The association between cognitive reserve and time to conversion from normal cognition to mild cognitive impairment

Mild cognitive impairment (MCI) is a subclinical cognitive decline in the elderly that increases the risk of conversion to Dementia. Delaying the onset of conversion from normal cognition to MCI has public health relevance by potentially reducing the magnitude of cognitive dysfunction related disability. It has been suggested that cognitive reserve, comprised of IQ and behaviors associated with memory facilitation and problem solving, may delay onset of MCI. Time to onset of MCI may also be associated with the risk factor of the APOE-4 allele. MCI classification criteria is inconsistent across studies, suggesting additional public health need to standardize an accurate method of screening. This study examined the association between cognitive reserve, APOE-4, and time to onset of MCI. Data from the 8 year Gingko Evaluation of Memory Study (GEM) clinical trial were used to examine these aims in a sample of n=2,284 cognitively normal individuals. The GEM MCI classification algorithm was extended over 8 years to examine normal cognition survival. Indicators of cognitive reserve were IQ, average monthly frequency of cognitive reserve behaviors, and number of different cognitive reserve behaviors engaged in each month. APOE-4 presence was defined as having at least one copy of the APOE-4 allele. N=1,226 (53.68%) individuals remained cognitively normal over the eight year followup compared to n=1,058 (46.32%) who developed incident MCI over eight year followup. Incident MCI individuals had significantly higher age (p<0.0001) and education (p=0.0320) at entry and were more likely to be male (p=0.0497), Asian/Pacific Islander, Black, or “Other” identified race (p=0.0078). Incident MCI individuals had significantly lower frequency of reading newspapers (p=0.0228) and solving crosswords (p=0.0301), as well as IQ (p=0.0002). Neither the average monthly frequency of cognitive reserve behaviors (p=0.6662) nor the number of different cognitive reserve behaviors engaged in each month were significantly associated with MCI onset (p=0.7809). Age (p<0.0001), education (p<0.0001), IQ (p<0.0001), and APOE-4 presence (p<0.0001) were significantly associated with time to MCI onset in a Cox proportional hazard model adjusted for age, education, IQ, APOE-4 presence, cognitive reserve behavior frequency, and number of different cognitive reserve behaviors engaged in each month

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated