Pro‐Saccades Predict Cognitive Decline in Parkinson's Disease: ICICLE‐PD

Abstract

A BS TRACT: Background: Cumulative dementia incidence in Parkinson's disease (PD) is significant, with major personal and socioeconomic impacts on individuals with PD and their carers. Early identification of dementia risk is vital to ensuring optimal intervention. Saccadic deficits often distinguish neurodegenerative disorders and cognitive impairment, but their ability to predict cognitive decline in PD has yet to be determined. The aims of this study were to (1) evaluate baseline (6.4 AE 6.1 months since PD diagnosis) differences in pro-saccadic metrics between those with early PD and healthy age-matched adults; and (2) assess the ability of baseline pro-saccades to predict subsequent cognitive decline over 4.5 years. Methods: One hundred and forty-one PD and 90 agematched participants recruited at diagnosis underwent saccadometric assessment of pro-saccades at baseline and had cognition assessed at baseline, 18, 36, and 54 months. Pro-saccadic characteristics included latency, duration, amplitude, peak, and average velocity. Cognitive assessment included executive function, attention, fluctuating attention, and memory. Linear mixed-effects models examined pro-saccadic metrics as predictors of cognitive decline over 54 months. Results: Pro-saccades were significantly impaired at baseline in PD compared with controls. Pro-saccadic characteristics of latency, duration, peak, and average velocity predicted decline in global cognition, executive function, attention, and memory over 54 months in PD. In addition, only reduction in global cognition and attention were predicted by pro-saccadic metrics in age-matched adults, indicating that PD findings were not purely age related. Conclusions: Saccadic characteristics are impaired in early PD and are predictive of cognitive decline in several domains. Assessment of saccades may provide a useful non-invasive biomarker for long-term PD cognitive decline in early disease.

Saccade and Fixation Eye Movements During Walking in People With Mild Traumatic Brain Injury

“…Similar deficits in saccadic eye movements have been reported in older adults and other neurological populations while executing dynamic tasks such as walking (Dowiasch et al, 2015;Stuart et al, 2017). For example, reduced saccade frequency has been associated with deficits in cognition (Nelson et al, 2004) and slower saccade peak velocity has been found to be a predictor of attention decline in patients with Parkinson's disease (Stuart et al, 2019a).The deficits we observed in saccadic function (i.e. reduced saccade frequency, duration and peak velocity) are outcomes that have been linked to attentional processes (Stuart et al, 2017).…”

Senescence and Inflammatory Markers for Predicting Clinical Progression in Parkinson’s Disease: The ICICLE-PD Study

“…We used baseline predictors of cognitive change and therefore did not account for increase in LEDD between baseline and 36 months in this analysis. A previous publication from our group had demonstrated that LEDD did significantly increase over time, however, it was not associated with change in cognitive scores [53].…”

Freezing of saccades in dopa-responsive parkinsonian syndrome

“… 9 , 10 , 11 , 23 Previous reports demonstrated that some of these eye movement manifestations improve with dopamine replacement therapy. 29 , 30 , 31 , 32 Saccade latency in healthy subjects is generally around 200 ms. 33 Previous studies show that reflexive saccade latency in PD may have no difference from control subject, 22 , 23 , 34 or may be prolonged, particularly when associated with other conditions such as dementia or freezing of gait, 35 , 36 and that prolongation in PD is typically less than 1 s. 37 The study of Bronstein and Kennard shows that freezing could occur during a rhythmic saccade task, but the period of freezing typically lasts just 1.8 s. 38 Although our patient did not exhibit freezing of gait, there is an association between delayed saccade latency and freezing of gait in PD, 36 which is associated with degeneration of the supranuclear motor pathway. 39 , 40 , 41 …”