Memory performance will be calculated as an average Z-score of two cognitive tests; the Rey auditory verbal learning test for measuring verbal memory and the location learning test for measuring visual memory. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from both tests will be averages to form one outcome measurement representing memory performance.

Attention performance will be calculated as an average Z-score of three cognitive tests; the Stroop color-word test, the digit span and the Vienna test system reaction time measurement. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all three tests will be averages to form one outcome measurement representing attention performance.

Executive function performance will be calculated as an average Z-score of four cognitive tests; the trail making test, the Wisconsin card sorting test, the Hayling Sentence completion test and the letter fluency test. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing executive performance.

Cognitive visuospatial abilities will be calculated as an average Z-score of two cognitive tests; the Judgement of line orientation and the Map search subtest of the test of everyday attention. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing visuospatial abilities.

Language performance will be calculated as an average Z-score of two cognitive tests; the Boston Naming test and the verbal fluency test. Based on established normative data, a z-score for each test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from all tests will be averages to form one outcome measurement representing language performance.

Social cognition abilities will be represented as a z-score calculated from the performance on the FEEST; Facial Expression of Emotion Stimuli and tests. Based on established normative data, a z-score of the test outcome will be calculated, representing performance compared to an age-, gender- and educational level-matched control group. A Z-score of 0 (zero) represents a performance similar to the normative data. A positive z-score represents better performance, while a negative z-score represents worse performance. There is no minimum or maximum z-score. These z-scores from the FEEST test represents social cognition performance.

Grey matter volume as measured by structural MRI.

resting state functional MRI

cerebral blood perfusion as measured by arterial spin labeling MRI

White matter assessment as measured by diffusion weighted image

Brain hemorrhage and iron storage as measured by susceptibility weighted image

Imaging of the retinal cell layers

fecal zonulin as one of the measures of intestinal wall permeability

Taxonomic classification of gut microbiota composition based on 16s ribosomal RNA-gene sequencing.

fecal alpha1-antitrypsin as one of the measures of intestinal wall permeability

serum zonulin as one of the measures of intestinal wall permeability

serum lipopolysaccharide binding protein as one of the measures of intestinal wall permeability

multi-sugar urinary excretion test as one of the measures of intestinal wall permeability

Saliva samples will be collected for clinical-genetic subtyping based on genome wide single-nucleotide polymorphism (SNP) analysis using the Illumina Screening Array (GSA-MD)

Motor assessment measured by the Movement Disorders Society Unified Parkinson's Disease Rating Scale III, a scale describing motor performance specific for patients with Parkinson's disease. Score between 0 and 72, with a higher score indicating more severe motor impairment.

Change in cortical and subcortical cholinergic innervation over a time period of 3 years, as measured by baseline and follow-up [18F] FEOBV

Questionnaire assessing dysexecutive problems in daily life. The DEX comprises of 20 items. All items are rates in terms of frequency on a 5-point scale: 0 (never), 1 (occasionally), 2 (sometimes), 3 (fairly often), 4 (very often). Scores are summed and the total scores range from 0 to 80, with higher scores indicating greater problems with executive functioning.

Questionnaire assessing fatigue. The questionnaire consists of 38 items which can be rated on a 5-point scale. Scores are summed, with higher scores indicating more severe fatigue reported by the participant.

Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease Rating Scale (QUIP) is a questionnaire with 27 yes/no questions on impulsive-compulsive behavior. The total number of questions answered with "yes" is the main outcome measurement, with a higher score indicating more impulsive-compulsive symptoms.

The Apathy Evaluation Scale (AES) is a questionnaire assessing apathy, comprised of 18 items, describing the subject's thoughts, feelings, and activity in the past 4 weeks. All items are rates in terms on a 4-point scale. Scores are summed and the total score ranges from 0 to 72, with higher scores indicating more severe presence of apathy symptoms

Questionnaire assessing non-motor symptoms specific for patients with Parkinson's disease. The questionnaire consists of 30 yes/no questions on the occurrence of certain non-motor symptoms. The total number of questions answered with "yes" is used as outcome measure, indicating more presence of non-motor symptoms.

Questionnaire assessing Rapid eye movement (REM) sleep behavioral disorder. The questionnaire is a 10-item questionnaire with yes/no answers, of which question 6 consists of subitems. The number of questions answered with "yes" is considered the outcome measure, with a score ranging between 0 and 13. Higher scores indicate more REM sleep behavioral disorder symptoms.

Dietary assessment. Participants are asked to complete a daily diary on their intake, including detailed description of what type of food/drinks, time of day and amount of intake for three consecutive days.

Participants are asked to record their stool frequency for one week. Based on the questionnaire an average daily stoolfrequency is calculated and used as outcome measure.

Stool consistency is recorded for one week by the patients using the Bristol Stool chart. The Bristol Stool chart is a 7 point rating scale with 1 representing separate hard lumps as stool consistency and 7 entirely liquid stool. An average is calculated representing average stool consistency for the participant.