Objective: This study aimed to determine the functional neural correlates of neuropsychiatric symptoms (NPS), including mood disorders, anxiety and psychosis, in prodromal Lewy body dementia (LBD) using resting-state functional MRI (rs-fMRI).

Background: NPS are a common feature of LBD. Occurring early in disease progression, such symptoms are associated with a poorer quality of life, increased caregiver burden and greater severity of cognitive impairment. Despite this, the underlying pathological mechanisms of neuropsychiatric symptoms remain poorly understood.

Method: Fifty-seven participants with mild cognitive impairment with Lewy bodies (MCI-LB, n=28) or Parkinson’s disease (PD-MCI, n=29) underwent rs-fMRI. Twenty bilateral cortical seeds (6mm spheres) assessed functional connectivity (FC) in five resting-state networks (RSNs): default mode network (DMN), dorsal attention network (DAN), salience network (SN), limbic network (LN) and visual network (VN). Affective disorder (depression/apathy), anxiety, and psychosis (hallucinations/delusions) were measured by the Neuropsychiatric Inventory. Seed-based connectivity maps were analysed to determine associations between each NPS and FC between seed regions and the rest of the brain.

Results: In PD-MCI, greater connectivity between the DMN, LN and subgenual cortex and weaker connectivity between the LN and brainstem were associated with severity of affective disorder and anxiety. Anxiety was additionally associated with weaker connectivity between subgenual cortex and the insula node of the SN. Psychosis severity related to greater FC between frontal regions and both the DMN and DAN, and between the VN and temporal lobe. In MCI-LB, none of the NPS were found to significantly relate to FC within any resting-state network.

Conclusion: Connectivity patterns associated with NPS in PD-MCI reflect established neural mechanisms of mood disorders and theoretical models of PD-related hallucinations. Lower brainstem-limbic connectivity further suggests LBD-related neurotransmitter denervation within limbic regions may contribute to affective symptoms in PD-MCI. It is unclear from the present study, however, whether such mechanisms overlap across LBD sub-types. This study provides a basis for future research establishing functional neural signatures of NPS in LBD, representing an important first step in identifying symptomatic treatment targets.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/aberrant-connectivity-in-resting-state-brain-networks-underlying-neuropsychiatric-symptoms-in-prodromal-lewy-body-dementia/