LRRK2 Associated Parkinson's Disease: Definition of a Clinical, Molecular and Neurophysiological Fingerprint

To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

* Clinical assessment: the following scale will be used: Movement Disorders Society- Unified PD Rating Scale (MDS-UPDRS), H\&Y staging, Unified dyskinesia rating scale (UDysRS), Non-Motor symptoms scale (NMSS), Montreal Cognitive Assessment (MoCA), Mini Mental status evaluation (MMSE), Questionnaire for impulsive-compulsive disorders (QUIP), Beck depression inventory (BDI) and Beck Anxiety Inventory (BAI). * Molecular markers assessment: A panel of pro- and anti-inflammatory mediators will be analysed (IL1-b, TNFa, IFNg, IL4, IL5, IL6, IL17, IL10) along with Neurofilament light chain

1) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Movement Disorders Society- Unified PD Rating Scale (MDS-UPDRS). The scoring basis is 0 to 4. The total score across all parts ranges from 0 (no disability) to 260 (total disability). The higher the score, the more advanced or severe the symptoms are.

2) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

The Hoehn and Yahr (H\&Y) scale. Stage 0: No signs of disease. Stage 1: Unilateral (one-sided) disease involvement only, with minimal or no functional impairment. Stage 1.5: Unilateral plus axial (neck/torso) involvement. Stage 2: Bilateral or midline involvement, without impairment of balance. Stage 2.5: Mild bilateral disease, with recovery on the clinical "pull test" (balance reflex assessment). Stage 3: Mild to moderate bilateral disease; some postural instability, but the patient remains physically independent. Stage 4: Severe disability; however, the patient is still able to walk or stand unassisted. Stage 5: Wheelchair-bound or bedridden unless aided.

3) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Unified dyskinesia rating scale (UDysRS). Scoring uses a 0 to 4 Likert-type scale, where higher scores indicate greater dyskinesia severity and impairment.

9) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Beck Anxiety Inventory (BAI). Scoring basis: ranging from 0 (not at all) to 3 (severely). Total score: 0-7: Minimal anxiety 8-15: Mild anxiety 16-25: Moderate anxiety 26-63: Severe anxiety

4) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Non-Motor symptoms scale (NMSS). Each of the 30 items is scored by multiplying its severity (0-3) by its frequency (1-4), yielding a possible subscore from 0-12 per item and a total score ranging from 0 to 360. Severity: 0 = None, 1 = Mild: symptoms present but causes little distress or disturbance to patient; 2 = Moderate: some distress or disturbance to patient; 3 = Severe: major source of distress or disturbance to patient. Frequency: 1 = Rarely (\<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time).

5) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Montreal Cognitive Assessment (MoCA). Total Score: 30 points possible. Normal Result: A score of 26 or higher is typically considered normal.

6) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Mini Mental status evaluation (MMSE). While the scoring is out of 30 points, results are often categorized to gauge severity: 25-30: Normal cognitive function. 21-24: Mild cognitive impairment. 10-20: Moderate cognitive impairment. Below 10: Severe cognitive impairment.

7) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Questionnaire for impulsive-compulsive disorders (QUIP). A rating scale measuring symptom severity. It evaluates 4 primary impulse control disorders (gambling, sexual, buying, eating) and related behaviors, scoring them from 0 to 16 based on thoughts, urges, and difficulty to control.

8) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.

时间窗: Through the study completion, about 3 years

Beck depression inventory (BDI). Each statement is assigned a value from 0 to 3. The scores for all 21 questions are added together to produce a total score between 0 and 63. Total score: 0 to 13: Minimal depression 14 to 19: Mild depression 20 to 28: Moderate depression 29 to 63: Severe depression

10) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping

时间窗: Through the study completion, about 3 years

Molecular markers assessment: A panel of pro- and anti-inflammatory mediators will be analysed (IL1-b, TNFa, IFNg, IL4, IL5, IL6, IL17, IL10) along with Neurofilament light chain. The unit of measure is pg/mL.