Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease

Introduction: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure

Advanced Large Area Plastic Scintillator Project (ALPS): Final Report

The advanced Large-Area Plastic Scintillator (ALPS) Project at Pacific Northwest National Laboratory investigated possible technological avenues for substantially advancing the state-of-the-art in gamma-ray detection via large-area plastic scintillators. The three predominant themes of these investigations comprised the following: * Maximizing light collection efficiency from a single large-area sheet of plastic scintillator, and optimizing hardware event trigger definition to retain detection efficiency while exploiting the power of coincidence to suppress single-PMT "dark current" background; * Utilizing anti-Compton vetoing and supplementary spectral information from a co-located secondary, or "Back" detector, to both (1) minimize Compton background in the low-energy portion of the "Front" scintillator's pulse-height spectrum, and (2) sharpen the statistical accuracy of the front detector's low-energy response prediction as impelmented in suitable energy-windowing algorithms; and * Investigating alternative materials to enhance the intrinsic gamma-ray detection efficiency of plastic-based sensors

Evaluation of exercise on individuals with dementia and their carers: a randomised controlled trial

Background Almost all of the 820,000 people in the UK with dementia will experience Behavioural and Psychological Symptoms of Dementia (BPSD). However, research has traditionally focused on treating cognitive symptoms, thus neglecting core clinical symptoms that often have a more profound impact on living with dementia. Recent evidence (Kales et al, 2007; Ballard et al, 2009) indicates that the popular approach to managing BPSD - prescription of anti-psychotic medication - can increase mortality and the risk of stroke in people with dementia as well as impair quality of life and accelerate cognitive decline. Consequently, there is a need to evaluate the impact that non-pharmacological interventions have on BPSD; we believe physical exercise is a particularly promising approach. Methods/Design We will carry out a pragmatic, randomised, single-blind controlled trial to evaluate the effectiveness of exercise (planned walking) on the behavioural and psychological symptoms of individuals with dementia. We aim to recruit 146 people with dementia and their carers to be randomized into two groups; one will be trained in a structured, tailored walking programme, while the other will continue with treatment as usual. The primary outcome (BPSD) will be assessed with the Neuropsychiatric Inventory (NPI) along with relevant secondary outcomes at baseline, 6 and 12 weeks. Discussion Designing this study has been challenging both ethically and methodologically. In particular to design an intervention that is simple, measurable, safe, non-invasive and enjoyable has been testing and has required a lot of thought. Throughout the design, we have attempted to balance methodological rigour with study feasibility. We will discuss the challenges that were faced and overcome in this paper

Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid- (A ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of A plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with A plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than A and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with A and tau

Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease

Introduction: As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD. Methods: Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers. Results: AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1 %. Cross-sectionally, mutation carriers with AD neurological examination findings showed a more than two-fold faster cognitive decline and had greater parieto-temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time. Discussion: ADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs

Results of Large-Scale Testing on Effects of Anti-Foam Agent on Gas Retention and Release

The U.S. Department of Energy (DOE) Office of River Protection’s Waste Treatment Plant (WTP) will process and treat radioactive waste that is stored in tanks at the Hanford Site. The waste treatment process in the pretreatment facility will mix both Newtonian and non-Newtonian slurries in large process tanks. Process vessels mixing non-Newtonian slurries will use pulse jet mixers (PJMs), air sparging, and recirculation pumps. An anti-foam agent (AFA) will be added to the process streams to prevent surface foaming, but may also increase gas holdup and retention within the slurry. The work described in this report addresses gas retention and release in simulants with AFA through testing and analytical studies. Gas holdup and release tests were conducted in a 1/4-scale replica of the lag storage vessel operated in the Pacific Northwest National Laboratory (PNNL) Applied Process Engineering Laboratory using a kaolin/bentonite clay and AZ-101 HLW chemical simulant with non-Newtonian rheological properties representative of actual waste slurries. Additional tests were performed in a small-scale mixing vessel in the PNNL Physical Sciences Building using liquids and slurries representing major components of typical WTP waste streams. Analytical studies were directed at discovering how the effect of AFA might depend on gas composition and predicting the effect of AFA on gas retention and release in the full-scale plant, including the effects of mass transfer to the sparge air. The work at PNNL was part of a larger program that included tests conducted at Savannah River National Laboratory (SRNL) that is being reported separately. SRNL conducted gas holdup tests in a small-scale mixing vessel using the AZ-101 high-level waste (HLW) chemical simulant to investigate the effects of different AFAs, their components, and of adding noble metals. Full-scale, single-sparger mass transfer tests were also conducted at SRNL in water and AZ-101 HLW simulant to provide data for PNNL’s WTP gas retention and release modeling