New paper in Parkinsonism & Related Disorders: “The patient’s perspective: the effect of levodopa on Parkinson symptoms”

BACKGROUND:

Dopaminergic medication adjustments in Parkinson‘s disease are often solely based on patient reports. However, it is unclear how well patient-based ratings of the levodopa response correlate with clinician-based ratings, and whether this correlation differs between motor symptoms. Here we compare patient-clinician agreement for the effect of levodopa on resting tremor and bradykinesia/rigidity. Furthermore, given patients’ reports that tremor is most troublesome during stress, we test for differences in patient-clinician agreement between tremor at rest and stress-induced tremor.

METHODS:

We included 42 tremulous Parkinson patients, who were clinically rated (using the MDS-UPDRS) in a practically defined OFF-state and after levodopa-benserazide 200/50 mg. Using accelerometry, we quantified the effect of dopaminergic medication and behavioral context (rest vs. cognitive stress) on tremor intensity. Patients rated medication effects on tremor and bradykinesia/rigidity using visual analogue scales.

RESULTS:

There was only moderate patient-clinician agreement for the effect of levodopa on bradykinesia/rigidity (R2 = 0.18; p < 0.01), and a tendency towards larger agreement for tremor (R2 = 0.44; p < 0.001; difference between correlation coefficients: z = 1.64; p = 0.051). Patient ratings of tremor changes correlated significantly better with accelerometry for tremor during cognitive stress (R2 = 0.35; p < 0.001) vs. tremor at rest (R2 = 0.12; p < 0.05; difference: z = -2.35, p < 0.01).

CONCLUSION:

The moderate correlations between patient ratings and clinical/accelerometry changes indicate the need for methods to better monitor symptom severity and impairments in daily life, for example wearable sensors. Our findings also suggest that context matters: Parkinson patients’ subjective experience of levodopa effectiveness on tremor was largely based on the ability of levodopa to reduce tremor during cognitive stress.

 

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Paper in CNS Neuroscience & Therapeutics: “Cognitive stress reduces the effect of levodopa on Parkinson’s resting tremor”

AIMS:

Resting tremor in Parkinson’s disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of resting tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on resting tremor.

METHODS:

Tremulous PD patients (n = 69) were measured in two treatment conditions (OFF vs. ON levodopa) and in two behavioral contexts (rest vs. cognitive co-activation). Using accelerometry, we tested the effect of both interventions on tremor intensity and tremor variability.

RESULTS:

Levodopa significantly reduced tremor intensity (across behavioral contexts), while cognitive co-activation increased it (across treatment conditions). Crucially, the levodopa effect was significantly smaller during cognitive co-activation than during rest. Resting tremor variability increased after levodopa and decreased during cognitive co-activation.

CONCLUSION:

Cognitive stress reduces the levodopa effect on Parkinson’s tremor. This effect may be explained by a stress-related depletion of dopamine in the basal ganglia motor circuit, by stress-related involvement of nondopaminergic mechanisms in tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment. Clinical tremor assessments under evoked cognitive stress (e.g., counting tasks) may avoid overestimation of treatment effects in real life.

 

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