Trail Making Test Part B as a Preclinical Indicator and Proxy for Spatial Navigation Change in Alzheimer's Disease

Abstract

Abstract Background Preclinical Alzheimer's disease (AD) may create unrecognized risks for physical injury and death due reduction of acetylcholine and disease presence in brain areas involved with spatial navigation (SN). Possible preclinical changes in SN, such as driving, might be indicated by performance on the Trails Making Test Part B (TMT-B). This neuropsychiatric test has time to completion scores associated with at-risk driving ability.Methods A retrospective longitudinal secondary analysis with linear mixed-effects were performed on TMT-B spanning 1 to 15 years of data on cognitively normal (pre-AD) individuals who later developed AD dementia and compared to those who did not develop the disease (non-AD). Effect size analysis was performed on individual annual time points without confidence interval overlap.Results 1104 pre-AD and 14,663 non-AD participants were included from the National Alzheimer's Coordinating Center. The pre-AD individuals demonstrated scores associated with at-risk driving. The pre-AD group increased by 3.498 seconds per year, p < .001, whereas the non-AD group increased by 1.845 seconds, p < .001. Effect size range: Cohens d = .217 to .631. Pre-Ad females increased by 3.695 seconds per year, p < .001, .843 p < .001. Effect size range: Cohens d = .383 to .692. Pre-AD males increased by 3.189 seconds per year, p < .001, compared to non-AD males increase of 1.890 seconds, p < .001, with an effect size range of Cohens d = 0.259 to 0.520.Conclusion The TMT-B may serve as a preclinical screening instrument in longitudinal studies, inform further inquiry for SN risks in this population, and correlation with changes in brain acetylcholine levels