Objective: To investigate imaging and CSF markers of disease pathology associated with anxiety in drug-naïve idiopathic Parkinson’s disease (PD) patients.

Background: Anxiety is a frequent symptom appearing early in PD; however, the underlying neuropathology remains unclear. There are limited studies investigating the aetiology of anxiety in early stages of PD.

Method: The Parkinson’s Progression Markers Initiative database was utilised to identify 423 drug-naïve PD patients. The severity of anxiety was assessed using the State-Trait Anxiety Inventory (STAI) based on the 2 subscales; the State Anxiety Scale (S-Anxiety), which evaluates the current state of anxiety, and the Trait Anxiety Scale (T-Anxiety) which evaluates relatively stable aspects of ‘anxiety proneness’. The relationship between grey matter volumetric loss (regional-based morphometry), microstructural changes (diffusion tensor imaging), and CSF biomarkers with S-Anxiety and T-Anxiety was investigated in limbic regions-of-interest, controlling for age, disease duration and depression (geriatric depression scale). P values were FDR corrected.

Results: Based on a cut-off ≥40 for clinically significant anxiety, the prevalence of S-Anxiety was 25% (n=104) and T-Anxiety was 20% (n=85) in the drug-naïve PD patients. Lower CSF amyloid-β42 levels correlated with higher S-Anxiety (r=-0.14; P=0.007) and T-Anxiety (r=-0.16; P=0.004) scores; while lower α-synuclein (r=-0.16; P=0.004) and total tau (r=-0.14; P=0.008) levels correlated with higher S-Anxiety scores. Higher T-Anxiety was associated with decreased fractional anisotropy in the accumbens (r=-0.19; P=0.018), amygdala (r=-0.19; P=0.019), thalamic primary sensory nuclei (r=-0.19; P=0.020), midbrain (r=-0.18; P=0.021) and the temporal cortex (r=-0.21; P=0.011). Grey matter volumetric loss in the temporal (r=-0.12; P=0.023) and insula (r=-0.12; P=0.015) cortex, midbrain (r=-0.15; P=0.003), median raphe (r=-0.13; P=0.011) and locus coeruleus (r=-0.11; P=0.035) correlated with the severity of T-Anxiety.

Conclusion: These results suggest that in early PD anxiety could be associated with structural and microstructural damage in the limbic system and with abnormal protein accumulation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-markers-of-anxiety-in-drug-naive-parkinsons-disease/