Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases
Heidi C. Riek, Donald C. Brien, Brian C. Coe, Jeff Huang, Julia E. Perkins, Rachel Yep, Paula McLaughlin, J. B. Orange, Alicia Peltsch, Angela Roberts, Malcolm A. Binns, Wendy Lou, Agessandro Abrahão, Stephen R. Arnott, Derek Beaton, Sandra E. Black, Dar Dowlatshahi, Elizabeth Finger, Corinne E. Fischer, Andrew Frank, David A. Grimes, Sanjeev Kumar, Anthony E. Lang, Jane M. Lawrence‐Dewar, Jennifer Mandzia, Connie Marras, Mario Masellis, Stephen Pasternak, Bruce G. Pollock, Tarek K. Rajji, Demetrios J. Sahlas, Gustavo Saposnik, Dallas Seitz, Christen Shoesmith, Thomas Steeves, Stephen C. Strother, Kelly M. Sunderland, Richard H. Swartz, Brian Tan, David F. Tang‐Wai, Maria Carmela Tartaglia, John Turnbull, Lorne Zinman, Douglas P. Munoz, the ONDRI Investigators, Sabrina Adamo, Robert Bartha, Courtney Berezuk, Alanna Black, Michael Borrie, Susan E. Bronskill, Dennis E. Bulman, Leanne K. Casaubon, Ben Cornish, Sherif Defrawy, Allison A. Dilliott, Roger A. Dixon, Sali M.K. Farhan, Frederico Faria, Julia Fraser, Morris Freedman, Mahdi Ghani, Barry Greenberg, Hassan Haddad, Ayman Hassan, Wendy Hatch, Rob Hegele, Melissa F. Holmes, Chris Hudson, Mandar Jog, Peter Kleinstiver, Donna Kwan, Elena Leontieva, Brian Levine, Efrem D. Mandelcorn, Ed Margolin, Bill McIlroy, Manuel Montero‐Odasso, David G. Munoz, Nuwan D. Nanayakkara, Miracle Ozzoude, Joel Ramirez, Natalie Rashkovan, John F. Robinson, Ekaterina Rogaeva, Yanina Sarquis Adamson, Christopher J.M. Scott, Michael J. Strong, Sujeevini Sujanthan, Sean Symons, Athena Theyers, Angela K. Troyer, Karen Van Ooteghem, John Woulfe, Mojdeh Zamyadi
Abstract
Abstract Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer’s disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and cerebrovascular disease; n = 391, age 40–87) and healthy controls (n = 149, age 42–87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer’s disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.