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

Nevers, Jennifer · 2023 · OpenAlex-citations

DOI: 10.21203/rs.3.rs-3318513/v1

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Summary

This study investigates whether the Trail Making Test Part B (TMT-B) can serve as a preclinical indicator and proxy for spatial navigation (SN) decline in individuals who later develop Alzheimer’s disease (AD). The research is motivated by the potential safety risks, such as impaired driving, associated with unrecognized cognitive changes during the 20- to 30-year preclinical phase of AD. The authors hypothesize that AD pathology, specifically tau-related neuronal damage in the medial temporal lobe and reduced acetylcholine levels, impairs the neural networks supporting SN. Because direct SN testing is not standard in clinical settings, the study evaluates TMT-B, a neuropsychiatric test of executive function and visuospatial processing, as a feasible screening tool for these subclinical deficits. The researchers conducted a retrospective longitudinal secondary analysis using data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. The study compared TMT-B performance over time between two groups: 1,104 individuals classified as cognitively normal who were later diagnosed with AD (pre-AD) and 14,663 individuals who remained cognitively healthy (non-AD). Data spanned up to 15 years, with participants maintaining a Clinical Dementia Rating global score of 0 throughout the analysis period. Linear mixed-effects models were used to analyze changes in TMT-B completion times, with effect sizes calculated using Glass’s delta converted to Cohen’s d values. The analysis included stratification by sex to examine potential differences in progression. The results demonstrated that the pre-AD group exhibited a significantly faster decline in TMT-B performance compared to the non-AD group. The pre-AD group’s completion time increased by an average of 3.498 seconds per year, whereas the non-AD group increased by 1.845 seconds per year (both p < .001). Statistical separation between the groups began seven years before the final cognitively normal visit for the combined cohort, six years for females, and five years for males. By the final year of observation, pre-AD participants had scores associated with at-risk driving behavior. Effect sizes ranged from Cohen’s d = 0.217 to 0.631 for the total group, with females showing slightly larger effects (d = 0.383 to 0.692) than males (d = 0.259 to 0.520). The study concludes that TMT-B is a viable longitudinal screening instrument for detecting preclinical AD-related cognitive decline linked to spatial navigation risks. The findings suggest that subtle impairments in executive function and visuospatial processing occur years before clinical diagnosis, potentially correlating with underlying cholinergic decline and medial temporal lobe pathology. The authors argue that TMT-B could help identify individuals at risk for SN-related harms, such as unsafe driving, during the preclinical stage. They recommend further research to establish specific cutoff scores for navigational risk and to explore the relationship between TMT-B progression, acetylcholine levels, and mortality risks associated with spatial navigation deficits.

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• mci dementia driving