Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV

In the present study, we examined the relationships among cognitive function, magnetic resonance spectroscopy (MRS) brain metabolite indices measured in the basal ganglia, and quantitative magnetic resonance imaging (MRI) of the caudate nucleus and the putamen in the earliest stages of HIV-related cognitive involvement. Participants included 22 HIV-positive individuals and 20 HIV-negative individuals. HIV-positive individuals performed significantly more poorly than the HIV-negative individuals on several cognitive measures. In addition, the choline/creatine ratio was significantly higher and the N-acetyl aspartate/choline ratio was significantly lower among HIV patients. The caudate and putamen sizes were smaller among HIV-positive patients compared with controls; however, the differences did not reach statistical significance. Correlation analyses revealed associations between cognitive function and select MRS indices. In addition, caudate size was significantly correlated with performances on higher-order thinking tests whereas putamen size was significantly correlated with performances on motor tests. The results suggest that MRS differences are more pronounced than area size differences between seropositive and seronegative individuals in mild stages of HIV-related cognitive impairment. However, basal ganglia size remains an important contributor to cognitive status in this population. Longitudinal studies are needed to determine the evolution of these imaging correlates of HIV-cognitive impairment in HIV

Disrupted cerebral metabolite levels and lower nadir CD4+ counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatmentpatients on stable treatment

AbstractCognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV+ patients scanned with whole-brain MRI at 1.5T (mean age: 48.6±8.4years; all receiving cART). We identified brain regions where the degree of atrophy was related to HIV clinical measures and cerebral metabolite levels assessed with magnetic resonance spectroscopy (MRS). Regional brain volume reduction was linked to lower nadir CD4+ count, with a 1–2% white matter volume reduction for each 25-point reduction in nadir CD4+. Even so, brain volume measured by TBM showed no detectable association with current CD4+ count, AIDS Dementia Complex (ADC) stage, HIV RNA load in plasma or cerebrospinal fluid (CSF), duration of HIV infection, antiretroviral CNS penetration-effectiveness (CPE) scores, or years on cART, after controlling for demographic factors, and for multiple comparisons. Elevated glutamate and glutamine (Glx) and lower N-acetylaspartate (NAA) in the frontal white matter, basal ganglia, and mid frontal cortex — were associated with lower white matter, putamen and thalamus volumes, and ventricular and CSF space expansion. Reductions in brain volumes in the setting of chronic and stable disease are strongly linked to a history of immunosuppression, suggesting that delays in initiating cART may result in imminent and irreversible brain damage

Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy

Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet whether neurological injury can progress in this setting remains uncertain

Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

International audienceIMPORTANCE Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawnto date.OBJECTIVE To examine structural brain associations with the most commonly collected clinicalassessments of HIV burden (CD4+T-cell count and viral load), which are generalizable acrossdemographically and clinically diverse HIV-infected individuals worldwide.DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study established the HIV WorkingGroup within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortiumto pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and NorthAmerica. Regional and whole brain segmentations were extracted from data sets as contributingstudies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019.MAIN OUTCOMES AND MEASURES Volume estimates for 8 subcortical brain regions wereextracted from T1-weighted magnetic resonance images to identify associations with blood plasmamarkers of current immunosuppression (CD4+T-cell counts) or detectable plasma viral load (dVL) inHIV-positive participants. Post hoc sensitivity analyses stratified data by cART status.RESULTS After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5]years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+cell counts wereassociated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3per 100 cells/mm3;P< .001)and thalamic (mean [SE] β = 32.24 [8.96] mm3per 100 cells/mm3;P< .001) volumes and largerventricles (mean [SE] β = −391.50 [122.58] mm3per 100 cells/mm3;P= .001); in participants nottaking cART, however, lowercurrent CD4+cell counts were associated with smaller putamen volumes(mean [SE] β = 57.34 [18.78] mm3per 100 cells/mm3;P= .003). A dVL was associated with smallerhippocampal volumes (d= −0.17;P= .005); in participants taking cART, dVL was also associated withsmaller amygdala volumes (d= −0.23;P= .004

The AIDS dementia complex: II. Neuropathology

In order to define the histopathological substrate of the dementia that frequently complicates the acquired immune deficiency syndrome (AIDS), we analyzed the neuropathological findings in 70 autopsied adult AIDS patients, 46 of whom had suffered clinically overt dementia. Less than 10% of the brains were histologically normal. Abnormalities were found predominantly in the white matter and in subcortical structures, with relative sparing of the cortex. Their frequency and severity generally correlated well with the degree and duration of clinical dementia. Most commonly noted was diffuse pallor in the white matter, which in the pathologically milder cases was accompanied by scanty perivascular infiltrates of lymphocytes and brown‐pigmented macrophages, and in the most advanced cases by clusters of foamy macrophages and multinucleated cells associated with multifocal rarefaction of the white matter. However, in nearly one third of the demented cases the histopathological findings were remarkably bland in relation to the severity of clinical dysfunction. In addition, similar mild changes were noted in over one half of the nondemented patients, consistent with subclinical involvement. Vacuolar myelopathy was found in 23 patients and was generally more common and severe in patients with advanced brain pathology. Evidence of cytomegalovirus (CMV) infection was noted in nearly one quarter of the brains and was associated with a relative abundance of microglial nodules, but correlated neither with the major subcortical neuropathology nor with the clinical dementia, indicating that CMV infection likely represented a second, superimposed process. This study establishes the AIDS dementia complex as a distinct clinical and pathological entity and, together with accumulating virological evidence, suggests that it is caused by direct LAV/HTLV‐III brain infection

Relative Sensitivity of Magnetic Resonance Spectroscopy and Quantitative Magnetic Resonance Imaging to Cognitive Function Among Nondemented Individuals Infected with HIV

In the present study, we examined the relationships among cognitive function, magnetic resonance spectroscopy (MRS) brain metabolite indices measured in the basal ganglia, and quantitative magnetic resonance imaging (MRI) of the caudate nucleus and the putamen in the earliest stages of HIV-related cognitive involvement. Participants included 22 HIV-positive individuals and 20 HIV-negative individuals. HIV-positive individuals performed significantly more poorly than the HIV-negative individuals on several cognitive measures. In addition, the choline/creatine ratio was significantly higher and the N-acetyl aspartate/choline ratio was significantly lower among HIV patients. The caudate and putamen sizes were smaller among HIV-positive patients compared with controls; however, the differences did not reach statistical significance. Correlation analyses revealed associations between cognitive function and select MRS indices. In addition, caudate size was significantly correlated with performances on higher-order thinking tests whereas putamen size was significantly correlated with performances on motor tests. The results suggest that MRS differences are more pronounced than area size differences between seropositive and seronegative individuals in mild stages of HIV-related cognitive impairment. However, basal ganglia size remains an important contributor to cognitive status in this population. Longitudinal studies are needed to determine the evolution of these imaging correlates of HIV-cognitive impairment in HIV. (JINS, 2008, 14, 725–733.