Imaging amyloid deposition in Lewy body diseases
Gomperts SN, Rentz DM, Moran E, Becker JA, Locascio JJ, Klunk WE, et al.;
Commented by , 21 Nov 2008
Aim of the study
To determine whether amyloid deposition assessed by PET imaging with the ß-amyloid-binding Pittsburgh Compound B (PiB) can distinguish dementia with Lewy bodies (DLB) from dementia in Parkinson's disease (PDD), and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.
Methods
Subjects with different diagnosis (8 DLB; 7 PDD; 11 PD; 15 AD, 37 controls) underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.
Results
Cortical amyloid burden was comparable to AD in the DLB group and higher than the PDD group, which had a low amyloid deposition comparable to PD and control group. Relative to the global cortical retention, occipital PiB retention was lower in the Ad group than in the other groups.
For the DLB, PDD and PD groups, amyloid deposition in the parietal (lateral and precuneus) and posterior cingulated region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.
Professor Gauthier's comments
The authors conclude that ß-amyloid may contribute selectively to the cognitive impairment of DLB and to the timing of dementia relative to the motor signs of parkinsonism.
This study must be put in the context of two Lewy body diseases, e.g. DLB and PDD, where the clinical diagnosis is currently made by the emergence of cognitive/behavioral symptoms first (in DLB) or motoric symptoms followed at least a year later by cognitive symptoms (in PDD) (ref. 1).
The observation that PiB-PET can help in the diagnosis of DLB is useful information, as clinicians are trying to make earlier diagnosis than before in neurodegenerative conditions (ref. 2).
In terms of pathophysiology, for equivalent severity of cognitive impairment, the DLB group had an amyloid burden that was higher than the PDD group. So if amyloid deposition accounts for cognitive impairment in DLB (as it does in AD), what explains the cognitive decline in PDD? This is an open question.
The relative sparing of the occipital cortex in the AD group compared to DLB has been noted in previous studies using SPECT studies (ref. 3). Readers interested in biomarkers for DLB will find the review by Aarsland et al particularly interesting (ref. 4).
A final comment from the current study: 51% of the "controls" were "PiB positive" e.g. half of the cognitively normal subjects had evidence of amyloid deposition. This raises the issue of the usefulness of PiB-PET in clinical practice for diagnosis or prediction of progression to AD or a related disorder (which DLB can now be considered to be!).
References
1. Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Movement Disorders 2007; 22 (12); 1689-1707; quiz 1837
2. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurology 2007; 6 (8); 734-746
3. Lobotesis K, Fenwick JD, Phipps A, Ryman A, Swann A, Ballard C, et al. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology 2001; 56 (5); 643-649
4. Aarsland D, Kurz M, Beyer M, Bronnick K, Piepenstock Nore S, Ballard C. Early discriminatory diagnosis of dementia with Lewy bodies. The emerging role of CSF and imaging biomarkers. Dementia and Geriatric Cognitive Disorders 2008; 25 (3); 195-205. [Epub 2008 Jan 17]