%0 Journal Article %J J Alzheimers Dis %D 2018 %T Dual Time-Point [18F]Florbetaben PET Delivers Dual Biomarker Information in Mild Cognitive Impairment and Alzheimer's Disease. %A Florek, Lisa %A Tiepolt, Solveig %A Schroeter, Matthias L %A Berrouschot, Jörg %A Saur, Dorothee %A Hesse, Swen %A Jochimsen, Thies %A Luthardt, Julia %A Sattler, Bernhard %A Patt, Marianne %A Hoffmann, Karl-Titus %A Villringer, Arno %A Classen, Joseph %A Gertz, Hermann-Josef %A Sabri, Osama %A Barthel, Henryk %X

BACKGROUND: Current research diagnostic criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD include biomarkers to supplement clinical testing. Recently, we demonstrated that dual time-point [18F]FBB PET is able to deliver both blood flow and amyloid-β (Aβ) load surrogates.

OBJECTIVE: The aim of this study was to investigate whether these surrogates can be utilized as AD biomarkers.

METHODS: 112 subjects (41 with MCI, 50 with probable/possible AD, 21 with other dementias) underwent dual time-point [18F]FBB PET. Data were visually and relative quantitatively (Herholz scores for the early and composite SUVRs for the late PET data) analyzed.

RESULTS: In the early images AD-typical patterns were present in 42% /27% /33% of probable/possible AD/MCI/other dementia cases. In late [18F]FBB PET, 42% /29% /38% of probable/possible AD/ MCI/other dementia cases were Aβ-positive. 17% of the MCIs were categorized as "MCI due to AD-high likelihood", 44% of the probable ADs as "probable AD with high evidence of AD pathophysiological process" and 28% of the possible ADs as "possible AD with evidence of AD pathophysiological process". 27% of all subjects showed a positive diagnostic and progression biomarker. Herholz scores were lower (0.85±0.05 versus 0.88±0.04, p = 0.015) for probable/possible AD versus MCI. Composite late phase SUVRs were significantly higher (1.65±0.23 versus 1.15±0.17, p < 0.005) in Aβ-positive versus Aβ-negative patients. Herholz and MMSE scores were positively correlated (R = 0.30 p = 0.006).

CONCLUSION: Dual time-point [18F]FBB PET provides dual biomarker information which enables to categorize MCI and AD dementia patients according to established diagnostic criteria. Thus, dual time-point [18F]FBB PET has great potential to supplement diagnostic dementia workups.

%B J Alzheimers Dis %V 66 %P 1105-1116 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/30400095?dopt=Abstract %R 10.3233/JAD-180522 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Quantitative Susceptibility Mapping of Amyloid-β Aggregates in Alzheimer's Disease with 7T MR. %A Tiepolt, Solveig %A Schäfer, Andreas %A Rullmann, Michael %A Roggenhofer, Elisabeth %A Gertz, Hermann-Josef %A Schroeter, Matthias L %A Patt, Marianne %A Bazin, Pierre-Louis %A Jochimsen, Thies H %A Turner, Robert %A Sabri, Osama %A Barthel, Henryk %X

BACKGROUND: PET imaging is an established technique to detect cerebral amyloid-β (Aβ) plaques in vivo. Some preclinical and postmortem data report an accumulation of redox-active iron near Aβ plaques. Quantitative susceptibility mapping (QSM) at high-field MRI enables iron deposits to be depicted with high spatial resolution.

OBJECTIVE: Aim of this study was to examine whether iron and Aβ plaque accumulation is related and thus, whether 7T MRI might be an additive diagnostic tool to Aβ PET imaging.

METHODS: Postmortem human Alzheimer's disease (AD) and healthy control (HC) frontal gray matter (GM) was imaged with 7T MRI which resulted in T1 maps and QSM. Aβ plaque load was determined by histopathology. In vivo, 10 Aβ PET-positive AD patients (74.1±6.0a) and 10 Aβ PET-negative HCs (67.1±4.4a) underwent 7T MR examination and QSM maps were analyzed. Severity of cognitive deficits was determined by MMSE.

RESULTS: Postmortem, the susceptibility of Aβ plaque-containing GM were higher than those of Aβ plaque-free GM (0.011±0.002 versus - 0.008±0.003 ppm, p < 0.001). In vivo, only the bilateral globus pallidus showed significantly higher susceptibility in AD patients compared to HCs (right: 0.277±0.018 versus - 0.009±0.009 ppm; left: 0.293±0.014 versus - 0.007±0.012 ppm, p < 0.0001). The pallidal QSM values were negatively correlated with those of the MMSE (r = - 0.69, p = 0.001).

CONCLUSION: The postmortem study revealed significant susceptibility differences between the Aβ plaque-containing and Aβ plaque-free GM, whereas in vivo only the QSM values of the globus pallidus differed significantly between AD and HC group. The pallidal QSM values correlated with the severity of cognitive deficits. These findings encourage efforts to optimize the 7T-QSM methodology.

%B J Alzheimers Dis %V 64 %P 393-404 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29865069?dopt=Abstract %R 10.3233/JAD-180118 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Histopathology and Florbetaben PET in Patients Incorrectly Diagnosed with Alzheimer's Disease. %A Sabbagh, Marwan N %A Schäuble, Barbara %A Anand, Keshav %A Richards, Danielle %A Murayama, Shigeo %A Akatsu, Hiroyasu %A Takao, Masaki %A Rowe, Christopher C %A Masters, Colin L %A Barthel, Henryk %A Gertz, Hermann-Josef %A Peters, Oliver %A Rasgon, Natalie %A Jovalekic, Aleksandar %A Sabri, Osama %A Schulz-Schaeffer, Walter J %A Seibyl, John %X

Of 57 individuals diagnosed with Alzheimer's disease (AD) in a phase III study, 13 (23%) had amyloid-β (Aβ) levels on postmortem histopathology that did not explain the dementia. Based on postmortem histopathology, a wide range of different non-AD conditions was identified, including frontotemporal dementia, hippocampal sclerosis, and dementia with Lewy bodies. Of the histopathologically Aβ negative scored cases ante-mortem Florbetaben PET scans were classified as negative for Aβ in 11 patients based on visual analysis and in all 12 quantifiable cases based on composite standardized uptake value ratios. Thus, florbetaben PET can assist physicians in the differential diagnosis of neurodegenerative disorders by reliably excluding Aβ pathology.

%B J Alzheimers Dis %V 56 %P 441-446 %8 2017 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27983552?dopt=Abstract %R 10.3233/JAD-160821 %0 Journal Article %J J Alzheimers Dis %D 2016 %T The Latent Dementia Phenotype δ is Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Predicts Conversion to Dementia in Subjects with Mild Cognitive Impairment. %A Koppara, Alexander %A Wolfsgruber, Steffen %A Kleineidam, Luca %A Schmidtke, Klaus %A Frölich, Lutz %A Kurz, Alexander %A Schulz, Stefanie %A Hampel, Harald %A Heuser, Isabella %A Peters, Oliver %A Reischies, Friedel M %A Jahn, Holger %A Luckhaus, Christian %A Hüll, Michael %A Gertz, Hermann-Josef %A Schröder, Johannes %A Pantel, Johannes %A Rienhoff, Otto %A Rüther, Eckart %A Henn, Fritz %A Wiltfang, Jens %A Maier, Wolfgang %A Jessen, Frank %A Kornhuber, Johannes %A Wagner, Michael %K Activities of Daily Living %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Biomarkers %K Cognitive Dysfunction %K Dementia %K Disease Progression %K Female %K Humans %K Logistic Models %K Longitudinal Studies %K Male %K Mental Status Schedule %K Middle Aged %K Neuropsychological Tests %K Peptide Fragments %K Phenotype %K Predictive Value of Tests %K Retrospective Studies %K tau Proteins %X

BACKGROUND: The recently proposed latent variable δ is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer's disease (AD) research and clinical trials.

OBJECTIVE: To investigate the association of δ with AD biomarkers and to compare the prediction of δ with established scales for conversion to dementia in patients with mild cognitive impairment (MCI).

METHODS: Using data from a multicenter memory clinic study, we examined the external associations of the latent variable δ and compared δ with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences.

RESULTS: In patients with MCI, δ based on a broad range of cognitive scales (including the ADAS-cog, the MMSE, and the CERAD neuropsychological battery) predicted an abnormal CSF Aβ42/tau ratio indicative of AD (n = 340, AUC = 0.78, p <  0.001), and predicted incident dementia within 1-3 years of follow-up (n = 525, AUC = 0.84, p <  0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of δ based on reduced test batteries yielded somewhat lower effects.

CONCLUSION: These findings support the interpretation of δ as a construct capturing the disease-related "essence" of cognitive and functional impairments in patients with MCI and dementia, and suggest that δ might become an analytical tool for dementia research.

%B J Alzheimers Dis %V 49 %P 547-60 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26484902?dopt=Abstract %R 10.3233/JAD-150257