Biomarkers Differentiating Dementia with Lewy Bodies from Other Dementias: A Meta-Analysis

Article type: Research Article

Authors: Mishima, Aki^{a; 1} | Nihashi, Takashi^{b; 1} | Ando, Yoshio^c | Kawai, Hisashi^b | Kato, Takashi^d | Ito, Kengo^d | Terasawa, Teruhiko^{a; e; *}

Affiliations: [a] Section of General Internal Medicine, Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan | [b] Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan | [c] Department of Radiology, Toyota Memorial Hospital, Toyota, Aichi, Japan | [d] Department of Radiology, Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [e] Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Teruhiko Terasawa, MD, PhD, Section of General Internal Medicine, Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan. Tel./Fax: +81 562 93 2497; E-mail: [email protected]

Note: [1] These authors contributed equally to the study and manuscript.

Abstract: Background:Several nuclear imaging and cerebrospinal fluid (CSF) biomarkers are under investigation, aimed at facilitating the differential diagnosis of dementias. Objective:To quantitatively synthesize data on test performance in differentiating dementia with Lewy bodies (DLB) from other dementias. Methods:We searched PubMed (January 2000– March 2015) for English-language publications that assessed a selected set of five imaging and three CSF biomarkers for this purpose. We meta-analyzed measures of agreement between biomarker results and clinical diagnosis. Results:Forty-five publications were eligible. The majority of evidence was based on studies that enrolled representative disease populations. For differentiating between DLB and Alzheimer’s disease (AD) or other dementias, metaiodobenzylguanidine scintigraphy and dopamine transporter (DAT) single photon emission computed tomography (SPECT) showed, respectively, excellent (summary kappa = 0.85; 95% confidence interval [95% CI], 0.74–0.96) and good (summary kappa = 0.71; 95% CI, 0.43–0.99) agreement. Metaiodobenzylguanidine scintigraphy appeared superior to fluorodeoxyglucose– positron emission tomography (summary kappa = 0.53; 95% CI, 0.36–0.69) and cerebral blood flow SPECT (summary kappa = 0.40; 95% CI, 0.33–0.47). For differentiating DLB from AD, CSF t-tau levels (summary kappa = 0.68; 95% CI, 0.55–0.82) performed comparably to metaiodobenzylguanidine scintigraphy and DAT SPECT. Sparse direct comparative evidence failed to corroborate these indirect comparisons. Conclusion:Metaiodobenzylguanidine scintigraphy and DAT SPECT are highly concordant with clinical diagnosis in differentiating DLB from other dementias. However, given the limitations in the study design, the applicability of these results to real-world differential diagnosis remains unclear. Prospective studies targeting patients with atypical presentations that adopt gold standard tests would reliably estimate the true test performance of these promising biomarkers.

Keywords: Alzheimer’s disease, dementia, dementia with Lewy bodies, diagnosis, meta-analysis

DOI: 10.3233/JAD-150675

Journal: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 161-174, 2016