A study of the clinical features of PIB-negative dementia patients in amyloid PET

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Background/Aims : We previously found that some cases of clinically diagnosed Alzheimer's disease(AD) were rated as Pittsburgh compound-B(PiB)-negative by amyloid imaging(ie, cases of PiB-negative dementia). These may involve diseases that do not have pathological amyloid accumulation in the brain, such as dementia with Lewy bodies(DLB), frontotemporal lobar degeneration(FTLD), argyrophilic grain disease(AGD), and neurofibrillary tangle-predominant dementia(NFTD), as well as AD itself. The present study was designed to analyze the clinical features of PiB-negative dementia patients in detail with cerebrospinal fluid(CSF) analysis and neuroradiological tests. Methods : Of the 64 cases of clinically diagnosed AD, 14 were rated PiB-negative with PiB-positron emission tomography(PET). Eleven of these were further analyzed using CSF biomarker levels and findings from magnetic resonance imaging(MRI), fluorodeoxyglucose(FDG)-PET,<123>^I-metaiodobenzylguanidine(MIBG) myocardial scintigraphy, and voxel-based morphometry(VBM). Results : When examined by<123>^I-MIBG myocardial scintigraphy, the PiB-negative dementia group differed slightly from the healthy control group in both the early and delayed phases, and the H/M ratio was significantly higher in the PiB-negative dementia group than in the DLB group. Analyses of CSF biomarkers and MRI and FDG-PET findings among the 11 cases of PiB-negative dementia suggested AGD in 3 cases, FTLD in 3 cases, NFTD in 1 case, and AD in 2 cases. Conclusion : PiB-negative dementia is unlikely to include DLB, while it most likely includes diseases of tauopathy, such as FTLD, AGD, and NFTD. A better understanding of PiB-negative dementia is expected to further improve the accuracy of clinical diagnosis of AD.