Diffusion tensor imaging analysis of aged dogs with and without canine cognitive dysfunction

Canine cognitive dysfunction (CCD) is a naturally occurring disease in aged dogs that shares behavioral and pathological similarities with Alzheimer's disease (AD). Despite this, in vivo imaging of CCD has been limited, and to our knowledge, no studies have investigated the use of diffusion tensor imaging (DTI) to assess brain atrophy in this condition. The primary aim of this study was to determine whether DTI could detect differences in white matter microstructure between aged dogs with CCD and cognitively healthy aged dogs. A secondary aim was to evaluate correlations between DTI parameters and cognitive scores derived from the Canine Dementia Scale (CADES). We hypothesized that dogs with CCD would show lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the corpus callosum (CC) and thalamus. We further hypothesized that these changes would correlate with cognitive dysfunction severity.

DTI revealed significant differences in white matter diffusivity between CCD and cognitively healthy aged dogs. Dogs with CCD had higher MD in the thalamus compared to healthy controls (CCD: 0.00063 mm²/s, IQR 0.00062-0.00066; n = 20, Healthy: 0.00060 mm²/s, IQR 0.00060-0.00063; n = 10; p = 0.022). CADES scores positively correlated with MD in the CC (rho=0.343, p = 0.0471) and thalamus (rho=0.483, p = 0.0038), and with RD in the thalamus (rho=0.416, p = 0.0144).

These results demonstrate that DTI can detect changes in white matter integrity in the canine brain in both CCD and cognitively healthy aged dogs. Our findings suggest that axonal degeneration, as reflected by increased MD and RD values, correlates with worsening cognitive impairment. These patterns align with findings reported in Alzheimer's disease and support the potential use of DTI to monitor neuropathological progression in dogs with CCD. Overall, our results highlight the utility of DTI in characterizing structural brain changes associated with CCD and reinforce the translational relevance of CCD as a model for AD. Further research is required to determine whether DTI can reliably differentiate CCD from normal aging in clinical settings.