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Using a large magnetic resonance (MR) imaging data set (n = 532), we investigated the utility of total intracranial volume (TICV) as a correction factor for head size variability when assessing total brain volume (TBV) and the subcortical volumes of the temporal horn of the lateral ventricular system and the hippocampus.A uniform tissue segmentation procedure (analyze) was used to calculate volumes. Total brain volume was compared with TICV in 357 control subjects and 175 patients with various dementing and neuropsychiatric disorders (mixed dementia/neuropsychiatric group). These MR-based TBV/TICV relationships were compared with actual postmortem (n = 87) values obtained from a study of neurologically healthy subjects at the time of death. Comparisons were also made in which temporal horn and hippocampal volumes were corrected by TICV and TBV. Lastly, the ability of corrected TBV and temporal horn and hippocampal volumes to distinguish subjects in the mixed dementia/neuropsychiatric group from controls was examined by logistic regression.In the control sample, brain volume averaged 9% of TICV, regardless of age. In contrast, TBV in the mixed dementia/neuropsychiatric subjects showed, on average, a 22% reduction compared with TICV. By plotting TBV/TICV curves, highly significant but different regression lines emerged, wherein a reduction in brain volume in conditions of mixed dementia/neuropsychiatric disorder showed a distinct separation from the norm. The TBV/TICV regression line generated from MR imaging in controls did not differ from the postmortem TBV/TICV regression line. Logistic regression showed a 96% correct classification of mixed dementia/neuropsychiatric subjects from controls by using the TBV/TICV ratio. This technique has the advantage that each subject serves as his or her own control.In cases of dementia and neuropsychiatric disorder in persons 65 and older, TBV corrected by TICV readily differentiated this clinical population from controls. This technique is easy and simple to use and has various clinical applications. For temporal horn and hippocampal volume, corrections with TBV rather than TICV may provide more clinically meaningful corrections.

This study compared a fornix cross-sectional-area measurement and hippocampal volume in 86 traumaticbrain injury (TBI) subjects with 46 normal controls. The TBI group showed a significant reduction in fornixarea and hippocampal volume. It was also shown that initial injury severity was related to the degree ofatrophy in both structures. Although fornix size and hippocampal volume correlated, such a modestcorrelation between these two structures suggests differential and potentially independent mechanisms ofinjury. The General Memory Index score from the Wechsler Memory Scale–Revised was shown to besignificantly correlated with hippocampal volume following TBI.When the neuroanatomical basis of memory and learning isdiscussed, reference typically is made to temporal lobestructures, particularly limbic system structures (D’Espositoet al. 1995; Aggleton 1999). Disorders of memory and learn-ing are common in traumatic brain injury (TBI) (Dixon et al.1993; Bigler et al. 1996), and although the neuroanatomicbasis for disordered memory in TBI has not been fully ad-dressed, the limbic system is implicated. There are severalmechanisms whereby TBI may result in pathologicalchanges in the temporal lobes. For example, with highspeed impact and/or acceleration–deceleration injuries, themedial temporal lobe is particularly vulnerable to mechani-cal deformation and contusion because of its location in themiddle cranial fossa (Levin et al. 1982; Adams et al. 1985;Sweeney 1992; Gean 1994). In addition to these tissue de-rangements resulting from direct-impact forces, perturba-tion of temporal lobe limbic structures such as the hippo-campus results in excitotoxic reactions leading to furthercellular damage or death (Faden et al. 1989; Nilsson et al.1990; Palmer et al. 1993; Fujita et al. 1996; White and Rey-nolds 1996; Shah et al. 1997). Acutely, each of these patho-logical reactions (either individually or in combination) mayresult in secondary localized edematous and vascularchanges that may add to the damage (Gean 1994). Further-more, postacutely, hippocampal deafferentation and/or de-efferentation may result in transneuronal degeneration,causing hippocampal cell death. Thus, in theory, TBI-relatedhippocampal damage may be a combination of direct injury,excitotoxic neuropathological changes, vascular compro-mise, metabolic changes, and/or transneuronal degenera-tion (Gennarelli et al. 1998).The fornix represents the major aspect of hippocampaloutput, comprised of axonal projections from the hippo-campus to the mamillary bodies (MB) (Brodal 1981; Carpen-ter and Sutin 1983). This delicate white-matter pathwayemerges from the posterior portion of the hippocampusfirst curving upward, projecting anteriorally, and then de-scending downward, as the column of the fornix, to the MB.Although not all of the axons of the fornix have their originin the hippocampus, the majority of the fibers do and it isconsidered the limbic structure that interconnects the hip-pocampus with the MB and, hence, the rest of the limbicsystem (Brodal 1981).In separate independent studies, we have shown pre-viously that trauma results in hippocampal (Bigler et al.1996, 1997) as well as fornix atrophy (Gale et al. 1993).However, none of these investigations examined the rela-tionship between hippocampal atrophy and fornix atrophy.At an anatomical level, it seems reasonable to assume thatatrophy of the hippocampus would, in some fashion, resultin proportional atrophy of the fornix, because the white-matter tracts of the fornix originate mainly from hippocam-pal neurons. On the other hand, the hippocampus is pre-dominantly a gray-matter structure housed in the mesialtemporal lobe, whereas approximately half the length of thefornix, a white-matter structure, is suspended in ventricularspace as it makes its arch from the alveus to the MB. Be-cause of the length of the axons that comprise the fornix,these long-coursing, suspended white-matter fiber tractsmay be more susceptible to shear, strain, or tensile effects.Accordingly, pathology associated with head injury may bepartly independent for these two structures because of dif-ferences in the mechanism of injury to two different tissuetypes.Lastly, because memory disorders accompany damageto either the hippocampus or fornix (D’Esposito et al. 1995;Aggleton 1999), what is the relationship between atrophyof these limbic structures and memory in TBI? To addressthese issues, hippocampal volume and fornix cross-sec-tional area were examined in TBI patients with varying de-grees of injury severity. The relationship between theseatrophic changes and memory was further studied using the

Both environmental and genetic factors appear to contribute to the risk for suicide. The serotonergic system has been implicated in depression, impulsivity and suicidality. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Suicide has been associated with polymorphisms in intron 7 of the TPH gene. These alleles were studied in samples from 47 deceased Caucasian males as part of the Utah Youth Suicide Study. A 918 base pair fragment spanning the region of interest was amplified. The A218C polymorphism was visualized by restriction fragment length polymorphism (RFLP) and the A779C was sequenced. Neither A218C nor A779C appeared to be associated with suicide in this population. These results did not change when the sample was stratified by age (10-21 years, 22-31 years) or when violent suicides were selected. The complexity of the phenotype of suicide may reflect multiple biological and social etiologic factors, and poses a worthy challenge for genetic studies.

Fractional anisotropy (FA) of water diffusion in cerebral white matter (WM), derived from diffusion tensor imaging (DTI), is a sensitive index of microscopic WM integrity. Physiological and metabolic factors that explain intersubject variability in FA values were evaluated in two cohorts of healthy adults of different age spans (N=65, range: 28–50 years; and N=25, age=66.6±6.2, range:57–80 years). Single voxel magnetic resonance spectroscopy (MRS) was used to measure N-acetylaspartate (NAA), total choline-containing compounds, and total creatine, bilaterally in an associative WM tract: anterior corona radiata (ACR). FA values were calculated for the underlying, proximal and two distal WM regions. Two-stage regression analysis was used to calculate the proportion of variability in FA values explained by spectroscopy measurements, at the first stage, and subject’s age, at the second stage. WM NAA concentration explained 23% and 66% of intersubject variability (p

This study examined the association between recent trends in CD4 and viral loads and cognitive test performance with the expectation that recent history could predict cognitive performance. Eighty-three human immunodeficiency virus (HIV)-infected patients with a mean CD4 count of 428 copies/ml were examined in this study (62% with undetectable plasma viral load [PVL]). We investigated the relationships between nadir CD4 cell count, 1-year trends in immunologic function/PVLs, and cognitive performance across several domains using linear regression models. Nadir CD4 cell count was predictive of current executive function (p = .004). One year clinical history for CD4 cell counts and/or PVLs were predictive of executive function, attention/working memory, and learning/memory measures (p < .05). Models that combined recent clinical history trends and nadir CD4 cell counts suggested that recent clinical trends were more important in predicting current cognitive performance for all domains except executive function. This research suggests that recent CD4 and viral load history is an important predictor of current cognitive function across several cognitive domains. If validated, clinical variables and cognitive dysfunction models may improve our understanding of the dynamic relationships between disease evolution and progression and CNS involvement.

In this review of the current literature, we examine the role of medical imaging in providing new and relevant information on central nervous system (CNS) injury associated with human immunodeficiency virus (HIV) infection and various clinical manifestations of this injury. Common imaging modalities used to examine CNS injury in HIV infection include structural magnetic resonance imaging, magnetic resonance spectroscopy, diffusion tensor imaging, functional MRI, and positron emissions tomography. Clinical implications for the findings are discussed for each of these modalities individually and collectively. In addition, the direction for future studies is suggested in an attempt to provide possible methods that might answer the many questions that remain to be answered on the evolution and progression of CNS injury in the context of HIV infection.

Relatively speaking, the human immunodeficiency virus (HIV) is a recent epidemic and was only first identified in the mid 1980s. Since this time, it has become clear that HIV is an efficient negative moderator of host immune function with deadly consequences. In fact, it is estimated that nearly 60 million people have died from the consequences of the virus since the mid 1980s. Despite our current efforts at education and prevention, we continue to see increases in the number of new infections (2.5 million) each year with an estimated 33 million people throughout the world currently infected. Sub-Saharan Africa bears the brunt of the pandemic with more than half the world’s infections occurring within the region (~25 million). With infections occurring across the globe, HIV truly is a global pandemic with significant economic, political, and social ramifications.

Visual exploration is essential to the visualization and analysis of densely sampled 3D DTI fibers in biological speciments, due to the high geometric, spatial, and anatomical complexity of fiber tracts. Previous methods for DTI fiber visualization use zooming, color-mapping, selection, and abstraction to deliver the characteristics of the fibers. However, these schemes mainly focus on the optimization of visualization in the 3D space where cluttering and occlusion make grasping even a few thousand fibers difficult. This paper introduces a novel interaction method that augments the 3D visualization with a 2D representation containing a low-dimensional embedding of the DTI fibers. This embedding preserves the relationship between the fibers and removes the visual clutter that is inherent in 3D renderings of the fibers. This new interface allows the user to manipulate the DTI fibers as both 3D curves and 2D embedded points and easily compare or validate his or her results in both domains. The implementation of the framework is GPU based to achieve real-time interaction. The framework was applied to several tasks, and the results show that our method reduces the user's workload in recognizing 3D DTI fibers and permits quick and accurate DTI fiber selection.

The automated volumetric output of FreeSurfer and Individual Brain Atlases using Statistical Parametric Mapping (IBASPM), two widely used and well published software packages, was examined for accuracy and consistency relative to auto-assisted manual (AAM) tracings (i.e., manual correction of automated output) when measuring the caudate, putamen, amygdala, and hippocampus in the baseline scans of 120 HIV-infected patients (86.7% male, 47.3+/-6.3y.o., mean HIV duration 12.0+/-6.3years) from the NIH-funded HIV Neuroimaging Consortium (HIVNC) cohort. The data was examined for accuracy and consistency relative to auto-assisted manual tracing, and construct validity was assessed by correlating automated and AAM volumetric measures with relevant clinical measures of HIV progression. When results were averaged across all patients in the eight structures examined, FreeSurfer achieved lower absolute volume difference in five, higher sensitivity in seven, and higher spatial overlap in all eight structures. Additionally, FreeSurfer results exhibited less variability in all measures. Output from both methods identified discrepant correlations with clinical measures of HIV progression relative to AAM segmented data. Overall, FreeSurfer proved more effective in the context of subcortical volumetry in HIV-patients, particularly in a multisite cohort study such as this. These findings emphasize that regardless of the automated method used, visual inspection of segmentation output, along with manual correction if necessary, remains critical to ensuring the validity of reported results.

Diffusion tensor fields reveal the underlying anatomical structures in biological tissues such as neural fibers in the brain. Most current methods for visualizing the diffusion tensor field can be categorized into two classes: integral curves and glyphs. Integral curves are continuous and represent the underlying fiber structures, but are prone to integration error and loss of local information. Glyphs are useful for representing local tensor information, but do not convey the connectivity in the anatomical structures well. We introduce a simple yet effective visualization technique that extends the streamball method in flow visualization to tensor ellipsoids. Each tensor ellipsoid represents a local tensor, and either blends with neighboring tensors or breaks away from them depending on their orientations and anisotropies. The resulting visualization shows the connectivity information in the underlying anatomy while characterizing the local tenors in detail. By interactively changing an iso-value parameter, users can examine the diffusion tensor field in the entire spectrum between the continuous integral curves and the discrete glyphs. Expert evaluation indicates that this method conveys very useful visual information about local anisotropy in white matter fibers. Such information was previously unavailable in tractography models. Our method provides a visual tool for assessing variability in DTI fiber tract integrity and its relation to function.

There have been many studies examining HIV-infection-related alterations of magnetic resonance imaging (MRI) diffusion metrics. However, examining scalar diffusion metrics ignores the orientation aspect of diffusion imaging, which can be captured with tractography. We examined five different tractography metrics obtained from global tractography maps (global tractography FA, average tube length, normalized number of streamtubes, normalized weighted streamtube length, and normalized total number of tubes generated) for differences between HIV positive and negative patients and the association between the metrics and clinical variables of disease severity. We also examined the relationship between these metrics and cognitive performance across a wide range of cognitive domains for the HIV positive and negative patient groups separately. The results demonstrated a significant difference between the groups for global tractography FA (t = 2.13, p = 0.04), but not for any of the other tractography metrics examined (p-value range = 0.39 to 0.95). There were also several significant associations between the tractography metrics and cognitive performance (i.e., tapping rates, switching 1 and 2, verbal interference, mazes; ror = 0.42) for HIV infected patients. In particular, associations were noted between tractography metrics, speed of processing, fine motor control/speed, and executive function for the HIV-infected patients. These findings suggest that tractography metrics capture clinically relevant information regarding cognitive performance among HIV infected patients and suggests the importance of subtle white matter changes in examining cognitive performance.

Another general reason for examining HIV-associated CNS injury is that despite the improvements in HIV medication regimens, there continues to be pathological evidence of CNS involvement. In fact, when examining the postmortem samples (7, 8) , the incidence of HIV encephalitis continues to grow regardless of treatment improvements. This finding is perhaps the most important reason for conducting imaging studies, as it will be imperative to understand why these symptoms persist and what effects treatment does or does not have on CNS preservation

There is a growing evidence that elevated body mass index (BMI) is associated with adverse neurocognitive outcome, though no study has examined whether morphometric differences are found in persons across the adult life span. We compared 201 healthy individuals in normal weight, overweight, and obese groups (aged 17-79). After correcting for demographic differences, obese individuals showed smaller whole brain and total gray matter volume than normal weight and overweight individuals. These findings support an independent relationship between BMI and brain structure and demonstrate that these differences are not limited to older adults.

To prospectively relate C-reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1-year follow-up period.Prospective 1-year follow-up.Outpatient university medical setting.Seventy-eight adults (aged 56-84; 39% female) with cardiovascular disease.CRP levels were measured using a high-sensitivity assay, and participants completed a neuropsychological battery at study entry. Neuropsychological assessment was repeated 1 year later.The association between CRP and change in cognition over the 1-year follow-up was examined using hierarchical linear regression modeling for five cognitive domains (global cognition, language, memory, visuospatial abilities, and attention-executive-psychomotor). High CRP levels were associated with subtle declines in attention-executive-psychomotor performance (CRP beta=-0.22, P=.04) after adjusting for the effects of age and cognitive performance at study entry. CRP was not significantly associated with change in language, memory, or visuospatial performance.These data provide preliminary evidence that inflammation, potentially contributing to atherosclerotic processes, may underlie the association between high CRP and changes in attention-executive-psychomotor performance.

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.)

BACKGROUND AND PURPOSE: Lesion volume change (LVC) assessment is essential in monitoring MS progression. LVC is usually measured by independently segmenting serial MR imaging examinations. Subtraction imaging has been proposed for improved visualization and characterization of lesion change. We compare segmentation of subtraction images (SSEG) with serial single time-point conventional segmentation (CSEG) by assessing the LVC relationship to brain atrophy and disease duration, as well as scan-rescan reproducibility and annual rates of lesion accrual. MATERIALS AND METHODS: Pairs of scans were acquired 1.5 to 4.7 years apart in 21 patients with multiple sclerosis (MS). Scan-rescan MR images were acquired within 30 minutes in 10 patients with MS. LVC was measured with CSEG and SSEG after coregistration and normalization. Coefficient of variation (COV) and Bland-Altman analyses estimated method reproducibility. Spearman rank correlations probed associations between LVC and other measures. RESULTS: Atrophy rate and net LVC were associated for SSEG ( R = −0.446; P < .05) but not when using CSEG ( R = −0.180; P = .421). Disease duration did not show an association with net lesion volume change per year measured by CSEG ( R = −0.360; P = .11) but showed an inverse correlation with SSEG-derived measurements ( R = −0.508; P < .05). Scan-rescan COV was lower for SSEG (0.98% ± 1.55%) than for CSEG (8.64% ± 9.91%). CONCLUSION: SSEG unveiled a relationship between T2 LVC and concomitant brain atrophy and demonstrated significantly higher measurement reproducibility. SSEG, a promising tool providing detailed analysis of subtle alterations in lesion size and intensity, may provide critical outcome measures for clinical trials of novel treatments, and may provide further insight into progression patterns in MS.

Aims: The purpose of the present case is to describe the functional outcome of a patient with human immunodeficiency virus (HIV) and progressive multifocal leukoencephalopathy (PML) on treatment with antiretroviral therapy using a multidisciplinary approach. Methods: Neuropsychological tests and diffusion tensor imaging (DTI) were obtained at baseline and after 12 months to define the severity of white matter damage. Neuropsychological and neuroimaging data were compared to an HIV-infected patient without PML and with good immune system health, and to a second HIV-infected patient without PML but with notable immunosuppression. Results: Review of the HIV/PML patient's cognitive data at both time points revealed significant impairments compared to the control subjects. Similarly, the HIV/PML patient's white matter lesion load and whole brain volume were markedly different from the control subjects at both time points. The tractography-defined metrics suggest significant white matter fiber loss associated with HIV/PML that was not evident in either HIV control patient. Discussion: Our findings suggest that PML is associated with marked cognitive and neuroimaging abnormalities in the context of antiretroviral therapy. Integrative Significance: To our knowledge this is the first study to integrate both quantitative DTI and cognitive assessment to define white matter damage associated with HIV and PML. This integrative approach provides a robust methodology to examine the integrity of brain systems mediating cognitive function.

The neurocognitive impact of the clade C viral strain of human immunodeficiency virus (HIV) has not been determined. The purpose of this study was to examine neurocognitive function in southern India among individuals with the clade C virus with advanced HIV. A battery of cognitive tasks sensitive to the effects of HIV on brain function was translated and administered in Tamil and Telegu, two widely spoken languages in southern India. A sample of 30 treatment-naive HIV-positive individuals with a median CD4 cell count of 97, and 30 age and education matched healthy controls obtained from the same region of India, were included in the study. Results revealed significant differences on most cognitive tests, with lower performances obtained by the HIV-positive individuals. These results suggest that cognitive difficulties are present among individuals with the clade C virus in India, with as many as 56% of the patients with advanced HIV meeting the criterion for impairment in two cognitive domains. Additional study is needed to determine if clade C HIV infection is more or less prone to cause neurocognitive deficit than the clade B virus. Furthermore, the impact of antiretroviral therapy on neurocognitive dysfunction in clade C virual infection needs to be determined.

Cardiovascular disease (CVD) is associated with cognitive deficits long before the onset of stroke or dementia. Recent work has extended these findings and shown that patients with congestive heart failure also exhibit reduced cognitive performance. Brain natriuretic peptide (BNP) is used to help diagnose heart failure, but no study has examined whether BNP predicts cognitive dysfunction in older patients with CVD. BNP values and performance on the Dementia Rating Scale were assessed in 56 older adults with documented CVD. Forty-eight percent of the participants were women, and their average age was 70 +/- 8 years. All participants had Mini-Mental State Examination scores greater than the cutoff for dementia and no histories of neurologic or severe psychiatric disorders. The average BNP level was 122 +/- 202 pg/ml. Hierarchical regression analyses showed that log-transformed BNP levels predicted Dementia Rating Scale total score after adjusting for possible demographic and medical confounders (DeltaR2 = 0.09, F[1, 44] = 6.14, p = 0.017). Partial correlation analysis adjusting for these possible confounders showed a particularly strong relation to the conceptualization subtest (r = -0.44, p = 0.002), a measure of verbal and nonverbal abstraction abilities. In conclusion, the results of the present study provide the first evidence for an independent relation between BNP and cognitive dysfunction in older adults with CVD.

Recent findings suggest obesity is associated with reduced memory performance in older adults. The present study examined whether similar deficits also exist in younger adults and the degree to which the relationship between body mass index (BMI) and memory varies as a function of age. Prior to inclusion, participants were rigorously screened and excluded for medical conditions known to impact cognitive functioning, including neurological disorders, head injury, cardiovascular disease, and diabetes. A total of 486 healthy adults completed a verbal list-learning task. Participants were categorized into normal weight, overweight, and obese groups based on their BMI. Performance on learning, delayed recall, and recognition performance were compared across BMI groups. Results showed obese individuals had poorer memory performance when comparing persons across the adult lifespan (age 21-82 yr), but also when examining only younger and middle-aged adults (age 21-50 yr). Regression analyses found no evidence of an interaction between BMI and age on any memory variable, suggesting the relationship between BMI and memory does not vary with age. These findings provide further support for an independent relationship between obesity and reduced memory performance and suggest these effects are not limited to older adults. Further research is needed to identify etiological factors.

We present a system which visualizes the geometric disparity between white matter tracts obtained from DT-MRI by coloring in perceptually uniform color space and allows expert users of the application to select regions interactively with a 2D based sketching mechanism. This approach, in contrast to automatically clustering tracts, better reflects the uncertainity in forming scientific model from geometric information and the 2D sketching interface exploits neuroscientists' expertise with sectional anatomy.

There is growing evidence that obesity is linked to adverse neurocognitive outcome, including reduced cognitive functioning and Alzheimer disease. However, no study to date has determined whether the relationship between body mass index (BMI) and cognitive performance varies as a function of age. We examined attention and executive function in a cross-section of 408 healthy persons across the adult life span (20-82 years). Bivariate correlation showed that BMI was inversely related to performance on all cognitive tests. After controlling for possible confounding factors, overweight and obese adults (BMI > 25) exhibited poorer executive function test performance than normal weight adults (BMI, 18.5-24.9). No differences emerged in attention test performance, and there was no evidence of a BMI × age interaction for either cognitive domain. These results provide further evidence for the relationship between elevated BMI and reduced cognitive performance and suggest that this relationship does not vary with age. Further research is needed to identify the etiology of these deficits and whether they resolve after weight loss.

Background Early life stress (ELS) is linked to adult psychopathology and may contribute to long-term brain alterations, as suggested by studies of women who suffered childhood sexual abuse. We examine whether reported adverse ELS defined as stressful and/or traumatic adverse childhood events (ACEs) is associated with smaller limbic and basal ganglia volumes. Method 265 healthy Australian men and women without psychopathology or brain disorders were studied. ACEs were assessed by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1-weighted MRI. Analyses examined ROI volumetric associations with reported ACEs and DASS scores. Results Participants with greater than two ACEs had smaller ACC and caudate nuclei than those without ACEs. A significant association between total ACEs and ROI volumes for these structures was observed. Regression analysis also revealed that ELS was more strongly associated than current emotional state (DASS) with these ROI volumes. Conclusions Reported ELS is associated with smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The reasons for these brain effects are not entirely clear, but may reflect the influence of early stress and traumatic events on the developing brain.

Apathy is a prominent neuropsychiatric symptom associated with human immunodeficiency virus (HIV). The increased frequency of apathy in this population may reflect the direct involvement of the virus on the central nervous system (CNS), but the severity of apathy has not been shown to consistently relate to markers of disease activity or other neuropsychiatric complications of the virus. We examined the relationship between ratings of apathy and performance on measures of cognitive function and immune system status in a sample of HIV-infected patients. Apathy was significantly elevated among HIV-infected individuals compared to healthy comparison subjects. Apathy was significantly related to performance on measures of learning efficiency and a measure of cognitive flexibility. Ratings of apathy did not relate to CD4 cell count, but they were associated with disease duration. In addition, ratings of depression were independent of ratings of apathy. These findings suggest that apathy does not co-vary with a proxy measure of active disease status, but apathy does relate to several measures of cognitive dysfunction in patients with HIV. As such, the increased prevalence of apathy among HIV-infected adults may reflect HIV-associated neurologic dysfunction.

Previous studies have examined the impact of subcortical hyperintensities (SH), a proxy measure of cerebrovascular disease, on the cognitive abilities of otherwise healthy older adults. However, there remains a limited understanding as to what extent this MRI marker of pathological processes explains the decline in specific cognitive functions that occur nearly ubiquitously with advanced age, especially in relation to other age-related imaging markers. In the present study we compared cognitive abilities between a sample of 53 older healthy adults (age range = 50–79) and a sample of 53 younger adults (age range = 21–40). As expected, the older group performed significantly worse on most cognitive measures compared to the younger group. Frontal volume and total grey matter volume were also significantly reduced among the older individuals compared to the younger individuals. SH volume was consistently associated with cognitive function in older adults, though, this relationship was evident only for a relatively small subset of older individuals with the most severe SH. These data suggest that the relationship between SH and cognition in the elderly is driven by a subset of individuals who may be in the earliest stages of vascular cognitive impairment. Further, the findings suggest that cognitive aging is largely determined by factors other than SH for most older adults.

Apathy refers to decreased self-initiation and goal-directed behavior. Apathy is a relatively common neuropsychiatric symptom associated with HIV, yet the impact of apathy on health-related quality of life (QOL) has not been investigated. We examined the relationship between apathy, depression, and QOL among individuals infected with HIV. Apathy was quantified using the Marin Apathy scale and QOL was measured with the Medical Outcomes Study Short-Form 36 (SF-36). Results of the study revealed that both apathy and depression were more common among patients with HIV than healthy control subjects. Twenty-six percent of the patients with HIV reported clinically significant apathy while 80% of the patients reported clinically significant depression. Apathy did not relate to ratings of overall QOL, but it was modestly associated with ratings of mental health and role disruption secondary to mental health. By contrast, ratings of depression were strongly related to overall QOL and most indices of SF-36. Regression equations revealed that depression and apathy independently contributed to mental health and role disruption secondary to mental health. Importantly, ratings of depression accounted for the majority of variance for ratings of QOL. The findings indicate that while apathy is more common among individuals with HIV compared to healthy control subjects, the impact of apathy on QOL is less significant than depression. Clinicians should continue to focus on depression as an important neuropsychiatric symptom associated with HIV.

The medial surface areas of the cingulate gyrus (CG) and other midline structures (corpus callosum, thalamus, lateral ventricle) were examined in 27 traumatically brain injured (TBI) and 12 age- and gender-matched control subjects from an established TBI data base. Significant atrophy, primarily in the posterior CG, was found in TBI patients. Degree of atrophy was related to severity of injury. TBI subjects also had significantly reduced corpus callosum and thalamic cross-sectional surface areas with associated increased lateral ventricular volume, as well as reduced brain volume and increased ventricle-to-brain ratio. Despite significant atrophy of the posterior CG, neuropsychological performance was not related to changes in CG cross-sectional surface area in the TBI subjects. This apparent discrepancy is discussed.

The authors performed quantitative and qualitative image analysis on a sample of the elderly population of Cache County, Utah, relating neuroimaging findings to Mini-Mental Status Examination (MMSE) scores and the presence of the apolipoprotein E epsilon4 allele. Neuroimaging measures included white, gray, and hippocampal volumes; a ventricle-to-brain ratio (VBR); and qualitative ratings of white matter lesions (WMLs) in the periventricular (PV) and centrum semiovale (CS) regions. Subjects included 85 persons with possible and probable Alzheimer disease (AD), 21 with vascular dementia (VaD), 30 with cognitive symptoms classified as mild/ambiguous (M/A), a heterogenous group of 39 non-AD or VaD subjects but diagnosed with some form of neuropsychiatric disorder ("Mixed Neuropsychiatric" group), and 20 normal control subjects aged 65 years or older. Controlling for age, sex, and length of disease, the authors found that AD and VaD subjects differed significantly from control subjects on WMLs, but only the VaD subjects significantly differed from M/A subjects. The two dementia groups also displayed, as expected, significant cerebral atrophy. The WMLs generally increased with age and severity of dementia. PV WMLs were significantly but only modestly associated with white matter volume loss and greater impairment on the MMSE. Modest correlations were also present between the quantitative measures of cerebral structure and MMSE performance. However, when degree of cerebral atrophy was controlled by using the VBR measure, WML effects on MMSE performance became nonsignificant, with the only significant relationship remaining being that between hippocampal volume and MMSE performance. There were no significant qualitative or quantitative findings related to presence of the epsilon4 allele and MMSE performance. The role of WMLs in aging and dementia is discussed.

Objective To delineate the probability of contact between government agencies and youths who complete suicide, to investigate the nature of those contacts, and to identify new risk factors for suicide. Method A descriptive epidemiological analysis of data from multiple Utah government agencies on consecutive youth suicides ( n = 151) between August 1, 1996, and June 6, 1999, aged 13–21 years. Data were collected from four government agencies: Office of the Medical Examiner, Juvenile Justice, Department of Human Services, and the Department of Education. Results Utah descriptive data were similar to national statistics, with the majority of completers being male (89%) and firearms the most common method of suicide (58%). The data demonstrated an association between youth suicide and contact with Juvenile Justice. Sixty-three percent of youths who completed suicide in Utah had contact with Juvenile Justice, and there was a direct correlation between number of referrals and increased suicide risk. Suicide completers had multiple minor offenses over many years. A significant minority of school-age subjects could not be located within the school system. Few suicide completers had evidence of active psychiatric treatment. Conclusions Juvenile Justice is identified as a novel site for the screening and identification of youths at risk for suicide.

There are several magnetic resonance (MR) imaging methods to measure brain volume and cerebral atrophy; however, the best measure for examining potential relationships between such measures and neuropsychological performance has not been established. Relationships between seven measures of MR derived brain volume or indices of atrophy and neuropsychological performance in the elderly subjects of the population-based Cache County, Utah Study of Aging and Memory (n = 195) were evaluated. The seven MR measures included uncorrected total brain volume (TBV), TBV corrected by total intracranial volume (TICV), TBV corrected by the ratio of the individuals TICV by group TICV (TBVC), a ventricle-to-brain ratio (VBR), total ventricular volume (TVV), TVV corrected by TICV, and a measure of parenchymal volume loss. The cases from the Cache County Study were comprised of elderly individuals classified into one of four subject groups based on a consensus diagnostic process, independent of quantitative MR imaging findings. The groups included subjects with Alzheimer's disease (AD, n = 85), no dementia but mild/ambiguous (M/A) deficits (n = 30), a group of subjects with non-AD dementia or neuropsychiatric disorder including vascular dementia (n = 60), and control subjects (n = 20). Neuropsychological performance was based on the Mini-Mental Status Exam (MMSE) and an expanded neuropsychological test battery (consortium to establish a registry for Alzheimer's disease (CERAD). The results demonstrated that the various quantitative MR measures were highly interrelated and no single measure was statistically superior. However, TBVC, TBV/TICV and VBR consistently exhibited the more robust relationships with neuropsychological performance. These results suggest that a single corrected brain volume measure or index is sufficient in studies examining global MR indicators of cerebral atrophy in relation to cognitive function and recommends use of either TBVC, TBV/TICV, or VBR.

a Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence Veteran's Affairs Medical Center, (116) 830 Chalkstone Ave. Providence, RI 02908-4799, USA b Department of Computer Science, Brown University, USA c Vrije Universitet, Amsterdam, Faculty of Earth and Life Sciences, The Netherlands d Departments of Radiology and Psychiatry, Center for Neurological Imaging, Brigham and Women's Hospital, Harvard Medical School, USA e University of Missouri, St. Louis, Department of Psychology, Behavioral Neuroscience, USA f Mississippi State University, Department of Computer Science and Engineering, USA g Department of Clinical Neuroscience, Warren Alpert Medical School of Brown University, USA

Background: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated with the vascular responses. Methods: Eighty-eight independent, community-dwelling older adults (70.02 ± 7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-D ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. Results: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. Conclusions: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.