Cerebrospinal Fluid β-amyloid 1-42 Predicts Freezing of Gait in Early Parkinson Disease

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The cumulative incidence of freezing of gait was 16.5%, 21.0%, 28.2%, and 36.7% at the 1-, 2-, 3-, and 4-year follow-up, respectively.
The cumulative incidence of freezing of gait was 16.5%, 21.0%, 28.2%, and 36.7% at the 1-, 2-, 3-, and 4-year follow-up, respectively.

Freezing of gait among individuals in early stages of Parkinson disease can be predicted by cerebrospinal fluid β-amyloid 1-42 (CSF Aβ42), according to a study recently published in Neurology. The risk model put forth in this research allows for accurate prediction of freezing of gait within 4 years of diagnosis.

This study included the data of 393 individuals from the Parkinson's Progression Markers Initiative who were recently diagnosed with Parkinson disease, none of whom had freezing of gait at study initiation. Among criteria for inclusion were an age of ≥30 years at diagnosis, a diagnosis within the past 2 years, and 2 of the following: rigidity, an asymmetric resting tremor, bradykinesia.

Participants' clinical records, demographic features, and dopamine transporter imaging were examined as part of analysis. Cerebrospinal fluid was assessed for total tau, Aβ42, α-synuclein, phosphorylated tau181, and the baseline proportion of CSF Aβ42 to total tau. Predictive factors for freezing of gait were identified using Cox proportional hazards regression.

Among cerebrospinal fluid biomarkers, Aβ42 showed a lone association with freezing of gait during the 4-year follow-up period (hazard ratio 0.997; 95% CI, 0.996-0.999; =.009). Freezing of gait was also predicted by male sex, caudate dopamine transporter uptake, and scores on the Montreal Cognitive Assessment, the motor section of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, and postural instability gait difficulty.

By merging CSF Aβ42, postural instability gait difficulty score, and caudate dopamine transporter uptake, the study researchers compiled a model with improved discrimination compared with any one factor (area under curve=0.755; 95% CI, 0.700-0.810) as well as improved goodness of fit (χ2 statistic=63.648; P <.001).

The study researchers concluded that “CSF Aβ42 [is] a predictor for the development of [freezing of gait] in patients with early [Parkinson disease]. In addition, although our results need to be confirmed by further studies, we showed that the development of [freezing of gait] within 4 years after diagnosis of [Parkinson disease] can be predicted with acceptable accuracy with a model integrating 3 independent parameters: the [postural instability gait difficulty] score, caudate [dopamine transporter] activity, and CSF Aβ42.”


Kim R, Lee J, Kim HJ, et al. CSF β-amyloid42 and risk of freezing of gait in early Parkinson disease [published online November 30, 2018]. Neurology. doi: 10.1212/WNL.0000000000006692

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