In Vivo Involvement of the Cholinergic and Dopaminergic Systems in the Pathophysiology of Apathy.

Apathy is a neurocognitive syndrome characterized by reduced goal-directed behaviors, contributing to decreased patient and caregiver quality of life. Apathy pathophysiology involves disruption of cortico-striato-thalamo-cortical loops, modulated by several neurotransmitter systems including dopamine and acetylcholine, thus complexifying pharmacological management. Post-stroke apathy (PSA) can provide a proper in vivo model to study the underlying neurochemical substrates of apathy as a syndrome. The present project aims to provide a better characterization of the cholinergic and dopaminergic functioning in apathy as a syndrome. In order to precise the respective alterations of these two systems, investigators will use a positron emission tomography (PET) molecular imaging of dopaminergic (with \[18F\]-FDOPA, a marker of the decarboxylating enzyme of dopamine) and - for the first time in apathetic patients - cholinergic (with \[18F\]-FEOBV, a marker of the vesicular acetylcholine transporter) transmissions in 15 apathetic and 15 unapathetic patients 3 months after stroke, without overlapping depression. This dual imaging study may provide help in guiding therapeutic management of PSA. The functional network analysis allowed by functional MRI is crucial to complement regional neurotransmitter deficits observed with PET. Altogether, a multimodal approach in apathy, combining PET and MRI, can allow identifying which circuits of the cortico-striato-thalamo-cortical loops are disrupted and how these circuits are modulated by other neurotransmitters.

NCT Number	NCT03998852
Lead Sponsor	University Hospital, Bordeaux
Conditions	Apathy
Enrollment	30 participants
Start Date	2021-04-13
Primary Completion	2027-04-13 (estimated)
Study Completion	2027-05-13 (estimated)
Updated on ClinicalTrials.gov	2026-06-10