Objective: To evaluate the influence of comorbidity on clinical phenotype, dopaminergic function and CSF biomarkers in a population of de novo Parkinson’s disease (PD) patients.

Background: Whilst neurodegeneration of the substantia nigra is the primary contributor to cardinal motor symptoms of PD, it is unclear whether co-occurring comorbidities may also be contributory to PD pathology, and whether they have an impact on clinical phenotype. Though several studies have established that PD is accompanied by substantial comorbidity, the impact of comorbidity on motor and non-motor symptoms, imaging and CSF biomarkers remains to be explored.

Methods: Using the Parkinson’s Progression Marker’s Initiative database, 366 PD patients that had data on comorbidity were extracted and divided into three groups of 0-1, 2-4 or ≥5 comorbidities. Comorbidity was evaluated using a semi-structured questionnaire and correlated with motor and non-motor features, [¹²³I]FP-CIT SPECT molecular imaging and CSF biomarkers.

Results: Thirty-six PD patients had 0-1 comorbidity, 162 had 2-4 and 168 had ≥5. Compared to those who had 0-1 or 2-4 comorbidities, PD patients with ≥5 comorbidities were significantly older (p=0.003 vs 0-1; p=0.006 vs 2-4) with a longer disease duration (p=0.05 vs 0-1; p=0.006 vs 2-4) and exhibited higher burden of non-motor symptoms (MDS-UPDRS part 1, p=0.011 vs 0-1; p=0.027 vs 2-4) and autonomic dysfunction (SCOPA-AUT, p=0.005 vs 0-1; p=0.001 vs 2-4). Among non-motor symptoms, comorbidity was correlated with anxiety (Pearson’s Correlation [C]=0.107, p=0.042), apathy (C=0.134, p=0.010), sleep problems (C=0.123, p=0.019), sleepiness (C=0.236, p<0.0001), constipation (C=0.154, p=0.003), dizziness (C=0.104, p=0.048), and fatigue (C=0.208, p<0.0001). There was no difference in motor burden (MDS-UPDRS part 3, H&Y stage), nigrostriatal dysfunction or any CSF biomarkers between PD comorbidity groups.

Conclusions: Our study highlights the detrimental impact of health comorbidities on PD patient’s non-motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comorbidity-and-parkinsons-disease-phenotype-dopaminergic-function-and-csf-biomarkers/