Thalamic connectivity changes along the progression of the alzheimer's disease

Neuropathological alterations take place before Alzheimer's disease (AD) symptoms start to appear. However, in the period of the disease progression, the effect of these neuropathological alterations spread to anterior thalamic nuclei (ATN), which are one of the basic components of the Papez circuit. Therefore, present study aims to examine the functional connectivity changes of the structures affected in AD including the ATN during resting state along the AD progression that consists of Subjective Cognitive Impairment (SCI), Mild Cognitive Impairment (MCI) and Dementia due to Alzheimer's Disease (ADD). In this study, clinical assessment scores and functional magnetic resonance imaging (fMRI) data from 18 patients with ADD, 44 patients with MCI and 26 patients with SCI, who took part in a previous study, were analyzed. In the first step, cortical parcellation and subcortical segmentation were applied on the anatomic MRI data of each patient by FreeSurfer software in order to obtain the structures among which the functional connectivity is analyzed. On the next step, fMRI data is spatially registered to the anatomic regions of interest (ROI). On the last step, functional connectivities between pairs of ROIs were obtained by computing correlation coefficients between mean time series of each ROI pair. The posterior cingulate cortex as one of the basic hubs of default mode network (DMN) decreased its functional connectivity with retrosplenial cortex (RSC) and anterior cingulate cortex in ADD stage in addition to the decreased connectivity between the RSC and subiculum. These findings are in line with the hypothesis that in ADD the Tau-protein is spread through the cingulum path to DMN nodes. Furthermore, the connectivity of the ATN with frontopolar cortex was declined in ADD, while no ATN connectivity change was observed in earlier stages of the disease. Our findings, while supporting previous functional neuroimaging studies related with the decreased functional connectivity among core structures of the DMN, contribute to the knowledge on neurobiological changes along the AD progression in terms of the relatively late inclusion of the thalamus with its frontal connections. Subsequent studies with larger samples and ultra-high resolution imaging methods are needed to confirm this important result.