Auxillary methods

These include laboratory examinations and neuroimaging; occasionally electrophysiological investigations such as electroencephalography may be needed. Laboratory examinations may help to differentiate acute confusion (delirium) from dementia, and also to exclude or reveal other causes of dementia such as metabolic, endocrine, or toxic disorders. One should not forget that PD patients with mental dysfunction are usually elderly people—they are also prone to other causes of dementia which can affect the elderly population at large. Therefore, a basic laboratory screening should be performed in PD patients who develop mental dysfunction, including hae- matological, biochemical, and urine tests. The array of laboratory examinations can be limited or expanded based on the clinical presentation. In typical cases with an insidious onset and slow progression, laboratory examinations may still be helpful to exclude concomitant diseases such as diabetes.

In a patient with established, long-standing PD who then develops symptoms of dementia with a clinical presentation typical for PD-D, renewed structural imaging may not be necessary. There is no single pattern of atrophy in computed tomography or magnetic resonance imaging (MRI) scans that would help to diagnose dementia in individual patients; nevertheless imaging may help to exclude an alternative diagnosis. Findings in structural and functional imaging are described in detail in Chapter 10, whereas those relevant for diagnosis are summarized here.

In structural imaging with MRI there is a four-fold increased rate of whole-brain atrophy and also more cortical atrophy in PD-D compared with PD without dementia and controls [22]. In general, medial temporal lobe atrophy including the hippocampus and parahippocampal gyrus is more severe in AD patients, with more severe atrophy of the thalamus and parieto-occipital lobes in patients with PD-D [23].

Functional imaging will rarely be required for routine diagnosis. Cerebral blood flow studies as assessed using single photon emission computed tomography (SPECT), often demonstrate frontal hypoperfusion or bilateral temporo-parietal deficits in PD-D patients [24]. Perfusion deficits in the precuneus and inferior lateral parietal regions, areas associated with visual processing, have also been described in PD-D compared with AD, where perfusion deficits are found in a more anterior and inferior location [25]. Reduced metabolism in temporo-parietal regions of patients with PD-D compared with PD is also observed in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) studies [26], both PD-D and DLB patients demonstrating similar patterns of decreased metabolism in bilateral inferior and medial frontal lobes and the right parietal lobe [27].

2p-Carbomethoxy-3p-(4-iodophenyl)-N-(3-fluoropropyl)-N-nortropane (FP-CIT) SPECT demonstrates the integrity of nigrostriatal dopaminergic pre-synaptic terminals and can help to differentiate Lewy body-related dementias from AD with extrapyramidal features, for example due to neuroleptic use. Significant reductions were found in [123I]-FP-CIT binding in the caudate, anterior, and posterior putamen in subjects with DLB and PD-D compared with those with AD and controls, the greatest loss in all three areas being seen in patients with PD-D [28].

Another imaging method which can differentiate Lewy body-related dementias from other disorders such as AD is metaiodobenzylguanidine (MIBG)-SPECT. [123I]-MIBG is an analogue of noradrenaline, and its imaging with SPECT can be used to quantify post-ganglionic sympathetic cardiac innervation. The heart to mediastinum (H:M) ratio is lower in PD and DLB, but normal in patients with AD [29, 30].

Finally, another method, still in its infancy with regard to routine diagnosis, is imaging of specific protein depositions in the brain. Imaging of a-synuclein has not yet been achieved in humans, but amyloid burden can be quantified using substances binding to amyloid-beta. In PET studies with the Pittsburgh compound B (PIB), mean cortical levels of amyloid were increased two-fold in AD [31] and by 60% in DLB [32]. In PD-D the mean cortical amyloid load was not significantly elevated, although 20% of individuals showed an AD pattern of increased PIB uptake [33]. Once established with reliable cut-off values, quantitative assessment of amyloid versus a-synuclein burden may help in differential diagnosis.

There are as yet no blood or cerebrospinal fluid (CSF) biomarkers to diagnose PD-D. CSF levels of a-synuclein may help to diagnose PD, with no further value to diagnose PD-D [34]. CSF levels of amyloid-beta and tau proteins, which are helpful for diagnosing AD, have been suggested to predict dementia in PD [35, 36]; they may also help to differentiate PD from DLB and AD [37], but this assertion needs further confirmation (see Chapter 11).

 
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