The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease

The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimer disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region, with different subdivisions reflecting distinct connectivity profiles. However, little is understood about PMC functional connectivity and its differential vulnerability to AD pathogenesis. Using a data-driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project (HCP) to characterise the distinct functional subdivisions and unique functional-anatomic connectivity patterns of the PMC. These connectivity profiles were subsequently quantified in the Alzheimers Disease Neuroimaging Initiative (ADNI) study, to examine functional connectivity differences in (1) AD patients and cognitively normal (CN) participants and (2) the entire AD pathological spectrum, ranging from CN participants and participants with subjective memory complaints (SMC), through to those with mild cognitive impairment (MCI), and finally, patients diagnosed with AD. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex, and the central precuneus in AD patients compared to CN participants. Functional abnormalities in these subdivisions were also related to high amyloid burden and lower hippocampal volumes. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease progression and specific deficits in memory and executive function. These findings provide new evidence showing that specific vulnerabilities in PMC functional connectivity are associated with large-scale network disruptions in AD and that these patterns may be useful for elucidating potential biomarkers for measuring disease progression in future work.

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