Longitudinal structural and metabolic changes in frontotemporal dementia.

OBJECTIVE: To compare the sensitivity of structural MRI and 18F-fludeoxyglucose PET (18FDG-PET) to detect longitudinal changes in frontotemporal dementia (FTD). METHODS: Thirty patients with behavioral variant FTD (bvFTD), 7 with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), 16 with semantic variant primary progressive aphasia (svPPA), and 43 cognitively normal controls underwent 2-4 MRI and 18FDG-PET scans (total scans/visit = 270) as part of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study. Linear mixed-effects models were carried out voxel-wise and in regions of interest to identify areas showing decreased volume or metabolism over time in patients as compared to controls. RESULTS: At baseline, patients with bvFTD showed bilateral temporal, dorsolateral, and medial prefrontal atrophy/hypometabolism that extended with time into adjacent structures and parietal lobe. In nfvPPA, baseline atrophy/hypometabolism in supplementary motor cortex extended with time into left greater than right precentral, dorsolateral, and dorsomedial prefrontal cortex. In svPPA, baseline atrophy/hypometabolism encompassed the anterior temporal and medial prefrontal cortex and longitudinal changes were found in temporal, orbitofrontal, and lateral parietal cortex. Across syndromes, there was substantial overlap in the brain regions showing volume and metabolism loss. Even though the pattern of metabolic decline was more extensive, metabolic changes were also more variable and sample size estimates were similar or higher for 18FDG-PET compared to MRI. CONCLUSION: Our findings demonstrated the sensitivity of 18FDG-PET and structural MRI for tracking disease progression in FTD. Both modalities showed highly overlapping patterns of longitudinal change and comparable sample size estimates to detect longitudinal changes in future clinical trials.

Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia.

Importance: The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. Objective: To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). Design, Setting, and Participants: This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. Main Outcomes and Measures: Clinical, cognitive, neuroimaging, and pathology results. Results: Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. Conclusions and Relevance: Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.

Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease.

The relationships between ß-amyloid (Aß), tau and neurodegeneration within Alzheimer's Disease pathogenesis are not fully understood. To explore these associations in vivo, we evaluated 30 Aß PET-positive patients (mean ± sd age 62.4 ± 8.3) with mild probable AD and 12 Aß PET-negative healthy controls (HC) (mean ± sd age 77.3 ± 6.9) as comparison. All participants underwent 3 T MRI, 11C-PiB (Aß) PET and 18F-AV1451 (tau) PET. Multimodal correlation analyses were run at both voxel- and region-of-interest levels. 11C-PiB retention in AD showed the most diffuse uptake pattern throughout association neocortex, whereas 18F-AV1451 and gray matter volume reduction (GMR) showed a progressive predilection for posterior cortices (p<0.05 Family-Wise Error-[FWE]-corrected). Voxel-level analysis identified negative correlations between 18F-AV1451 and gray matter peaking in medial and infero-occipital regions (p<0.01 False Discovery Rate-[FDR]-corrected). 18F-AV1451 and 11C-PiB were positively correlated in right parietal and medial/inferior occipital regions (p<0.001 uncorrected). 11C-PiB did not correlate with GMR at the voxel-level. Regionally, 18F-AV1451 was largely associated with local/adjacent GMR whereas frontal 11C-PiB correlated with GMR in posterior regions. These findings suggest that, in mild AD, tau aggregation drives local neurodegeneration, whereas the relationships between Aß and neurodegeneration are not region specific and may be mediated by the interaction between Aß and tau.

Biological grafts for hemodialysis access: historical lessons, state-of-the-art and future directions.

The vast majority of arteriovenous grafts (AVG) have been constructed using expanded polytetrafluoroethylene (ePTFE). While ePTFE grafts have the advantage of being relatively inexpensive and easy to manufacture, distribute, ship, and store, their primary patency rates are disappointing when compared with the native AVF. Though use of arteriovenous fistulas (AVF) in the United States has increased substantially, approximately 25% of hemodialysis patients continue to use AVG as their vascular access. We present here a comprehensive review of biological grafts and their use in hemodialysis vascular access. In this review, we discuss the use of synthetics and then explore the evolution of biological grafts over the past 20 years, their clinical impact, and future challenges in widespread clinical use in hemodialysis patients. Provided are in depth descriptions of currently used nonbiological arteriovenous grafts and the recent approaches in increasing the patency of synthetic grafts. Recent technological advances using tissue-engineered AVGs have shown promise for patients receiving hemodialysis and their potential to provide an attractive, viable option for vascular access have been discussed.

Radiation exposure in dialysis access-related procedures decreases with increase in number of procedures performed by the interventional nephrologist.

An appreciation of the inherent risks with radiation exposure to patients and to the physician performing the procedure and the staff is urgently needed. The objective of this study is to assess radiation exposure to both patients and interventional nephrologists performing procedures and see any trends in the procedure and fluoroscopy times over a 2-year period. A total of 400 procedures performed at our vascular access center by a new to practice interventional nephrologist were recorded and retrospectively analyzed. Fluoroscopic time and procedure time for various procedures over the course of 2 years were recorded. This data were subsequently separated into eight groups (four quarters per year) based on the date of the procedure. Our study demonstrates a decrease in mean and median fluoroscopy times and procedure times for newly trained interventional with gain in number of procedures. The mean fluoroscopy time for the first two quarters was 5 minutes and 4 seconds, and the median was 3 minutes and 37 seconds. The mean procedure time for the first two quarters was 38 minutes, and the median was 32 minutes. The mean fluoroscopy time for the last two quarters was 1 minute and 54 seconds, and the median was 1 minute and 26 seconds. The mean procedure time for the last two quarters was 27 minutes, and the median was 21 minutes. In conclusion, gain of experience by the practicing Interventional Nephrologist from performing an increasing number of procedures leads to decreased procedure times and fluoroscopy times, which lowers the risk of radiation.