Aß imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study.

BACKGROUND: We assessed the clinical utility of ß-amyloid (Aß) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aß, hippocampal volume (HV) and memory over time. METHODS: 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥ 1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <-1.5. RESULTS: At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB-, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB- developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB- had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB-. CONCLUSIONS: (18)F-florbetaben Aß imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aß, seems to drive memory decline. TRIAL REGISTRATION NUMBER: NCT01138111.

Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT.

Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video-recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).

Prediction of amyloid-ß pathology in amnestic mild cognitive impairment with neuropsychological tests.

Assessment of disease biomarkers, particularly the in vivo assessment of amyloid-ß (Aß) burden with positron emission tomography (PET), is gradually becoming central to the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD). However, the incorporation of biomarker evidence to the diagnostic process is currently restricted mainly to research settings. The identification of memory measures that are associated with Aß is of clinical relevance as this may enhance the confidence in making a diagnosis of MCI due to AD in clinical settings. Forty one persons with amnestic MCI underwent Aß imaging with (18)F-Florbetaben PET, magnetic resonance imaging, and a comprehensive neuropsychological assessment. All measures of episodic memory were significantly correlated with Aß burden, but regression analyses revealed a strong and selective association between story recall and Aß over and beyond the effects of age, education, global cognition, hippocampal volume, or other memory tests. Analyses of sensitivity and specificity of memory measures to detect high versus low Aß scans suggested that word-list recall performed better when high sensitivity was preferred, whereas story recall performed better when high specificity was preferred. In conclusion, a measure of story recall may increase the confidence in making a diagnosis of MCI due to AD in clinical settings.

(18)F-florbetaben Aß imaging in mild cognitive impairment.

INTRODUCTION: (18)F-florbetaben and positron emission tomography were used to examine the relationships between ß-amyloid (Aß) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impairment (MCI). METHODS: Forty-five MCI participants were evaluated. A neocortical standardized uptake value ratio threshold ≥ 1.45 was used to discriminate high from low Aß burden. Correlations were adjusted for age, gender and years of education. RESULTS: High Aß burden was found in 53% of MCI. Regression analyses showed standardized uptake value ratio (r = -0.51, P = 0.0015) and hippocampal volume (r = 0.60, P = 0.024) both contributing to episodic memory impairment in independent fashion. White matter hyperintensities correlated with nonmemory cognition, and this correlation was particularly associated with Aß burden. CONCLUSION: Higher Aß deposition in MCI is associated with more severe memory impairment and is contributing to early amnestic symptoms independent of hippocampal atrophy.

Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias.

UNLABELLED: Amyloid imaging with (18)F-labeled radiotracers will allow widespread use, facilitating research, diagnosis, and therapeutic development for Alzheimer disease. The purpose of the study program was to compare cortical amyloid deposition using (18)F-florbetaben and PET in controls and subjects with mild cognitive impairment (MCI), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), vascular dementia (VaD), Parkinson disease (PD), and Alzheimer disease (AD). METHODS: One hundred nine subjects in 3 clinical studies at Austin Health were reviewed: 32 controls, 20 subjects with MCI, and 30 patients with AD, 11 with FTLD, 7 with DLB, 5 with PD, and 4 with VaD underwent PET after intravenous injection of 300 MBq of (18)F-florbetaben. Standardized uptake value ratios (SUVR) using the cerebellar cortex as a reference region were calculated between 90 and 110 min after injection. RESULTS: When compared with the other groups, AD patients demonstrated significantly higher SUVRs (P < 0.0001) in neocortical areas. Most AD patients (96%) and 60% of MCI subjects showed diffuse cortical (18)F-florbetaben retention. In contrast, only 9% of FTLD, 25% of VaD, 29% of DLB, and no PD patients and 16% of controls showed cortical binding. Although there was a correlation between Mini Mental State Examination and ß-amyloid burden in the MCI group, no correlation was observed in controls, FTLD or AD. CONCLUSION: (18)F-florbetaben had high sensitivity for AD, clearly distinguished patients with FTLD from AD, and provided results comparable to those reported with (11)C-Pittsburgh Compound B in a variety of neurodegenerative diseases.

Endovascular repair of inflammatory abdominal aortic aneurysms: a valuable alternative?--Case report and review of literature.

While endovascular repair (ER) has become a routine procedure in the treatment of arteriosclerotic abdominal aortic aneurysms with a suitable configuration, only rare reports of interventional treatment of inflammatory aortic abdominal aneurysms (IAAA) exist. We present a case study of a male patient with IAAA, who presented with inflammatory thickening involving the entire circumference of the aortic vessel wall. The MRI performed 8 months after successful ER demonstrated complete regression of vessel wall induration. A patient with the appropriate anatomical configuration of IAAA should benefit from the lower morbidity and mortality of endovascular aneurysm repair (EVAR). In our view, EVAR is preferable to open surgical repair in the specific situation of IAAA.