Key Points A novel recombinant factor VIII with prolonged half-life, rFVIIIFc, was developed to reduce prophylactic injection frequency. rFVIIIFc was well-tolerated in patients with severe hemophilia A, and resulted in low bleeding rates when dosed 1 to 2 times per week.

Importance Midlife vascular risk factors have been associated with late-life dementia; whether these risk factors directly contribute to brain amyloid deposition is less well understood. Objective To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET). Design, Setting, and Participants Prospective cohort study in 3 U.S. communities (Washington County, MD; Forsyth County, NC; and Jackson, MS). 346 participants without dementia in the Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study; evaluation of vascular risk factors and markers since 1987-1989, with florbetapir PET scans (2011-2013). Exposures Vascular risk factors at ARIC baseline (ages 45-64) were evaluated in multivariable models including age, sex, race, APOE genotype, and educational level. Outcome Standardized Uptake Value Ratios (SUVR) were calculated from PET scans; a mean global cortical SUVR was calculated. Elevated florbetapir (defined at SUVR>1.2) was the dependent variable. Results In 322 participants without dementia and with nonmissing midlife vascular risk factors at baseline (43% black, 58% female, mean age 52), SUVR (positive in 164 (50.9%) of participants) was measured >20 years later (median followup 23.5; IQR 23.0-24.3) when participants were 67-88 (mean 76 y). Elevated body mass index midlife (BMI) was associated with elevated SUVR (OR 2.06, 95% CI 1.16, 3.65). At baseline, 65 participants had no vascular risk factors, 123 had one, and 134 had two or more; a higher number of midlife risk factors was associated with elevated amyloid SUVR at followup, 30.8% (n=20), 50.4% (n=62), and 61.2% (n=82), respectively. In adjusted models, compared to 0 midlife vascular risk factors, the odds ratio for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI 0.95-3.72) and was 2.88 (95% CI 1.46-5.69) for 2 or more vascular risk factors No significant race by risk factor interactions were found. Late-life vascular risk factors were not associated with late-life brain amyloid: (2 or more late-life vascular risk factors compared to 0: OR 1.66, 95% CI 0.75-3.69). Conclusions and Relevance An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors. These findings are consistent with a role of vascular disease in the development of Alzheimer’s Disease.

Objective: To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE e4 allele status. Methods:Recruited from the longitudinal Atherosclerosis Risk in Communities study, 329 participants without dementia, ages 67-88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR .1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE e4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status.Results: A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.01-2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23-3.51) but did not differ by educational level. Each e4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61-4.39).Conclusions: In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE e4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study. The prevailing hypothesis behind the pathophysiology of Alzheimer disease (AD) focuses on the accumulation of brain amyloid in b-amyloid (Ab) plaques as a critical mechanism. Use of PET ligands that bind to Ab allows for the evaluation of Ab in persons with or without clinical symptoms. Although a recent meta-analysis reported positive amyloid scans in 10% of healthy 50-to 90-year-old participants, and in 27% of similarly aged adults with mild cognitive impairment (MCI), 1 few studies in persons of European extraction 2,3 have evaluated patterns of Ab deposition using PET, and none in black participants, to our knowledge. Using Ab imaging in a biracial cohort would allow further exploration of racial disparities in dementia etiology.Dementia is more prevalent in blacks than in whites, 4-6 although AD-type neuropathologic findings are found on autopsy with equal prevalence in both groups. 7,8 Thus, a larger component

BackgroundIron deficiency anemia is the most common form of anemia in India. Hemoglobin A1c (HbA1c) is used in diabetic patients as an index of glycemic control reflecting glucose levels of the previous 3 months. Like blood sugar levels, HbA1c levels are also affected by the presence of variant hemoglobins, hemolytic anemias, nutritional anemias, uremia, pregnancy, and acute blood loss. However, reports on the effects of iron deficiency anemia on HbA1c levels are inconsistent. We conducted a study to analyze the effects of iron deficiency anemia on HbA1c levels and to assess whether treatment of iron deficiency anemia affects HbA1c levels.MethodsFifty patients confirmed to have iron deficiency anemia were enrolled in this study. HbA1c and absolute HbA1c levels were measured both at baseline and at 2 months after treatment, and these values were compared with those in the control population.ResultsThe mean baseline HbA1c level in anemic patients (4.6%) was significantly lower than that in the control group (5.5%, p<0.05). A significant increase was observed in the patients' absolute HbA1c levels at 2 months after treatment (0.29 g/dL vs. 0.73 g/dL, p<0.01). There was a significant difference between the baseline values of patients and controls (0.29 g/dL vs. 0.74 g/dL, p<0.01).ConclusionsIn contrast to the observations of previous studies, ours showed that HbA1c levels and absolute HbA1c levels increased with treatment of iron deficiency anemia. This could be attributable to nutritional deficiency and/or certain unknown variables. Further studies are warranted.