Regional susceptibility of the default mode network is associated with clinical phenotypes of Alzheimer's disease

Ziel/Aim:

Alzheimer's disease (AD) is characterized by heterogeneous clinical phenotypes, which present distinct tau-pathology patterns. The posterior default mode network (pDMN) seems, however, to be similarly affected by tau-pathology across clinical phenotypes. In this study, we investigated whether the tau-peaks in the pDMN of AD variants are associated with different functional connectivity networks.

Methodik/Methods:

We included three age-matched groups: a typical AD group (n = 14), a group with the logopenic variant (n = 6), and a group with posterior cortical atrophy (n = 6). For all patients, an [¹⁸F]AV-1451 scan was available, which was normalized, intensity-standardized to the cerebellum, and z-transformed employing a [¹⁸F]AV-1451 template of a healthy control sample. Following the z-standardization, one-sample t-tests were performed (p < 0.0001) for each group, respectively, in SPM12. The coordinate of maximum t-value coinciding in the pDMN was extracted for each group and used in a seed-based analysis conducted on functional imaging data of a healthy control group (FWE corrected). Finally, using the dice similarity coefficient, the spatial overlap was computed between the seed-based networks (SBNs), known functional connectivity networks, and the thresholded t-maps of the three groups.

Ergebnisse/Results:

The three seeds were located in middle-superior temporal and parietal regions. The AD-derived SBN fairly overlapped with the executive control network (Dice = 35%), the PCA-derived SBN overlapped well with the visuospatial network (Dice = 51%), and the SBN of the logopenic group coincided with the language network (Dice = 24%). The respective SBNs poorly-to-fairly overlapped with the group-specific tau-pathology patterns (Dice = 9 – 27%).

Schlussfolgerungen/Conclusions:

The tau-peak in the pDMN may determine the spread of tau-pathology across distinct functional networks, which are associated with clinical phenotypes of AD.