Regular articleRegional cerebral blood flow in Parkinson's disease with and without dementia
Introduction
People with Parkinson's disease (PD) are six times more likely to develop dementia (classified as “PD with dementia” or PDD), compared with age-matched controls (Aarsland et al., 2001). In many cases, the clinical picture of this dementia resembles dementia with Lewy bodies (DLB), with cognitive decline being associated with recurrent visual hallucinations and fluctuations in cognitive performance. However, the current consensus diagnostic criteria for DLB do not allow the diagnosis of DLB to be made in those who have had PD for more than 12 months (McKeith et al., 1996) and such cases are termed PDD. It is unclear, but important to determine, whether the underlying neurobiology of cognitive impairment in PDD is the same as in DLB. Similarities have been described in motor phenotype (Burn et al., 2003), neuropsychological profile (McKeith and Burn, 2000), and positive response to cholinergic therapy Aarsland et al., 2002, McKeith et al., 2000a.
Single Photon Emission Computed Tomography (SPECT) imaging using Tc-HMPAO has been used to investigate differences in cerebral blood flow in those with dementia compared to healthy controls. The SPECT data has been analysed utilising either region of interest analysis (Holman et al., 1992), which allows the investigation of blood flow abnormalities in predefined regions, or with statistical parametric mapping (SPM), which allows the generation of images of blood flow abnormalities in an unbiased fashion on a pixel by pixel basis across the whole brain (Imran et al., 1999). In Alzheimer's disease (AD), these studies have found loss of SPECT signal in the parietotemporal and frontal regions. In DLB, there are greater parietooccipital deficits compared to AD, but no temporal hypoperfusion. (Colloby et al., 2002)
In Parkinson's disease, most SPECT blood flow studies have used ROI analysis. Several studies have found parietal hypoperfusion in PDD Antonini et al., 2001, Pizzolato et al., 1988, Sawada et al., 1992, Spampinato et al., 1991, with evidence of a link between parietal hypoperfusion and overall cognitive decline Jagust et al., 1992, Sawada et al., 1992, Tachibana et al., 1995. Temporal hypoperfusion has also been reported Antonini et al., 2001, Spampinato et al., 1991. In PD without dementia, findings are less clear, with reports of no difference from controls Sawada et al., 1992, Spampinato et al., 1991, but also of frontal Markus et al., 1994, Antonini et al., 2001, temporal (Jagust et al., 1992) and parietal Markus et al., 1994, Tachibana et al., 1995 hypoperfusion. A study using SPM (Abe et al., 2003) reported occipitoparietal hypoperfusion in PD, and found that this correlated with a test of visual functioning.
Region of interest findings can be difficult to compare across studies, due to differences in the positioning and size of the regions. They also are limited by the predetermined choice of region location.
Due to the spatial resolution of SPECT imaging (∼1 cm), it suffers from partial volume averaging, and it is difficult to distinguish whether a loss of signal is due to a reduction in blood flow or brain atrophy. The additional structural information provided by MRI can be used to clarify patterns of blood flow change.
In this study we use MRI scans in combination with SPECT scans of the same individuals in order to locate areas of perfusion change occurring independently of brain atrophy.
The aim of this work was to investigate blood flow loss in people with PD with and without dementia, and compare it to healthy controls, and people with AD and DLB. We hypothesized that the blood flow loss would be greater in PDD than in PD, and that the pattern of blood flow loss would be more similar to DLB than to AD.
Section snippets
Subjects
The sample consisted of 149 subjects (32 with AD, 15 with DLB, 34 with PD, 31 with established PD who subsequently developed the neuropsychiatric features of DLB (PDD), and 37 normal older controls). Patients were obtained from a community-dwelling population of patients referred to geographically based local old age psychiatry and (for patients with PD, and PDD) neurology services in addition. Normal controls were recruited from among friends and spouses of patients included in this and other
Results
Patient demographics are summarised in Table 1. As expected, MMSE score was lower in all dementia groups than control subjects (P < 0.001) while there were no statistically significant differences between dementia groups. The PD patients had a slightly lower MMSE score than controls. There was a sex difference between the AD and PD groups, in keeping with the known distribution of these diseases in the general population Launer et al., 1999, Twelves et al., 2003.
Fig. 2 shows the maximum
Discussion
We looked for regions showing a greater decrease in HMPAO SPECT signal than could be accounted for by brain atrophy. These regions correspond to areas showing a loss of blood flow per unit brain tissue. PDD and DLB showed similar patterns of loss of rCBF in the precuneus and lateral parietooccipital region. Subjects with Alzheimer's disease also showed a midline parietal deficit in blood flow, but in a more anterior and ventral location than PDD and DLB, involving the posterior cingulate, with
References (41)
- et al.
Voxel-based morphometry—the methods
NeuroImage
(2000) - et al.
Patterns of cerebral atrophy in dementia with Lewy bodies using voxel based morphometry
NeuroImage
(2002) - et al.
A practical method for grading the cognitive state of patients for the clinician
J. Psychiatr. Res.
(1975) Hallucinations in Parkinson's disease
Lancet
(2001)- et al.
Spectrum of Parkinson's disease, Parkinson's dementia, and Lewy body dementia
Neurol. Clin.
(2000) - et al.
Efficacy of rivastigmine in dementia with Lewy bodiesa randomised, double-blind, placebo-controlled international study
Lancet
(2000) - et al.
Statistical parametric mapping of 99mTc-HMPAO-SPECT images for the diagnosis of Alzheimer's diseasenormalizing to cerebellar tracer uptake
NeuroImage
(2002) - et al.
Risk of dementia in Parkinson's disease—a community-based, prospective study
Neurology
(2001) - et al.
Donepezil for cognitive impairment in Parkinson's diseasea randomised controlled study
J. Neurol. Neurosurg. Psychiatry
(2002) - et al.
Occipital hypoperfusion in Parkinson's disease without dementiacorrelation to impaired cortical visual processing
J. Neurol. Neurosurg. Psychiatry
(2003)
Perfusion ECD/SPECT in the characterisation of cognitive deficits in Parkinson's disease
Neurol. Sci.
Extrapyramidal features in Parkinson’s disease with and without dementia and dementia with Lewy bodies: A cross-sectional comparative study
Mov. Disord.
A method for attenuation correction in radionuclide computed tomography
IEEE Trans Nucl. Sci.
A comparison of Tc-99m-HMPAO SPET changes in dementia with Lewy bodies and Alzheimer's disease using statistical parametric mapping
Eur. J. Nucl. Med.
Cerebral Blood Flow and Metabolism
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease
J. Neurol. Neurosurg. Psychiatry
Parametric mapping of cerebral blood flow deficits in Alzheimer's diseasea SPECT study using HMPAO and image standardization technique
J. Nucl. Med.
Cognitive function and regional cerebral blood flow in Parkinson's disease
Brain
Comparative diagnostic utility of different MR modalities in mild cognitive impairment and Alzheimer's disease
Dement. Geriatr. Cogn. Disord.
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