TY - JOUR
T1 - Sub-regional hippocampal injury is associated with fornix degeneration in Alzheimer's disease
AU - Lee, Dong Young
AU - Fletcher, Evan
AU - Carmichael, Owen Thomas
AU - Singh, Baljeet
AU - Mungas, Dan M
AU - Reed, Bruce R
AU - Martinez, Oliver
AU - Buonocore, Michael H.
AU - Persianinova, Maria
AU - DeCarli, Charles
PY - 2012
Y1 - 2012
N2 - We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer's disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.
AB - We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer's disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.
KW - Alzheimer's disease
KW - Fornix
KW - Fractional anisotropy
KW - Hippocampus
KW - Mild cognitive impairment
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UR - http://www.scopus.com/inward/citedby.url?scp=84862544484&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2012.00001
DO - 10.3389/fnagi.2012.00001
M3 - Article
C2 - 22514534
AN - SCOPUS:84862544484
VL - 4
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - APR
M1 - Article 1
ER -