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Table 1.  

Differential Imaging Findings in Parkinsonian Syndromes

Table 2.  

Differential Imaging Findings in Dementias

Technology Insight: Imaging Neurodegeneration in Parkinson's Disease: Dementia and Parkinson's Disease


Dementia and Parkinson's Disease

MRI Volumetry

Summerfield and colleagues used MRI with voxel-based morphometry to localize regional reductions in brain volume in patients who had PD with or without later dementia.[59] They studied 16 patients with PDD, 13 patients with PD, and 13 age-matched healthy control individuals. The patients with PDD showed decreased bilateral gray matter volumes in the putamen, nucleus accumbens, hippocampus and parahippocampal regions, and in the anterior cingulate gyrus. The left thalamus was also atrophic in these individuals. Patients with PD but without dementia also showed volume decreases in the right hippocampus, the left anterior cingulate gyrus and the left superior temporal gyrus. These researchers concluded that the structural correlate of dementia in PD is hippocampal, thalamic and anterior cingulate gyrus atrophy, and that subclinical volume loss in these areas can be detected in PD. In a subsequent prospective series that involved a 2-year follow-up, Ramirez-Ruiz and co-workers noted that, in PDD, progressive volume loss occurred primarily in neocortical areas, whereas in PD it was seen primarily in limbic and temporal association areas.[60] By use of the boundary shift integral approach, Burton and colleagues compared whole brain volume reductions over 1 year between patients with PD and those with PDD.[61] The loss of brain volume in patients with PD (0.31% per annum) occurred at a rate comparable to that seen in healthy controls, but an increased rate, approaching that reported for AD (2% per annum), was seen in patients with PDD (1.12% per annum).[61] These researchers concluded that MRI could be a useful tool for monitoring the progression of PDD.

Resting Brain Metabolism

In patients who have PD with frank dementia, 18FDG-PET scans show an AD-like pattern of impaired resting brain glucose utilization, with posterior parietal and temporal asso ciation areas being most affected, frontal association areas being affected to a lesser degree, and primary cortical regions, basal ganglia and cerebellum being spared.[62] Interestingly, up to a third of patients with established PD but without dementia also show reduced parietal and temporal metabolism, but to a lesser extent than in those with frank dementia, which suggests that these patients with PD might be at risk for later dementia.[63]

Currently, it remains unclear whether the pattern of resting glucose hypometabolism in patients who have PD with dementia reflects coincidental AD, cortical Lewy body disease, loss of cholinergic projections, or some other degenera tive process. Clinicopathological series suggest that there is considerable overlap in cortical 18FDG-PET findings between coincidental AD and cortical Lewy body disease, but that patients with cortical Lewy body disease show a greater reduction of resting glucose metabolism in the primary visual cortex.[62] PET imaging agents that can be used to assess the amyloid-β plaque load in patients with dementia are now available (Figure 4).[64] By use of PET with 11C-Pittsburgh Compound B, a thioflavin marker of amyloid deposition, Edison and colleagues recently reported that 80% of patients with DLB but only 20% of patients with PDD have significantly raised cortical amyloid loads.[65] This finding suggests that amyloid pathology contributes to later dementia only in a minority of PD cases.

Figure 4. (click image to zoom) PET scan with 11C-Pittsburgh Compound B, a thioflavin-based marker of amyloid-β plaque load. (A) An elderly individual without Parkinson’s disease and (B) a patient who has Parkinson’s disease with late dementia both show no significant plaque deposition in the brain when compared with (C) a patient with Alzheimer’s disease in whom amyloid-β deposition is extensive. Pictures courtesy of Paul Edison.

Dopaminergic Function

In around 20% of individuals with a clinical picture of AD in the general population, the pathological diagnosis is found to be DLB, whereas many other dementia cases have mixed pathology.[66] It is unclear whether DLB and PD represent opposite ends of a spectrum. Patients with DLB show not only cerebral cortical neuronal loss, with Lewy bodies in the surviving neurons, but also loss of nigrostriatal dopaminergic neurons. By contrast, nigral pathology is mild in AD.

Walker and colleagues examined striatal DAT binding by use of 123I-FP-CIT SPECT in patients with clinically presumed DLB, patients with AD, drug-naive patients with PD, and healthy controls.[67,68] Patients with presumed DLB or PD had significantly lower uptake of 123I-FP-CIT in the caudate and putamen than did patients with AD (P <0.001) or controls (P <0.001). The authors were subsequently able to correlate their SPECT findings with 10 postmortem examinations. In all, 9 out of 10 patients with dementia were thought to have DLB in life, but only 4, all of whom had reduced striatal 123I-FP-CIT uptake, had this diagnosis at autopsy. Of the 10 patients, 5 showed AD pathology—4 of these 5 individuals had normal 123I-FP-CIT SPECT scans, and the fifth had concomitant vascular disease.

Walker et al. subsequently extended their postmortem series, collecting data over a 10-year period on 20 patients who had been followed up from the time of their first assessment and 123I-FP-CIT SPECT scan through to death and subsequent detailed neuro pathological autopsy.[66] Eight patients fulfilled the neuropathological diagnostic criteria for DLB and nine patients had AD; most of the patients with AD had coexisting cerebrovascular disease. The sensitivity of an initial clinical diagnosis of DLB was found to be 75% and the specificity was 42%. By contrast, the sensitivity of 123I-FP-CIT SPECT for the diagnosis of DLB was 88% and the specificity was 100%. The authors concluded that DAT transporter imaging substantially enhanced the accuracy of the diagnosis of DLB compared with clinical criteria alone.

The findings from 18F-dopa PET scans have also been compared between patients who had PD with dementia and patients who had PD without dementia, but who were matched for locomotor disability.[69] The two PD cohorts showed equivalent levels of dopamine storage capacity in the putamen, but 18F-dopa uptake in the cingulate and mesial prefrontal regions was reduced in the PDD group. Frontal 18F-dopa uptake has previously been shown to correlate with performance on executive tasks by patients who have PD without dementia.[70]

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