Dementia with Lewy Bodies vs Parkinson's Disease with Dementia: Different Patterns of Cortical Atrophy

Abstract & Commentary

By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg does research for Boehringer-Ingelheim.

Synopsis: Dementia with Lewy bodies is associated with greater temporal, parietal, and occipital lobe atrophy than Parkinson's disease with dementia.

Source: Beyer, MK et al. Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies, Neurology 2007; 69(8):747-754.

The combination of dementia, parkinsonism, and Lewy body pathology occurs in both dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD). Postmortem studies of DLB and PDD have shown widely distributed Lewy bodies, with no clear-cut pathological distinction between the two. DLB and PDD are therefore defined by consensus clinical criteria, with the onset of dementia within the first year of disease in DLB, and after at least a year of parkinsonism in PDD. Although this distinction is somewhat arbitrary, it is clinically useful for estimating prognosis and predicting responsiveness to dopaminergic medications.

In this study, the authors used MRI voxel-based morphometry (VBM) to evaluate and compare the patterns of cortical atrophy in patients who met consensus clinical criteria for DLB (n = 18), PDD (n = 15), or Alzheimer's disease (AD) (n = 21), versus healthy, elderly control subjects (n = 20). The baseline characteristics of these groups differed in several respects, with a significantly higher mean age of subjects in the DLB than the PDD or control groups, and a significantly longer duration of dementia in the DLB and AD than in the PDD group. The groups also differed in educational background, gender distribution, and current medications. Mini-mental State Examination scores were comparable in the 3 disease groups, and lower than those of control subjects.

The major finding of the study was the presence of significantly greater gray matter atrophy in the temporal, parietal, and occipital lobes in DLB than in PDD, even after statistical adjustment for age. As expected, there was also significantly greater cortical atrophy in AD than either DLB or PDD, particularly in the medial temporal lobes. All subjects with dementia (DLB, PDD, or AD) exhibited diffuse gray matter atrophy compared with healthy, non-demented controls. The results suggest that PDD and DLB can be distinguished by differences in cortical gray matter atrophy.

Commentary

Most neurodegenerative disorders have characteristic neuropathological findings that allow for a definitive postmortem diagnosis, which can be used as a "gold standard" against which the sensitivity and specificity of clinical diagnostic criteria or biomarkers can be evaluated. DLB and PDD, however, cannot be distinguished on this basis. This highlights the need for biomarkers to distinguish between DLB and PDD, and calls into question whether they are distinct entities or part of a spectrum of Lewy body dementias.

This study provides new evidence that there may be greater temporal, parietal, and occipital lobe atrophy in DLB than PDD, providing an anatomical substrate for observed clinical differences between the two disorders, and supporting the hypothesis that they are distinct nosological entities. Limitations include the relatively small sample size, potential confounders (due to baseline differences between the study groups), and lack of neuropathological diagnosis. The findings contradict those of a prior VBM study in which no significant differences between DLB and PDD were observed. Future studies with larger sample sizes, more closely matched subjects, and neuropathological correlation would be helpful to confirm and expand the findings of the current study. Given the wide range of normal anatomical variation, VBM may eventually be useful for distinguishing DLB from PDD on a population basis, but is unlikely to facilitate diagnosis within individual patients.

Additional Reading:

Seppi O and Rascol O. Dementia with Lewy bodies and Parkinson disease with dementia: Can MRI make the difference? Neurology 2007; 69(8):717-718.