Imaging of Vesicular Acetylcholine and Dopamine Transporters in Dementia With Lewy Bodies
Condition: Dementia With Lewy Bodies
MeSH terms: Dementia; Lewy Body Disease
Study type: Interventional

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.
    

Intervention name(s): Imaging with IBVM; Imaging with DATSCAN; neuropsychological evaluation
Intervention type(s): Other; Other; Behavioral
Intervention description(s): in vivo molecular imaging of presynaptic molecular target of cholinergic systems with [123I]-iodobenzovesamicol; in vivo molecular imaging of presynaptic molecular target of dopaminergic systems (DAT) with DATSCAN; neuropsychological evaluation using neuropsychological tests
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: dementia with Lewy bodies; imaging; acetylcholine; dopamine; IBVM; DATSCAN