Cortical brain atrophy and intra-individual variability in neuropsychological test performance in HIV disease.

To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD's) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests.

Gray matter atrophy associated with extrapyramidal signs in the Lewy body variant of Alzheimer's disease.

Up to 60% of the patients with Alzheimer's disease (AD) can have cortical or brainstem Lewy bodies (LB), and extrapyramidal signs (EPS) have been found to be associated with LB in AD patients. However, the relationship between EPS and brain volumes has not been studied in the LB variant of AD using structural magnetic resonance imaging (MRI). The purpose of this study was to determine the relationship between patterns of brain atrophy and clinical EPS in patients with pathologically confirmed AD. We compared gray matter structure using voxel-based morphometry in 29 Definite AD cases, 16 (55%) of whom also had LBs identified with α-synuclein immunohistochemistry. Multivariate models analyzed brain volume at a voxel level accounting for subject group, Mini-Mental State Examination (MMSE), EPS, total brain volume, and the time from MRI scan to death. There was no significant difference in gray matter volume in the Definite AD patients as a function of LB. There was a significant association between gray matter volumes and the MMSE in AD patients, both with and without LBs. There was a significant correlation between gray matter volume and EPS only in the group of AD patients with LBs, and not in those with pure AD. These findings suggest that that the etiology of EPS in patients with the LB variant of AD is associated with neuronal loss in the nigrostriatal tracts. By contrast, the source of the EPS in AD alone appears to be less well localized.

Factors affecting brain structure in men with HIV disease in the post-HAART era.

INTRODUCTION: The purpose of this study was to characterize brain volumetric differences in HIV seropositive and seronegative men and to determine effects of age, cardiovascular risk, and HIV infection on structural integrity. METHODS: Magnetic resonance imaging was used to acquire high-resolution neuroanatomic data in 160 men aged 50 years and over, including 84 HIV seropositive and 76 seronegative controls. Voxel-based morphometry was used to derive volumetric measurements at the level of the individual voxel. Data from a detailed neuropsychological test battery were recombined into four summary scores representing psychomotor speed, visual memory, verbal memory, and verbal fluency. RESULTS: Both age and HIV status had a significant effect on both gray matter (GM) and white matter (WM) volume. The age-related GM atrophy was primarily in the superior temporal and inferior frontal regions; the HIV-related GM loss included the posterior and inferior temporal lobes, the parietal lobes, and the cerebellum. Among all subjects, the performance on neuropsychological tests, as indexed by a summary variable, was related to the volume of both the GM and WM. Contrary to our predictions, the CVD variables were not linked to brain volume in statistically adjusted models. CONCLUSION: In the post-HAART era, having HIV infection is still linked to atrophy in both GM and WM. Secondly, advancing age, even in this relatively young cohort, is also linked to changes in GM and WM volume. Thirdly, CNS structural integrity is associated with overall cognitive functions, regardless of the HIV infection status of the study volunteers.

Subcortical brain atrophy persists even in HAART-regulated HIV disease.

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy.