Saccadic eye movement variables as biomarkers for cognitive decline in elderly individuals.

Alzheimer's disease (AD) is the leading cause of Dementia, and mild cognitive impairment (MCI) is often considered a precursor to the development of AD dementia and other types of Dementia. Biomarkers such as amyloid beta are specific and sensitive in identifying AD and can identify individuals who have biological evidence of the disease but have no symptoms, but clinicians and researchers may not easily use them on a large scale. Ocular biomarkers, such as those obtained through eye tracking (ET) technology, have the potential as a diagnostic tool due to their accuracy, affordability, and ease of use. In this study, we show that eye movement (EM) metrics from an interleaved Pro/Anti-saccade (PS/AS) ET task can differentiate between cognitively normal (CN) and MCI subjects and that the presence of Aß brain deposits, a biomarker of AD, significantly affects performance on these tasks. Individuals with Aß deposits (Aß+) performed worse than those without (Aß-). Our findings suggest that eye-tracking measurements may be a valuable tool for detecting amyloid brain pathology and monitoring changes in cognitive function in CN and MCI individuals over time.Clinical Relevance- The PS/AS paradigm, which measures saccadic eye movements, can accurately detect subtle cognitive impairments and changes in the brain associated with Alzheimer's disease in CN and MCI individuals. This makes it a valuable tool for identifying individuals at risk for cognitive decline and tracking changes in cognitive function over time.

Eye movement changes as an indicator of mild cognitive impairment.

Background: Early identification of patients at risk of dementia, alongside timely medical intervention, can prevent disease progression. Despite their potential clinical utility, the application of diagnostic tools, such as neuropsychological assessments and neuroimaging biomarkers, is hindered by their high cost and time-consuming administration, rendering them impractical for widespread implementation in the general population. We aimed to develop non-invasive and cost-effective classification models for predicting mild cognitive impairment (MCI) using eye movement (EM) data. Methods: We collected eye-tracking (ET) data from 594 subjects, 428 cognitively normal controls, and 166 patients with MCI while they performed prosaccade/antisaccade and go/no-go tasks. Logistic regression (LR) was used to calculate the EM metrics' odds ratios (ORs). We then used machine learning models to construct classification models using EM metrics, demographic characteristics, and brief cognitive screening test scores. Model performance was evaluated based on the area under the receiver operating characteristic curve (AUROC). Results: LR models revealed that several EM metrics are significantly associated with increased odds of MCI, with odds ratios ranging from 1.213 to 1.621. The AUROC scores for models utilizing demographic information and either EM metrics or MMSE were 0.752 and 0.767, respectively. Combining all features, including demographic, MMSE, and EM, notably resulted in the best-performing model, which achieved an AUROC of 0.840. Conclusion: Changes in EM metrics linked with MCI are associated with attentional and executive function deficits. EM metrics combined with demographics and cognitive test scores enhance MCI prediction, making it a non-invasive, cost-effective method to identify early stages of cognitive decline.

Inhibitory Control of Saccadic Eye Movements and Cognitive Impairment in Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) may occur due to several forms of neurodegenerative diseases and non-degenerative conditions and is associated with cognitive impairment that does not affect everyday activities. For a timely diagnosis of MCI to prevent progression to dementia, a screening tool of fast, low-cost and easy access is needed. Recent research on eye movement hints it a potential application for the MCI screening. However, the precise extent of cognitive function decline and eye-movement control alterations in patients with MCI is still unclear. Objective: This study examined executive control deficits and saccade behavioral changes in patients with MCI using comprehensive neuropsychological assessment and interleaved saccade paradigms. Methods: Patients with MCI (n = 79) and age-matched cognitively healthy controls (HC) (n = 170) completed four saccadic eye-movement paradigms: prosaccade (PS)/antisaccade (AS), Go/No-go, and a battery of neuropsychological tests. Results: The findings revealed significantly longer latency in patients with MCI than in HC during the PS task. Additionally, patients with MCI had a lower proportion of correct responses and a marked increase in inhibition errors for both PS/AS and Go/No-go tasks. Furthermore, when patients with MCI made errors, they failed to self-correct many of these inhibition errors. In addition to the increase in inhibition errors and uncorrected inhibition errors, patients with MCI demonstrated a trend toward increased correction latencies. We also showed a relationship between neuropsychological scores and correct and error saccade responses. Conclusion: Our results demonstrate that, similar to patients with Alzheimer's dementia (AD), patients with MCI generate a high proportion of erroneous saccades toward the prepotent target and fail to self-correct many of these errors, which is consistent with an impairment of inhibitory control and error monitoring. Significance: The interleaved PS/AS and Go/No-go paradigms are sensitive and objective at detecting subtle cognitive deficits and saccade changes in MCI, indicating that these saccadic eye movement paradigms have clinical potential as a screening tool for MCI.

Saccadic Eye Movement in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is the leading cause of dementia, and mild cognitive impairment (MCI) is considered the transitional state to AD dementia (ADD) and other types of dementia, whose symptoms are accompanied by altered eye movement. In this work, we reviewed the existing literature and conducted a meta-analysis to extract relevant eye movement parameters that are significantly altered owing to ADD and MCI. We conducted a systematic review of 35 eligible original publications in saccade paradigms and a meta-analysis of 27 articles with specified task conditions, which used mainly gap and overlap conditions in both prosaccade and antisaccade paradigms. The meta-analysis revealed that prosaccade and antisaccade latencies and frequency of antisaccade errors showed significant alterations for both MCI and ADD. First, both prosaccade and antisaccade paradigms differentiated patients with ADD and MCI from controls, however, antisaccade paradigms was more effective than prosaccade paradigms in distinguishing patients from controls. Second, during prosaccade in the gap and overlap conditions, patients with ADD had significantly longer latencies than patients with MCI, and the trend was similar during antisaccade in the gap condition as patients with ADD had significantly more errors than patients with MCI. The anti-effect magnitude was similar between controls and patients, and the magnitude of the latency of the gap effect varied among healthy controls and MCI and ADD subjects, but the effect size of the latency remained large in both patients. These findings suggest that, using gap effect, anti-effect, and specific choices of saccade paradigms and conditions, distinctions could be made between MCI and ADD patients as well as between patients and controls.