The aim of this study was to determine the role of Alzheimer's Disease (AD) pathology in patients with frontotemporal lobar degeneration (FTLD)-related syndromes by exploring whether default mode network (DMN) connectivity differences exist between patients with FTLD subtypes with AD pathology (FTLD-AD), FTLD subtypes without AD pathology (FTLD-nonAD), and AD clinical presentation and pathology.

FTLD-related syndromes are a family of progressive diseases characterized by changes in personality, cognition and motor function. There is significant heterogeneity in the presentation within each syndrome and its cause is unknown. There is increasing evidence of co-pathology in neurodegenerative diseases including FTLD. The relationship of AD pathology or co-pathology to these presentations remains unknown. Reduced connectivity within the DMN has been reported in AD patients relative to FTLD patients. Changes in the DMN may contribute to the heterogeneity seen in some patients with FTLD-syndrome positive for AD biomarkers.

Reduced connectivity was observed between the left angular gyrus and the left lateral parietal region (T(23) = -4.02, p-False Discovery Rate (FDR) = 0.0194) in the AD group relative to the FTLD-nonAD group, covarying for age and sex. Reduced connectivity was observed between the left angular gyrus and posterior cingulate cortex (T(11) = -4.72, p-FDR = 0.0228) in the FTLD-AD group compared to the FTLD-nonAD group. No differences were observed within the DMN between the FTLD-AD and AD groups.

In keeping with previous findings, DMN connectivity is reduced in patients with AD pathology. The results here support the hypothesis that the DMN is vulnerable to AD pathology even in FTLD-related syndromes.