Background and Purpose: Vascular depression has negative effects on physical activity, which is a robust preventive factor against Alzheimer's disease or hippocampal atrophy. Therefore, we investigated the relationship among vascular depression (i.e., apathy associated with deep white matter lesions [DWMLs]), physical activity, hippocampal atrophy, and memory function using structural equation modeling (SEM).
Subjects and Methods: We examined 213 non-demented elderly subjects without clinically apparent depression. All participants underwent Mini-Mental State Examination, Rivermead Behavioral Memory Test [RBMT] for episodic long-term memory, and a visual analogue version of the Starkstein’s apathy scale (Yao et al., Hypertens Res 2009;32:586). Physical activities were assessed with a questionnaire consisted of 3 components: leisure-time, work, and sport activities (Baecke et al., Am J Clin Nutr 1982;36:936). We evaluated the degree of hippocampal atrophy, using a software program the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD advance) based on SPM8 plus DARTEL (Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra).
Results: When possible confounders were entered into the logistic regression model, the independent predictors of hippocampal atrophy (the highest quintile of VSRAD z-score) were age (OR per 10 years 3.257, 95%CI 1.988-5.338), and leisure-time physical activity (OR per 1-point 0.810, 95%CI 0.707-0.928). Path analysis based on SEM indicated that the direct paths from DWMLs to apathy (β= -0.18, p<0.01) and from apathy to leisure-time activity (β= 0.23, p<0.001) were significant. Furthermore, the direct paths from leisure-time activity to hippocampal atrophy (β= -0.18, p<0.01) and from hippocampal atrophy to memory dysfunction (RBMT) (β= -0.26, p<0.001) were significant. The presented model reasonably fit the data: goodness of fit index = 0.97, adjusted goodness of fit index = 0.93, comparative fit index = 0.97, and root mean square error of approximation = 0.04.
Conclusions: Based on the present SEM analysis, we propose a hypothesis that physical inactivity associated with vascular depression would lead to hippocampal atrophy or Alzheimer’s disease.