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Imaging of Vesicular Acetylcholine and Dopamine Transporters in Dementia With Lewy Bodies

Not Applicable
Completed
Conditions
Dementia With Lewy Bodies
Interventions
Other: Imaging with IBVM
Other: Imaging with DATSCAN
Behavioral: neuropsychological evaluation
Registration Number
NCT00917709
Lead Sponsor
University Hospital, Bordeaux
Brief Summary

The general aim of this research project is to determine the relationships between alterations of central cholinergic (ACh) and dopaminergic (DA) systems and neurobehavioral features of dementias with Lewy bodies (DLB).

Both clinical and neurochemical data support the view that DLB is not a homogeneous entity and it can be hypothesized that differential alterations of central ACh systems (i.e. anterior vs posterior vs striatal interneurons) in association or not with a DA nigrostriatal dysfunction could partly support the clinical heterogeneity observed in this disease. ACh in vivo imaging has been relatively underutilized to date and to our knowledge only on the postsynaptic side. Furthermore, ACh/DA interactions and their relationships with the symptomatology of DLB and related pathologies (PDD) had never been investigated.

Detailed Description

Neurochemical investigations and observations suggest a crucial physiopathological role of central ACh systems in dementias with Lewy bodies (DLB). Alterations of cholinergic neurons could be involved in the general cognitive decline (central feature) but also in fluctuating attentional performances and rapid eye movement sleep disorder as it was shown in thalamus.

Post synaptic in vivo SPECT imaging recently demonstrated an increase in muscarinic receptors in DLB patients in the occipital cortex that could be associated with the visuospatial dysfunction often reported in DLB or even in visual hallucinations.From a pharmacological point of view, the involvement of ACh systems in DLB is confirmed by the consistently reported efficacy of cholinesterase inhibitor therapy, considered as greater than in AD.

Concerning DA systems, presynaptic in vivo SPECT imaging studies of DA transporter have shown a decreased striatal uptake in DLB patients, different when compared with Parkinson's disease patients or Alzheimer's disease patients.

Strategy, procedure In this project we will use for the first time in vivo molecular imaging of presynaptic molecular target of ACh systems (VAChT) with \[123I\]-iodobenzovesamicol and of DA systems (DAT) with DATSCAN in order to better analyse the link between neurobehavioral profiles of patients and a differential alteration of ACh/DA systems in DLB.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
34
Inclusion Criteria
  • Patients: man or woman probable DLB, with and without extrapyramida syndrome
  • Healthy subjects: man or woman with no neuropsychiatric disorders
Exclusion Criteria
  • Diagnostic or therapeutic irradiation during the 12 months before SPECT imaging
  • Age less than 18 and more than 90
  • Iodine sensibility
  • Brain-vascular disease, severe brain injury, type I and II diabetes mellitus, thyroid dysfunction, chronic alcoholism
  • Pregnant and breast feeding women, women in age to procreate
  • Impossibility to undergo MRI study (pace-maker, claustrophobia)
  • Persons under guardianship, outside state to express their assent or in emergency situation
  • Healthy subjects: cognitive impairment, dementia

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
healthy volunteersImaging with IBVMhealthy volunteers
DLB with extrapyramidal syndromeneuropsychological evaluationpatients dementia with Lewy bodies with extrapyramidal syndrome
DLB with extrapyramidal syndromeImaging with IBVMpatients dementia with Lewy bodies with extrapyramidal syndrome
healthy volunteersImaging with DATSCANhealthy volunteers
DLB without extrapyramidal syndromeImaging with IBVMpatients dementia with Lewy bodies without extrapyramidal syndrome
DLB without extrapyramidal syndromeImaging with DATSCANpatients dementia with Lewy bodies without extrapyramidal syndrome
DLB with extrapyramidal syndromeImaging with DATSCANpatients dementia with Lewy bodies with extrapyramidal syndrome
DLB without extrapyramidal syndromeneuropsychological evaluationpatients dementia with Lewy bodies without extrapyramidal syndrome
healthy volunteersneuropsychological evaluationhealthy volunteers
Primary Outcome Measures
NameTimeMethod
Binding Potential (BP) quantification of each radioligandDay 1 ; Day 1 and between day 14 to 28
Secondary Outcome Measures
NameTimeMethod
Ratio dopaminergic system/cholinergic system Binding PotentialDay 1 and between day 14 to 28

Trial Locations

Locations (1)

Groupe Hospitalier Pellegrin - C.H.U. de Bordeaux

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Bordeaux, France

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