Preclinical Alzheimer's disease and longitudinal driving decline

Roe, Catherine M.; Babulal, Ganesh M.; Head, Denise; Stout, Sarah H.; Vernon, Elizabeth K.; Ghoshal, Nupur; Garland, Brad; Barco, Peggy P.; Williams, Monique; Johnson, Ann; Fierberg, Rebecca; Fague, M. Scot; Xiong, Chengjie; Mormino, Elizabeth C.; Grant, Elizabeth; Holtzman, David M.; Benzinger, Tammie L.S.; Fagan, Anne M.; Ott, Brian R.; Carr, David B.; Morris, John C. · 2016 · OpenAlex-citations

DOI: 10.1016/j.trci.2016.11.006

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Summary

This study investigates whether biomarkers indicative of preclinical Alzheimer’s disease (AD) predict the longitudinal onset of driving difficulties in cognitively normal older adults. The research was motivated by the need for sensitive functional outcomes in primary and secondary AD prevention trials, as well as the public health imperative to identify at-risk drivers before accidents occur. While cross-sectional links between AD pathology and driving performance had been established, this study aimed to determine if biomarkers could forecast future driving decline in individuals without dementia symptoms. The researchers conducted a longitudinal analysis of 104 older adults (mean age 72.5 years) with normal cognition who were recruited from the Knight Alzheimer’s Disease Research Center. Participants underwent baseline assessments including cerebrospinal fluid (CSF) collection for amyloid-beta 42 (Ab42), tau, and phosphorylated tau (ptau181), and Pittsburgh compound B (PIB) amyloid PET imaging. They also completed annual on-road driving tests using the modified Washington University Road Test (mWURT), which yields pass, marginal, or fail ratings, and self-reported driving habits via the Driving Habits Questionnaire (DHQ). Statistical analyses employed Cox proportional hazards models to test if higher biomarker values predicted time to a marginal or fail driving rating, adjusting for age, education, gender, race, and APOE ε4 genotype. Linear mixed models assessed changes in self-reported driving behaviors and global cognitive scores. The results demonstrated that higher ratios of CSF tau/Ab42 and ptau181/Ab42 significantly predicted a shorter time to receiving a marginal or fail rating on the driving test. The hazard ratios were 5.75 (P = .005) for CSF tau/Ab42 and 6.19 (P = .005) for CSF ptau181/Ab42. In contrast, amyloid burden measured by PIB imaging did not significantly predict driving decline (P = .12). Notably, despite the objective decline in driving performance, participants with preclinical AD biomarkers did not report changes in their everyday driving habits, such as miles driven or driving space, nor did they show significant declines in global cognitive measures like the Clinical Dementia Rating Sum of Boxes or Mini-Mental State Examination during the same period. These findings indicate that driving performance is a sensitive functional outcome that detects the effects of preclinical AD earlier than global cognitive tests or self-reported behavioral changes. The study suggests that driving decline is specifically associated with neural injury markers (tau/ptau) rather than amyloidosis alone. This supports the use of on-road driving tests as viable endpoints in clinical trials for AD prevention, offering a clinically meaningful measure that reflects the underlying disease process before the onset of frank dementia.

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• mci dementia driving
• cognitive impairment