White matter changes have been investigated in Alzheimer's disease (AD) in a number of studies using diffusion imaging. Fewer studies have investigated dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy subjects. We found increased mean diffusivity in the temporal lobe of AD, and reduced fractional anisotropy (FA) in a small cluster in the right postcentral gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS (Unified Parkinson's Disease Rating Scale) motor score. We had previously reported reduced visibility in the AD group of a dark appearing layer of the hippocampus in the high-resolution images. In an SPM analysis on all subjects, there were significant clusters of reduced FA in the corpus callosum, fornix and stria terminalis that correlated with the visual rating of the hippocampus. These results suggest that changes to the hippocampus are associated with structural changes to the white matter fibres of the hippocampus output, and that changes in motor function are associated with changes in white matter underlying somatosensory cortex.
Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia following Alzheimer's disease (AD), accounting for approximately 15% of cases at autopsy (McKeith et al., 2004). DLB shares clinical and pathological features with AD, making it potentially difficult to distinguish in clinical practice. Early and accurate diagnosis of DLB is important for optimum management, including provision of appropriate information to patients and carers, initiation of effective treatments and avoidance of potentially life-threatening antipsychotic drugs.
Diffusion imaging with magnetic resonance has been widely used to investigate the integrity of the white matter microstructure. Mean diffusivity (MD) of water is typically higher where there are fewer barriers to diffusion such as cell walls. Fractional anisotropy (FA) indicates the degree of angular variation in the magnitude of water motion (diffusion), and is highest in directionally coherent fibre bundles such as those found in corpus callosum. Change in MD and FA of the frontal, temporal and parietal lobes has been observed in AD (Kantarci et al., 2001, Bozzali et al., 2002, Head et al., 2004, Naggara et al., 2006, Firbank et al., 2007 and Kiuchi et al., 2009) though some studies have found few differences between AD and comparable healthy subjects (Bozzao et al., 2001). Studies vary as to which regions are found to be altered, with, for instance, findings of only limited changes in FA of temporal lobe (Damoiseaux et al., 2009), change in temporal lobe MD (Stahl et al., 2007), and changes in frontal lobe and corpus callosum of MD and FA (Chen et al., 2008). However, diffusion changes in the temporal lobe have been consistently reported, with suggestions that the connectivity of the hippocampus is reduced in AD (Kalus et al., 2006, Ringman et al., 2007 and Zhou et al., 2008). A recent study (Kiuchi et al., 2011), using tractography, found decreased FA in the uncinate fasciculus of both AD and DLB, with DLB additionally showing more posterior change. The few other studies in DLB also suggest more posterior changes (Firbank et al., 2007, Ota et al., 2009 and Kantarci et al., 2010), with the temporal lobe relatively unaffected, in keeping with structural preservation in DLB compared to AD (Whitwell et al., 2007). We hypothesised that in this study we would find decreases in FA and increases in MD principally in the temporal lobe of AD, and more parietal changes in DLB.
In an analysis of high resolution coronal magnetic resonance images (MRI) of the hippocampus, we found that a structure probably representing the stratum moleculare, stratum lacunosum and stratum radiatum was less visible in AD subjects than in DLB (Firbank et al., 2010). Neuropathological studies have found that this layer is one of the earliest affected by Alzheimer type pathology (Lace et al., 2009) and that pathology spreads through the hippocampus in stages defined broadly by the internal connectivity — i.e. from input to output layers. We hypothesised that these hippocampal changes would be associated with changes to the white matter (WM) connecting the hippocampus to other brain areas, in particular, the fornix, which is the main output from the hippocampus, and the cingulum bundle, which is the main input (Duvernoy, 1998 and Mori et al., 2005). Although medial temporal lobe atrophy is less common in DLB, it is still present (Tam et al., 2005), and we hypothesised that any alterations in connecting WM would be present regardless of the origin of the hippocampal changes.
In this study, we used diffusion-weighted imaging to investigate differences in WM integrity between AD, DLB and healthy subjects. We also investigated the relationship between the changes seen on the high-resolution hippocampus imaging and FA changes in WM.
