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Table 1 A detail summary of risk factors for FOG development in Parkinson’s disease

From: Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Main findingsParticipantsAssessmentFollow-up durationFOG defineRef
CSF Aβ42 was a predictor of FOG in patients with early PD. PIGD score, caudate DAT uptake, and CSF Aβ42 together could predict FOG within 4 years after diagnosis of PD (AUC = 0.755).PPMI database (393 early do novo PD without FOG at baseline)CSF (Aβ42, α-synuclein, t-tau, p-tau, Aβ42/ t-tau); motor; non-motor (olfactory, sleep, cognition, depression, anxiety, autonomic function); DAT imaging (striatal region)Median 4.0 yearsMDS-UPDRS item 2.13 or item 3.11 ≥ 1[16]
DAT uptakes in the caudate nucleus and putamen predicted the development of FOG. Male sex, higher PIGD score, and lower MoCA score were also significant predictors of FOG.PPMI data (390 early do novo PD without FOG at baseline)DAT imaging (striatal region); motor; cognitionMedian 4.0 yearsMDS-UPDRS item 2.13 or item 3.11 ≥ 1[17]
FOGQ total score and the anxiety score were the strongest predictors, and using only these two factors could significantly predict FOG in the next 15 months with 82% accuracy.221 PD in which 88 patients had FOG at baselineMotor; non-motor (cognition, anxiety, depression, sleep); medication useMean 14 monthsFOGQ item 3 ≥ 1[18]
Depressive, gait speed and UPDRS-III (off vs. on) were the independent predictors of future FOG.57 PD patients without FOG at baselineMotor; non-motor (sleep, cognition, autonomic, depression, and others); medication useMean 5 yearsNFOGQ (item1 = 1) and objective observation[19]
Increased risk: Onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration; absence of tremor. Decreased risk: Deprenyl treatmentDATATOP data (800 early PD in which 57 patients had FOG at study entry)Motor; non-motor (speech, cognition, depression); initial symptomsMean 14 ± 5 monthsUPDRS II-item14 ≥ 1[20]
Motor fluctuations, higher levodopa dose were independent risk factors; none of the cardinal features independently predicted FOG.232 PD without FOG at baselineMotor and motor complication; non-motor (psychosis (UPDRS I item2, hallucinations or delusions), cognition); medication use12 yearsUPDRS II-item14 ≥ 1[21]
Lower education, akinetic-rigid style, not using dopamine receptor agonists, sleep disorders (insomnia); cognitive disturbances were predictors of FOG.248 early PD without FOG at baselineMotor; non-motor (anxiety; depression); medication use;3 yearsFOGQ item 3 ≥ 1 and objective observation[22]
Longer disease duration, visuospatial function deterioration, onset in lower limbs, presence of festination, falls, and hallucinations were independent predictors of FOG.225 PD without FOG at baselineMotor (including festination and fall); non-motor (anxiety, depression, cognition); medication use;3 yearsFOGQ item 3 ≥ 1 and objective observation[23]
Baseline processing speed, learning and daytime sleepiness were predictive of FOG.PPMI database (50 PD + FOG, and 50 PD-FOG at the fourth year)Motor; non-motor (cognition, anxiety, depression, sleep)4 yearsMDS-UPDRS item 2.13 ≥ 1[24]
A more severe depletion of presynaptic dopamine (low 123I-FP-CIT binding in the putamen and striatum) in early PD predicted FOG41 early PD without FOG at baselineMotor (including falls) and motor complication; DAT imaging (striatal region); medication use9.51 ± 3.18 yearsUPDRS II-item14 ≥ 1[25]
PD group with moderate to severe WMH showed a higher risk of developing FOG (HR, 3.29; 95% CI, 1.79–6.05; P < 0.001) than the PD patients with minimal WMH.268 patients with de novo PD without FOGMRI WMH; motor (UPDRS-III, phenotype); non-motor (olfactory, cognition, depression) DAT imaging; medication; vascular risk factors>  3 yearsInquiry and observation[26]
  1. A total of 11 longitudinal follow-up studies were reviewed and summarized. Main findings, recruited participants and their FOG define criteria, assessment parameters, follow-up duration were all included
  2. CSF Cerebrospinal fluid, FOG Freezing of gait, PD Parkinson’s disease, PIGD Postural instability and gait difficulty, DAT Dopamine transporter, AUC Area under the ROC curve, PPMI Parkinson’s Progression Markers Initiative, MDS-UPDRS Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, MoCA Montreal Cognitive Assessment, FOGQ Freezing of Gait-Questionnaire, NFOGQ New Freezing of Gait Questionnaire, DATATOP Deprenyl and tocopherol antioxidative therapy of parkinsonism, WMH White matter hyperintensitie