Objective: Investigating how neuropsychiatric symptoms (NPS)—depression, anxiety, and apathy—relate to functional connectivity between monoaminergic nuclei and the limbic network (LN), default mode network (DMN), and subgenual cingulate (SgC), across the Lewy body disease (LBD) spectrum.
Background: Mood-related NPS are highly prevalent in LBD and associated with poorer outcomes and cognitive decline. Their neural basis remains unclear but may involve dysfunction in distributed neuronal networks and neurotransmission pathways.
Method: Participants included individuals with Parkinson’s disease with normal cognition (PD-NC,n=52) or cognitive impairment (PD-CI,n=45), dementia with Lewy bodies (DLB,n=46), and healthy controls (n=78). NPS were measured via Geriatric Depression Scale or Cornell Scale for Depression in Dementia (GDS/CSDD), and Neuropsychiatric Inventory (NPI). Resting-state 3T fMRI measured connectivity between brainstem nuclei—ventral tegmental area (VTA), substantia nigra (SN), dorsal and median raphe nuclei (DRN/MRN)—and the DMN, LN and SgC. General linear models, adjusted for demographics and confounding NPS, compared connectivity between controls and patients with >median or ≤median depression, anxiety or apathy scores in each subgroup.
Results: In PD-NC, GDS/CSDD-rated depression related to hyperconnectivity between dopaminergic nuclei and SgC versus controls (family-wise error corrected p-value,[pFWE]<0.01). NPI depression related to SN-LN hypoconnectivity versus non-depressed PD-NC (pFWE=0.013). In PD-CI, GDS/CSDD-rated depression related to SN-DMN and VTA-DMN hypoconnectivity versus controls (pFWE<0.05), and MRN-LN hyperconnectivity versus non-depressed PD-CI (pFWE=0.029). Anxiety related to DRN-DMN hyperconnectivity versus controls and non-anxious PD-CI (pFWE<0.05). Apathy related to DRN-DMN and DRN-LN hypoconnectivity versus non-apathetic PD-CI (pFWE<0.05). DLB presented with no NPS-related connectivity differences.
Conclusion: NPS in LBD show distinct connectivity patterns across symptom, cognitive stage, and diagnosis. Where compensatory dopaminergic hyperconnectivity may underlie mild depression in PD-NC, serotonergic and dopaminergic changes differentially contribute to NPS in PD-CI. In DLB, monoaminergic associations with NPS may be obscured by other neurotransmission changes, co-pathologies or neuronal loss. Such findings may inform targeted symptom management across the LBD spectrum.
To cite this abstract in AMA style:
L. Wright, D. Burn, J. Taylor, J. O'Brien, A. Yarnall, M. Firbank, A. Thomas, R. Lawson. Neuropsychiatric Symptoms in Lewy Body Disease: Monoaminergic Activity and Resting State Networks [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/neuropsychiatric-symptoms-in-lewy-body-disease-monoaminergic-activity-and-resting-state-networks/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/neuropsychiatric-symptoms-in-lewy-body-disease-monoaminergic-activity-and-resting-state-networks/