Homocysteine and Real-Space Navigation Performance among Non-Demented Older Adults

Background: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults. Objective: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. Methods: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML. Results: In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (beta = 0.31; p = 0.003 and beta = 0.23; p = 0.017) but not allocentric (p > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance. Conclusion: Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults.