Overall aim |
To discover and validate biomarkers for Parkinson’s disease (PD) subtypes, progression and pathophysiology. |
General |
1. |
To combine clinical assessment of both motor and non-motor symptoms with outcome measures across multiple domains, including neuropsychology, gastroenterology and ophthalmology. |
Cognition |
2. |
To establish the relationship between cognitive impairment and cholinergic innervation in treatment-naïve PD patients. |
3. |
To determine the relationship between cognitive impairment and dopaminergic innervation in treatment-naïve PD patients. |
4. |
To investigate the progression of the cognitive profile of de novo PD patients and determine the incidence of PD associated mild cognitive impairment over time. |
5. |
To identify potential biomarkers of longitudinal cognitive decline within the brain neurotransmitter system. |
6. |
To identify potential biomarkers of longitudinal cognitive decline within the brain functional connectivity and white matter tracts using functional MRI and diffusion tensor imaging. |
Gastrointestinal function |
7. |
To establish the gut microbiome composition of treatment-naïve PD subjects compared to age- and sex-matched control subjects. |
8. |
To determine the possible influence of dopaminergic medication on gut microbiome composition in PD after 1 year of dopaminergic medication use. |
9. |
To determine the specificity of gut microbiome changes for PD diagnosis by additionally correcting for possible confounders other than dopaminergic medication, eg. dietary habits, presence and severity of constipation, non-dopaminergic medication, disease history. |
10. |
To identify potential biomarkers of PD within the gut microbiome, ranging in complexity from the identification of key microbes, suitable for rapid quantification, to complex microbial fingerprints. Potential biomarkers of PD should be further validated for their specificity compared to other neurological and neurodegenerative disorders, as well as their robustness in other PD microbiome studies. |
11. |
To correlate changes in gut microbiome composition in PD to specific PD subtypes in terms of clinical presentation, rate of progression, genetic risk profile and/or imaging parameters. |
12. |
To investigate the gut permeability of treatment-naïve PD subjects through the assessment of fecal and serum markers, as well as a urinary sugar excretion test. |
Vision |
13. |
To determine retinal cell layer thickness in treatment-naïve PD subjects compared to age- and sex-matched control subjects. |
14. |
To determine retinal cell layer thickness in treatment-naïve PD subjects compared to age- and sex-matched glaucoma subjects. |
15. |
To determine clinical correlates of structural retinal changes and functional tests, including visual, motor, non-motor and neuropsychological scores. |
16. |
To determine the effect of dopaminergic medication on retinal layer thickness and visual function. |