Ola A. Selnes

Dementia in AIDS patients Incidence and risk factors

We determined incidence and future projections of dementia after AIDS onset in 492 homosexual men with AIDS in the Baltimore/Los Angeles sites of the Multicenter AIDS Cohort Study, 64 of whom developed dementia. We studied various risk factors for dementia, including demographic and clinical features, medical history, markers of immune status before AIDS, and zidovudine use. During the first 2 years after AIDS, HIV dementia developed at an annual rate of 7%. Overall, 15% of the cohort followed through death developed dementia. The median survival after dementia was 6.0 months. Using a proportional hazards model, risk factors for more rapid development of dementia were lower hemoglobin (relative hazard, 0.59 per additional 2 g/dl;p = 0.0005) and body mass index (relative hazard, 0.64 per additional 5 kg/m2; p = 0.05) 1 to 6 months before AIDS, more constitutional symptoms 7 to 12 months before AIDS (relative hazard, 1.68 per additional symptom, p = 0.005), and older age at AIDS onset (relative hazard, 1.60 per decade older; p = 0.009). In a multivariate model, pre-AIDS hemoglobin remained the most significant predictor of dementia. There were no significant risks defined from demographic characteristics, specific AIDS-defining illnesses, zidovudine use before AIDS, or CD4+ lymphocyte count before AIDS. We project that 12 months after the first AIDS diagnosis, 7.1% of survivors will have dementia. The observed association between anemia, low weight, constitutional symptoms, and dementia suggests a role for cytokines inducing both systemic and neurologic disease.

HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998

This study examined the temporal trends in the incidence rates of HIV dementia, cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy, and CNS lymphoma from January 1990 to December 1998 in the Multicenter AIDS Cohort Study. The incidence rates for HIV dementia, cryptococcal meningitis, and lymphoma decreased following the introduction of highly active antiretroviral therapy (HAART). The proportion of new cases of HIV dementia with a CD4 count in a higher range (i.e., 201 to 350) since 1996 may be increasing.

2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

L. David Hillis, MD, FACC, Chair†; Peter K. Smith, MD, FACC, Vice Chair*†; Jeffrey L. Anderson, MD, FACC, FAHA*‡; John A. Bittl, MD, FACC§; Charles R. Bridges, MD, SCD, FACC, FAHA*†; John G. Byrne, MD, FACC†; Joaquin E. Cigarroa, MD, FACC†; Verdi J. DiSesa, MD, FACC†; Loren F. Hiratzka, MD, FACC, FAHA†; Adolph M. Hutter, Jr, MD, MACC, FAHA†; Michael E. Jessen, MD, FACC*†; Ellen C. Keeley, MD, MS†; Stephen J. Lahey, MD†; Richard A. Lange, MD, FACC, FAHA†§; Martin J. London, MD ; Michael J. Mack, MD, FACC*¶; Manesh R. Patel, MD, FACC†; John D. Puskas, MD, FACC*†; Joseph F. Sabik, MD, FACC*#; Ola Selnes, PhD†; David M. Shahian, MD, FACC, FAHA**; Jeffrey C. Trost, MD, FACC*†; Michael D. Winniford, MD, FACC†

2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery

Alice K. Jacobs, MD, FACC, FAHA, Chair Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect Nancy Albert, PhD, CCNS, CCRN, FAHA Mark A. Creager, MD, FACC, FAHA Steven M. Ettinger, MD, FACC Robert A. Guyton, MD, FACC Jonathan L. Halperin, MD, FACC, FAHA Judith S. Hochman, MD, FACC, FAHA

Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort.

Background: Antiretroviral therapy has improved survival for HIV-1-infected individuals. The neuroepidemiologic implications of HIV-1 in an aging population are not well known, particularly the prevalence of HIV-associated dementia (HAD). Methods: The authors report a baseline cross-sectional analysis of 202 HIV-1-seropositive individuals enrolled into one of two groups of the Hawaii Aging with HIV Cohort: older (50 or more years old, n = 106) and younger (20 to 39 years old, n = 96). Neuropsychological, neurologic, medical, and laboratory data were obtained at enrollment. Participant cognitive status was classified (research case definitions) using American Academy of Neurology (1991) criteria in a consensus conference of physicians and neuropsychologists. Results: HAD was more frequent in older (25.2%) compared to younger (13.7%) individuals (p = 0.041) corresponding to an OR of 2.13 (95% CI: 1.02 to 4.44) for the older compared to the younger group. After adjusting for education, race, substance dependence, antiretroviral medication status, viral load, CD4 lymphocyte count, and Beck Depression Inventory score, the odds of having HAD among individuals in the older group was 3.26 (1.32 to 8.07) times that of the younger group. Conclusions: Older age is associated with increased HAD in this HIV-1 cohort. Underlying mechanisms are unclear but do not appear related to duration of HIV-1 infection.

Neuropsychological performance in HIV‐1‐infected homosexual men The Multicenter AIDS Cohort Study (MACS)*

We administered a battery of standardized neuropsychological measures to assess cognitive functions in a group of 769 HIV-1 seronagative, 727 asymptomatic HIV-1 seropositive (CDC Groups 2 and 3), and 84 symptomatic HIV-1 seropositive (CDC Group 4) homosexual/bisexual men enrolled in the Multicenter AIDS Cohort Study (MACS). Measures included tests of attention, memory, and psychomotor speed. Comparison of group means revealed significant differences in performance between HIV-1 seropositive and symptomatic HIV-1 seropositive subjects on measures of memory and on measures with strong motor and psychomotor timed components. These findings support the sensitivity of these neuropsychological instruments for detecting cognitive changes that may be related to HIV-1, and are consistent with other reports of neuropsychological abnormalities in symptomatic HIV-1-infected individuals. Asymptomatic seroropositive men, on the other hand, did not differ significantly from seronegative subjects on any of the neuropsychological measures. Only 5.5% of the asymptomatic HIV-1 seropositive men showed abnormal performance on individual tests. This proportion did not differ significantly from that of seronegative controls. Further, among asymptomatic seropositive subjects, we found no statistically significant differences as a function of duration of HIV infection or level of immune system functioning. Thus, results from this study support the hypothesis that the frequency of neuropsychological abnormalities in asymptomatic HIV-1-infected homosexual men is low, and not statistically different from that of seronegative controls.

Temporal trends in the incidence of HTV‐1‐related neurologic diseases Multicenter AIDS Cohort Study, 1985‐1992

OBJECTIVE To describe temporal trends in the incidence of human immunodeficiency virus (HIV)-related neurologic diseases in the Multicenter AIDS Cohort Study from 1985 to 1992. METHODS The incidence rates of six neurologic disorders were examined: toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy, HIV dementia, and sensory neuropathy. Poisson modeling was used to test linear trends over time and the effects of progressive immunosuppression, antimicrobial prophylaxis, and antiretroviral drug therapy. RESULTS There was an upward temporal trend in all incidence rates, except for HIV dementia. Progressive immunosuppression in the cohort explained all calendar trends except for sensory neuropathy, where an increasing temporal trend remained even after adjusting for CD4+ cell count, and for HIV dementia where a slight decline was noted, although the effects were not statistically significant. We noted a protective trend of antimicrobial prophylaxis on toxoplasmosis and cryptococcal meningitis, but, in contrast, use of antiretroviral agents was not protective against HIV dementia. Men receiving didanosine, zalcitabine, or stavudine were more likely to develop sensory neuropathy. CONCLUSION Despite the earlier and more widespread use of antimicrobial and antiretroviral agents, neurologic conditions still occurred frequently in this cohort, with annual rates above 1.5 per 100 person-years for HIV dementia and sensory neuropathy. Sensory neuropathy seems to be increasing in incidence and HIV dementia declining slightly in this cohort. As the epidemic matures and more people with profound immunosuppression live longer, the overall incidence of HIV-related neurologic diseases can be expected to rise.Objective: To describe temporal trends in the incidence of human immunodeficiency virus (HIV)-re-lated neurologic diseases in the Multicenter AIDS Cohort Study from 1985 to 1992. Methods: The incidence rates of six neurologic disorders were examined: toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy, HIV dementia, and sensory neuropathy. Poisson modeling was used to test linear trends over time and the effects of progressive immunosuppression, antimicrobial prophylaxis, and antiretroviral drug therapy. Results: There was an upward temporal trend in all incidence rates, except for HIV dementia. Progressive immunosuppression in the cohort explained all calendar trends except for sensory neuropathy, where an increasing temporal trend remained even after adjusting for CD4+ cell count, and for HIV dementia where a slight decline was noted, although the effects were not statistically significant. We noted a protective trend of antimicrobial prophylaxis on toxoplasmosis and cryptococcal meningitis, but, in contrast, use of antiretroviral agents was not protective against HIV dementia. Men receiving didanosine, zalcitabine, or stavudine were more likely to develop sensory neuropathy. Conclusion: Despite the earlier and more widespread use of antimicrobial and antiretroviral agents, neurologic conditions still occurred frequently in this cohort, with annual rates above 1.5 per 100 person-years for HIV dementia and sensory neuropathy. Sensory neuropathy seems to be increasing in incidence and HIV dementia declining slightly in this cohort. As the epidemic matures and more people with profound immunosuppression live longer, the overall incidence of HIV-related neurologic diseases can be expected to rise.

Clinical‐neuropathologic correlation in HIV‐associated dementia

The structural abnormalities that correlate with the clinical manifestations of HIV-associated dementia (HIVD) are unclear. In a prospectively categorized group of patients with and without HIVD who were followed to autopsy, we correlated HIV-related neuropathologic changes with the presence and severity of HIVD. We also assessed the effect of antiretroviral therapy on the neuropathologic changes. Finally, using reverse transcriptase-poly-merase chain reaction on homogenized brain tissue, we correlated the relative expression of mRNA for tumor necrosis factor-α (TNF-α) with cognitive impairment and with the patterns of neuropathologic changes. The presence of multinucleated giant cells and diffuse myelin pallor were specific for HIVD, but these pathologic changes occurred in only 50% of patients with dementia. Patients treated with antiretroviral agents for >12 months were less likely to show multinucleated giant cells or diffuse myelin pallor. Levels of mRNA for TNF-α from frontal subcortical white matter were significantly greater in patients with HIVD than in AIDS patients without dementia or in seronegative controls. We conclude that routine histopathologic examination of the brain fails to detect multinucleated giant cells and diffuse myelin pallor in 50% of patients dying with HIVD. This suggests that more subtle neuropathologic correlates for the clinical manifestations of HIVD exist. Our observations of elevated levels of TNF-α mRNA in HIVD indicate that indirect mechanisms of brain dysfunction, such as abnormal cytokine expression, may contribute to the pathogenesis of HIVD.

Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy

Objective: To determine the predictive value of plasma HIV RNA and CD4 lymphocytes for HIV-associated dementia and sensory neuropathy. Methods: A total of 1,604 AIDS-free HIV seropositive men from the Multicenter AIDS Cohort Study were followed over a 10-year period (1985 to 1995). HIV-associated dementia and sensory neuropathy were diagnosed according to standard definitions. Baseline samples were used to measure plasma HIV RNA levels with a branched DNA assay and levels of β2-microglobulin, CD4 lymphocyte counts, and hemoglobin levels. Results: Seventy-seven patients with HIV-associated dementia and 213 patients with sensory neuropathy were identified. Baseline HIV RNA levels above 3,000 copies/mL and CD4 counts below 500 cells/mm3 were predictive of both neurologic outcomes, but neither hemoglobin, body mass index, nor β2-microglobulin were independently predictive. After adjusting for age and level of education, individuals with baseline plasma HIV RNA >30,000 copies/mL had a relative hazard for dementia 8.5 times (p < 0.001) that of those with <3,000 copies/mL, and those with CD4 counts <200 cells/mm3 had a 3.5-fold (p = 0.003) greater hazard relative to those with CD4 counts >500 cells/mm3. Individuals with HIV RNA >10,000 copies/mL had a 2.3-fold (p = 0.008) greater hazard of sensory neuropathy than those with <500 copies/mL, and men with <750 CD4 cells/mm3 had a 1.4-fold (p = 0.03) greater hazard than those with >750 CD4 cells/mm3. Conclusions: High levels of systemic HIV replication may “drive” the initiation of neurologic disease; effective suppression of HIV may reduce the incidence of dementia and neuropathy. Levels of plasma HIV RNA and CD4 counts, determined before the initiation of antiretroviral therapy, were predictive of HIV-associated dementia and sensory neuropathy.

Cognitive Outcome After Coronary Artery Bypass: A One-Year Prospective Study

BACKGROUND Cognitive deficits have been reported in patients after coronary artery bypass grafting, but the incidence of these deficits varies widely. We studied prospectively the incidence of cognitive change and whether the changes persisted over time. METHODS Cognitive testing was done preoperatively and 1 month and 1 year postoperatively in 127 patients undergoing coronary artery bypass grafting. Tests were grouped into eight cognitive domains. A change of 0.5 standard deviation or more at 1 month and 1 year from patients preoperative Z score was the outcome measure. RESULTS We identified four main outcomes for each cognitive domain: no decline; decline and improvement; persistent decline; and late decline. Only 12% of patients showed no decline across all domains tested; 82% to 90% of patients had no decline in visual memory, psychomotor speed, motor speed, and executive function; 21% and 26% had decline and improvement in verbal memory and language; approximately 10% had persistent decline in the domains of verbal memory, visual memory, attention, and visuoconstruction; and 24% had late decline (between 1 month and 1 year) in visuoconstruction. CONCLUSIONS This study establishes that the incidence of cognitive decline varies according to the cognitive domain studied and that some patients have persistent and late cognitive changes in specific domains after coronary artery bypass grafting.