Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in alzheimer's disease

Abstract Background Apathy is a common and early symptom in Alzheimer's disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions. Objective To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD. Methods Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and non-apathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates. Results At a p FWE Conclusion Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions.