Dopamine Transporter Loss Visualized With FP-CIT SPECT in the Differential Diagnosis of Dementia With Lewy Bodies

Abstract

Background: Dementia with Lewy bodies (DLB) is a common form of late-life dementia that can be difficult to differentiate from other disorders, especially Alzheimer disease (AD), during life. At autopsy the striatal dopaminergic transporter is reduced. Objectives: To examine the extent and pattern of dopamine transporter loss using iodine I 123-radiolabeled 2 ␤ -c a r b o m e t h o x y -3 ␤ -( 4 -i o d o p h e n y l ) -N -( 3fluoropropyl) nortropane (FP-CIT) with single-photon emission computed tomography (SPECT) in DLBs compared with other dementias and to assess its potential to enhance a differential diagnosis. Design: Cohort study comparing FP-CIT with criterion standard of consensus clinical diagnosis. Setting: General hospital. Participants: One hundred sixty-four older subjects (33 healthy older control subjects, 34 with NINCDS/ADRDA [National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association]-confirmed AD, 23 with consensus guideline-confirmed DLB, 38 with United Kingdom's Parkinson Disease Society Brain Bank-confirmed Parkinson disease [PD], and 36 with PD and dementia).Interventions: Injection of 123 I-2␤-carbomethoxy-3␤-(4-iodophenyl)-N-(3-fluoropropyl) nortropane with SPECT scan performed at 4 hours. Main Outcome Measures: Visual ratings of scans and region of interest analysis.Results: Significant reductions (PϽ.001) in FP-CIT binding occurred in the caudate and anterior and posterior putamens in subjects with DLB compared with subjects with AD and controls. Transporter loss in DLBs was of similar magnitude to that seen in PD, but with a flatter rostrocaudal (caudate-putamen) gradient (P=.001), while the greatest loss in all 3 areas was seen in those who had PD and dementia. Both region of interest analysis and visual ratings provided good separation between DLBs and AD (region of interest: sensitivity, 78%; specificity, 94%; positive predictive value, 90%) but not among subjects with DLB, PD, and PD with dementia.Conclusions: Dopamine transporter loss can be detected in vivo using FP-CIT SPECT in DLB. Further studies, especially of subjects with DLB without PD, are required to fully establish use in clinical practice.

Validation of an automated morphological MRI-based 123I-FP-CIT SPECT evaluation method

“…Our results showed almost perfect interobserver agreement between the two observers in visually interpreting 123 I-FP-CIT SPECT images, which is consistent with an earlier study using the same 4-point visual rating scale [21]. Other studies are also reported a high interobserver agreement for visual analysis when using only a dichotomous division of normal versus abnormal SPECT images [22,23].…”

Multivariate Spatial Covariance Analysis of 99MTc-Exametazime SPECT Images in Dementia with Lewy Bodies and Alzheimer'S Disease: Utility in Differential Diagnosis

“…For 123 I-FP-CIT, a consensus visual rating score was used as the classification variable as previously reported. 8,15 The ROC curve analysis revealed diagnostic characteristics of (0.80 ± 0.06, 72%, 90%) and (0.83 ± 0.06, 81%, 84%) for the multivariate SCA approach and 123 I-FP-CIT visual rating, respectively, indicating similar diagnostic accuracy in this cohort (D ¼ 0.02 ± 0.09, Z ¼ 0.3, P ¼ 0.80). Table 2 depicts the association between 123 I-FP-CIT imaging and the multivariate SCA measures in classifying AD and DLB using clinical diagnosis as the 'gold' standard.…”

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

“…In vivo striatum dopaminergic denervation with loss of presynaptic striatal dopamine transporter (DAT), as measured by single-photon emission tomography (SPECT) and PET, is a consistent finding among patients with probable DLB, compared to clinically normal controls and patients with Alzheimer's disease dementia (Walker et al, 2002(Walker et al, , 2004O'Brien et al, 2004;McKeith et al, 2007). While the dopaminergic degeneration has been widely documented to affect the striatum of patients with DLB (Walker et al, 2004;Klein et al, 2010), a cholinergic network alteration involving the striatum has been postulated in the Lewy body disease spectrum of disorders (Langlais et al, 1993) but its mechanism is still poorly understood (Bohnen and Albin, 2011).…”