Amyloid and cerebrovascular burden divergently influence brain functional network changes over time

Objective: To examine the effects of baseline Alzheimer’s disease and cerebrovascular disease markers on longitudinal default mode network (DMN) and executive control network (ECN) functional connectivity (FC) changes in mild cognitive impairment (MCI) patients.
Methods: We studied 30 amnestic (aMCI) and 55 subcortical vascular MCI (svMCI) patients with baseline Pittsburgh Compound B (PiB)–positron emission tomography (PET) scans and longitudinal magnetic resonance imaging (MRI) scans. Participants were followed up clinically with annual MR imaging for up to four years (aMCI: 26 with two time-points, 4 with three time-points; svMCI: 13 with two time-points, 16 with three time-points, 26 with four time-points).
Results: Amyloid-β burden was associated with longitudinal DMN FC declines, while cerebrovascular burden was associated with longitudinal ECN FC changes. When patients were divided into PiB+ and PiB- groups, PiB+ patients showed longitudinal DMN FC declines, while svMCI patients showed longitudinal ECN FC increases. Direct comparisons between the two groups without mixed pathology (aMCI PiB+ and svMCI PiB-) recapitulated this divergent pattern: aMCI PiB+ patients showed steeper longitudinal DMN FC declines, while svMCI PiB- patients showed steeper longitudinal ECN FC increases. Finally, using baseline PiB uptake and lacune numbers as continuous variables, baseline PiB uptake showed inverse U-shape associations with longitudinal DMN FC changes in both MCI subtypes, while baseline lacune numbers showed both mainly inverse-U shape relationships with longitudinal ECN FC changes in svMCI patients.
Conclusions: Our findings underscore the divergent effects of amyloid-β and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the pre-dementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer’s disease and cerebrovascular disease.