Neuropathology, diagnosis, and potential treatment of feline cognitive dysfunction syndrome and its similarities to Alzheimer's disease

Cognitive dysfunction syndrome (CDS) is a common age-related condition in domestic cats that is characterised by behavioural changes that ultimately lead to cognitive decline and dementia. The most common behavioural changes displayed by cats affected by CDS have been summarised under the acronym VISHDAAL and include excessive Vocalisation, especially at night, alterations in their Interaction with their owners (e.g., increased affection), alterations in their Sleep-wake cycles, House-soiling, spatial and/or temporal Disorientation, alterations in Activity levels, Anxiety, and/or Learning/memory deficits. Cats with CDS develop neuropathologies that share many similitudes to those seen in the brains of humans with Alzheimer’s disease (AD), which are the abnormal accumulation of amyloid-ß (Aß) forming senile plaques, and the presence of neurofibrillary tangles (NFT) formed by hyperphosphorylated tau deposits. In the present study, immunohistochemistry of seven different brain regions of cats of various ages, with and without CDS, revealed that cats accumulate intra and extracellular Aß deposits, plus intranuclear and intracytoplasmic hyperphosphorylated tau deposits. The intracytoplasmic deposits of Aß were mainly found in younger cats, whereas elderly cats accumulated large diffuse extracellular Aß deposits. While Aß senile plaques in people with AD have a dense core, the diffuse Aß deposits in cats are believed to be an early stage of senile plaques. In this study, intranuclear labelling for hyperphosphorylated tau was mainly found in the younger cats. In contrast, intranuclear labelling was rarely found in elderly cats, especially if pre-tangles were present. Furthermore, intracytoplasmic immunolabelling for hyperphosphorylated tau was mainly found in the brains of elderly cats. Due to its ultrastructural features, these deposits are considered to be pre-tangles, which are an early stage of the characteristic NFT seen in the human AD brain. Diagnosing CDS can be challenging, especially as the diagnosis can only be achieved by ruling out all other potential causes for the behavioural changes displayed by the cats. Veterinarians can only diagnose CDS after performing thorough examinations of the cats, which can be a slow, time-consuming, and expensive task. Hence, diagnostic tools and/or methods that may facilitate prompt diagnosis are urgently needed. Imaging techniques, such as magnetic resonance imaging (MRI), have recently emerged as potential diagnostic tools for assessing brain changes associated with ageing and AD in humans. These imaging techniques also have the potential to be effective in vivo diagnostic tools for assessing age-related brain changes and CDS in cats. In this study, age-related changes were assessed in different brain regions of cats of various ages, with and without CDS, by using MRI. Elderly cats in this study were shown to develop atrophy of the whole brain, the hippocampus, and the occipital lobe, plus enlargement of the ventricles. Most of these changes have also been described in elderly humans, especially in those with AD. While there is currently no treatment available for CDS in cats, interventions that can be considered for its management include environmental enrichment, dietary supplementations, specific diets, and potentially, medication (licensed for the treatment of dogs with CDS). Telmisartan is an angiotensin receptor blocker and an activator of PPARγ that has shown to reduce neuroinflammation, provide neuroprotection, and to restore cognition in humans and rodents. In this study, a three-month double-blinded placebo-controlled trial was performed in cats with severe CDS. Even though no statistically significant differences were found between the treatment groups, further studies are needed to determine the true potential of telmisartan for the treatment of CDS in cats. The present work furthers our understanding about the neuropathology of ageing and CDS in cats. Furthermore, it proposes the use of imaging techniques, especially of MRI, as a potential in vivo diagnostic tool for age-related changes that may lead to cognitive decline. Finally, it proposes the use of telmisartan as a potential treatment to reduce the clinical signs of CDS in cats.