Introduction: Spatial navigation deficits are observed in Alzheimer's disease cross-sectionally, but prediction of longitudinal clinical decline has been less examined. Methods: Cognitive mapping (CM) was assessed in 95 participants and route learning (RL) was assessed in 65 participants at baseline. Clinical progression over an average of 4 to 5 years was assessed using the clinical dementia rating (CDR) scale. Relative predictive ability was compared to episodic memory, hippocampus, and cerebrospinal fluid biomarkers (phosphorylated tau/amyloid β 42 (ptau181/Aβ42) ratio). Results: CM and RL were predictors of clinical progression (P’s < 0.032). All measures, except RL-Learning remained predictors with episodic memory in models (P’s < 0.048). Only RL-Retrieval remained a predictor when ptau181/Aβ42 was included (P < 0.001). CM interacted with hippocampus and ptau181/Aβ42 in prediction (P’s < 0.013). CM, RL, and episodic memory evidenced strong diagnostic accuracy (area under the curve (AUC) = 0.894, 0.794, and 0.735, respectively); CM tended to perform better than episodic memory (P = 0.056). Discussion: Baseline spatial navigation performance may be appropriate for assessing risk of clinical progression.
- place learning
- preclinical Alzheimer's disease
- response learning