b; Madari et al., 2015). Madari et al. (2015) have proposed criteria for discrimination of three stages of the disease, these are mild cognitive impairment, moderate cognitive impairment, and severe cognitive impairment. The severity and progression of CCD disease is identified by Canine Dementia Scale (CADES), which contains 17 items distributed into four domains related to changes in dogs’ behavior (spatial orientation, social interactions, sleep–wake cycles, and house soiling) (Madari et al., 2015). The Canine Cognitive Dysfunction Rating Scale (CCDR) is another questionnaire (Salvin et al., 2011), which is comprised of 13 behavioral items distributed into four domains, namely orientation, memory, apathy, impaired olfaction, and locomotion (Salvin et al., 2011). The cognitive deficits in dogs with CCD with regards to affected brain regions are summarized in Table 1. Cognitive impairment parallels the symptomology of AD. Performance on tasks involving complex learning and working memory are impaired first, along with executive function, visuospatial ability and complex learning deficits, with disease progression impairments in discrimination learning and behavioral changes are common (Neilson et al., 2001; Tapp et al., 2003; Studzinski et al., 2006; Madari et al., 2015).
MRI diagnosis is only rarely performed in dogs, due to possible complications during anesthesia and cost restraints. In dogs with CCD, as in humans with AD, MRI shows brain atrophy and include ventricular enlargement as well as widened and well-demarcated cerebral sulci. Measuring the thickness of the interthalamic adhesion in CCD was employed as a parameter for quantifying canine brain atrophy (Hasegawa et al., 2005; Noh et al., 2017). In demented canine brain MRI can be a useful tool to detect other abnormalities of the brain, possibly causing dementia such as leukoaraiosis (periventricular white matter hyperintensities) and brain microhemorrhages (Dewey et al., 2019). In human brain imaging a variant of amyloid-binding histological dye Thioflavin T, [11C]PiB, has been used as a tracer to detect Aβ using PET (positron-emission tomography) scans. In dogs this compound failed to detect the full amyloid load in the brain, established by ex vivo histopathological investigation (Fast et al., 2013a).
In general, the diagnosis of human AD is set similarly. First by ruling out other possible causes for symptoms and then by detection of CSF and plasma biomarker levels, tests of memory, problem solving, attention, counting, and language, which can be followed by MRI and PET scans (Hane et al., 2017). As in dogs, the cause of dementia can only be confirmed with certainty postmortem.