Background: Gait impairments are emerging predictors of dementia. However, few studies have examined whether gait predicts decline in specific cognitive domains. Objective: This study aimed to determine whether gait speed or other gait characteristics were associated with decline in specific cognitive domains and the role of the ApoE4 genotype in modifying these associations. Methods: Participants (n = 410; mean age 72.0±7.0 years) were randomly selected from the electoral roll. At baseline, gait speed was assessed using the GAITRite walkway. Gait variability in step time, step length, step width, and double support time (DST) was calculated as the standard deviation of each measure across all steps. In a subsample (n = 177), speed was measured under fast pace. The difference between usual and fast pace was calculated. At baseline, 2.6 and 4.6 years processing speed, memory, executive and visuospatial function were measured using neuropsychological tests. Multivariable mixed models were used to examine 1) associations between gait and the different cognitive domains over time and 2) whether the presence of ApoE4 genotype modified these associations. Results: Higher DST variability was associated with greater decline in memory (p for interaction 0.03). Slow gait speed predicted decline in processing speed (p = 0.02) and visuospatial function (p = 0.03). In ApoE4 carriers, gait speed also predicted decline in memory (p = 0.02). Other gait characteristics did not predict decline in any of the cognitive domains (p > 0.05). Conclusions: These findings add to the evidence that gait is an early indicator of cognitive decline, but that specific gait measures may provide diagnostic insights into specific cognitive domains.