Abstract
The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson’s Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.
Highlights
Postural and gait disturbances represent therapeutically demanding symptoms with high impact on quality of life in Parkinsons disease (PD)
73% were classified as postural instability/gait difficulty (PIGD) subtypes according to PIGD scores
Our main findings were that in PD patients with advanced disease (1) serum Neurofilament light chain (NfL) levels were increased in PIGD subtype (2) PIGD patients had worse Montreal cognitive assessment (MoCA), but similar MDSUPDRS III total scores compared with non-PIGD patients and (3) increased serum NfL concentrations were incrementally associated with higher PIGD score
Summary
Postural and gait disturbances represent therapeutically demanding symptoms with high impact on quality of life in Parkinsons disease (PD). PIGD subtype patients exhibit a faster disease progression, a higher risk of cognitive decline, sleep disturbances, fatigue and autonomic dysfunction, an increased risk of freezing and falls, a shorter survival time and a worse quality of life compared with TD patients (Huang et al 2019; Kwon et al 2021; Lord et al 2020; Ren et al 2020a, b, 2021). Based on this phenomenological, symptom-orientated descriptive classification, motor subtypes change with disease progression and treatment (Luo et al 2019).
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