Lost before forgetting: objective driving metrics track navigation deficits tied to preclinical Alzheimer's disease

Navigation is a complex, multisensory process in which subtle changes may emerge before the onset of symptomatic Alzheimer's disease (AD). This study investigated whether navigation abilities were associated with amyloid and tau pathology in cognitively normal older adults.

Among 285 cognitively unimpaired older adults, navigation and objective driving behaviors were assessed using the self-reported Santa Barbara Sense of Direction Scale (SBSOD) and a datalogger, respectively. Amyloid and tau burden were quantified using PET-MRI 2 years post-initial driving data collection. Linear mixed-effects models were used to evaluate the associations between biomarker status and longitudinal navigation changes.

At baseline, there were no significant differences in SBSOD, trip chaining, or entropy, a metric that quantifies the variability in one's driving patterns based on PET biomarker status. Over 6.1 years (SD = 3.3), compared to amyloid- participants, amyloid+ participants experienced faster declines in SBSOD and entropy and increases in trip chain counts and percentages of chained trips/distances, indicating more deliberate compensatory planning for subtle deficits. Conversely, tau+ participants exhibited slower declines in SBSOD and greater increases in driving unpredictability (i.e., higher entropy, greater percentages of chained trips/distances) across 5.6 years (SD = 2.9), but not in total trip counts compared to tau- participants.

Changes in navigation may reflect the accumulation of amyloid (compensatory planning) and tau (diminished planning, increased randomness) in distinct brain regions. These findings highlight the promise of driving and navigation metrics as sensitive, noninvasive markers of preclinical AD, underscoring a critical window for intervention.