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1.  Impact of human immunodeficiency virus on neurocognition and risky behaviors in young adults 
Journal of neurovirology  2014;20(5):466-473.
Previous studies have identified cognitive impairments due to human immunodeficiency virus (HIV) in adults. However, few studies have examined the impact of HIV on cognition in young adults (18-24 years old). Yet, this group is one of the largest populations of individuals with new HIV infection. Young adulthood is also an important developmental window as the brain has not fully matured and individuals are prone to engage in risky behavior. The purpose of the present study was to examine the impact of HIV on neurocognition and risky behaviors. We hypothesized that HIV+ young adults (n=23) would exhibit greater cognitive impairment and risky behaviors compared to seronegative controls (n=21). In addition, we predicted that self-reported risky behavior as assessed by the Risk Assessment Battery (RAB) would covary with cognitive performances. Results revealed poorer executive function in HIV+ young adults compared to seronegative controls. HIV+ young adults also exhibited significantly greater risk scores on the RAB (p < 0.01) compared to HIV- young adults. However, there were no relationships between risky behavior and cognitive performance. Overall, our results suggest that HIV is associated with poorer cognition and increased risky behaviors in young adults.
doi:10.1007/s13365-014-0264-4
PMCID: PMC4305333  PMID: 24970235
HIV; Cognition; Risky Behavior; Neuropsychology; Executive Function
2.  Bariatric Surgery Patients Exhibit Improved Memory Function 12 Months Post-Operatively 
Obesity surgery  2013;23(10):1527-1535.
Introduction/Purpose
Previous work from our group demonstrated improved memory function in bariatric surgery patients at 12 weeks post-operatively relative to controls. However, no study has examined longer term changes in cognitive functioning following bariatric surgery.
Materials and Methods
A total of 137 individuals (95 bariatric surgery patients, 42 obese controls) were followed prospectively to determine whether post-surgery cognitive improvements persist. Potential mechanisms of change were also examined. Bariatric surgery participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 12-month follow-up; obese controls completed measures at equivalent time points.
Results
Bariatric surgery patients exhibited cognitive deficits relative to well established standardized normative data prior to surgery, and obese controls demonstrated similar deficits. Analyses of longitudinal change indicated an interactive effect on memory indices, with bariatric surgery patients demonstrating better performance post-operatively than obese controls.
Conclusion
While memory performance was improved 12 months post-bariatric surgery, the mechanisms underlying these improvements were unclear and did not appear attributable to obvious post-surgical changes, such as reductions in BMI or co-morbid medical conditions. Future studies employing neuroimaging, metabolic biomarkers, and more precise physiological measurements are needed to determine the mechanisms underlying memory improvements following bariatric surgery.
doi:10.1007/s11695-013-0970-7
PMCID: PMC3773052  PMID: 23636994
obesity; cognitive function; bariatric surgery; longitudinal assessment
3.  Patient reports of cognitive problems are not associated with neuropsychological test performance in bariatric surgery candidates 
Background
Recent work shows that cognitive deficits are common in bariatric surgery candidates and associated with reduced weight loss at 12 months post-operatively. As pre-operatively neuropsychological assessment is not available for all patients at all sites, many care providers ask patients to self-report their level of cognitive dysfunction. However, the accuracy of patient self-report of cognitive abilities has not been empirically examined.
Setting
Longitudinal Assessment of Bariatric Surgery (LABS), United States; Medical Center
Methods
Eighty-one bariatric surgery candidates completed self-report measures of cognitive functioning and neuropsychological tests of memory and other cognitive abilities.
Results
Analyses found no association between subjective report of cognitive function and objective performance on neuropsychological testing. However, persons with history of major depressive disorder reported experiencing greater cognitive deficits.
Conclusions
These findings suggest that bariatric surgery candidates have little insight into their current level of cognitive function. Future work is needed to confirm these findings and identify brief, objective measures of cognitive function that are sensitive to deficits in bariatric surgery candidates.
doi:10.1016/j.soard.2012.10.008
PMCID: PMC3610809  PMID: 23245496
Bariatric; Cognition; Self-report; Memory; Executive Function
4.  Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: A quantitative tractography DTI study 
Brain imaging and behavior  2013;7(3):10.1007/s11682-013-9225-4.
The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer’s disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N=23) versus no e4 allele (non-carriers, N=41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p=.038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.
doi:10.1007/s11682-013-9225-4
PMCID: PMC3726531  PMID: 23475756
ApoE; ApoE4; Tractography; DTI; White matter; Fiber bundle lengths; Aging
5.  Impact of body mass index on neuronal fiber bundle lengths among healthy older adults 
Brain imaging and behavior  2013;7(3):10.1007/s11682-013-9230-7.
Increased body mass index (BMI) has been linked to various detrimental health outcomes, including cognitive dysfunction. Recent work investigating associations between obesity and the brain has revealed decreased white matter microstructural integrity in individuals with elevated BMI, independent of age or comorbid health conditions. However, the relationship between high BMI and white matter fiber bundle length (FBL), which represents a novel metric of microstructural brain integrity, remains unknown. The present study utilized quantitative tractography based on diffusion tensor imaging (DTI) to investigate the relationship between BMI and FBL in 72 otherwise healthy older adults (24 males, 48 females). All participants were between 51 and 85 years of age (M = 63.26, SD = 8.76). Results revealed that elevated BMI was associated with shorter FBL in the temporal lobe, independent of age (p < .01). In addition, increased age was associated with shorter frontal, temporal, and whole brain FBL (all p values < .01). These findings indicate that, while increased age is an important factor associated with reduced FBL, high BMI is uniquely associated with reduced FBL in the temporal lobe. These data offer evidence for additive adverse effects of high BMI on the brain, especially in areas already vulnerable to aging processes and age-related neurodegenerative diseases. Further research is necessary to determine the physiological mechanisms associated with the shortening of FBL in individuals with high BMI.
doi:10.1007/s11682-013-9230-7
PMCID: PMC3830712  PMID: 23564371
Tractography; BMI; DTI; White Matter; Fiber Bundle Length; Aging
6.  Trail Making Test A Improves Performance Characteristics of the International HIV-Dementia Scale to Identify Symptomatic HAND 
Journal of neurovirology  2013;19(2):137-143.
Although HIV-Associated Dementia (HAD) occurs in less than 5% of individuals with access to combination antiretroviral therapy (cART), rates of milder forms of HIV-Associated Neurocognitive Disorder (HAND) are much higher. We sought to define an optimal cut-point for the International HIV-Dementia Scale (IHDS) in Thailand for the identification of symptomatic HAND, defined as both HAD and Mild Neurocognitive Disorder (MND). We then sought to determine if adding a simple test from a larger neuropsychological battery could improve the performance characteristics for identifying symptomatic HAND. In this study 75 seropositive adults in Bangkok, Thailand, subjects completed neuropsychological tests and underwent a full neurological assessment. HAND diagnoses were determined by consensus conference using the 2007 Frascati criteria, blinded to the IHDS results. The optimal IHDS cut-point was determined by Receiver Operating Characteristic analysis with cross-validation. Individual neuropsychological tests were then evaluated and combined with the IHDS to test performance characteristics. The IHDS was poor at detecting symptomatic HAND at the optimized cut-point of ≤10 (sensitivity: 53.3%, specificity: 89.8%). The Trail Making Test A was most effective in improving performance characteristics when combined with the IHDS, with net sensitivity of 86% and specificity of 79%. In this setting, the IHDS performed poorly in identifying symptomatic HAND, but was substantially improved by the addition of Trail Making Test A, which typically requires less than two minutes to complete. This combination should be validated in a larger setting since it may address the critical need for HAND screening instruments in international settings.
doi:10.1007/s13365-013-0151-4
PMCID: PMC3644005  PMID: 23483520
HIV Dementia; Neuropsychology; Asia; Neuropsychological Tests; Trail Making Test
7.  Reduced memory in fat mass and obesity-associated allele carriers among older adults with cardiovascular disease 
Background
Much attention has been paid to the prevalence and predisposition of the fat mass and obesity-associated (FTO) gene to obesity, although only a few studies have characterized the extent to which this affects cognitive function. This study examined differences between risk allele carriers (i.e. FTO-AC/AA) and non-carriers (i.e. FTO-CC) on indices of attention/executive function/psychomotor speed, memory, language, and visual-spatial ability in a sample of older patients with cardiovascular disease.
Methods
We recruited 120 older adults from an outpatient cardiology clinic who underwent blood draw and completed neuropsychological testing. Participants were classified into two groups: one for those who were homozygous for the non-risk-conferring allele (i.e. FTO-CC) (n = 49) and the other for those who had at least one copy of the obesity risk-conferring A allele (i.e. FTO-AC/AA) (n = 71).
Results
Mancova analyses adjusting for age and years of education revealed the FTO-AC/AA group performed significantly worse on indices of memory (λ = 0.94, F(2, 115) = 3.58, P = 0.03, partial η2 = 0.06). Follow-up tests revealed a significant effect for the FTO-AC/AA group, relative to the non-carrier group, on encoding (i.e. California Verbal Learning Test Total Learning) and California Verbal Learning Test long-delay free recall (P < 0.05). No such differences between FTO carriers and non-carriers emerged on tests of attention/executive function/psychomotor speed, language, or visual-spatial ability (P > 0.05 for all).
Conclusions
These findings suggest that the FTO risk allele is associated with reduced memory performance, particularly on aspects of memory encoding and delayed recall. To elucidate underlying mechanisms, these findings will need to be replicated in larger samples that utilize neuroimaging.
doi:10.1111/j.1479-8301.2012.00424.x
PMCID: PMC3806216  PMID: 23551410
cardiovascular disease; cognitive function; FTO risk allele; memory; obesity
8.  Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals 
Journal of neurovirology  2012;18(4):303-312.
HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.
doi:10.1007/s13365-012-0106-1
PMCID: PMC3420956  PMID: 22585287
HIV; Cerebrovascular disease; Diffusion tensor imaging
9.  Global NeuroAIDS Roundtable 
Journal of neurovirology  2013;19(1):1-9.
In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the roundtable were to evaluate HIV-associated neurocognitive impairment and determine if it may be directly attributable to distinct HIV subtypes or clades and to discuss the future priorities for global NeuroAIDS research. At the “Global NeuroAIDS Roundtable”, presentations of preliminary research indicated that HIV-associated neurocognitive impairment is prevalent in all countries examined regardless of which HIV clade is present in the region. The only clear-cut difference between HIV-1 clades was in relation to subtypes A and D in Uganda. However, a key point that emerged from the discussions was that there is an urgent need to standardize neurocognitive assessment methodologies across the globe before definitive conclusions can be drawn regarding the relationship between HIV clade diversity and neuropathogenesis. Future research directions were also discussed at the roundtable with particular emphasis on the potential of viral and host factor molecular interactions to impact the pathophysiology of HIV-associated neurocognitive disorders (HAND) from a global perspective.
doi:10.1007/s13365-012-0143-9
PMCID: PMC3713197  PMID: 23354550
Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2); Acquired immunodeficiency syndrome (AIDS); HIV clade; NeuroAIDS; HIV-associated neurocognitive disorders (HAND); Neuropathogenesis
10.  Drug Abuse and Hepatitis C Infection as Comorbid Features of HIV Associated Neurocognitive Disorder: Neurocognitive and Neuroimaging Features 
Neuropsychology review  2009;19(2):215-231.
Substance abuse and co-infection with hepatitis C (HCV) are two highly relevant determinants of neurocognitive and neuroimaging abnormalities associated with HIV. Substance abuse and HCV are common in the HIV population and there is increasing evidence that the CNS is directly compromised by these comorbid conditions via additive or synergistic processes. In this article we review the current literature regarding mechanisms of neuronal injury as well as the neuropsychological and neuroimaging signatures associated with substance abuse and HCV status among HIV patients. We discuss specific methodological challenges and threats to validity associated with studies of HIV and comorbid substance use disorders or HCV and review potential strategies for minimizing their confounding effects. Efforts to understand the interactions between HIV, substance abuse and HCV co-infection will lead to more complete models of neuropathogenesis of HIV and a greater understanding of the variability in neuropsychological expression of HIV Associated Neurocognitive Disorder.
doi:10.1007/s11065-009-9101-6
PMCID: PMC3635478  PMID: 19468837
HIV; Drug abuse; Hepatitis C; Addiction; Neurocognition; Neuroimaging; Dementia
11.  Recent Clinical History and Cognitive Dysfunction for Attention and Executive Function among Human Immunodeficiency Virus-Infected Patients 
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.
doi:10.1093/arclin/acr065
PMCID: PMC3243921  PMID: 21873325
HIV; Cognition; Neuropsychology; Executive function; Recent clinical history
12.  Lower Cardiac Output Is Associated with Greater White Matter Hyperintensities in Older Adults with Cardiovascular Disease 
OBJECTIVES
To preliminarily examine the association between cardiac output, a measure of systemic blood flow, and structural brain magnetic resonance imaging indices of white matter hyperintensities (WMHs).
DESIGN
Cross-sectional.
SETTING
University medical setting.
PARTICIPANTS
Thirty-six older adults without dementia with prevalent cardiovascular disease (aged 56–85).
MEASUREMENTS
Cardiac output, WMHs.
RESULTS
Partial correlations, adjusting for age and history of hypertension, yielded an inverse relationship between WMHs adjacent to subcortical nuclei and cardiac output (correlation coefficient = −0.48, P = .03); as cardiac output decreased, WMHs increased significantly. No significant associations were found between cardiac output and total WMHs or periventricular WMHs.
CONCLUSION
These preliminary data suggest that systemic blood flow, measured according to cardiac output, is inversely associated with WMHs adjacent to the subcortical nuclei. Cerebrovascular degeneration and the chronicity of hypoperfusion may exacerbate the susceptibility of white matter integrity to alterations in blood flow in older adults.
doi:10.1111/j.1532-5415.2007.01226.x
PMCID: PMC2721459  PMID: 17608877
systemic perfusion; aging; cardiovascular disease; MRI
13.  Improved Memory Function 12 Weeks after Bariatric Surgery 
Background
There is growing evidence that obesity is associated with poor neurocognitive outcome. Bariatric surgery is an effective intervention for morbid obesity and improves many comorbid medical conditions that are associated with cognitive dysfunction. The effects of bariatric surgery on cognition are unknown.
Methods
Prospective study total of 150 individuals (109 bariatric surgery patients enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) project and 41 obese controls that did not undergo surgery) completed cognitive evaluation at baseline and 12 week follow-up. Demographic, medical, and psychosocial information was also collected to elucidate possible mechanisms of change.
Results
Many bariatric surgery patients exhibited impaired performance on cognitive testing at baseline (range from 4.6%–23.9%). However, surgery patients were no more likely to exhibit decline on two or more cognitive tests at 12-week follow-up than obese controls [12.84% vs. 23.26%; χ2 (1) = 2.51, p = .11]. Group comparisons using repeated measures MANOVA showed surgery patients had improved memory performance at 12 week follow-up [λ = .86, F(4, 147) = 5.88, p<.001], whereas obese controls actually declined. Regression analyses showed surgery patients without hypertension had better short delay recall at 12 weeks than those that did [β = 0.31, p = .005], though other demographic and medical variables were largely unrelated to test performance.
Conclusion
The current results suggest that cognitive impairment is common in bariatric surgery patients, though these deficits may be at least partly reversible. Future studies are needed to clarify underlying mechanisms, particularly longitudinal studies employing neuroimaging and blood markers.
doi:10.1016/j.soard.2010.09.015
PMCID: PMC3117085  PMID: 21145295
obesity; cognitive function; bariatric surgery; Integneuro
15.  Neuroimaging and Cardiac Correlates of Cognitive Function among Patients with Cardiac Disease 
In the present study, we examined the relationships between whole brain volume (WBV), subcortical hyperintensities (SH), indices of cardiac disease and cognitive function in nondemented cardiac patients with evidence of mild cerebrovascular disease. A total of 27 individuals with evidence of cardiac disease underwent neuropsychological examination, neuroimaging, and cardiac assessment. Cognition was assessed with the Dementia Rating Scale-2 (DRS). WBV and SH were quantified using a semi-automated thresholding program based on MRI. Correlational analyses revealed that WBV predicted performance on the overall DRS score, the attention subscale and the initiation/perseveration scale. SH were significantly associated with performance on the attention subscale, and the initiation/perseveration subscale. Regression analyses revealed that SH accounted for most of the variance in the initiation/perseveration scale, whereas WBV accounted for most of the variance in the attention scale. The only cardiac structural or functional variable related to the neurological indices was aortic diameter, which was strongly related to both neuroimaging variables, as well as performances on the DRS attention and initiation/perseveration subscales. Our results highlight the importance of overall brain parenchyma in determining cognitive status among patients at risk for cognitive decline and suggest that select indices of structural cardiac morphology may be related to the early phases of cerebrovascular disease and cognitive status.
doi:10.1159/000086803
PMCID: PMC3222237  PMID: 16006761
Cardiac disease; MRI; Cognition; Neuropsychology; Subcortical hyperintensities
16.  Blood pressure variability and white matter hyperintensities in older adults with cardiovascular disease 
Blood pressure  2005;14(6):353-358.
The present study examined the relationship between multiple blood pressure (BP) indices and white matter hyperintensities (WMH) in a sample of 39 older adults with cardiovascular disease (CVD). Resting BP was measured using an automated monitor every 10 min for 2 h. WMH were quantified on FLAIR images and separate indices were generated for neocortical, periventricular and subcortical brain regions. Correlation analyses revealed systolic BP variability was related to neocortical and total WMH. A function of systolic BP variability and average diastolic pressure showed the strongest relationships, including significant correlation to neocortical, subcortical and total WMH. No BP index was related to WMH in periventricular regions. Exploratory analyses showed only the function of systolic BP variability and average diastolic pressure predicted total WMH, whereas as age, CVD conditions and psychosocial factors did not. These findings demonstrate BP variability is an important contributor to WMH in older adults with CVD and suggests it may have differential relationships to WMH in different brain regions. Additional studies are needed to examine the role of autoregulatory systems in the development of WMH, particularly those using beat-to-beat measures of BP.
doi:10.1080/08037050500364117
PMCID: PMC3215278  PMID: 16403689
Blood pressure; cardiovascular disease; cerebrovascular disease
17.  Link Between Change in Cognition and Left Ventricular Function following Cardiac Resynchronization Therapy 
PURPOSE
In patients with heart failure, reduced cardiac ejection fraction has been associated with impaired cognition. Improving cardiac function may have beneficial effects on cognition; however, no controlled intervention studies have examined this possibility. Cardiac resynchronization therapy (CRT) is 1 intervention that has been shown to increase cardiac function. The goals of the current study were to: 1) evaluate neuropsychological performance before and 3-months after CRT and 2) examine follow-up neuropsychological performance of patients classified based on extent of improved left ventricular ejection fraction (LVEF).
METHODS
Twenty-seven patients with moderate to severe heart failure completed a neuropsychological assessment, 6-minute walk test, and transthoracic echocardiogram prior to and 3-months post-CRT. Patients were classified based on improvement in LVEF. Results of a MANOVA revealed a significant effect of improvement in LVEF on change in cognition (Wilk’s lambda, P=.031).
RESULTS
Patients with improved LVEF demonstrated significant increases on measures of executive functioning (F=8.57, P=.007) and visuospatial function (F=7.52, P=.011) and less decline on global cognition (F=5.73, P=.024) than those without LVEF improvement.
CONCLUSIONS
Findings provide preliminary evidence that improved LVEF in response to CRT is associated with enhanced cognitive outcomes within 3 months of CRT. Patients with improved LVEF showed better outcomes on measures of executive functioning, global cognition, and visuospatial functioning. Future controlled large scale trials will be necessary to determine whether there is an underlying causal relationship linking increase in LVEF and cognition.
doi:10.1097/HCR.0b013e3181e1739a
PMCID: PMC2978265  PMID: 20562712
Heart failure; Cardiac resynchronization therapy; Cognition; Neuropsychology; Left ventricular ejection fraction
18.  Quantitative Diffusion Tensor Imaging Tractography Metrics are Associated with Cognitive Performance Among HIV-Infected Patients 
Brain imaging and behavior  2010;4(1):68-79.
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; r≥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.
doi:10.1007/s11682-009-9086-z
PMCID: PMC2909656  PMID: 20503115
HIV; DTI; Neuropsychological performance; Tractography
19.  Vascular Health and Cognitive Function in Older Adults with Cardiovascular Disease 
Artery research  2008;2(1):35-43.
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 to 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.
doi:10.1016/j.artres.2008.01.001
PMCID: PMC3004172  PMID: 21179381
Cardiovascular Disease; vascular function; age; endothelium; neurocognitive performance
20.  Subjective Cognitive Complaints Relate to White Matter Hyperintensities and Future Cognitive Decline in Patients with Cardiovascular Disease 
Objective
Elderly patients with cardiovascular disease (CVD) often report cognitive difficulties including reduced cognitive processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to objective measures of cognitive performance, thus questioning the validity of subjective cognitive complaints as a marker of neurodegenerative processes. This study examined the longitudinal relationship between self-reported cognitive difficulties, depression, and performance on objective tests of global cognition in patients with CVD.
Participants and Methods
Forty-seven CVD patients (ages 55 to 85 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale), a medical history questionnaire, the Dementia Rating Scale (DRS), and the Beck Depression Inventory (BDI) at baseline and 12 months later. Baseline brain imaging was available on a small sub-sample (n = 17).
Results
Hierarchical linear regression revealed that increased report of cognitive difficulties at baseline was significantly associated with poorer DRS performance at follow-up (F(3, 43) = 4.45, p = .008, CDS partial r = −.30, p = .048), independent of age, education, baseline DRS and BDI scores. Greater perceived cognitive dysfunction at baseline also related to higher level of white matter lesions (r = .53, df = 15, p = .028).
Conclusions
Self-reported cognitive difficulties may reflect early changes in cognitive aging that are difficult to detect using global cognitive screening measures at a single time point. Yet, these perceived difficulties relate to objectively measured cognitive decline over time. Thus, they may provide important clinical information about early neurodegenerative processes that should be carefully monitored.
doi:10.1097/JGP.0b013e3181b208ef
PMCID: PMC2813459  PMID: 20104055
Subjective Cognitive Complaints; Cognition; Cardiovascular Diseases; Dementia Ratings Scale; White Matter Hyperintensities
21.  SELP 1087G/A Polymorphism is Associated with Neuropsychological Test Performance in Older Adults with Cardiovascular Disease 
Background and Purpose
There is growing evidence that the cell adhesion molecule P-selectin (SELP) contributes to the adverse vascular processes that promote cognitive impairment in individuals with cardiovascular disease. Previous research has shown that SELP genotypes moderate circulating levels of P-selectin and that coronary artery bypass graft (CABG) patients with the SELP 1087A allele were less likely to show post-operative cognitive decline and more likely to exhibit lower levels of C-reactive protein (CRP) than non-carriers. Thus, we expected that carriers of the 1087A allele (n = 43) would exhibit better cognitive functioning than persons with two 1087G alleles (n = 77) and that CRP levels would be important for this relationship.
Methods
120 older adults with diagnosed cardiovascular disease (CVD) were recruited from outpatient cardiology clinics. Each participant underwent a comprehensive neuropsychological test battery and a blood draw.
Results
Participants with the SELP 1087A allele performed more poorly on tests of attention [TMT-A: t(116)=3.20, p=.002], executive function [TMT-B: t(116)=2.89, p=.005], psychomotor speed [Digit-Symbol Coding: t(117)=2.54, p=.012], and memory [CVLT Discrimination: t(116)=2.05, p=.04]. There were no significant differences between the SELP genotype groups on demographic/medical variables or CRP levels.
Conclusions
Contrary to expectations, the present analyses showed that older CVD patients with the SELP 1087A allele performed more poorly on neuropsychological testing. Findings from the present study were counter to previous research with CABG candidates. Further work using neuroimaging and alternative measures of cardiovascular function is needed to clarify the mechanisms of this association.
doi:10.1161/STROKEAHA.109.553339
PMCID: PMC2752956  PMID: 19590054
P-selectin; Cognitive Function; Heart Disease
22.  Blood Pressure and Cognitive Function in Older adults with Cardiovascular Disease 
Background
Past studies link elevated blood pressure (BP) and BP variability to adverse neurocognitive changes in community samples. However, little is known about the relationship between BP indices and cognitive function in older CVD patients.
Methods
A total of 99 older adults with CVD completed a comprehensive neuropsychological test battery. Resting BP measurements were collected every 10 minutes for two hours during a separate cardiac assessment. Five BP indices were generated: average and standard deviation of systolic blood pressure, average and standard deviation of diastolic blood pressure, and a function of systolic variability and average diastolic pressure. We examined the relationship between these BP indices and cognitive function.
Results
Partial correlation adjusting for age and education revealed that the function of systolic variability and average diastolic pressure (systolic BP standard deviation divided by the average diastolic BP) was most closely related to test performance, showing significant associations to both Learning/Memory (r = 0.25) and Language functioning (r = 0.22). Systolic BP indices were also related to Language functioning (SBP avg, r = 0.22; SBP sd, r = 0.25), though diastolic BP indices were unrelated to performance in any cognitive domain.
Conclusions
The current findings indicate that BP is modestly related to cognitive function in older CVD patients. Contrary to expectations, greater BP variability was associated with better, not poorer, cognitive test performance. Such findings suggest that the relationship between BP and cognitive function is more complicated than typically hypothesized and requires further examination.
doi:10.3109/00207450903139713
PMCID: PMC2899480  PMID: 19916851
Blood Pressure; Cognitive Function; Heart Disease
23.  Normative scores for a brief neuropsychological battery for the detection of HIV-associated neurocognitive disorder (HAND) among South Africans 
BMC Research Notes  2010;3:28.
Background
There is an urgent need to more accurately diagnose HIV-associated neurocognitive disorder (HAND) in Africa. Rapid screening tests for HIV-associated dementia are of limited utility due to variable sensitivity and specificity. The use of selected neuropsychological tests is more appropriate, but norms for HIV seronegative people are not readily available for sub-Saharan African populations. We sought to derive normative scores for two commonly used neuropsychological tests that generate four test scores -- namely the Trail-Making Test (Parts A and B) and the Digit Span Test [Forward (DSF) and Backward (DSB)]. To assess memory and recall, we used the memory item of the International HIV Dementia Scale (IHDS).
Findings
One hundred and ten HIV seronegative participants were assessed at McCord Hospital, Durban, South Africa between March 3rd and October 31st, 2008. We excluded people with major depressive disorder, substance use abuse and dependence and head injuries (with or without loss of consciousness). All the participants in this study were African and predominantly female with an average age of 28.5 years and 10 years of education. Age and gender influenced neuropsychological functioning, with older people performing worse. The effect of gender was not uniform across all the tests.
Conclusion
These two neuropsychological tests can be administered with the IHDS in busy antiretroviral clinics. Their performance can be measured against these norms to more accurately diagnose the spectrum and progression of HAND.
doi:10.1186/1756-0500-3-28
PMCID: PMC2843737  PMID: 20181051
24.  Category and letter verbal fluency across the adult lifespan: relationship to EEG theta power 
The purpose of this study was to examine the impact of age, sex, and education on category and letter verbal fluency task performance. A secondary goal was to examine whether resting EEG theta power in bilateral frontal and temporal lobes impacts age-associated decline in verbal fluency task performance. A large sample (N=471) of healthy, normal participants, age 21–82, was assessed for letter fluency (i.e., FAS), and for category fluency (i.e., Animal Naming), and with a 32-channel EEG system for ‘eyes-open’ resting theta power. The effects of age, sex, and education were examined using analyses of variance. Correlation analyses were used to test the impact of theta power on age and fluency performance by controlling for the effects of theta when examining the relationship between the other two variables. The results indicated that performance on both fluency tests declined linearly with age, but that the rate of decline was greater for category fluency. These age changes were not associated with education level, and there were no sex differences. While theta power was negatively associated with age and positively associated with Animal Naming performance, it did not moderate the relationship between the two. The differential age-associated decline between category and letter fluency suggests separate neurobiological substrates underlying the two domains of performance, which is not related to theta activity.
doi:10.1016/j.acn.2004.12.006
PMCID: PMC2758771  PMID: 15939182
Normal aging; Category fluency; Letter fluency; EEG; Theta
25.  Regional White Matter Signal Abnormalities and Cognitive Correlates Among Geriatric Patients with Treated Cardiovascular Disease 
Brain imaging and behavior  2008;2(3):200-206.
The purpose of this study was to investigate the relations between regional white matter signal abnormalities (WMSA) and cognitive functioning among individuals being treated for cardiovascular risk factors and/or clinical events. Forty-one participants with cardiovascular disease underwent a comprehensive neuropsychological assessment and MRI. Total WMSAs were quantified using a semi-automated thresholding technique. Unique to this study, total WMSA volume was divided into three separate anatomically related regions: WMSA in the periventricular (PERIWMSA) region, WMSA adjacent to subcortical nuclei (SUBWMSA), and WMSA in the deep white matter (DEEPWMSA). A ratio of these measures to total cerebral brain volume was compared to cognitive measures assessing attention, executive functioning, psychomotor speed, immediate and delayed memory, language, and visuospatial functioning. PERIWMSA, SUBWMSA, and total WMSA were significantly associated with performance on measures of attention/processing speed. No other significant relationships between WMSA and cognition were noted. Secondary analyses suggested that PERIWMSA volume was increased in individuals with clinical evidence of atherosclerosis. These results emphasize the utility of studying the associations between regional WMSA and cognitive/functional performance in patients undergoing cardiovascular treatment.
doi:10.1007/s11682-008-9032-5
PMCID: PMC2753539  PMID: 19789657
Cardiovascular disease; MRI; Hyperintensities; Cognition

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