Brain mineral concentrations in canine cognitive dysfunction

Canine cognitive dysfunction (CCD) is a prevalent age-related neurodegenerative condition in dogs that shares several features with Alzheimer's disease (AD). Although mineral dyshomeostasis has been implicated in the pathogenesis of AD, its role in CCD remains largely unexplored. This retrospective study aimed to investigate regional brain mineral concentrations in 24 dogs with CCD and 15 dogs exhibiting successful cognitive aging (non-CCD). CCD diagnosis was based on the results of caregiver questionnaires, physical examination and laboratory analyses after ruling out any other intracranial disease. Four cortical regions with high β-amyloid pathology (prefrontal, parietal, temporal and occipital cortex) and one generally unaffected region (cerebellum) were analysed to determine the concentrations of 20 minerals by using plasma-based optical techniques and mass spectrometry. Compared to non-CCD dogs, CCD dogs had significantly lower concentrations of Ca, Fe, Mg, Mn and Zn, and higher levels of Cd, Mo, Ni and Pb in specific brain regions. The greatest number of significant differences were observed in the prefrontal cortex, the earliest and most consistently affected region in CCD, whereas the cerebellum remained largely unchanged. Principal component analysis distinguished CCD from non-CCD dogs and, within the CCD group, showed clustering of the cerebellum separately from cortical regions. The regional specificity of these alterations and their ability to distinguish CCD from non-CCD dogs support a link between disrupted mineral homoeostasis and CCD. Notably, lower concentrations affected essential trace elements involved in antioxidant defence, neuronal signalling and neurotransmission, raising the possibility of functional implications that warrants further investigation.