1 research outputs found
Multivariate MR Biomarkers Better Predict Cognitive Dysfunction in Mouse Models of Alzheimers Disease
To understand multifactorial conditions such as Alzheimers disease (AD) we
need brain signatures that predict the impact of multiple pathologies and their
interactions. To help uncover the relationships between brain circuits and
cognitive markers we have used mouse models that represent, at least in part,
the complex interactions altered in AD. In particular, we aimed to understand
the relationship between vulnerable brain circuits and memory deficits measured
in the Morris water maze, and we tested several predictive modeling approaches.
We used in vivo manganese enhanced MRI voxel based analyses to reveal regional
differences in volume (morphometry), signal intensity (activity), and magnetic
susceptibility (iron deposition, demyelination). These regions included the
hippocampus, olfactory areas, entorhinal cortex and cerebellum. The image based
properties of these regions were used to predict spatial memory. We next used
eigenanatomy, which reduces dimensionality to produce sets of regions that
explain the variance in the data. For each imaging marker, eigenanatomy
revealed networks underpinning a range of cognitive functions including memory,
motor function, and associative learning. Finally, the integration of
multivariate markers in a supervised sparse canonical correlation approach
outperformed single predictor models and had significant correlates to spatial
memory. Among a priori selected regions, the fornix also provided good
predictors, raising the possibility of investigating how disease propagation
within brain networks leads to cognitive deterioration. Our results support
that modeling approaches integrating multivariate imaging markers provide
sensitive predictors of AD-like behaviors. Such strategies for mapping brain
circuits responsible for behaviors may help in the future predict disease
progression, or response to interventions.Comment: 23 pages, 3 Tables, 6 Figures; submitted for publicatio