Parkinson's disease outcome

Axial motor signs-including gait impairment, postural instability and postural abnormalities-are common and debilitating symptoms in patients with advanced Parkinson disease. Dopamine replacement therapy and physiotherapy provide, at best, partial relief from axial motor symptoms.

The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement.

see Parkinsons Disease Questionnaire.

Commonly used neuroimaging biomarkers in Parkinson's disease (PD) are useful for diagnosis but poor at predicting outcomes. We explored whether an atrophy pattern from whole-brain structural MRI, measured in the drug-naïve early stage, could predict PD prognosis.

362 de novo PD patients with T1-weighted MRI (n = 222 for the main analysis, 140 for the validation analysis) were recruited from the Parkinson's Progression Markers Initiative (PPMI). We investigated a previously identified PD-specific network atrophy pattern as a potential biomarker of disease severity and prognosis. Progression trajectories of motor function (MDS-UPDRS-part III), cognition (Montreal Cognitive Assessment (MoCA)), and a global composite outcome measure were compared between atrophy tertiles using mixed effect models. The prognostic value of the MRI atrophy measure was compared with 123I ioflupane Single-photon emission computed tomography, the postural-instability-gait-disturbance score, and cerebrospinal fluid markers.

After 4.5 years follow-up, PD-specific atrophy network score at baseline significantly predicted change in UPDRS-part III (r = -0.197, p = .003), MoCA (r = 0.253, p = .0002) and global composite outcome (r = -0.249, p = .0002). Compared with the 3rd tertile (i.e. least atrophy), the tertile with the highest baseline atrophy (i.e. the 1st tertile) had a 3-point annual faster progression in UPDRS-part III (p = .012), faster worsening of posture-instability gait scores (+0.21 further annual increase, p < .0001), faster decline in MoCA (-0.74 further annual decline in MoCA, p = .0372) and a + 0.38 (p = .0029) faster annual increase in the global composite z-score. All findings were replicated in a validation analysis using 1.5T MRI. Receiver operating characteristic analysis confirmed the superiority of the MRI biomarker, although it had modest AUC values (0.63). By comparison, the other biomarkers were limited in their ability to predict prognosis either in the main or validation analysis.

A PD-specific network atrophy pattern predicts progression of motor, cognitive, and global outcome in PD, and is a better predictor of prognosis than any of the other tested biomarkers. Therefore, it has potential as a prognostic biomarker for clinical trials of early PD 1).

Fear of progression (FoP) is a reactive, conscious concern about chronic disease progression and its consequences which may limit the quality of life substantially. Only one study has examined FoP in Parkinson's disease (PD), showing the second highest FoP scores among chronic diseases.

Objective: To examine FoP prevalence and to exploratorily analyze determinants of FoP in PD.

Methods: Within a multicenter cross-sectional study, 120 PD inpatients (age: 64.45±9.20; 60.8% male; UPDRS-III: 28.86±16.12) were examined with the FoP questionnaire (FoP-Q; max. 20 points). Stepwise multiple linear regression analysis examined sociodemographic, clinical, and (neuro-) psychological determinants of FoP.

Results: With a mean FoP-Q score of 8.08±2.17, 63.0% of the patients were classified with moderate FoP and 17.6% with dysfunctional (i.e., severe) FoP. The highest scores were shown for the subscale 'loss of autonomy'. Increased levels of anxiety, less self-efficacy, female gender, current employment, and lower health literacy were identified as significant determinants associated with FoP.

With more than 80% of patients showing moderate to dysfunctional Fear of progression, it must be regarded as a frequent symptom of Parkinson's Disease, which needs to be further understood and addressed in clinical practice. Clinical parameters like Parkinson's Disease duration and severity were no determinants for Fear of progression, indicating that Fear of progression awareness must be considered by professionals at all disease stages 2).

Zeighami Y, Fereshtehnejad SM, Dadar M, Collins DL, Postuma RB, Dagher A. Assessment of a prognostic MRI biomarker in early de novo Parkinson's disease. Neuroimage Clin. 2019 Aug 19;24:101986. doi: 10.1016/j.nicl.2019.101986. [Epub ahead of print] PubMed PMID: 31514113.
Folkerts AK, Haarmann L, Nielsen J, Saliger J, Eschweiler M, Karbe H, Allert N, Vida V, Trenkwalder C, Kruse A, Oelsner H, Ebersbach G, Kalbe E. Fear of Progression Is Determined by Anxiety and Self-Efficacy but not Disease-Specific Parameters in Patients with Parkinson's Disease: Preliminary Data from a Multicenter Cross-Sectional Study. J Parkinsons Dis. 2022 Sep 30. doi: 10.3233/JPD-223314. Epub ahead of print. PMID: 36189603.
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