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Practitioners can be reassured that this antihistamine-releasing contact lens has no additional effect on corneal epithelial integrity.To evaluate the effect of an antihistamine-releasing soft contact lens on corneal epithelium integrity when worn on a daily disposable modality for 12 weeks.Two clinical trials using the same randomised, double-masked, placebo-controlled, parallel-group design enrolled healthy contact lens wearers. Participants wore either etafilcon A with 0.019 mg ketotifen (test; n = 374) or etafilcon A with no added drug (placebo; n = 186). Assessments were conducted at baseline, 1 week and 4, 8, and 12 weeks. Slit-lamp evaluations of corneal staining (using sodium fluorescein) in all regions of the corneas of both eyes were graded on a 0-4 scale. Data from all randomised participants were analysed.Corneal staining was infrequent and, where present, was mild (Grade 2) or trace (Grade 1). There were no Grade 3 or 4 findings of corneal staining. The overall proportion of findings of Grade 0 corneal staining was 95.86% with the test lens and 95.88% with the placebo lens. The odds of no staining were not statistically different between the test and placebo lenses (Odds Ratio: 0.96, 95% Confidence Intervals: 0.76 to 1.20). There were no serious ocular adverse events or signs of ocular surface medicamentosa.Both test and placebo lenses were well tolerated by subjects during the 3 months of wear. The antihistamine-releasing contact lens does not significantly impact corneal epithelial integrity.

Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUC

Current rat alveolar ridge preservation models have not been well standardized. In this study, we proposed decoronation-induced infected alveolar socket model of rat. The bilateral maxillary first molars (M1) of twenty-four rats were decoronized or extracted. After 2, 6, 10, and 14 weeks, bone and soft tissue changes at M1 and periodontal conditions of maxillary second (M2) and third molars (M3) were evaluated by micro-computed tomography and histological analysis. Additional eighteen rats with standardized size defects were grafted with Bio-Oss Collagen to compare with unmanipulated contralateral side. Decoronation preserved greater bone and soft tissue dimensions at M1, provided larger three-dimensional (3D) bone contour volume, but also promoted periodontal breakdown of M2 Histological results showed intense inflammatory cell infiltrations and severe bone resorption within M1 socket and at mesial aspect of M2. The critical dimensions to accommodate largest standardized defect at M1 were 2.2–2.3 mm at vertical bone height and 2.8–3.2 mm at alveolar crestal width. Bio-Oss Collagen could not fully preserve buccal or palatal bone height but could be beneficial in preserving ridge width in large alveolar defects. Collectively, if periodontally-involved alveolar bone defect is preferred, we suggest extracting M1 roots 6 weeks after decoronation to allow periodontitis to occur at M2. If standardized critical dimension defect is preferred, we suggest extracting M1 roots 2 weeks after decoronation, and creating defect in the middle of M1 site with size no larger than 2.7 mm diameter to its full depth.

BACKGROUND: Screening to identify individuals with elevated brain amyloid (Aβ+) for clinical trials in Preclinical Alzheimer’s Disease (PAD), such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) trial, is slow and costly. The Trial-Ready Cohort in Preclinical/Prodromal Alzheimer’s Disease (TRC-PAD) aims to accelerate and reduce costs of AD trial recruitment by maintaining a web-based registry of potential trial participants, and using predictive algorithms to assess their likelihood of suitability for PAD trials. OBJECTIVES: Here we describe how algorithms used to predict amyloid burden within TRC-PAD project were derived using screening data from the A4 trial. DESIGN: We apply machine learning techniques to predict amyloid positivity. Demographic variables, APOE genotype, and measures of cognition and function are considered as predictors. Model data were derived from the A4 trial. SETTING: TRC-PAD data are collected from web-based and in-person assessments and are used to predict the risk of elevated amyloid and assess eligibility for AD trials. PARTICIPANTS: Pre-randomization, cross-sectional data from the ongoing A4 trial are used to develop statistical models. MEASUREMENTS: Models use a range of cognitive tests and subjective memory assessments, along with demographic variables. Amyloid positivity in A4 was confirmed using positron emission tomography (PET). RESULTS: The A4 trial screened N=4,486 participants, of which N=1323 (29%) were classified as Aβ+ (SUVR ≥ 1.15). The Area under the Receiver Operating Characteristic curves for these models ranged from 0.60 (95% CI 0.56 to 0.64) for a web-based battery without APOE to 0.74 (95% CI 0.70 to 0.78) for an in-person battery. The number needed to screen to identify an Aβ+ individual is reduced from 3.39 in A4 to 2.62 in the remote setting without APOE, and 1.61 in the remote setting with APOE. CONCLUSIONS: Predictive algorithms in a web-based registry can improve the efficiency of screening in future secondary prevention trials. APOE status contributes most to predictive accuracy with cross-sectional data. Blood-based assays of amyloid will likely improve the prediction of amyloid PET positivity.

Background: Computerized cognitive assessments may improve Alzheimer’s disease (AD) secondary prevention trial efficiency and accuracy. However, they require validation against standard outcomes and relevant biomarkers. Objective: To assess the feasibility and validity of the tablet-based Computerized Cognitive Composite (C3). Design: Cross-sectional analysis of cognitive screening data from the A4 study (Anti-Amyloid in Asymptomatic AD). Setting: Multi-center international study. Participants: Clinically normal (CN) older adults (65-85; n=4486). Measurements: Participants underwent florbetapir-Positron Emission Tomography for Aβ+/- classification. They completed the C3 and standard paper and pencil measures included in the Preclinical Alzheimer’s Cognitive Composite (PACC). The C3 combines memory measures sensitive to change over time (Cogstate Brief Battery-One Card Learning) and measures shown to be declining early in AD including pattern separation (Behavioral Pattern Separation Test- Object- Lure Discrimination Index) and associative memory (Face Name Associative Memory Exam- Face-Name Matching). C3 acceptability and completion rates were assessed using qualitative and quantitative methods. C3 performance was explored in relation to Aβ+/- groups (n=1323/3163) and PACC. Results: C3 was feasible for CN older adults to complete. Rates of incomplete or invalid administrations were extremely low, even in the bottom quartile of cognitive performers (PACC). C3 was moderately correlated with PACC (r=0.39). Aβ+ performed worse on C3 compared with Aβ- [unadjusted Cohen’s d=-0.22 (95%CI: -0.31,-0.13) p

To evaluate the comfort performance of ACUVUE OASYS® 1-Day with HydraLuxe™ Technology among symptomatic contact lens wearers by using Contact Lens User Experience (CLUE) comfort scores and Contact Lens Dry Eye Questionnaire 8 (CLDEQ-8) discomfort and dryness scores.Three clinical trials evaluated comfort and dryness when refitting symptomatic contact lens wearers to ACUVUE OASYS® 1-Day with HydraLuxe™ lenses. This analysis combined the CLUE comfort and CLDEQ-8 scores obtained at baseline and 2-week follow-up and compared average scores between visits. Subjects were grouped by habitual lens modality (daily disposable or daily wear reusable) and habitual lens material (silicone hydrogel or hydrogel). The analysis included data from 107 subjects.Significant increases in mean CLUE comfort scores between baseline and 2-week follow-up occurred in all subject groups across habitual lens modality and material, indicating an improvement in overall comfort. CLUE comfort score improved clinically (≥5-point increase) among 75.7% of subjects (81/107). Similarly, significant decrease in mean CLDEQ-8 scores between baseline and 2-week follow-up occurred in all subject groups, indicating a decrease in the prevalence of dryness and discomfort symptoms. CLDEQ-8 score improved clinically (≥3-point reduction) among 82.2% of subjects (88/107). A majority of subjects (57.0%) became asymptomatic (CLDEQ-8 score ≤ 11 points) after 2 weeks of bilateral wear.Refitting symptomatic contact lens patients to ACUVUE OASYS® 1-Day with HydraLuxe™ can improve overall comfort and reduce symptoms of dryness and discomfort, irrespective of the previous lens modality or habitual lens material.

Background: Greater subjective cognitive changes on the Cognitive Function Index (CFI) was previously found to be associated with elevated amyloid (Aß) status in participants screening for the A4 Study, reported by study partners and the participants themselves. While the total score on the CFI related to amyloid for both sources respectively, potential differences in the specific types of cognitive changes reported by either participants or their study partners was not investigated. Objectives: To determine the specific types of subjective cognitive changes endorsed by participants and their study partners that are associated with amyloid status in individuals screening for an AD prevention trial. Design, Setting, Participants: Four thousand four hundred and eighty-six cognitively unimpaired (CDR=0; MMSE 25-30) participants (ages 65-85) screening for the A4 Study completed florbetapir (Aß) Positron Emission Tomography (PET) imaging. Participants were classified as elevated amyloid (Aß+; n=1323) or non-elevated amyloid (Aß-; n=3163). Measurements: Prior to amyloid PET imaging, subjective report of changes in cognitive functioning were measured using the CFI (15 item questionnaire; Yes/Maybe/No response options) and administered separately to both participants and their study partners (i.e., a family member or friend in regular contact with the participant). The impact of demographic factors on CFI report was investigated. For each item of the CFI, the relationship between Aß and CFI response was investigated using an ordinal mixed effects model for participant and study partner report. Results: Independent of Aß status, participants were more likely to report ‘Yes’ or ‘Maybe’ compared to the study partners for nearly all CFI items. Older age (r= 0.06, p

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel, the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.

Introduction There is an unmet need for effective methods for conducting dementia prevention trials. Methods Home-based assessment study compared feasibility and efficiency, ability to capture change over time using in-home instruments, and ability to predict cognitive conversion using predefined triggers in a randomized clinical trial in (1) mail-in questionnaire/live telephone interviews, (2) automated telephone/interactive voice recognition, and (3) internet-based computer Kiosk technologies. Primary endpoint was defined as cognitive conversion. Results Analysis followed a modified intent-to-treat principle. Dropout rates were low and similar across technologies but participants in Kiosk were more likely to dropout earlier. Staff resources needed were higher in Kiosk. In-home instruments distinguished conversion and stable groups. Cognitively stable group showed improvement in cognitive measures. Triggering was associated with higher likelihood of conversion but statistically significant only in mail-in questionnaire/live telephone interviews. Discussion Relatively low efficiency of internet-based assessment compared with testing by live-assessors has implications for internet-based recruitment and assessment efforts currently proposed for diverse populations.

Importance Insulin modulates aspects of brain function relevant to Alzheimer disease and can be delivered to the brain using intranasal devices. To date, the use of intranasal insulin to treat persons with mild cognitive impairment and Alzheimer’s disease dementia remains to be examined in a multi-site trial. Objective To examine the feasibility, safety, and efficacy of intranasal insulin for the treatment of persons with mild cognitive impairment and Alzheimer disease dementia in a phase 2/3 multisite clinical trial. Design, Setting, and Participants A randomized (1:1) double-blind clinical trial was conducted between 2014 and 2018. Participants received 40 IU of insulin or placebo for 12 months during the blinded phase, which was followed by a 6-month open-label extension phase. The clinical trial was conducted at 27 sites of the Alzheimer’s Therapeutic Research Institute. A total of 432 adults were screened, and 144 adults were excluded. Inclusion criteria included adults aged 55 to 85 years with a diagnosis of amnestic mild cognitive impairment or Alzheimer disease (based on National Institute on Aging–Alzheimer Association criteria), a score of 20 or higher on the Mini-Mental State Examination, a clinical dementia rating of 0.5 or 1.0, and a delayed logical memory score within a specified range. A total of 289 participants were randomized. Among the first 49 participants, the first device (device 1) used to administer intranasal insulin treatment had inconsistent reliability. A new device (device 2) was used for the remaining 240 participants, who were designated the primary intention-to-treat population. Data were analyzed from August 2018 to March 2019. Interventions Participants received 40 IU of insulin (Humulin-RU-100; Lilly) or placebo (diluent) daily for 12 months (blinded phase) followed by a 6-month open-label extension phase. Insulin was administered with 2 intranasal delivery devices. Main Outcomes and Measures The primary outcome (mean score change on the Alzheimer Disease Assessment Scale–cognitive subscale 12) was evaluated at 3-month intervals. Secondary clinical outcomes were assessed at 6-month intervals. Cerebrospinal fluid collection and magnetic resonance imaging scans occurred at baseline and 12 months. Results A total of 289 participants (155 men [54.6%]; mean [SD] age, 70.9 [7.1] years) were randomized. Of those, 260 participants completed the blinded phase, and 240 participants completed the open-label extension phase. For the first 49 participants, the first device used to administer treatment had inconsistent reliability. A second device was used for the remaining 240 participants (123 men [51.3%]; mean [SD] age, 70.8 [7.1] years), who were designated the primary intention-to-treat population. No differences were observed between treatment arms for the primary outcome (mean score change on ADAS-cog-12 from baseline to month 12) in the device 2 ITT cohort (0.0258 points; 95% CI, −1.771 to 1.822 points;P = .98) or for the other clinical or cerebrospinal fluid outcomes in the primary (second device) intention-to-treat analysis. No clinically important adverse events were associated with treatment. Conclusions and Relevance In this study, no cognitive or functional benefits were observed with intranasal insulin treatment over a 12-month period among the primary intention-to-treat cohort. Trial Registration ClinicalTrials.gov Identifier:NCT01767909

Introduction Little is known about factors affecting motivation and satisfaction of participants in dementia prevention trials. Methods A Research Satisfaction Survey was administered to 422 nondemented older adults who participated in the Home-Based Assessment trial. Results Overall satisfaction was high, with means of all individual items near to above a value of 3 on a scale from 1 (worst) to 4 (best). Greater satisfaction was associated with staff-administered interviews versus automated technologies. The most liked aspects of research participation were volunteerism, opportunity to challenge and improve mental function, and positive interactions with staff. The least liked aspect was repetitiveness of the assessments. Participants requested more contact with staff and other older adults and more feedback on performance. Discussion Older adults' participation in research was primarily motivated by altruism. Methodologies that facilitate human contact, encourage feedback and novelty of tasks should be incorporated into future trial design.

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

Introduction Possession of the apolipoprotein E (APO E) ε4 allele advances amyloid β (Aβ) deposition and symptomatic onset of Alzheimer's disease (AD), whereas its effect on the rate of cognitive decline remained controversial. We examined the effects of APOE ε4 allele on cognition in biomarker‐confirmed late mild cognitive impairment (LMCI) and mild AD subjects in the Japanese Alzheimer's Disease Neuroimaging Initiative (J‐ADNI) and North American ADNI (NA‐ADNI). Methods The “early AD” (ie, combined LMCI and mild AD) cohort of 649 subjects from J‐ADNI and NA‐ADNI were selected based on positivity of Aβ confirmed by amyloid positron emission tomography (PET) or cerebrospinal fluid testing. The rates of cognitive decline in the Mini Mental State Examination (MMSE), the Clinical Dementia Rating Sum of Boxes (CDR‐SB), and the Alzheimer's Disease Assessment Scale‐cognitive subscale 13 (ADAS‐Cog) from baseline were examined using mixed‐effects model. The effect of ε4 on time to conversion to dementia was also analyzed in LMCI using the Kaplan‐Meier estimator and log‐rank test. Results The rates of cognitive decline were not significantly different between ε4 carriers and ε4 non‐carriers in the total early AD cohort, which were affected neither by region nor by the number of ε4 alleles. In LMCI, ε4 carriers showed almost the same progression rates as ε4 non‐carriers, except for a significantly faster decline in MMSE (P = .0282). Time to conversion to demenita was not significantly different between ε4 carriers and ε4 non‐carriers. In ε4‐positive mild AD, the rates of decline in MMSE (P = .003) and CDR‐SB (P = .0071) were slower than those in ε4 non‐carriers. DISCUSSION The APOE ε4 allele had little effect on the rates of cognitive decline in the overall biomarker‐confirmed early AD, regardless of region and number of ε4 alleles, with a slight variability in different clinical stages, the ε4 allele being slightly accelerative in LMCI, while decelerative in mild AD.

Introduction We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America. Methods A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid β(1–42)-positive LMCI and mild AD between J-ADNI and ADNI. Results Amyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J-ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid-positive LMCI in J-ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J-ADNI (n = 73) compared with ADNI (n = 230). Discussion These results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries.

Introduction We discuss optimization and validation of composite end points for presymptomatic Alzheimer's disease clinical trials. Optimized composites offer hope of substantial gains in statistical power or reduction in sample size. But there is tradeoff between optimization and face validity such that optimization should only be considered if there is a convincing rationale. As with statistically derived regions of interest in neuroimaging, validation on independent data sets is essential. Methods Using four data sets, we consider the optimized weighting of four components of a cognitive composite which includes measures of (1) global cognition, (2) semantic memory, (3) episodic memory, and (4) executive function. Weights are optimized to either discriminate amyloid positivity or maximize power to detect a treatment effect in an amyloid-positive population. We apply repeated 5 × 3-fold cross-validation to quantify the out-of-sample performance of optimized composite end points. Results We found the optimized weights varied greatly across the folds of the cross-validation with either optimization method. Both optimization methods tend to down-weight the measures of global cognition and executive function. However, when these optimized composites were applied to the validation sets, they did not provide consistent improvements in power. In fact, overall, the optimized composites performed worse than those without optimization. Discussion We find that component weight optimization does not yield valid improvements in sensitivity of this composite to detect treatment effects.

Importance Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline. Objective To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid. Design, Setting, and Participants Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada. Participants were observed from August 23, 2005, to June 7, 2016, for a median of 3.1 years (interquartile range, 2.0-4.2 years; maximum follow-up, 10.3 years) as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Exposures Individuals were classified at baseline as having normal (n = 243) or elevated (n = 202) brain amyloid using positron emission tomography amyloid imaging or a cerebrospinal fluid assay of amyloid β. Main Outcomes and Measures Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC; a sum of 4 baseline standardized z scores, which decreases with worse performance), Mini-Mental State Examination (MMSE; 0 [worst] to 30 [best] points), Clinical Dementia Rating Sum of Boxes (CDR–Sum of Boxes; 0 [best] to 18 [worst] points), and Logical Memory Delayed Recall (0 [worst] to 25 [best] story units). Results Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women. The mean score for PACC at baseline was 0.00 (2.60); for MMSE, 29.0 (1.2); for CDR–Sum of Boxes, 0.04 (0.14); and for Logical Memory Delayed Recall, 13.1 (3.3). Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10]; P P P = .002). For Logical Memory Delayed Recall, between-group score was not statistically significant at 4 years (mean difference, 0.73 story units [95% CI, −0.02 to 1.48]; P = .056). Conclusions and Relevance Exploratory analyses of a cognitively normal cohort followed up for a median of 3.1 years suggest that elevation in baseline brain amyloid level, compared with normal brain amyloid level, was associated with higher likelihood of cognitive decline, although the findings are of uncertain clinical significance. Further research is needed to assess the clinical importance of these differences and measure longer-term associations.

This report describes the baseline experience of the multicenter, Home-Based Assessment study, designed to develop methods for dementia prevention trials using novel technologies for test administration and data collection. Nondemented individuals of 75 years of age or more were recruited and evaluated in-person using established clinical trial outcomes of cognition and function, and randomized to one of 3 assessment methodologies: (1) mail-in questionnaire/live telephone interviews [mail-in/phone (MIP)]; (2) automated telephone with interactive voice recognition; and (3) internet-based computer Kiosk. Brief versions of cognitive and noncognitive outcomes were adapted to each methodology and administered at baseline and repeatedly over a 4-year period. "Efficiency" measures assessed the time from screening to baseline, and staff time required for each methodology. A total of 713 individuals signed consent and were screened; 640 met eligibility and were randomized to one of 3 assessment arms; and 581 completed baseline. Dropout, time from screening to baseline, and total staff time were highest among those assigned to internet-based computer Kiosk. However, efficiency measures were driven by nonrecurring start-up activities suggesting that differences may be mitigated over a long trial. Performance among Home-Based Assessment instruments collected through different technologies will be compared with established outcomes over this 4-year study.

Background Caffeine consumption has been reported to decrease bone mineral density (BMD), increase the risk of hip fracture, and negatively influence calcium retention. In this study, we investigated the influence of caffeine on the osteoblasts behaviour. Method Osteoblasts derived from newborn Wistar-rat calvaria was used in this study. The effects of various concentrations of caffeine on bone cell activities were evaluated by using MTT assay. Alkaline phosphatase (ALP) staining, von Kossa staining and biochemical parameters including ALP, lactate dehydrogenase (LDH), prostaglandin E2 (PGE2) and total protein were performed at day 1, 3, and 7. DNA degradation analysis under the caffeine influence was also performed. Results and discussion The results showed that the viability of the osteoblasts, the formation of ALP positive staining colonies and mineralization nodules formation in the osteoblasts cultures decreased significantly in the presence of 10 mM caffeine. The intracellular LDH, ALP and PGE2 content decreased significantly, the LDH and PGE2 secreted into the medium increased significantly. The activation of an irreversible commitment to cell death by caffeine was clearly demonstrated by DNA ladder staining. Conclusion In summary, our results suggest that caffeine has potential deleterious effect on the osteoblasts viability, which may enhance the rate of osteoblasts apoptosis.