Dataset Information

Decrease in A?42 predicts dopa-resistant gait progression in early Parkinson disease.

ABSTRACT:

Objective

This prospective observational study investigates the role of CSF biomarkers in predicting progression of dopa-resistant gait impairments in Parkinson disease (PD) in the first 36 months from diagnosis.

Methods

Quantitative gait analysis was carried out longitudinally using an instrumented walkway (GAITRite) in 108 people with PD and 130 age-matched controls. A subgroup of 44 people with PD underwent lumbar puncture from which a battery of CSF biomarkers was measured: ?-amyloid 1-42 and 1-40 (A?42 and A?40), total and phosphorylated tau protein (t-tau/p-tau₁₈₁), and ?-synuclein (?Syn). Linear mixed models examined the association between CSF and dopa-resistant gait characteristics (defined as substantial progression despite optimal medication).

Results

Low baseline CSF A?42, and to a lesser extend A?40, predicted decline in gait characteristics in the first 3 years following diagnosis, independently explaining up to 12% of progression of step time variability (single task) and step length variability (dual-task). Interestingly, these findings were independent of age and cognition.

Conclusions

These findings implicate underlying amyloid pathology in neural networks involved in locomotor control. Results suggest that disturbed A? metabolism may be a biomarker for dopa-resistant gait impairments in early PD. Our findings raise interesting questions regarding therapeutic interventions such as compounds or molecules aimed at reducing amyloid burden to mitigate gait disturbance in early PD and potentially falls risk. Finally, progression of discrete gait characteristics suggests they may have potential as clinical biomarkers of pathology and disease progression.

SUBMITTER: Rochester L

PROVIDER: S-EPMC5395075 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Decrease in Aβ42 predicts dopa-resistant gait progression in early Parkinson disease.

Rochester Lynn L Galna Brook B Lord Sue S Yarnall Alison J AJ Morris Rosie R Duncan Gordon G Khoo Tien K TK Mollenhauer Brit B Burn David J DJ

Neurology 20170322 16

<h4>Objective</h4>This prospective observational study investigates the role of CSF biomarkers in predicting progression of dopa-resistant gait impairments in Parkinson disease (PD) in the first 36 months from diagnosis.<h4>Methods</h4>Quantitative gait analysis was carried out longitudinally using an instrumented walkway (GAITRite) in 108 people with PD and 130 age-matched controls. A subgroup of 44 people with PD underwent lumbar puncture from which a battery of CSF biomarkers was measured: β- ...[more]

PMID: 28330963

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