Diagnostic Accuracy of ¹²³I-Meta-Iodobenzylguanidine Myocardial Scintigraphy in Dementia with Lewy Bodies: A Multicenter Study

<div><p>Background and Purpose</p><p>Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer’s disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand ¹²³I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study.</p><p>Methods</p><p>We performed a multicenter study in which we used ¹²³I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of ¹²³I-MIBG uptake were also calculated using an automated region-of-interest based system.</p><p>Results</p><p>Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio.</p><p>Conclusions</p><p>Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with ¹²³I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.</p></div

Clinical characteristics of the subjects.

<p>Data are mean (SD).</p><p>*χ² test.</p><p>†ANOVA.</p><p>‡Kruskal-Wallis test.</p><p>MMSE: mini-mental state examination; CDR-J: clinical dementia rating scale-Japan; CDT: clock drawing test.</p><p>Clinical characteristics of the subjects.</p

Flow diagram of the eligible patients and the enrolling process of the study.

<p>Flow diagram of the eligible patients and the enrolling process of the study.</p

Sensitivity and specificity of H/M ratio in differentiating between probable DLB and probable AD.

<p>PPV: positive predictive value; NPV: negative predictive value</p><p>Sensitivity and specificity of H/M ratio in differentiating between probable DLB and probable AD.</p

Sensitivity and specificity of visual assessment in differentiating between probable DLB and probable AD.

<p>Sensitivity and specificity of visual assessment in differentiating between probable DLB and probable AD.</p

Normal and abnormal planar image of ¹²³I-MIBG cardiac scintigraphy.

<p>Normal and abnormal planar image of ¹²³I-MIBG cardiac scintigraphy.</p

ROC curves for the detection of probable DLB from probable AD based on H/M ratio of each group.

<p>The area under the ROC curve of the early H/M ratio was 0.805 (<i>p</i> < 0.001) for the all patients group, 0.901 (<i>p</i> < 0.0001) for the mild dementia group, and 0.732 (<i>p</i> = 0.001) for the moderate/severe dementia group, whereas that for the delayed H/M ratio was 0.817 (<i>p</i> < 0.001), 0.942 (<i>p</i> < 0.0001), and 0.747 (<i>p</i> = 0.007), respectively. ROC: receiver operating characteristic. AUC: area under the curve.</p

Meta-analysis of top-ranked association results with <i>SORL1</i> in Japanese, Korean, and Caucasian datasets.

<p>CH:MB, chromosome:position (in megabase pairs, build 19); MA, minor allele; MAF, minor allele frequenc; OR, odds ratio; <i>P</i> P-value.</p

Sample size and characteristics of the discovery and replication datasets.

<p>Sample size and characteristics of the discovery and replication datasets.</p

Forest plots of the two most strongly associated SNPs, rs3781834 (A) and rs11218343 (B), in the <i>SORL1</i> region showing the strength and pattern of significance in the Japanese discovery and each replication dataset in the model of adjusting for population structure, age, and sex.

<p>Forest plots of the two most strongly associated SNPs, rs3781834 (A) and rs11218343 (B), in the <i>SORL1</i> region showing the strength and pattern of significance in the Japanese discovery and each replication dataset in the model of adjusting for population structure, age, and sex.</p