Diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease

https://doi.org/10.1016/j.pscychresns.2007.01.001Get rights and content

Abstract

Dementia with Lewy bodies (DLB) is a common form of dementia, with fewer memory deficits, and more visuo-perceptual problems than Alzheimer's disease (AD). We hypothesized that there would be disease specific alterations revealed by diffusion tensor imaging with AD showing temporal lobe and DLB more parietal changes. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with diffusion tensor FLAIR imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated, and data were analysed using pre-defined regions of interest (ROI) and also with SPM. We found a significant decrease in the FA map in a ROI in the parietal lobe (precuneus) of the DLB group. Using SPM we found increased ADC in the left temporal lobe of AD subjects compared to controls. There were no other significant differences between groups. We conclude that there are subtle changes visible with diffusion imaging in DLB and AD which may reflect disrupted connectivity and underlie observed perfusion changes in these disorders.

Introduction

Dementia with Lewy bodies (DLB) is a common form of dementia in older people, with clinical symptoms differing from Alzheimer's disease (AD) — people with DLB typically have fewer memory deficits, and more visuo-perceptual problems, fluctuating awareness, and Parkinsonian motor features (McKeith et al., 2004). The underlying pathological substrates for these features are not fully understood.

Magnetic resonance (MR) diffusion weighted imaging (DWI) is a technique which allows images of the diffusion of water in the brain to be produced. Because of the highly structured nature of axons, water tends to diffuse along the direction of white matter tracts rather than perpendicular to them. DWI is a sensitive indicator of changes to the integrity of axons (Bammer and Fazekas, 2002). From DW images can be calculated the apparent diffusion coefficient, and the fractional anisotropy. The apparent diffusion coefficient (ADC) is a direction independent measure of the overall diffusivity of water. Damage to axons, or a decrease in cell density, increases the ADC as the barriers to water diffusion decrease. The fractional anisotropy (FA) depends on the relative diffusivity of water in different directions and varies from zero, where diffusion is equal in all directions, to 1, where diffusion occurs along a single direction. FA is high in regions of coherent white matter tracts (such as the corpus callosum) since the fibres all go in the same direction. A decrease in FA indicates water diffusing more isotropically — this may be caused by damage to the walls of the axons, allowing water to diffuse perpendicularly to the axon direction.

There have been a number of studies of diffusion imaging in Alzheimer's disease. The most consistent finding has been increased ADC in the temporal and parietal lobes (Kantarci et al., 2001, Bozzali et al., 2005, Head et al., 2004), though some studies have found few differences between AD and comparable healthy subjects (Bozzao et al., 2001). The only study of diffusion imaging in dementia with Lewy bodies (Bozzali et al., 2005) found reduction in FA and increase in ADC in DLB compared with controls in most white matter regions of the brain that were examined. We are not aware of any studies which have directly compared DLB with AD.

The purpose of this work was to compare the diffusion parameters ADC and FA between people with AD, DLB, and subjects of a similar age without dementia.

Most previous studies have used T2 weighted diffusion images, though Kantarci used a diffusion sequence with FLAIR (Fluid attenuated inversion recovery) to reduce the signal from the cerebrospinal fluid (CSF), and found higher ADC in the hippocampus of people with Alzheimer's disease (Kantarci et al., 2002). Previous work (Bhagat and Beaulieu, 2004) has shown that the use of FLAIR DWI results in lower ADC and higher FA values in the brain due to the decreased influence of CSF in the images. Since people with dementia frequently have a degree of brain atrophy, and since we were interested in comparing the diffusion values of brain, we chose to use a FLAIR sequence to minimise the effect of atrophy and partial volume of CSF on the diffusion images.

The measured diffusion coefficient in the brain depends upon the diffusion weighting used. The majority of studies have utilised a diffusion weighting of b = 1000 s·mm 2. For values of b up to about 1000 s·mm 2, the signal decreases in an approximately exponential manner with b. However, for higher b values, the signal decay becomes less rapid. It has been hypothesised that with higher b values, more of the signal comes from water whose movement is restricted by the tissue structure, and is thus potentially more indicative of the brain tissue (DeLano and Cao, 2002). Yoshiura et al. (2003) found greater differences between AD and healthy controls for higher b values. Hence we collected data with b values of both 1000 and 4000 s·mm 2.

In order to compare our findings with those of Bozzali et al., 2005, Bozzali et al., 2002, we utilised the same regions of interest as in their work, anticipating similar findings. In particular, in view of the role of the medial temporal lobe in memory function, and of the parietal lobe in visuo-perceptual functioning, and given that temporal hypoperfusion is apparent in AD (Colloby et al., 2002, Pasquier et al., 2002), and parietal hypoperfusion more severe in DLB than AD (Colloby et al., 2002, Firbank et al., 2003a) we hypothesized that these perfusion deficits would be related to adjacent tissue damage, and that DWI would show temporal lobe abnormalities in the AD group, and more prominent parietal changes in the DLB group.

Section snippets

Subjects

We recruited 15 people with Alzheimer's disease and 16 with dementia with Lewy bodies, from clinical Old Age Psychiatry, Geriatric Medicine and Neurology Services. Fifteen healthy subjects of similar age were also recruited.

All subjects were aged over 60, had mild to moderate dementia (MMSE > 10) and did not have contra-indications for MRI. All Alzheimer's disease subjects fulfilled criteria for probable AD according to NINCDS/ADRDA (McKhann et al., 1984). Dementia with Lewy body cases all met

Results

As shown in Table 1, the groups were well matched for age and sex, and the dementia groups were comparable in cognitive scores. There were no significant differences in WMH volume between the groups. Both dementia groups had significantly less grey and white matter than controls, but there was no difference between AD and DLB.

Fig. 4 shows typical ADC maps calculated for the two diffusion values. Table 2 shows the mean ADC and FA values determined from the ROI analysis of the b = 1000 s·mm 2 data.

Discussion

The values of apparent diffusion coefficient and fractional anisotropy in the control subjects are similar to those measured by Bhagat (Bhagat and Beaulieu, 2004) with a comparable sequence on normal subjects of similar age. The ADC values of the controls are also similar to those of Bozzali (Bozzali et al., 2005).

In AD, we found increase of ADC in the temporal lobe, consistent with the known pathological processes in the temporal lobe. The temporal lobe changes were not in the medial temporal

Acknowledgements

This work was generously funded by a grant from the Newcastle Healthcare Charity.

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