White Matter Imaging in Understanding Aging and Alzheimer's Disease

Background: Alzheimer's and Cerebrovascular disease are the two most common diseases of older individuals. Evolving evidence shows that both diseases affect white matter integrity in different ways. For example, white matter hyperintensities (WMH), have a major impact on periventricular white matter structure, whereas, AD pathology is likely to affect posterior white matter. Parietal subcortical white matter is a hypothesized area of pathological overlap for these two diseases. This brief presentation will review diffusion tensor imaging (DTI) data and introduce a biological model to explain these effects. Methods: Subjects consisted of 59 cognitively normal, 84 MCI and 28 AD with mean age of 74.1 +/- 8.0 years. All Subjects were imaged on 1.5 Tesla GE Machine using 3DT1, FLAIR and DTI. All images were warped to common anatomical space and WMH volumes calculated. Using automatic anatomical labeling methods, FA in Frontal, temporal and parietal lobar was compared across groups and associated with cognition. Results: Repeated measures analysis of variance found significant differences according to cognitive syndrome after adjusting for age and sex (p = 0.03). Correlational analyses found that parietal FA was associated with semantic and working memory and executive function after correcting for age, sex, ethnicity, brain, hippocampal and WMH volumes. Conversely, only hippocampal volume was associated with episodic memory performance. Conclusions: Cortical-cortical dissociation secondary to white matter injury is commonly associated with cerebrovascular disease. Our data show that AD can also affect white matter connectivity and reduced parietal white matter integrity is associated with cognition. These two pathologies, therefore, may combine to injure subcortical white matter--particularly in parietal regions--additively affecting cognition.

View Large Image Download to PowerPoint