Background: Alzheimer’s Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. Objective: To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. Methods: Patient-level longitudinal data from the National Alzheimer’s Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. Results: Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy. Conclusion: Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.

Resting-state functional connectivity (rs-FC) is a promising neuromarker for cognitive decline in aging population, based on its ability to reveal functional differences associated with cognitive impairment across individuals, and because rs-fMRI may be less taxing for participants than task-based fMRI or neuropsychological tests. Here, we employ an approach that uses rs-FC to predict the Alzheimer's Disease Assessment Scale (11 items; ADAS11) scores, which measure overall cognitive functioning, in novel individuals. We applied this technique, connectome-based predictive modeling, to a heterogeneous sample of 59 subjects from the Alzheimer's Disease Neuroimaging Initiative, including normal aging, mild cognitive impairment, and AD subjects. First, we built linear regression models to predict ADAS11 scores from rs-FC measured with Pearson's r correlation. The positive network model tested with leave-one-out cross validation (LOOCV) significantly predicted individual differences in cognitive function from rs-FC. In a second analysis, we considered other functional connectivity features, accordance and discordance, which disentangle the correlation and anticorrelation components of activity timecourses between brain areas. Using partial least square regression and LOOCV, we again built models to successfully predict ADAS11 scores in novel individuals. Our study provides promising evidence that rs-FC can reveal cognitive impairment in an aging population, although more development is needed for clinical application.

Scene content is thought to be processed quickly and efficiently to bias subsequent visual exploration.Does scene content bias spatial attention during task-free visual exploration of natural scenes?If so, is this bias driven by patterns of physical salience or content-driven biases formed through previous encounters with similar scenes? We conducted two eye-tracking experiments to address these questions. Using a novel gaze decoding method, we show that fixation patterns predict scene category during free exploration. Additionally, we isolate salience-driven contributions using computational salience maps and content-driven contributions using gaze-restricted fixation data. We find distinct time courses for salience-driven and content-driven effects. The influence of physical salience peaked initially but quickly fell off at 600 ms past stimulus onset. The influence of content effects started at chance and steadily increased over the 2000 ms after stimulus onset. The combination of these two components significantly explains the time course of gaze allocation during free exploration.

We have begun an exploration of how ubiquitous computing technology can facilitate different forms of audio communication within a family. We are interested in both intra-and inter-home communication. Though much technology exists to support this human-human communication, none of them make effective use of the context of the communication partners. In the Aware Home Research Initiative, we are exploring how to augment a domestic environment with knowledge of the location and activities of its occupants. The Family Intercom project is trying to explore how this context can be used to create a variety of lightweight communication opportunities between collocated and remote family members. It is particularly important that context about the status of the callee be communicated to the caller, so that the appropriate social protocol for continuing a conversation can be performed by the caller. In this paper, we will discuss our initial prototypes to develop a testbed for exploring these context-aware audio communication services.