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

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Highlights

  • We compare diffusion MRI changes over one year in AD and DLB.

  • Compared to normal elderly, AD showed ongoing deterioration of white matter.

  • DLB did not show increased rate of deterioration.

Abstract

Objective

Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done.

Methods

We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated.

Results

In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls.

Conclusions

In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.

Section snippets

Objective

Dementia with Lewy bodies (DLB) is a common form of neurodegenerative dementia in older people, second to Alzheimer's disease (AD). Studies of DLB have found relatively less overall brain atrophy than AD, particularly in the temporal lobes [1]. A number of studies have investigated the structural integrity of the white matter in DLB using MR diffusion tensor imaging (DTI) and have found mixed results, but generally, DLB subjects have DTI changes in parieto-occipital regions, whilst AD changes

Subjects

Seventy-one individuals aged over 60 (36 subjects with probable AD [4] and 35 with probable DLB [5]) were recruited from a community-dwelling population of patients referred to local old age psychiatry, geriatric medicine, or neurology services. Thirty-five control subjects were recruited from relatives and friends of subjects with dementia or volunteered via local advertisements. All subjects underwent clinical and neuropsychological evaluations with diagnostic procedures as previously

Statistics

We used SPSS (version 22, IBM, New York, USA) for analysis of non imaging data. Group comparisons were performed with ANOVA or Chi square. Comparison of mean FA and MD controlling for covariates was done with the general linear model, with fixed factors of group and sex, and covariates of age and deep WMH rating. Correlations were performed with Pearson correlation.

Results

Table 1 shows the subject demographics of the study participants with repeat DTI data. AD and DLB were well matched for overall cognitive impairment, though as expected, AD subjects performed worst on baseline episodic memory. The DLB subjects showed significant progression of motor features as assessed by increased UPDRS (p = 0.045). There were no significant differences between groups in WMH rating score. WMH score was significantly correlated (p < 0.001) with both mean FA and MD in the whole

Conclusions

We found increase of mean diffusivity over 1 year in the AD group to be greater than that in the control group over a wide range of brain areas. The increase in MD in AD was also greater than that in DLB in parietal and temporal regions. However, there was no evidence of longitudinal change in MD or FA in DLB relative to controls. This suggests that the widespread pattern of increased MD and reduced FA in AD that we saw at baseline is part of an ongoing degenerative process, whilst the

Study funding

The study was funded by the Sir Jules Thorn Charitable Trust (grant ref: 05/JTA).

Financial disclosure

John O'Brien has been a consultant for GE Healthcare, Servier, and Bayer Healthcare and has received honoraria for talks from Pfizer, GE Healthcare, Eisai, Shire, Lundbeck, Lilly, and Novartis. All other authors have no conflicts of interest to declare.

Acknowledgements

The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.

References (20)

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