ABSTRACT
The widespread deposition of amyloid-ß (Aß) plaques in late-stage Alzheimer disease is well defined and confirmed by in vivo PET. However, there are discrepancies between which regions contribute to the earliest topographic Aß deposition within the neocortex. Methods: This study investigated Aß signals in the perithreshold SUV ratio range using Pittsburgh compound B (PiB) PET in a population-based study cross-sectionally and longitudinally. PiB PET scans from 1,088 participants determined the early patterns of PiB loading in the neocortex. Results: Early-stage Aß loading is seen first in the temporal, cingulate, and occipital regions. Regional early deposition patterns are similar in both apolipoprotein ε4 carriers and noncarriers. Clustering analysis shows groups with different patterns of early amyloid deposition. Conclusion: These findings of initial Aß deposition patterns may be of significance for diagnostics and understanding the development of Alzheimer disease phenotypes.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Neocortex , Positron-Emission Tomography , Thiazoles , Humans , Neocortex/diagnostic imaging , Neocortex/metabolism , Amyloid beta-Peptides/metabolism , Male , Female , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Aniline Compounds , Middle Aged , Aged, 80 and over , Cross-Sectional Studies , Longitudinal Studies , RadiopharmaceuticalsABSTRACT
Reduced nigrostriatal uptake on N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-[123I]iodophenyl) nortropane (123I-FP-CIT) SPECT reflects dopamine dysfunction, while other imaging markers could be complementary when used together. We assessed how well 123I-FP-CIT SPECT differentiates dementia with Lewy bodies (DLBs) from Alzheimer's disease dementia (ADem) and whether multimodal imaging provides additional value. 123I-FP-CIT SPECT, magnetic resonance imaging, [18F]2-fluoro-deoxy-D-glucose-positron emission tomography (PET), and 11C-Pittsburgh compound B (PiB)-PET were assessed in 35 participants with DLBs and 14 participants with ADem (autopsy confirmation in 9 DLBs and 4 ADem). Nigrostriatal dopamine transporter uptake was evaluated with 123I-FP-CIT SPECT using DaTQUANT software. Hippocampal volume was calculated with magnetic resonance imaging, cingulate island sign ratio with FDG-PET, and global cortical PiB retention with PiB-PET. The DaTQUANT z-scores of the putamen showed the highest c-statistic of 0.916 in differentiating DLBs from ADem among the analyzed imaging biomarkers. Adding another imaging modality to 123I-FP-CIT SPECT had c-statistics ranging from 0.968 to 0.975, and 123I-FP-CIT SPECT in combination with 2 other imaging modalities presented c-statistics ranging from 0.987 to 0.996. These findings suggest that multimodal imaging with 123I-FP-CIT SPECT aids in differentiating DLBs and ADem and in detecting comorbid Lewy-related and Alzheimer's disease pathology in patients with DLBs and ADem.
Subject(s)
Alzheimer Disease/diagnostic imaging , Brain/diagnostic imaging , Lewy Body Disease/diagnostic imaging , Multimodal Imaging/methods , Tomography, Emission-Computed, Single-Photon/methods , Diagnosis, Differential , Female , Humans , Iodine Radioisotopes , Magnetic Resonance Imaging , Male , Positron-Emission Tomography , Radiopharmaceuticals , Software , TropanesABSTRACT
Our rationale was to conduct a retrospective study comparing 3 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathologic findings. Methods:123I-FP-CIT-SPECT and neuropathologic findings among patients with neurodegenerative syndromes from the Mayo Alzheimer Disease Research Center and Mayo Clinic Study of Aging were examined. Three 123I-FP-CIT SPECT quantitative assessment methods-MIMneuro, DaTQUANT, and manual region-of-interest creation on a workstation-were compared with neuropathologic findings describing the presence or absence of Lewy body disease (LBD). Striatum-to-background ratios (SBRs) generated by DaTQUANT were compared with the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen, and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro, the left, right, total, and average SBRs and z scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients (20 [83%] male, mean age for all patients at death, 75.4 ± 10.0 y). The antemortem clinical diagnoses were Alzheimer disease dementia (n = 6), probable dementia with Lewy bodies (n = 12), mixed Alzheimer disease dementia and probable dementia with Lewy bodies (n = 1), Parkinson disease with mild cognitive impairment (n = 2), corticobasal syndrome (n = 1), idiopathic rapid-eye-movement sleep behavior disorder (n = 1), and behavioral-variant frontotemporal dementia (n = 1). Seventeen (71%) had LBD. All 3 123I-FP-CIT SPECT quantitative methods had an area under the receiver-operating-characteristics curve ranging from more than 0.93 to up to 1.000 (P < 0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed (P < 0.001). There was no significant difference between the accuracy of the regions in discriminating the 2 groups, with good discrimination for both caudate and putamen. Conclusion: All 3 123I-FP-CIT SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z scores.
