Low incidence of advanced neurological burden but high incidence of age-related conditions that are dementia risk factors in aging people living with HIV: a data-linkage 10-year follow-up study.

Although increasing research is focusing on age-related comorbidities (ARC) among people living with HIV (PLHIV), no studies have concomitantly assessed non-HIV age-related neurological disorders (e.g., Alzheimer's dementia). A total of 254 PLHIV and 69 HIV-negative controls completed baseline medical history and cognitive testing. ARC data were collected from medical records over the subsequent 9-10 years and included all types of strokes, all types of dementia, mild cognitive impairment, Parkinson's disease, motor neuron disease (grouped into a non-HIV age-related neurological category), cardiovascular disease, chronic kidney disease, chronic liver disease, chronic lung disease, non-AIDS cancers, osteoporosis, and diabetes. Kaplan-Meier curves assessed differences in the incident rates (per 1000 person year) of groups of ARC as defined above and combined ARC (i.e., development of any of the ARC) among younger (baseline age < 50) and older (baseline age ≥ 50) PLHIV and younger and older controls. Cox-proportional hazard models assessed the individual and interaction effects of HIV status and chronological age, in addition to a range of demographic and clinical variables including historical and baseline HIV brain involvement on the risk of developing combined ARC. Older PLHIV had a higher incidence of cardiovascular disease, osteoporosis, and combined ARC compared to other groups (p < 0.05). Incident rate of non-HIV age-related neurological disorders was 2.3 [0.93, 4.79] per 1000 person year. While this incident rate was higher in older PLHIV (5.37 [1.97, 11.92]) than older HIV-negative participants (3.58 [0.18-17.67]), this was not significant. In multivariate analyses, HIV status and chronological age, but not their interaction, and smoking were associated with higher risk of combined ARC (p < 0.05). In analyses focusing on PLHIV, older age and taking abacavir/efavirenz/atazanavir/darunavir containing antiretroviral treatments at the time of diagnosis were associated with greater ARC (p < 0.05). Non-HIV age-related neurological disorders are uncommon in older PLHIV, where the majority were < 70 years of age at the end of follow-up. However, the greater burden of ARC among older PLHIV, most of which are established dementia risk factors, warrants the establishment of commensurate prevention strategies and greater attention to neurocognitive screening.

An examination of reliable change methods for measuring cognitive change with the Cogstate Computerized Battery: Research and clinical implications.

OBJECTIVE: To compare the performance of four reliable change (RC) methods with respect to measuring cognitive change on the Cogstate Computerized Battery (CCB). METHOD: We assessed cognitive change in 57 healthy, urban, well-educated males on the CCB at baseline and 6 months (Median age = 50, 65% university-educated). The study CCB version comprised seven measures covering attention, processing speed, verbal learning, and memory. Raw scores were z-score transformed using age-corrected Cogstate norms (CN) or the sample mean and standard deviation (internal standardization [IS]), and then averaged to create composite z-scores. Composite scores were entered into four RC formulae. RC was defined based on a 90% two-tailed confidence interval. Change scores were compared as continuous (z-scores) and ordinal variables (RC outcomes). RESULTS: CCB composite score reliability (rXY = .78-.79) was replicated in an age- and sex-matched Cogstate database sample of similar size. There was good overall agreement between the four RC methods (Bland-Altman Mdiff = .00; 95% limits of agreement with the mean-CN: z = ± .90; IS: z = ± .93), with each model adhering closely to the 10% rate of RC expected by chance alone (largest χ2 = .86, p = .99). Initial norming strategy (CN or IS) did not affect these outcomes. CONCLUSIONS: Norming strategy and RC method choice did not significantly impact cognitive change predictions on CCB composite scores. A series of example case data are provided to practically demonstrate the steps involved in applying the longitudinal norms generated in this study. Research in more diverse normative samples is warranted.

Determining optimal impairment rating methodology for a new HIV-associated neurocognitive disorder screening procedure.

INTRODUCTION: The current study sought to determine the optimal impairment rating definition for a new HIV-associated neurocognitive disorder (HAND) screening procedure as compared to standard neuropsychological testing. METHOD: A total of 55 HIV-infected (HIV+; 19% AIDS; 87% on combination antiretroviral therapy, cART; 80% plasma undetectable) and 22 demographically comparable HIV-uninfected (HIV-) control adults (all male) enrolled in an urban Australian primary care cohort study completed the CogState computerized cognitive screen, a standard independence in activities of daily living (ADL) questionnaire, and a standard neuropsychological test battery. Local or American demographically adjusted norms were applied to the neuropsychological data, taking into account premorbid reading level. CogState norms that corrected for age and sex were applied to raw CogState data. The HAND Frascati classification criteria were implemented to determine "impairment" on both the standard neuropsychological test and the CogState-based screen using two established methods: a battery-wide summary score (global deficit score; GDS), and cognitive domain rating, both combined with ADL independence data. Criterion validity was operationalized by comparing rate of impairment derived from the CogState-based screen to that obtained from the standard neuropsychological test battery first in the combined HIV- and HIV+ sample, and then in the HIV+ sample only. RESULTS: In the combined sample, CogState-based screen criterion validity was higher using the GDS (79% correct classification, 73% sensitivity, 82% specificity) over the cognitive domain rating (correct classification, sensitivity, specificity all 69%) method. A similar pattern was found for the HIV+ group separately [GDS (74% correct classification, 76% sensitivity, 71% specificity) versus cognitive domain rating (64% correct classification, 72% sensitivity, 57% specificity)]. The cases that resulted in disagreement across the two methods were those with borderline impaired/unimpaired cognitive performance. CONCLUSIONS: The GDS is a relatively easy statistical method for computing impairment rate when using the CogState-based screen that yields adequate criterion validity compared to standard neuropsychological testing. Feasibility of standardized test administration and appropriate interpretation of results for this CogState-based screen in primary care was enhanced by the training and consultation provided by study neuropsychologists.

A Screening Strategy for HIV-Associated Neurocognitive Disorders That Accurately Identifies Patients Requiring Neurological Review.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are not routinely assessed due to the lack of an adequate screening strategy. We aimed to develop a clinically relevant screening procedure for symptomatic HAND, validated against a gold standard neuropsychological (NP) test battery. METHODS: Representative HIV-infected (HIV+) and demographically matched HIV-uninfected (HIV-) participants in an observational study completed a standard evaluation for mood, drug and/or alcohol use, and activities of daily living and a newly designed 20-minute computerized CogState battery that assessed 5 cognitive domains. A subset completed standard NP assessment for 8 cognitive domains. HAND definition on screening and gold standard NP was determined using demographically corrected z scores and the global deficit score (≥ 0.5), applying the Frascati criteria. Participants were blinded to screening results, and the NP examiner was blinded to screening and HIV status. RESULTS: A total of 254 HIV+ participants were enrolled-mean age, 48.9 ± 10.2 years; median nadir CD4, 270 cells/mL; tertiary educated, 54%; and HIV- controls, 72. HIV+ HAND screening prevalence was 30.7% (HIV-associated dementia, 3.2%; mild neurocognitive disorder, 12.6%; and asymptomatic neurocognitive disorder, 15.0%; HIV- group: 13.9%; P = .004). Of the 75 participants who completed the NP battery, the HAND rate in the HIV+ group was 50.9% vs 43.4% by screening (P > .50). HAND screening vs gold standard NP sensitivity was 76% and specificity was 71%. Clinically relevant HIV-associated dementia and mild neurocognitive disorder sensitivity was 100% and specificity was 98% (positive predictive value 0.92). CONCLUSIONS: Symptomatic HAND warranting neurological review was accurately predicted using a CogState-based screening procedure.

Effectiveness of a team intervention in reducing modifiable cardiovascular disease risk in HIV-infected subjects on antiretroviral therapy.

INTRODUCTION: The increasing age, higher modifiable and inherent cardiovascular disease (CVD) risk of HIV-infected patients [1] necessitates improved approaches to reducing co-morbidities. We aimed to assess the effectiveness of a team intervention in reducing modifiable CVD risk. MATERIALS AND METHODS: HIV-infected patients ≥50 years attending a large HIV caseload primary-care practice, who were virologically suppressed on antiretroviral therapy (ART), with moderate or severe 10-year CVD Framingham risk (≥10%) were recruited for this prospective case-control study. Intervention participants were provided a team approach to care, which involved treatment by study doctors for lipid, hypertension and ART management, and monthly review by a team of research nurses and dieticians for smoking cessation, exercise and dietary advice over 12 months. Controls were matched on age and smoking status, and were given standard of care (SOC) by non-study doctors. Outcomes included CVD risk factors, body composition and CVD risk assessment, including Framingham 10-yr risk [2] and D:A:D 5-year estimated risk of coronary heart disease (CHD) [3]. Repeated measures analysis of variance was used to examine pre- and post-intervention differences, with p-values used to assess time and main effects of approach to care (Intervention, SOC). RESULTS: A total of 33 patients completed the intervention, with 33 controls (58.0±6.8 and 59.1±6.9 years, respectively). Smoking cessation occurred in 25% cases versus nil controls. There was a significant change in CVD risk between intervention and control groups, in both Framingham scores (time and group×time interaction) and D:A:D scores (group×time interaction only) (Table 1). There was also a significant difference in change in total cholesterol over the study period (time and group×time interaction). Body composition was only measured in intervention patients, with a significant loss in % body fat observed in pre- and post-intervention. CONCLUSIONS: Team intervention was significantly more effective than standard of care in reducing CVD risk in HIV-infected patients on ART. A team approach to care may be an important component of reducing CVD risk in this population.

Preterm outcome table (POT): a simple tool to aid counselling parents of very preterm infants.

BACKGROUND: Outcome figures published in scientific journals are often cumbersome and difficult to understand by parents during counselling before or immediately after a very premature birth. AIM: To provide simplified up-to-date outcome information in a table for ease of counselling. METHODS: Regional perinatal mortality rates for very premature births (23-31 weeks gestation) and incidence of significant neonatal events for those admitted to neonatal intensive care units (NICU) were obtained from the NSW Midwives Data Collection, ACT Maternal and Perinatal Data Collection and the NSW and ACT NICUS Data Collection for 2000 and 2001. Neurodevelopmental outcome was obtained for the same cohort at 2-3 years of age, corrected for prematurity. The percentage outcomes were rounded off to the closest conservative multiple of 5 for each data point in a table. RESULTS: The preterm outcome table (POT) for each gestational week was constructed from a total of 2315 births. Of these, 401 (17.3%) were reported as stillborn and were predominantly of 23 to 25 weeks gestation. Of those admitted to NICU, hospital survival rates were 30, 50, 65, 75, 80, 90 and > 95% for 23, 24, 25, 26, 27, 28-29 and 30-31 weeks, respectively. Neurodevelopmental outcome was available for 470 (75%) children, of whom 15% had a moderate to severe functional disability at 2-3 years of age, corrected for prematurity. Simplified data on survival to discharge and outcome were tabulated. CONCLUSION: POT appears simple and easy to use but also provides realistic data to assist clinicians in the counselling process.