ABSTRACT
Prior work has demonstrated that the memory dysfunction of Alzheimer's disease (AD) is accompanied by marked cortical pathology in medial temporal lobe (MTL) gray matter. In contrast, changes in white matter (WM) of pathways associated with the MTL have rarely been studied. We used diffusion tensor imaging (DTI) to examine regional patterns of WM tissue changes in individuals with AD. Alterations of diffusion properties with AD were found in several regions including parahippocampal WM, and in regions with direct and secondary connections to the MTL. A portion of the changes measured, including effects in the parahippocampal WM, were independent of gray matter degeneration as measured by hippocampal volume. Examination of regional changes in unique diffusion parameters including anisotropy and axial and radial diffusivity demonstrated distinct zones of alterations, potentially stemming from differences in underlying pathology, with a potential myelin specific pathology in the parahippocampal WM. These results demonstrate that deterioration of neocortical connections to the hippocampal formation results in part from the degeneration of critical MTL and associated fiber pathways.
Subject(s)
Alzheimer Disease/pathology , Hippocampus/pathology , Nerve Fibers, Myelinated/pathology , Aged , Anisotropy , Brain/pathology , Diffusion Tensor Imaging , Female , Humans , Image Processing, Computer-Assisted , Male , Nerve Fibers, Unmyelinated/pathology , Neural Pathways/pathology , Organ Size , Parahippocampal Gyrus/pathologyABSTRACT
In a randomized, double-blind, placebo-controlled study in 64 subjects with Huntington disease (HD), 8 g/day of creatine administered for 16 weeks was well tolerated and safe. Serum and brain creatine concentrations increased in the creatine-treated group and returned to baseline after washout. Serum 8-hydroxy-2'-deoxyguanosine (8OH2'dG) levels, an indicator of oxidative injury to DNA, were markedly elevated in HD and reduced by creatine treatment.
Subject(s)
Brain/metabolism , Creatine/pharmacokinetics , Creatine/therapeutic use , Deoxyguanosine/analogs & derivatives , Huntington Disease/drug therapy , Huntington Disease/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Adult , Biological Availability , Biomarkers/metabolism , Creatine/adverse effects , Deoxyguanosine/antagonists & inhibitors , Deoxyguanosine/blood , Double-Blind Method , Female , Humans , Huntington Disease/blood , Male , Middle AgedABSTRACT
The authors studied presymptomatic individuals with the Huntington disease (HD) mutation to determine whether cortical thinning was present. They found thinning that was regionally selective, semi-independent of striatal volume loss, and correlated with cognitive performance. Early, extensive cortical involvement occurs during the preclinical stages of HD.
Subject(s)
Cerebral Cortex/pathology , Cognition Disorders/pathology , Huntington Disease/pathology , Adult , Atrophy/genetics , Atrophy/pathology , Atrophy/physiopathology , Brain Mapping , Cerebral Cortex/physiopathology , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Corpus Striatum/pathology , Corpus Striatum/physiopathology , DNA Mutational Analysis , Female , Genetic Testing , Genotype , Humans , Huntingtin Protein , Huntington Disease/genetics , Huntington Disease/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Tissue Proteins/genetics , Neuropsychological Tests , Nuclear Proteins/genetics , Trinucleotide Repeats/geneticsABSTRACT
Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.