Dementia With Lewy Bodies Clinical Trial
Official title:
In Vivo SPECT Imaging of Vesicular Acetylcholine and Dopamine Transporters in Dementia With Lewy Bodies: Applying in Diagnostic and Identification of Pathological Subtypes.
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.
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.
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Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Health Services Research
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