Diffusion tensor imaging (DTI) studies show age-related differences in cerebral white matter
(WM)... more Diffusion tensor imaging (DTI) studies show age-related differences in cerebral white matter (WM). However, few have studied WM changes over time, and none evaluated individual differences in change across a wide age range. Here, we examined two-year WM change in 96 healthy adults (baseline age 19-78 years), individual differences in change, and the influence of vascular and metabolic risk thereon. Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) represented microstructural properties of normal appearing WM within 13 regions. Cross-sectional analyses revealed age-related differences in all WM indices across the regions. In contrast, latent change score analyses showed longitudinal declines in AD in association and projection fibers, and increases in anterior commissural fibers. FA and RD evidenced a less consistent pattern of change. Metabolic risk mediated the effects of age on FA and RD change in corpus callosum body and dorsal cingulum. These findings underscore the importance of longitudinal studies in evaluating individual differences in change, and the role of metabolic factors in shaping trajectories of brain aging.
Numerous cross-sectional studies have used diffusion tensor imaging (DTI) to link age-related dif... more Numerous cross-sectional studies have used diffusion tensor imaging (DTI) to link age-related differences in white matter (WM) anisotropy and concomitant decrements in cognitive ability. Due to a dearth of longitudinal evidence, the relationship between changes in diffusion properties of WM and cognitive performance remains unclear. Here we examine the relationship between two-year changes in WM organization and cognitive performance in healthy adults (N = 96, age range at baseline = 18–79 years). We used latent change score models (LCSM) to evaluate changes in age-sensitive cognitive abilities - fluid intelligence and associative memory. WM changes were assessed by fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) in WM regions that are considered part of established memory networks and exhibited individual differences in change. In modeling change, we postulated reciprocal paths between baseline measures and change factors, within and between WM and cognition domains, and accounted for individual differences in baseline age. Although baseline cross-sectional memory performance was positively associated with FA and negatively with RD, longitudinal effects told an altogether different story. Independent of age, longitudinal improvements in associative memory were significantly associated with linear reductions in FA and increases in RD. The present findings demonstrate the sensitivity of DTI derived indices to changes in the brain and cognition and affirm the importance of longitudinal models for evaluating brain-cognition relations.
The few extant reports of longitudinal white matter (WM) changes in healthy aging, using diffusio... more The few extant reports of longitudinal white matter (WM) changes in healthy aging, using diffusion tensor imaging (DTI), reveal substantial differences in change across brain regions and DTI indices. According to the last-in-first-out hypothesis of brain aging late-developing WM tracts may be particularly vulnerable to advanced age. To test this hypothesis we compared age-related changes in association, commissural and projection WM fiber regions using a skeletonized, region of interest DTI approach. Using linear mixed effects models, we evaluated the influences of age and vascular risk at baseline on seven-year changes in three indices of WM integrity and organization (axial diffusivity, AD, radial diffusivity, RD, and fractional anisotropy, FA) in healthy middle-aged and older adults (mean age = 65.4, SD = 9.0 years). Association fibers showed the most pronounced declines over time. Advanced age was associated with greater longitudinal changes in RD and FA, independent of fiber type. Furthermore, older age was associated with longitudinal RD increases in late-developing, but not early-developing projection fibers. These findings demonstrate the increased vulnerability of later developing WM regions and support the last-in-first-out hypothesis of brain aging.
An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on ex... more An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. MRI scans of a single...
We examined relationships between regional brain shrinkage and changes in cognitive performance, ... more We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19–79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (G f), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in G f scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in G f , but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in G f. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development.
Diffusion tensor imaging (DTI) studies show age-related differences in cerebral white matter
(WM)... more Diffusion tensor imaging (DTI) studies show age-related differences in cerebral white matter (WM). However, few have studied WM changes over time, and none evaluated individual differences in change across a wide age range. Here, we examined two-year WM change in 96 healthy adults (baseline age 19-78 years), individual differences in change, and the influence of vascular and metabolic risk thereon. Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) represented microstructural properties of normal appearing WM within 13 regions. Cross-sectional analyses revealed age-related differences in all WM indices across the regions. In contrast, latent change score analyses showed longitudinal declines in AD in association and projection fibers, and increases in anterior commissural fibers. FA and RD evidenced a less consistent pattern of change. Metabolic risk mediated the effects of age on FA and RD change in corpus callosum body and dorsal cingulum. These findings underscore the importance of longitudinal studies in evaluating individual differences in change, and the role of metabolic factors in shaping trajectories of brain aging.
Numerous cross-sectional studies have used diffusion tensor imaging (DTI) to link age-related dif... more Numerous cross-sectional studies have used diffusion tensor imaging (DTI) to link age-related differences in white matter (WM) anisotropy and concomitant decrements in cognitive ability. Due to a dearth of longitudinal evidence, the relationship between changes in diffusion properties of WM and cognitive performance remains unclear. Here we examine the relationship between two-year changes in WM organization and cognitive performance in healthy adults (N = 96, age range at baseline = 18–79 years). We used latent change score models (LCSM) to evaluate changes in age-sensitive cognitive abilities - fluid intelligence and associative memory. WM changes were assessed by fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) in WM regions that are considered part of established memory networks and exhibited individual differences in change. In modeling change, we postulated reciprocal paths between baseline measures and change factors, within and between WM and cognition domains, and accounted for individual differences in baseline age. Although baseline cross-sectional memory performance was positively associated with FA and negatively with RD, longitudinal effects told an altogether different story. Independent of age, longitudinal improvements in associative memory were significantly associated with linear reductions in FA and increases in RD. The present findings demonstrate the sensitivity of DTI derived indices to changes in the brain and cognition and affirm the importance of longitudinal models for evaluating brain-cognition relations.
The few extant reports of longitudinal white matter (WM) changes in healthy aging, using diffusio... more The few extant reports of longitudinal white matter (WM) changes in healthy aging, using diffusion tensor imaging (DTI), reveal substantial differences in change across brain regions and DTI indices. According to the last-in-first-out hypothesis of brain aging late-developing WM tracts may be particularly vulnerable to advanced age. To test this hypothesis we compared age-related changes in association, commissural and projection WM fiber regions using a skeletonized, region of interest DTI approach. Using linear mixed effects models, we evaluated the influences of age and vascular risk at baseline on seven-year changes in three indices of WM integrity and organization (axial diffusivity, AD, radial diffusivity, RD, and fractional anisotropy, FA) in healthy middle-aged and older adults (mean age = 65.4, SD = 9.0 years). Association fibers showed the most pronounced declines over time. Advanced age was associated with greater longitudinal changes in RD and FA, independent of fiber type. Furthermore, older age was associated with longitudinal RD increases in late-developing, but not early-developing projection fibers. These findings demonstrate the increased vulnerability of later developing WM regions and support the last-in-first-out hypothesis of brain aging.
An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on ex... more An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. MRI scans of a single...
We examined relationships between regional brain shrinkage and changes in cognitive performance, ... more We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19–79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (G f), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in G f scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in G f , but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in G f. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development.
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(WM). However, few have studied WM changes over time, and none evaluated individual
differences in change across a wide age range. Here, we examined two-year WM change in 96
healthy adults (baseline age 19-78 years), individual differences in change, and the influence of
vascular and metabolic risk thereon. Fractional anisotropy (FA), axial diffusivity (AD) and radial
diffusivity (RD) represented microstructural properties of normal appearing WM within 13
regions. Cross-sectional analyses revealed age-related differences in all WM indices across the
regions. In contrast, latent change score analyses showed longitudinal declines in AD in
association and projection fibers, and increases in anterior commissural fibers. FA and RD
evidenced a less consistent pattern of change. Metabolic risk mediated the effects of age on FA
and RD change in corpus callosum body and dorsal cingulum. These findings underscore the
importance of longitudinal studies in evaluating individual differences in change, and the role of
metabolic factors in shaping trajectories of brain aging.
relations.
(WM). However, few have studied WM changes over time, and none evaluated individual
differences in change across a wide age range. Here, we examined two-year WM change in 96
healthy adults (baseline age 19-78 years), individual differences in change, and the influence of
vascular and metabolic risk thereon. Fractional anisotropy (FA), axial diffusivity (AD) and radial
diffusivity (RD) represented microstructural properties of normal appearing WM within 13
regions. Cross-sectional analyses revealed age-related differences in all WM indices across the
regions. In contrast, latent change score analyses showed longitudinal declines in AD in
association and projection fibers, and increases in anterior commissural fibers. FA and RD
evidenced a less consistent pattern of change. Metabolic risk mediated the effects of age on FA
and RD change in corpus callosum body and dorsal cingulum. These findings underscore the
importance of longitudinal studies in evaluating individual differences in change, and the role of
metabolic factors in shaping trajectories of brain aging.
relations.