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ABSTRACT: The axons in the parahippocampal white matter (PWM) region that includes the perforant pathway relay multimodal sensory information, important for memory function, from the entorhinal cortex to the hippocampus. Previous work suggests that the integrity of the PWM shows changes in individuals with amnestic mild cognitive impairment and is further compromised as Alzheimer's disease progresses. The present study was undertaken to determine the effects of healthy aging on macro- and micro-structural alterations in the PWM. The study characterized in vivo white matter changes in the parahippocampal region that includes the perforant pathway in cognitively healthy young (YNG, n=21) compared to cognitively healthy older (OLD, n=21) individuals using volumetry, diffusion tensor imaging (DTI) and tractography. Results demonstrated a significant reduction in PWM volume in old participants, with further indications of reduced integrity of remaining white matter fibers. In logistic regressions, PWM volume, memory performance and DTI indices of PWM integrity were significant indicator variables for differentiating the young and old participants. Taken together, these findings suggest that age-related alterations do occur in the PWM region and may contribute to the normal decline in memory function seen in healthy aging by degrading information flow to the hippocampus.
Neuropsychologia 04/2012; 50(8):1759-65. · 3.64 Impact Factor
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ABSTRACT: Structural magnetic resonance imaging (MRI) studies of Alzheimer's disease and mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal cortex; gray matter structures in the medial temporal lobe. Few studies have investigated the integrity of white matter in patients with AD or MCI. Diffusion tensor imaging (DTI) is a MRI technique that allows for the interrogation of the microstructural integrity of white matter. Based on increases in translational diffusion (mean diffusivity: MD) and decreases directional diffusion (fractional anisotropy: FA) damage to white matter can be assessed. Studies have identified regions of increased MD and decreased FA in patients with AD and MCI in all lobes of the brain, as well as medial temporal lobe structures including the hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in AD and MCI. Recent studies have exploited inter-voxel directional similarities to develop models of white matter pathways, and have used these models to assess the integrity of inter-cerebral connections. Particular focus has been applied to the parahippocampal white matter (including the perforant path) and the posterior cingulum. Although many studies have found DTI indicators of impaired white matter in AD and MCI, other studies have failed to detect any differences in MD or FA between the groups, demonstrating the need for large replicative studies. DTI is an evolving technique and advances in its application ought to provide new insights into AD and MCI.
Behavioural neurology 01/2009; 21(1):39-49. · 1.77 Impact Factor
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ABSTRACT: In the present study, changes in the parahippocampal white matter (PWM), in the region that includes the perforant path, were investigated, in vivo, in 14 individuals with amnestic mild cognitive impairment (aMCI) compared to 14 elderly controls with no cognitive impairment (NCI). For this purpose, (1) volumetry; (2) diffusion tensor imaging (DTI) derived measures of mean diffusivity (MD) and fractional anisotropy (FA); and (3) tractography were used. In addition, regression models were utilized to examine the association of PWM measurements with memory decline. The results from this study confirm previous findings in our laboratory and others, showing that compared to controls, individuals with aMCI have PWM volume loss. In addition to volume reduction, participants with aMCI demonstrated a significant increase in MD, but no difference in FA, both in the PWM region and in fibers modeled to pass through the PWM region. Further, the DTI metric of MD was associated with declarative memory performance, suggesting it may be a sensitive marker for memory dysfunction. These results indicate that there is general tissue loss and degradation (decreased volume; increased MD) in individuals with aMCI compared to older people with normal cognitive function. However, the microstructural organization of remaining fibers, as determined by measures of anisotropic diffusion, is not significantly different from that of controls.
Behavioural neurology 01/2009; 21(1):51-61. · 1.77 Impact Factor
