TY - JOUR
T1 - Early brain loss in circuits affected by Alzheimer's disease is predicted by fornix microstructure but may be independent of gray matter
AU - Fletcher, Evan
AU - Carmichael, Owen
AU - Pasternak, Ofer
AU - Maier-Hein, Klaus H.
AU - DeCarli, Charles
PY - 2014
Y1 - 2014
N2 - In a cohort of community-recruited elderly subjects with normal cognition at initial evaluation, we found that baseline fornix white matter (WM) microstructure was significantly correlated with early volumetric longitudinal tissue change across a region of interest (called fornix significant ROI, fSROI), which overlaps circuits known to be selectively vulnerable to Alzheimer's dementia pathology. Other WM and gray matter regions had much weaker or non-existent associations with longitudinal tissue change. Tissue loss in fSROI was in turn a significant factor in a survival model of cognitive decline, as was baseline fornix microstructure. These findings suggest that WM deterioration in the fornix and tissue loss in fSROI may be the early beginnings of posterior limbic circuit and default mode network degeneration. We also found that gray matter baseline volumes in the entorhinal cortex and hippocampus predicted cognitive decline in survival models. But since GM regions did not also significantly predict brain-tissue loss, our results may imply a view in which early, prodromal deterioration appears as two quasi independent processes in white and gray matter regions of the limbic circuit crucial to memory.
AB - In a cohort of community-recruited elderly subjects with normal cognition at initial evaluation, we found that baseline fornix white matter (WM) microstructure was significantly correlated with early volumetric longitudinal tissue change across a region of interest (called fornix significant ROI, fSROI), which overlaps circuits known to be selectively vulnerable to Alzheimer's dementia pathology. Other WM and gray matter regions had much weaker or non-existent associations with longitudinal tissue change. Tissue loss in fSROI was in turn a significant factor in a survival model of cognitive decline, as was baseline fornix microstructure. These findings suggest that WM deterioration in the fornix and tissue loss in fSROI may be the early beginnings of posterior limbic circuit and default mode network degeneration. We also found that gray matter baseline volumes in the entorhinal cortex and hippocampus predicted cognitive decline in survival models. But since GM regions did not also significantly predict brain-tissue loss, our results may imply a view in which early, prodromal deterioration appears as two quasi independent processes in white and gray matter regions of the limbic circuit crucial to memory.
KW - Default mode network
KW - Fornix diffusivity
KW - Limbic circuit
KW - Longitudinal brain change
KW - Normal cognition
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UR - http://www.scopus.com/inward/citedby.url?scp=84987681483&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2014.00106
DO - 10.3389/fnagi.2014.00106
M3 - Article
AN - SCOPUS:84987681483
VL - 6
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - MAY
M1 - 106
ER -