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Biomedical subjects

Ola A Selnes

Publications and source records attributed to Ola A Selnes.

At least 19 recordsLinked to original sources
PubMed2007

An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection.

BACKGROUND: Several markers of immune activation have been identified as potential prognostic markers for human immunodeficiency virus (HIV)-associated morbidity and mortality, but the results from studies are conflicting. OBJECTIVE: To evaluate whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid tumor necrosis factor alpha (TNF-alpha), macrophage chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a cohort with advanced HIV infection. DESIGN: Cohort study. SETTING: Enrollees in the Northeast AIDS Dementia Study. PARTICIPANTS: Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/microL (or <300/microL but with cognitive impairment at baseline) were assessed for CD4 cell count, neurocognitive status, pertinent demographic and clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-alpha, MCP-1, MMP-2, and M-CSF levels. MAIN OUTCOME MEASURES: Cox proportional hazards regression models were used to examine the associations between the variables of interest (using time-dependent covariates, where applicable) and time to death, adjusting for possible confounders. RESULTS: There were 50 deaths in the cohort after a median of 25.2 months of follow-up. The cumulative incidences of death were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression analyses adjusting for demographic, clinical, and immunological variables, HIV-associated dementia (hazard rate, 6.10; P = .001) was significantly associated with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P = .08) trended toward significance. CONCLUSION: In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.

Adult↗
PubMed2006

Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging With HIV cohort.

OBJECTIVE: To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk. DESIGN: Cross-sectional analysis within the Hawaii Aging With HIV Cohort. METHODS: We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses. RESULTS: Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores. CONCLUSIONS: IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.

AIDS Dementia Complex↗
PubMed2006

Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome.

BACKGROUND AND PURPOSE: Watershed strokes are more prevalent after cardiac surgery than in other stroke populations, but their mechanism in this setting is not understood. We investigated the role of intraoperative blood pressure in the development of watershed strokes and used MRI to evaluate diagnosis and outcomes associated with this stroke subtype. METHODS: From 1998 to 2003 we studied 98 patients with clinical stroke after cardiac surgery who underwent MRI with diffusion-weighted imaging. We used logistic regression to explore the relationship between mean arterial pressure and watershed infarcts, between watershed infarcts and outcome, and chi(2) analyses to compare detection by MRI versus CT of watershed infarcts. RESULTS: Bilateral watershed infarcts were present on 48% of MRIs and 22% of CTs (P<0.0001). Perioperative stroke patients with bilateral watershed infarcts, compared with those with other infarct patterns, were 17.3 times more likely to die, 12.5 and 6.2 times more likely to be discharged to a skilled nursing facility and to acute rehabilitation, respectively, than to be discharged home (P=0.0004). Patients with a decrease in mean arterial pressure of at least 10 mm Hg (intraoperative compared with preoperative) were 4.1 times more likely to have bilateral watershed infarcts than other infarct patterns. CONCLUSIONS: Bilateral watershed infarcts after cardiac surgery are most reliably detected by diffusion-weighted imaging MRI and are associated with poor short-term outcome, compared with other infarct types. The mechanism may include an intraoperative drop in blood pressure from a patient's baseline. These findings have implications for future clinical practice and research.

Aged↗
PubMed2006

Cognitive and neurobehavioral dysfunction after cardiac bypass procedures.

From a cognitive standpoint, CABG as currently practiced appears to be safe for the great majority of patients, but transient changes involving memory, executive functions, and motor speed may still occur in a subset of patients during the first few days to weeks after CABG. The etiology most likely is multifactorial and includes a synergistic effect of microemboli, hypo-perfusion, and other variables associated with major surgery. Older age and degree of pre-existing cerebrovascular disease have been identified as important risk factors. The short-term cognitive changes appear to be reversible by 3 months after surgery for most patients. Late cognitive decline after CABG,occurring between 1 and 5 years after the surgery, has been well documented,but controlled studies demonstrating that this decline is specifically attributable to the use of cardiopulmonary bypass itself rather than to progression of underlying cerebrovascular disease or other age-related changes are pending.

Atrial Fibrillation↗
PubMed2006

Vascular cognitive impairment.

Cognitive impairment commonly accompanies clinical syndromes associated with vascular disease of the brain. Because of evolving definitional criteria, however, the frequency of cognitive impairment attributable to cerebrovascular disease is difficult to determine. Dementia occurs in up to one-third of elderly patients with stroke, a subset of whom have Alzheimer's disease (AD) rather than a pure vascular dementia syndrome. In fact, pure vascular dementia has been shown to be uncommon in most large autopsy series. A mixed etiology of AD and cerebrovascular disease is thought to become more common with increasing age, although no clinical criteria for the diagnosis of AD with cerebrovascular disease are currently available. Epidemiological studies have implicated subcortical small-vessel disease as a risk factor for cognitive impairment and dementia, but the cognitive expression and clinical significance of MRI white matter changes in individual patients is difficult to establish. The frequency of specific neuropathologic features of vascular cognitive impairment depends largely on study inclusion criteria. Cerebral meningocortical microangiopathies with distinctive clinicopathological profiles are associated with dementia in both sporadic cases and familial syndromes. In patients with AD, the contribution of amyloid-beta protein to the degree of cognitive impairment has not been clearly defined.

Aged↗
PubMed2006

A randomized trial of the impact of a programmable medication reminder device on quality of life in patients with AIDS.

This 6-month randomized controlled trial evaluated the impact on quality of life (QOL) of a medication reminder device for patients with HIV. Patients were eligible if they had taken three or fewer highly active antiretroviral therapy (HAART) regimens or were treatment naïve. The intervention group received the Disease Management Assistance System (DMAS), a prompting device that verbally reminds patients at medication times and electronically records doses, and a monthly 30 minute adherence educational session. Controls received education only. QOL was measured at baseline and 6 months using the Centers for Epidemiologic Studies Depression Scale (CES-D), Instrumental Activities of Daily Living (IADLs), and the Medical Outcomes Study HIV Health Survey (MOS-HIV). At baseline, 62 patients completed surveys (31 control, 31 DMAS); at month 6, 48 patients completed surveys (23 control, 25 DMAS). At month 6, controls had improved QOL scores for CES-D, IADLs, physical health, general health, pain, QOL, and role functioning, while participants in the DMAS arm had some deterioration in QOL scores. These differences persisted after controlling for demographics, baseline CD4, and adherence. DMAS was associated with improved adherence but decreased QOL.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Stroke and encephalopathy after cardiac surgery: an update.

BACKGROUND AND PURPOSE: As a result of advances in surgical, anesthetic, and medical management, cardiac surgery can now be performed on older, sicker patients, some of whom have had prior cardiac interventions. As surgical mortality has declined in recent years, attention has focused on the complications of stroke and encephalopathy after cardiac surgery. SUMMARY OF REVIEW: Patients with preexisting cerebrovascular disease are at increased risk for these untoward neurological outcomes, which are associated with longer lengths of hospital stay, higher costs, and greater mortality. The mechanisms underlying these neurological events may include microemboli and hypoperfusion during surgery, and postoperative atrial fibrillation. Predictive models, based on information available before surgery, allow identification of these "high risk" patients. CONCLUSIONS: Establishing the degree of functionally significant vascular disease of the brain before surgery should be an essential part of the preoperative evaluation, particularly when modifications in surgical technique or novel neuroprotective agents are being evaluated.

Aged↗
PubMed2005

The International HIV Dementia Scale: a new rapid screening test for HIV dementia.

OBJECTIVE: HIV dementia is an important neurological complication of advanced HIV infection. The use of a cross-cultural screening test to detect HIV dementia within the international community is critical for diagnosing this condition. The objective of this study was to evaluate the sensitivity and specificity of a new screening test for HIV dementia, the International HIV Dementia Scale (IHDS) in cohorts from the US and Uganda. DESIGN: Two cross-sectional cohort studies designed to evaluate for the presence of HIV dementia. METHODS: Sixty-six HIV-positive individuals in the US and 81 HIV-positive individuals in Uganda received the IHDS and full standardized neurological and neuropsychological assessments. The sensitivity and specificity of varying cut-off scores of the IHDS were evaluated in the two cohorts. RESULTS: In the US cohort, the mean IHDS score for HIV-positive individuals without dementia and with dementia were 10.6 and 9.3 respectively (P < 0.001). Using the cut-off of < or = 10, the sensitivity and specificity for HIV dementia with the IHDS were 80% and 57% respectively in the US cohort, and 80% and 55% respectively in the Uganda cohort. CONCLUSIONS: The IHDS may be a useful screening test to identify individuals at risk for HIV dementia in both the industrialized world and the developing world. Full neuropsychological testing should then be performed to confirm a diagnosis of HIV dementia.

AIDS Dementia Complex↗
PubMed2005

A programmable prompting device improves adherence to highly active antiretroviral therapy in HIV-infected subjects with memory impairment.

Background. Patients cite "forgetting" as a reason for nonadherence to highly active antiretroviral therapy (HAART). We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects.Methods. The study was a prospective, randomized, controlled trial involving 64 HIV-infected adults. The intervention was the Disease Management Assistance System (DMAS) device, combined with monthly adherence counseling. Control subjects received only adherence counseling. The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times. Adherence was measured for 24 weeks using electronic drug exposure monitor (eDEM) caps.Results. A total of 58 subjects completed the 24-week study period; 28 were HAART naive (12 DMAS users and 16 control subjects). Mean adherence scores did not differ significantly between DMAS users (80%) and control subjects (65%). Post hoc analysis of 31 memory-impaired subjects (14 DMAS users and 17 control subjects) revealed significantly higher adherence rates among DMAS users (77%), compared with control subjects (57%) (P=.001). However, analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users (83%), compared with control subjects (77%) (P=.25). At week twelve, 38% of the DMAS users and 14% of the control subjects had an undetectable plasma HIV RNA load (P=.014), and at week 24, the plasma HIV RNA load was undetectable for 34% of the DMAS users and 38% of the control subjects (P=.49). CD4(+) cell counts did not differ between the study arms. Virological and immunological responses were not related to DMAS use in memory-impaired subjects.Conclusion. The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects.

Anti-HIV Agents↗
PubMed2005

Diabetes, insulin resistance, and dementia among HIV-1-infected patients.

OBJECTIVES: Metabolic complications have been associated with HIV-1 infection and with long-term use of antiretroviral (ARV) medications. In some studies, such complications have been linked to cardiovascular events, yet limited data exist concerning metabolic complications and dementia. The objective of this study was to examine the relationship between HIV-associated dementia (HAD) and diabetes among patients with HIV-1 infection. DESIGN: Cross-sectional analysis of entry data for a longitudinal cohort study. METHODS: A total of 203 participants who were enrolled in the Hawaii Aging with HIV Cohort between October 2001 and November 2003 served as the study population. Research case definitions of HAD were determined in consensus conferences by a panel that included neurologists, neuropsychologists, and a geriatrician. Diabetes was determined by self-report or a fasting glucose level > 125 mg/dL. RESULTS: Participants' ages ranged between 20-76 years at enrollment with approximately one-half aged >/=50 years. After adjustment for important covariates including age, education, ethnicity, CD4 lymphocyte count, duration of HIV infection, and protease inhibitor-based ARV therapy, we found a statistically significant association of diabetes with HAD (odds ratio 5.43, 1.66-17.70). A significant association remained after adjustment for other vascular risk factors. Among participants without diabetes, fasting glucose levels were higher with increasing impairment category. CONCLUSIONS: Within the Hawaii Aging with HIV Cohort, a longitudinal study enriched with older HIV-1-infected individuals, diabetes is associated with prevalent dementia. This finding is not fully explained by age or coexisting vascular risk factors. Evaluation of underlying mechanisms is warranted.

AIDS Dementia Complex↗
PubMed2005

Neurocognitive complications after coronary artery bypass surgery.

Both short- and long-term cognitive changes continue to occur after coronary artery bypass grafting (CABG), but the pathophysiology of these neurobehavioral changes remains incompletely understood. The persistence of mild postoperative neurocognitive changes despite multiple improvements in the cardiopulmonary bypass procedure may be partially because of surgical populations being older and having more prevalent comorbid disease. The cause of the early postoperative changes is most likely multifactorial and may include ischemic injury from microemboli, hypoperfusion, and other factors resulting from major surgery. Several lines of evidence suggest that the late cognitive decline between 1 and 5 years after surgery may be secondary to high rates of cerebrovascular disease among candidates for CABG. A history of hypertension and other risk factors for vascular disease is known to be associated with increased risk for long-term cognitive decline in community-dwelling elderly individuals. Cerebrovascular risk factors are also associated with silent magnetic resonance imaging abnormalities in patients undergoing CABG. Thus, whereas both short- and long-term postoperative cognitive changes have been associated with CABG, only the short-term, transient changes appear to be directly related to the use of cardiopulmonary bypass.

Anesthesia↗
PubMed2005

Cognitive outcomes three years after coronary artery bypass surgery: a comparison of on-pump coronary artery bypass graft surgery and nonsurgical controls.

BACKGROUND: Coronary artery bypass grafting has been associated with both early and late postoperative cognitive decline, but interpretation of previous studies has been limited by lack of appropriate control groups. We compared changes in cognitive performance from baseline to 3 years in patients undergoing coronary artery bypass grafting with those of a control group of patients with known risk factors for coronary artery disease but without surgery. METHODS: Patients undergoing coronary artery bypass grafting (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) completed baseline neuropsychological assessment and were followed up prospectively at 3, 12, and 36 months. Cognitive performance was assessed with a battery of neuropsychological tests, measuring the cognitive domains of attention, language, verbal and visual memory, visuospatial, executive function, and psychomotor and motor speed. The statistical analyses were performed in two ways: using data from all tested individuals, and using a model imputing missing observations for individuals lost to follow-up. RESULTS: Both the coronary artery bypass grafting and nonsurgical control groups improved from baseline to 1 year, with additional improvement between 1 and 3 years for some cognitive tests. The coronary artery bypass grafting group had statistically significantly greater improvement than the nonsurgical controls for some subtests, and had a comparable longitudinal course for the remainder of the subtests. Both study groups had a trend toward nonsignificant decline at 3 years on some measures, but the overall differences between groups over time were not statistically significant. CONCLUSIONS: Prospective longitudinal neuropsychological performance of patients with coronary artery bypass grafting did not differ from that of a comparable nonsurgical control group of patients with coronary artery disease at 1 or 3 years after baseline examination. This finding suggests that previously reported late cognitive decline after coronary artery bypass grafting may not be specific to the use of cardiopulmonary bypass, but may also occur in patients with similar risk factors for cardiovascular and cerebrovascular disease.

Cognition↗
PubMed2005

Quantitative methods for tracking cognitive change 3 years after coronary artery bypass surgery.

The analysis and interpretation of change in cognitive function test scores after coronary artery bypass grafting (CABG) present considerable statistical challenges. Application of hierarchical linear statistical models can estimate the effects of a surgical intervention on the time course of multiple biomarkers. We use an "analyze then summarize" approach whereby we estimate the intervention effects separately for each cognitive test and then pool them, taking appropriate account of their statistical correlations. The model accounts for dropouts at follow-up, the chance of which may be related to past cognitive score, by implicitly imputing the missing data from individuals' past scores and group patterns. We apply this approach to a study of the effects of CABG on the time course of cognitive function as measured by 16 separate neuropsychological test scores, clustered into 8 cognitive domains. The study includes measurements on 140 CABG patients and 92 nonsurgical controls at baseline, and at 3, 12, and 36 months. Our "analyze then summarize" method allows us to identify differences between the treatment groups in individual tests as well as in aggregate measures. It takes into account the correlation structure of the data and thereby produces more precise results than summarizing before analyzing. The methods used have application to a wide range of intervention studies in which multiple biomarkers are followed over time to quantify health effects. Software to implement the methods in the R statistical package is available from the authors at http://www.biostat.jhsph.edu/sbarry/software/ATSrcode.pdf.

Cognition↗
PubMed2005

Depressive symptoms, quality of life, and neuropsychological performance in HIV/AIDS: the impact of gender and injection drug use.

Limited attention has been paid to the potential impact of gender and injection drug use (IDU) on mood, quality of life, and neuropsychological performance in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Several studies that describe the natural history of HIV/AIDS in terms of mental health and neuropsychological ability have focused solely on men or have excluded injection drug users. Women and injection drug users are two groups for whom the incidence of HIV infection is increasing. Additionally, the National Academy of Sciences recently recommended that studies concerned with health-related research include males and females, and that researchers analyze their data for gender differences. The goals of the current study were to investigate possible relationships between HIV and IDU status and depressive symptoms, quality of life, and neuropsychological performance in women and men matched for age, race, and education. Overall, women reported more depressive symptoms than men, and this gender difference was most evident in women who were both infected with HIV and who were also injection drug users. Women and HIV-infected individuals reported the poorest quality of life scores. Women outperformed men on a measure of verbal memory and HIV(-) participants outperformed HIV(+) participants on a measure of perceptual speed. Finally, gender and HIV status interacted such that uninfected women performed the best, and infected men performed the worst, on a test of verbal memory. A better understanding of how men and women with different drug use profiles respond to HIV/AIDS may substantially improve survival, as well as aspects of daily functioning, of affected individuals. Thus, further study and development of treatment protocols targeted at including women and IDU are needed.

Adult↗
PubMed2005

Memory loss in persons with HIV/AIDS: assessment and strategies for coping.

Although the incidence of HIV-related dementia has decreased significantly in the era of contemporary HAART, the prevalence of memory and cognitive symptoms remains steady in persons with HIV/AIDS. Recognition of which memory symptoms may be specifically related to HIV infection is becoming more and more challenging because of the increased survival and aging of those living with HIV disease. Therefore, numerous age-related causes of memory impairment may need to be ruled out. Depression can often result in subjective memory symptoms but rarely causes objective cognitive impairment. Because of the widespread use of thiamine food supplementation, alcohol is now a less common cause of severe memory impairment. HAART remains the treatment of choice for HIV-related dementia.

AIDS Dementia Complex↗