CSF β-amyloid
            <sub>42</sub>
            and risk of freezing of gait in early Parkinson disease

Kim, Ryul; Lee, Joongyub; Kim, Han Joon; Kim, Aryun; Jang, Mijung; Jeon, Beomseok; Kang, Un Jung

doi:10.1212/wnl.0000000000006692

Cited by 45 publications

(70 citation statements)

References 34 publications

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“…Zhang et al's study followed 248 early PD patients without FOG at baseline for 3 years and found that patients with a lower education level (≤9 years of education) were more prone to have FOG (OR = 0.012, P < 0.001) [22]. This study provided an explanation that patient with a higher education had a better understanding of PD and Onset age [16, 17, 20-23, 25, 26] Age [18,19,[21][22][23][24][25] Baseline longer disease duration [20,23] [ [16][17][18][19]21] b…”

Section: Low Education Levelmentioning

confidence: 83%

“…A total of 11 longitudinal follow-up studies were reviewed and summarized (Table 1). For these studies, cox proportional-hazards regression analyses [16,17,20,26] or logistic regression analysis [18,19,[22][23][24][25] were performed to identify the factors predictive of FOG except one study that used generalized estimating equations [21]. Here, we elaborated the risk factors including demographic information, motor symptoms, non-motor symptoms, neuroimaging, fluid parameters, and medication use.…”

Section: Risk Factors For Developing Fogmentioning

confidence: 99%

“…Two studies using the Parkinson's Progression Markers Initiative (PPMI) data included 390 (393) patients with newly diagnosed PD at baseline [16,17]. During a median follow-up of 4.0 years, male sex was found to be an independent risk factor of FOG (Hazard ratio (HR) = 1.512, P = 0.046) [16]. This finding is consistent with another study that included 41 patients with a mean follow-up disease duration of 9.51 ± 3.18 years [25].…”

Section: Demographic Risk Factors Male Sexmentioning

confidence: 99%

“…Insomnia [22], daytime sleepiness [24] RBD [16,18,24], daytime sleepiness [16,23] Others Speech problems [20], hallucination [23] Neuroimaging and fluid parameters…”

Section: Sleepmentioning

confidence: 99%

“…Lower striatal DAT update [16,17,25] White matter hyperintensities [26] CSF Aβ42 [16] Medication use…”

Section: Sleepmentioning

confidence: 99%

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

Gao

Tan

et al. 2020

Transl Neurodegener

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Background: Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers. The main focus of this review is to summarize the possible mechanisms underlying FOG, the risk factors for screening and predicting the onset of FOG, and the clinical trials involving various therapeutic strategies. In addition, the limitations and recommendations for future research design are also discussed. Main body: In the mechanism section, we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG. In the risk factor section, gait disorders, PIGD phenotype, lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence. In the treatment section, we summarized the clinical trials of pharmacological and non-pharmacological treatments. Despite the limited effectiveness of current medications for FOG, especially levodopa resistant FOG, there were some drugs that showed promise such as istradefylline and rasagiline. Non-pharmacological treatments encompass invasive brain and spinal cord stimulation, noninvasive repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS), and physiotherapeutic approaches including cues and other training strategies. Several novel therapeutic strategies seem to be effective, such as rTMS over supplementary motor area (SMA), dual-site DBS, spinal cord stimulation (SCS) and VNS. Of physiotherapy, wearable cueing devices seem to be generally effective and promising.Conclusion: FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise.

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Section: Low Education Levelmentioning

confidence: 83%

Section: Risk Factors For Developing Fogmentioning

confidence: 99%

Section: Demographic Risk Factors Male Sexmentioning

confidence: 99%

“…Insomnia [22], daytime sleepiness [24] RBD [16,18,24], daytime sleepiness [16,23] Others Speech problems [20], hallucination [23] Neuroimaging and fluid parameters…”

Section: Sleepmentioning

confidence: 99%

“…Lower striatal DAT update [16,17,25] White matter hyperintensities [26] CSF Aβ42 [16] Medication use…”

Section: Sleepmentioning

confidence: 99%

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

Gao

Tan

et al. 2020

Transl Neurodegener

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Pedunculopontine Nucleus Microstructure Predicts Postural and Gait Symptoms in Parkinson's Disease

et al. 2020

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BackgroundThere is an urgent need to identify individuals at risk of postural instability and gait difficulties, and the resulting propensity for falls, in Parkinson's disease.ObjectivesGiven known relationships between posture and gait and degeneration of the cholinergic pedunculopontine nucleus, we investigated whether metrics of pedunculopontine nucleus microstructural integrity hold independent utility for predicting future postural instability and gait difficulties and whether they could be combined with other candidate biomarkers to improve prognostication of these symptoms.MethodsWe used stereotactic mapping of the pedunculopontine nucleus and diffusion tensor imaging to extract baseline pedunculopontine nucleus diffusivity metrics in 147 participants with Parkinson's disease and 65 controls enrolled in the Parkinson's Progression Markers Initiative. We also recorded known candidate markers of posture and gait changes: loss of caudate dopamine and CSF β‐amyloid 1‐42 levels at baseline; as well as longitudinal progression motor symptoms over 72‐months.ResultsSurvival analyses revealed that reduced dopamine in the caudate and increased axial diffusivity in the pedunculopontine nucleus incurred independent risk of postural instability and gait difficulties. Binary logistic regression and receiver operating characteristics analysis in 117 participants with complete follow‐up data at 60 months revealed that only pedunculopontine nucleus microstructure provided more accurate discriminative ability for predicting future postural instability and gait difficulties than clinical and demographic variables alone.ConclusionDopaminergic and cholinergic loss incur independent risk for future postural instability and gait difficulties, and pedunculopontine nucleus microstructure can be used to prognosticate these symptoms from early Parkinson's disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design

et al. 2023

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BackgroundIn Parkinson's disease (PD), gait and balance is impaired, relatively resistant to available treatment and associated with falls and disability. Predictive models of ambulatory progression could enhance understanding of gait/balance disturbances and aid in trial design.ObjectivesTo predict trajectories of ambulatory abilities from baseline clinical data in early PD, relate trajectories to clinical milestones, compare biomarkers, and evaluate trajectories for enrichment of clinical trials.MethodsData from two multicenter, longitudinal, observational studies were used for model training (Tracking Parkinson's, n = 1598) and external testing (Parkinson's Progression Markers Initiative, n = 407). Models were trained and validated to predict individuals as having a “Progressive” or “Stable” trajectory based on changes of ambulatory capacity scores from the Movement Disorders Society Unified Parkinson's Disease Rating Scale parts II and III. Survival analyses compared time‐to‐clinical milestones and trial outcomes between predicted trajectories.ResultsOn external evaluation, a support vector machine model predicted Progressive trajectories using baseline clinical data with an accuracy, weighted‐F1 (proportionally weighted harmonic mean of precision and sensitivity), and sensitivity/specificity of 0.735, 0.799, and 0.688/0.739, respectively. Over 4 years, the predicted Progressive trajectory was more likely to experience impaired balance, loss of independence, impaired function and cognition. Baseline dopamine transporter imaging and select biomarkers of neurodegeneration were significantly different between predicted trajectory groups. For an 18‐month, randomized (1:1) clinical trial, sample size savings up to 30% were possible when enrollment was enriched for the Progressive trajectory versus no enrichment.ConclusionsIt is possible to predict ambulatory abilities from clinical data that are associated with meaningful outcomes in people with early PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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CSF β-amyloid ₄₂ and risk of freezing of gait in early Parkinson disease

Cited by 45 publications

References 34 publications

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

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

Pedunculopontine Nucleus Microstructure Predicts Postural and Gait Symptoms in Parkinson's Disease

Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design

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CSF β-amyloid 42 and risk of freezing of gait in early Parkinson disease

Cited by 45 publications

References 34 publications

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

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

Pedunculopontine Nucleus Microstructure Predicts Postural and Gait Symptoms in Parkinson's Disease

Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design

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CSF β-amyloid ₄₂ and risk of freezing of gait in early Parkinson disease