Longitudinal assessment of amyloid-beta deposition in initially amyloid-negative non-demented individuals with [11C]-PIB PET imaging.

ABSTRACT: This study aimed to assess the longitudinal changes in amyloid beta (Aß) deposition in cortical regions with [11C]-PIB PET in initially amyloid-negative non-demented subjects and evaluate whether amyloid-negative subjects convert to amyloid-positive.Sixteen cognitively normal (CN) and 7 mild cognitive impairment (MCI) subjects (aged 60-75 years), who were amyloid-negative at baseline, underwent 60-minute dynamic [11C]-PIB PET and cognitive assessment over 5.0 to 9.4 years of a long follow-up, and the apolipoprotein-E (APOE) genotype was assessed. Regions of interest were defined in the bilateral cortex on coregistered MRI. Quantitative analysis of [11C]-PIB was performed using the distribution value ratio (DVR). Longitudinal changes in global and regional PIB DVRs were evaluated in the same regions, and the annual rate of change in the PIB DVR was calculated.Seven (30.4%) of 23 initially amyloid-negative non-demented subjects converted to globally amyloid-positive (global PIB DVR ≥1.40) over a follow-up of 6.5 ±â€Š1.4 years (converter). The global PIB DVR in converters increased from 1.22 ±â€Š0.07 at baseline to 1.63 ±â€Š0.15 (n = 7, P < .01) at last follow-up, and an annual increase of global PIB DVR was 0.057 ±â€Š0.019/year (n = 7, P < .01). In contrast, the global PIB DVR in the remaining 16 subjects was 1.15 ±â€Š0.07 at baseline and did not change over a follow-up period (stable). The APOE ε4 allele was present in 4 (57.1%) of the 7 converters, differing from 2 (12.5%) of 16 stable subjects (Fisher's exact test, P < .05). Three amyloid-negative MCI subjects had an annual increase in global PIB DVR above 0.061/year and became positive at 2.8 ±â€Š0.5 years of follow-up, which was faster than 5.0 ±â€Š2.0 years in 4 CN subjects. The regional PIB DVR that increased early above the regional positivity threshold was most frequently found in the right lateral temporal cortex (71.4%), followed by the left frontal cortex (41.8%).Our results suggest that the initially amyloid-negative CN and MCI subjects, especially with APOE ε4, can become globally amyloid-positive over a longer time, based on early regional Aß deposition in the lateral temporal cortex and/or frontal cortex.

Longitudinal Assessment of Amyloid-ß Deposition by [18F]-Flutemetamol PET Imaging Compared With [11C]-PIB Across the Spectrum of Alzheimer's Disease.

This study evaluates the longitudinal changes in the amyloid-ß (Aß) deposition with [18F]-flutemetamol (FMM) PET imaging across the spectrum of Alzheimer's disease (AD), compared with [11C]-Pittsburgh Compound-B (PIB) PET. Eleven AD, 17 mild cognitive impairment (MCI) and 13 cognitively normal (CN) subjects underwent neuropsychological assessment and amyloid PET imaging using [18F]-FMM and [11C]-PIB during a follow-up period. Regions of interest were defined on co-registered MRI, and the FMM and PIB standardized uptake value ratio (SUVR) was used in the same cortical regions. The annual rate of change in FMM and PIB SUVRs was calculated. Cortical FMM SUVR in amyloid-positive subjects increased over a follow-up of 3.1 ± 0.5 years. An individual FMM SUVR was significantly correlated with PIB SUVR at baseline and at follow-up in the same AD, MCI, and CN subjects. The annual rate of increase in FMM SUVR was significantly greater in typical amyloid-positive (0.033 ± 0.023, n = 7), focal positive MCI (0.076 ± 0.034, n = 4) and positive CN (0.039 ± 0.027, n = 4) while that in AD (0.020 ± 0.018, n = 11) was smaller. Among amyloid-positive patients, the baseline FMM SUVR was inversely related with the increased rate in FMM SUVR (r=-0.44, n = 26, p < 0.05). An individual annual rate in change of cortical FMM SUVR was significantly correlated with that in cortical PIB SUVR. Our results suggest that the [18F]-FMM PET imaging can clarify the longitudinal assessment of Aß deposition across the AD spectrum, similarly to [11C]-PIB PET. The Increase in Aß deposition is faster in the predementia stage but not at a constant rate across the clinical stages of the AD spectrum.

Amyloid ß deposition and glucose metabolism on the long-term progression of preclinical Alzheimer's disease.

AIM: Longitudinal changes in beta amyloid (Aß) deposition and glucose metabolism over a long-term progression of preclinical Alzheimer's disease (AD) were evaluated. METHODS: 22 preclinical AD subjects with amyloid-positive scans underwent [11C]-labeled Pittsburgh Compound-B (PIB) positron emission tomography (PET) and [18F]-fluorodeoxyglucose (FDG) PET imaging over 6.0 ± 1.8 years. A quantitative analysis of [11C]-PIB and [18F]-FDG was used with a standardized uptake value ratio (SUVR) in the same regions. RESULTS: In preclinical AD subjects, the cortical PIB SUVR was higher at baseline and increased at follow-up. 12 of the preclinical AD subjects progressed to mild cognitive impairment, six of whom had reduced glucose metabolism. The annual change in PIB SUVR was not related to that in FDG SUVR. CONCLUSION: Increases in Aß deposition lead to the progression to mild cognitive impairment, but decreases in glucose metabolism do not contribute to progression.

Amyloid-ß Deposition and Long-Term Progression in Mild Cognitive Impairment due to Alzheimer's Disease Defined with Amyloid PET Imaging.

The aim was to evaluate brain amyloid-ß (Aß) deposition in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) using amyloid PET imaging and clarify the relationship between the annual change in Aß deposition and disease progression. Forty-eight MCI patients underwent neuropsychological assessment and amyloid PET imaging using [11C]-PIB over a follow-up of 5.7±1.5 years. Thirty-nine MCI patients who had an amyloid-positive scan were defined as MCI due to AD, and 9 MCI patients who had an amyloid-negative scan were included. Regions of interest were defined on co-registered MRI, and the PIB standardized uptake value ratio (SUVR) on the same regions was used over follow-up. Annual change in PIB SUVR was calculated. Patients with MCI due to AD had higher baseline PIB SUVR (1.81±0.32, n = 39, p < 0.01) and a greater annual rate of change in PIB SUVR (0.044±0.027, n = 39, p < 0.01) compared to amyloid-negative MCI patients. Twenty-eight (71.8%) progressed to AD. In patients who progressed during a short duration of 1.7±0.8 years, the annual rate of increase in PIB SUVR was 0.101±0.094 (n = 16, p < 0.05), which was greater compared to patients with long conversion or stable patients. There was a negative correlation between the annual rate of increase in PIB SUVR and duration of progression to AD among individual MCI converters (r = -0.47, n = 28, p < 0.05). The patients defined as MCI due to AD could progress to AD with a shorter period if they have a greater increased annual rate in brain Aß deposition.

[18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer's disease.

PURPOSE: The aim was to identify the amyloid beta (Aß) deposition by positron emission tomography (PET) imaging with the (18)F-labeled Pittsburgh compound B (PIB) derivative [(18)F]flutemetamol (FMM) across a spectrum of Alzheimer's disease (AD) and to compare Aß deposition between [(18)F]FMM and [(11)C]PIB PET imaging. METHODS: The study included 36 patients with AD, 68 subjects with mild cognitive impairment (MCI), 41 older healthy controls (HC) (aged ≥56), 11 young HC (aged ≤45), and 10 transitional HC (aged 46-55). All 166 subjects underwent 30-min static [(18)F]FMM PET 85 min after injection, 60-min dynamic [(11)C]PIB PET, and cognitive testing. [(18)F]FMM scans were assessed visually, and standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest identified on coregistered MRI (cerebellar cortex as a reference region). The PIB distribution volume ratios (DVR) were determined in the same regions. RESULTS: Of 36 AD patients, 35 had positive scans, while 36 of 41 older HC subjects had negative scans. [(18)F]FMM scans had a sensitivity of 97.2% and specificity of 85.3% in distinguishing AD patients from older HC subjects, and a specificity of 100% for young and transitional HC subjects. The [(11)C]PIB scan had the same results. Interreader agreement was excellent (kappa score = 0.81). The cortical FMM SUVR in AD patients was significantly greater than in older HC subjects (1.76 ± 0.23 vs 1.30 ± 0.26, p < 0.01). Of the MCI patients, 68 had a bimodal distribution of SUVR, and 29 of them (42.6%) had positive scans. Cortical FMM SUVR values were strongly correlated with PIB DVR (r = 0.94, n = 145, p < 0.001). CONCLUSION: [(18)F]FMM PET imaging detects Aß deposition in patients along the continuum from normal cognitive status to dementia of AD and discriminates AD patients from HC subjects, similar to [(11)C]PIB PET.

Diagnosed mild cognitive impairment due to Alzheimer's disease with PET biomarkers of beta amyloid and neuronal dysfunction.

The aim of this study is to identify mild cognitive impairment (MCI) due to Alzheimer's disease (AD) using amyloid imaging of beta amyloid (Aß) deposition and FDG imaging of reflecting neuronal dysfunction as PET biomarkers. Sixty-eight MCI patients underwent cognitive testing, [11C]-PIB PET and [18F]-FDG PET at baseline and follow-up. Regions of interest were defined on co-registered MRI. PIB distribution volume ratio (DVR) was calculated using Logan graphical analysis, and the standardized uptake value ratio (SUVR) on the same regions was used as quantitative analysis for [18F]-FDG. Thirty (44.1%) of all 68 MCI patients converted to AD over 19.2±7.1 months. The annual rate of MCI conversion was 23.4%. A positive Aß PET biomarker significantly identified MCI due to AD in individual MCI subjects with a sensitivity (SS) of 96.6% and specificity (SP) of 42.1%. The positive predictive value (PPV) was 56.8%. A positive Aß biomarker in APOE ε4/4 carriers distinguished with a SS of 100%. In individual MCI subjects who had a prominent impairment in episodic memory and aged older than 75 years, an Aß biomarker identified MCI due to AD with a greater SS of 100%, SP of 66.6% and PPV of 80%, compared to FDG biomarker alone or both PET biomarkers combined. In contrast, when assessed in precuneus, both Aß and FDG biomarkers had the greatest level of certainty for MCI due to AD with a PPV of 87.8%. The Aß PET biomarker primarily defines MCI due to AD in individual MCI subjects. Furthermore, combined FDG biomarker in a cortical region of precuneus provides an added diagnostic value in predicting AD over a short period.

Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging.

We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p < 0.01) than amyloid-negative healthy control (HC) subjects. The DVR values in 23 patients with very mild AD (CDR: 0.5) and 22 patients with mild AD (CDR: 1.0) were 2.32 ± 0.45 and 2.34 ± 0.42, respectively, similar to moderate AD. In contrast, 28 (48%) of the 58 mild cognitive impairment (MCI) patients (MMSE: 27.3 ± 1.7) showed a typical AD-like pattern with a DVR value of 2.07 ± 0.34. Further, 17 (18%) of 91 HC subjects had a typical AD-like pattern with a DVR value of 2.06 ± 0.28. They did not significantly differ from very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75 years or older increased greatly to 74% whereas that of amyloid positive HC decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD dementia is identified, based on cognitive function and amyloid deposition by PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

Dissecting aneurysms of bilateral anterior cerebral artery complicated by subarachnoid hemorrhage after cerebral infarction: a case report.

INTRODUCTION: Intracranial dissecting aneurysms have been increased due to recent advancements in diagnostic imaging. However there have been little article with subarachnoid hemorrhage and cerebral infarction occurring almost at the same time. We performed the surgical treatment and obtained good result. CASE PRESENTATION: A 47-year-old male presented to our hospital with chief complaints of sudden headache and mild paralysis of the left lower extremity. Brain imaging at admission revealed cerebral infarction in the right frontal lobe and subarachnoid hemorrhage in the frontal convexy and anterior interhemispheric fissure. The left and right internal carotid angiography showed a bulging cerebral aneurysm at the left A1-A2 junction and stenosis and arterial dissections in the peripheral of the bilateral anterior cerebral artery. Wrapping was performed for the dissecting aneurysm of the left anterior cerebral artery. For the right anterior cerebral artery, trapping was performed at the A2 segment without vascular anastomosis. The patient's postoperative course was uneventful. CONCLUSION: A consensus has not been reached on the treatment for intracranial dissecting aneurysms. Proximal trapping without vascular reconstruction was performed for the right anterior cerebral artery without vascular anastomosis to prevent rebleeding. However no symptoms of neurological deficiency were observed. Proximal trapping of dissecting aneurysm seems to be a good option when patient's functional and life prognosis are taken into account in case that vascular reconstruction will be anticipated difficulty.

Multifocal primary intracerebral malignant fibrous histiocytoma--case report.

A 58-year-old female presented with a unique case of multifocal primary intracerebral malignant fibrous histiocytoma (MFH) manifesting as partial seizure. Neuroimaging showed a mass lesion in the right frontal lobe, which was totally removed. The histological diagnosis was MFH. Follow-up neuroimaging one month after surgery showed another lesion rapidly growing in the left frontal lobe. This lesion was totally removed, and identified as MFH. Her condition gradually worsened. Neuroimaging performed 3 months after first operation revealed bilateral recurrence. She died of respiratory failure 7 months after the initial diagnosis of MFH. Primary intracranial MFH is an extremely rare entity with only 31 cases of solitary tumor previously reported.

Schwannoma of the spinal accessory nerve--case report.

A 60-year-old woman presented with a rare schwannoma arising from a spinal accessory nerve at the C1-2 levels manifesting as cervico-occipital pain. The tumor was removed by surgery with the involved segment of the nerve. She had no postoperative neurological deficit. Histological examination confirmed the diagnosis of schwannoma. Surgical removal is recommended for such cases.