Abstract

Spatial navigation deficits are observed in Alzheimer's disease cross-sectionally, but prediction of longitudinal clinical decline has been less examined. 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). 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). Baseline spatial navigation performance may be appropriate for assessing risk of clinical progression.

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