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.

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.

Associations between CD36 gene polymorphisms and metabolic response to a short-term endurance-training program in a young-adult population.

Recent studies have shown that CD36 gene variants are associated with an increased prevalence of chronic disease. Although a genetic component to trainability has been proven, no data are available specifically on the influence of CD36 on training response. Two single nucleotide polymorphisms (SNPs) (rs1527479 and rs1984112) were assessed for associations with whole-body substrate oxidation, response to a 75-g dextrose oral glucose tolerance test, fasting plasma lipids, and cardiovascular disease risk factors in a young healthy cohort, both using cross-sectional analysis and following a 4-week endurance-exercise training program. Genotyping was performed using real-time polymerase chain reaction. Cross-sectional data were collected in 34 individuals (age, 22.7 ± 3.5 years), with 17 completing the training program. At baseline, TT SNP carriers at rs1527479 and wild-type GG carriers at rs1984112 were associated with significantly greater whole-body rate of fat oxidation (Fatox) during submaximal exercise (P < 0.05), whilst AA carriers at the same position were associated with elevated triglyceride (TG) levels. A significant genotype × time interaction in Fatox at SNP rs1984112 was identified at rest. Significant genotype × time interactions were present at rs1527479, with TT carriers exhibiting a favourable response to training when compared with C-allele carriers for fasting TG, diastolic blood pressure (DBP), and mean arterial pressure (MAP). In conclusion, cross-sectional assessment identified associations with Fatox and TG. Training response at both SNPs identified "at-risk" genotypes responding favourably to the training stimulus in Fatox, TG, DBP, and MAP. Although these data show potential pleiotropic influence of CD36 SNPs, assessment in a larger cohort is warranted.

Interactions Between Fatty Acid Transport Proteins, Genes That Encode for Them, and Exercise: A Systematic Review.

Long-chain fatty acid (LCFA) movement into skeletal muscle involves a highly mediated process in which lipid rafts are utilized in the cellular membrane, involving numerous putative plasma membrane-associated LCFA transport proteins. The process of LCFA uptake and oxidation is of particular metabolic significance both at rest and during light to moderate exercise. A comprehensive systematic search of electronic databases was conducted to investigate whether exercise alters protein and/or gene expression of putative LCFA transport proteins. There were 31 studies meeting all eligibility criteria, of these 13 utilized an acute exercise protocol and 18 examined chronic exercise adaptations. Seventeen involved a study design incorporating an exercise stimulus, while the remaining 14 incorporated a combined exercise and diet stimulus. Divergent data relating to acute exercise, as well as prolonged exercise training (≥3 weeks), on protein content (PC) response was identified for proteins CD36, FABPpm and CAV1. Messenger ribonucleic acid (mRNA) data did not always correspond to functional PC, supporting previous suggestions of a disconnect due to potentially limiting factors post gene expression. The large array of study designs, cohorts, and primary dependent variables within the studies included in the present review elucidate the complexity of the interaction between exercise and LCFA transport proteins. Summary of the results in the present review validate the need for further targeted investigation within this topic, and provide an important information base for such research. J. Cell. Physiol. 231: 1671-1687, 2016. © 2015 Wiley Periodicals, Inc.

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.

The associations between polymorphisms in the CD36 gene, fat oxidation and cardiovascular disease risk factors in a young adult Australian population: a pilot study.

Our pilot study in a young adult Australian cohort aimed to investigate potential associations between CD36 polymorphisms (rs1527479 and rs1984112), fat oxidation and cardiovascular disease risk. CD36 genotype was associated with fat oxidation during sub-maximal exercise, resting heart rate and blood pressure, indicating increased chronic disease risk in this otherwise healthy cohort.