VAChT

Progressive age-related cognitive deficits occurring in both AD and DS have been connected to the degeneration of several neuronal populations, but mechanisms are not fully elucidated. The most consistent neuronal losses throughout the progression of AD are seen in cholinergic neurons where these losses negatively affect cognition, particularly in attention, learning, and memory formation. Evidence of reduced cholinergic integrity in DS is largely limited to animal models and post-mortem human data. The investigators propose to use molecular, functional, and structural biomarkers to assess the cholinergic integrity in adults with DS. The investigators anticipate using the data gathered in this pilot study to inform future study designs to determine AD risk stratification in DS by identifying individuals who show an accelerated decline in cholinergic integrity that correlates with cognitive and neurobehavioral changes. Also, our cholinergic biomarkers may identify whether individuals with DS are likely to respond to pro-cholinergic interventions, including the novel cholinergic modulators that are being developed to enhance cholinergic-sensitive cognitive functioning. The investigators anticipate using the data gathered here to inform future treatment studies in TRC-DS and beyond where novel cholinergic treatments may offer opportunities for early intervention in DS and be complementary to disease-modifying approaches such as anti-amyloid treatments.

Although PD is considered predominantly as a motor disease caused by loss of dopaminergic neurons, multiple studies indicate that cholinergic dysfunction already starts in early PD and is crucial for the development of dementia in addition to motor symptoms.Because of its crucial role in CNS functioning and neurodegenerative disorders, including PD, it is of great importance to get a better understanding of the cholinergic functioning in the brain. Pathways of acetylcholine synthesis, transport and release provide possible targets for in vivo imaging of the cholinergic system. However,previous approaches are considered as indirect biomarkers of cholinergic terminal integrity because they measure both pre- and post-synaptic expressions. The novel vesicular acetylcholine transporter (VAChT) tracer [18F]Fluoroethoxy-Benzovesamicol ([18F]FEOBV) provides a more direct measurement of presynaptic cholinergic function. The use of [18F]FEOBV as a Positron Emission Tomography (PET) imaging marker of cholinergic innervations has, however, only been studied in healthy human volunteers and no data is available on patients.
With this study the differences in cholinergic function between PD patients and healthy aged-matched volunteers will be quantified. In addition the test-retest variability will be determined

The main objectives of this protocol are as follows:
To assess the sensitivity and specificity of ANAM-PD in detecting cognitive status in patients with Parkinson disease (PD) and healthy controls (HC).
To validate the specific individual domains of the ANAM-PD cognitive battery by comparisons to available standardized cognitive evaluation scales administered to the patients with Parkinson disease with and healthy control subjects.
To evaluate the reliability of the ANAM-PD battery of tests by comparing repeated administrations of the ANAM-PD battery on a sub-set of subjects with Parkinson disease and healthy controls.
To characterize cholinergic neurotransmission through imaging the vesicular acetylcholine transporter binding with 123Iodobenzovesamicol (IBVM) and SPECT in PD patients and healthy controls.