Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer\u27s disease

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer\u27s disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score\u27s predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally. Results: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%-98.2%]) and improved prediction beyond established methods based on familial age of onset. Discussion: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials

Alien Registration- Fougere, William (Westbrook, Cumberland County)

https://digitalmaine.com/alien_docs/20861/thumbnail.jp

Alien Registration- Fougere, William (Westbrook, Cumberland County)

https://digitalmaine.com/alien_docs/20861/thumbnail.jp

Ultraviolet observations of the hydrogen coma of comet C/2013 A1 (Siding Spring) by MAVEN/IUVS

We used the Imaging Ultraviolet Spectrograph (IUVS) aboard the Mars Atmosphere and Volatile EvolutioN (MAVEN) orbiting spacecraft to construct images of the hydrogen coma of comet C/2013 A1 (Siding Spring) days before its close encounter with Mars. We obtain a water production rate of 1.1 ± 0.5 × 1028 molecules/s and determine the total impacting fluence of atoms and molecules corresponding to the photodissociation of water and its daughter species to be 2.4 ± 1.2 × 104 kg. We use these observations to confirm predictions that the mass of delivered hydrogen is comparable to the existing reservoir above 150 km. Furthermore, we reconcile disparity between observations and predictions about the detectability of the hydrogen perturbation and thermospheric response. © 2015. American Geophysical Union. All Rights Reserved

Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness

The aim of the present study was to determine whether lung volume recruitment (LVR) acutely increases respiratory system compliance (Crs) in individuals with severe respiratory muscle weakness (RMW). Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12) and healthy controls (n=12) underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O. Each LVR inflation was followed by brief breath-hold and a maximal expiration to residual volume. At baseline, individuals with RMW had lower Crs than controls (37±5 cmH2O versus 109±10 mL·cmH2O−1, p0.05). LVR had no significant effect on measures of pulmonary function at any time point in either group (all p>0.05). During inflations, mean arterial pressure decreased significantly relative to baseline by 10.4±2.8 mmHg and 17.3±3.0 mmHg in individuals with RMW and controls, respectively (both p<0.05). LVR acutely increases Crs in individuals with RMW. However, the high airway pressures during inflations cause reductions in mean arterial pressure that should be considered when applying this technique

T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease

Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (mu) and standard deviation (sigma) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-mu in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-sigma and FLAIR-sigma) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-mu decreased and T1-sigma and FLAIR-sigma increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients