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The two commonest causes of dementia are probably dementia of the Alzheimer type (DAT) and dementia with Lewy bodies (DLB), and although their pathology is relatively well characterised (albeit controversial in terms of diagnostic features) the clinical expression of these disorders can sometimes be difficult to distinguish. Typically DAT presents with deficits in episodic memory with language involvement whereas in DLB it is more hallucinations with a fluctuating dementia in the context of a parkinsonian syndrome. Distinguishing these two disorders, however, is not always straightforward and in this issue (pp583–588) Yoshito et al 1 claim that such a distinction can be made using, rather surprisingly, a peripheral marker of sympathetic activity—[123I] MIBG myocardial scintigraphy.
MIBG is a physiological analogue of noradrenaline (norepinephrine) and is used to label sympathetic postganglionic nerve terminals and so has been most extensively used for diseases targeting the autonomic nervous system, including a range of parkinsonian plus disorders.2 3 Yoshida et alnow report that myocardial [123I] MIBG is significantly reduced in patients with DLB irrespective of duration of disease or degree of autonomic failure, a situation that is not seen in DAT even when a degree of autonomic failure is documented. This therefore suggests that in both conditions there may be involvement of central autonomic pathways but that in DLB there is additional pathology involving peripheral sympathetic processes; an involvement that is not related to medication.
It is now established that some extrapyramidal diseases have pathology that can involve both the central and peripheral autonomic nervous system (see for example, Stoddard et al 4). However, DLB has not consistently been shown to have any such pathology but this study clearly suggests that this is likely, although it produces no postmortem data to confirm the fact. Indeed the study would be greatly strengthened if the MIBG abnormalities could be correlated with a specific pathological process and the absence of postmortem confirmation of disease in the two patient groups also limits interpretation. The recruitment of consecutive patients, with its inherent variability, can be seen as a strength of the study, but it also creates problems due to the range of disease seen—for example, patients' mini mental state examination scores ranged from 4 to 26. It is therefore not clear how confident one can be about the positive findings irrespective of disease duration or severity given the few patients at each data point. Indeed it could be argued that comparing only mildly affected patients may be more useful as it is this group that represent the greatest challenge both diagnostically and therapeutically—although the absence of effective long term therapies may even limit this potential at the present time.
In conclusion, this study highlights the possibility that neurodegenerative disorders targeting the cerebral cortex may be distinguished through their effects on sympathetic nerve endings in the heart. However, perhaps the most important message from this study is to highlight once more that neurodegenerative disorders display widespread pathology and that this needs to be accommodated in any theory of pathogenesis as well as novel therapeutic approaches.
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