***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation . It reduces pathology in transgenic models of Alzheimer 's disease ( AD ) and is a promising c and i date for treating human AD . The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD . Methods We performed a 24-week r and omized , double blind , placebo-controlled study of Curcumin C3 Complex ® with an open-label extension to 48 weeks . Thirty-six persons with mild-to-moderate AD were r and omized to receive placebo , 2 grams/day , or 4 grams/day of oral curcumin for 24 weeks . For weeks 24 through 48 , subjects that were receiving curcumin continued with the same dose , while subjects previously receiving placebo were r and omized in a 1:1 ratio to 2 grams/day or 4 grams/day . The primary outcome measures were incidence of adverse events , changes in clinical laboratory tests and the Alzheimer 's Disease Assessment Scale - Cognitive Subscale ( ADAS-Cog ) at 24 weeks in those completing the study . Secondary outcome measures included the Neuropsychiatric Inventory ( NPI ) , the Alzheimer 's Disease Cooperative Study - Activities of Daily Living ( ADCS-ADL ) scale , levels of Aβ1 - 40 and Aβ1 - 42 in plasma and levels of Aβ1 - 42 , t-tau , p-tau181 and F2-isoprostanes in cerebrospinal fluid . Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured . Results Mean age of completers ( n = 30 ) was 73.5 years and mean Mini-Mental Status Examination ( MMSE ) score was 22.5 . One subject withdrew in the placebo ( 8 % , worsened memory ) and 5/24 subjects withdrew in the curcumin group ( 21 % , 3 due to gastrointestinal symptoms ) . Curcumin C3 Complex ® was associated with lowered hematocrit and increased glucose levels that were clinical ly insignificant . There were no differences between treatment groups in clinical or biomarker efficacy measures . The levels of native curcumin measured in plasma were low ( 7.32 ng/mL ) . Conclusions Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms . We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex ® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound . Trial registration Clinical Trials.gov Identifier : NCT00099710 OBJECTIVE Because curcumin 's anti-inflammatory properties may protect the brain from neurodegeneration , we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography ( FDDNP-PET ) . METHODS Forty subjects ( age 51 - 84 years ) were r and omized to a bioavailable form of curcumin ( Theracurmin ® containing 90 mg of curcumin twice daily [ N = 21 ] ) or placebo ( N = 19 ) for 18 months . Primary outcomes were verbal ( Buschke Selective Reminding Test [ SRT ] ) and visual ( Brief Visual Memory Test-Revised [ BVMT-R ] ) memory , and attention ( Trail Making A ) was a secondary outcome . FDDNP-PET signals  ( 15 curcumin , 15 placebo ) were determined in amygdala , hypothalamus , medial and lateral temporal , posterior cingulate , parietal , frontal , and motor ( reference ) regions . Mixed effects general linear models controlling for age and education , and effect sizes ( ES ; Cohen 's d ) were estimated . RESULTS SRT Consistent Long-Term Retrieval improved with curcumin ( ES = 0.63 , p = 0.002 ) but not with placebo ( ES = 0.06 , p = 0.8 ; between-group : ES = 0.68 , p = 0.05 ) . Curcumin also improved SRT Total ( ES = 0.53 , p = 0.002 ) , visual memory ( BVMT-R Recall : ES = 0.50 , p = 0.01 ; BVMT-R Delay : ES = 0.51 , p = 0.006 ) , and attention ( ES = 0.96 , p < 0.0001 ) compared with placebo ( ES = 0.28 , p = 0.1 ; between-group : ES = 0.67 , p = 0.04 ) . FDDNP binding decreased significantly in the amygdala with curcumin ( ES = -0.41 , p = 0.04 ) compared with placebo ( ES = 0.08 , p = 0.6 ; between-group : ES = 0.48 , p = 0.07 ) . In the hypothalamus , FDDNP binding did not change with curcumin ( ES = -0.30 , p = 0.2 ) , but increased with placebo ( ES = 0.26 , p = 0.05 ; between-group : ES = 0.55 , p = 0.02 ) . CONCLUSIONS Daily oral Theracurmin may lead to improved memory and attention in non-demented adults . The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory Curcumin therapy in animals has produced positive cognitive and behavioural outcomes ; results of human trials , however , have been inconsistent . In this study , we report the results of a 12-month , r and omised , placebo-controlled , double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults . Individuals ( n 96 ) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months . A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessment s. A significant time × treatment group interaction was observed for the Montreal Cognitive Assessment ( repeated- measures analysis ; time × treatment ; F=3·85 , P<0·05 ) . Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group . No differences were observed between the groups for all other clinical and cognitive measures . Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures , ideally in conjunction with biological markers of neurodegeneration Factors that modify onset of Alzheimer 's disease ( AD ) may be revealed by comparing environmental exposures in affected and unaffected members of discordant twin pairs or sibships . Among siblings at high risk of AD , sustained use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) was associated with delayed onset and reduced risk of AD . After adjustment for use of NSAIDs , there was minimal effect on onset with reported history of any of three common illnesses ( arthritis , diabetes , or acid-peptic disease ) . However , independent of exposure to NSAIDs , onset was unexpectedly delayed in those reporting extended use of histamine H2 blocking drugs . R and omized clinical trials will be needed to affirm the utility of these drugs for prevention , but the present findings may have implication s for pathogenesis : because NSAIDs block the calcium-dependent postsynaptic cascade that induces excitotoxic cell death in NMDA-reactive neurons , and because histamine potentiates such events , excitotoxicity may deserve additional investigation in AD SCOPE Curcumin revealed various health-beneficial properties in numerous studies . However its bioavailability is low due to its limited intestinal uptake and rapid metabolism . The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences . METHODS AND RESULTS In this crossover study , healthy subjects ( 13 women , 10 men ) took , in r and om order , a single oral dose of 500 mg curcuminoids as native powder , micronized powder , or liquid micelles . Blood and urine sample s were collected for 24 h and total curcuminoids and safety parameters were quantified . Based on the area under the plasma concentration-time curve ( AUC ) , the micronized curcumin was 14- , 5- , and 9-fold and micellar curcumin 277- , 114- , and 185-fold better bioavailable than native curcumin in women , men , and all subjects , respectively . Thus , women absorbed curcumin more efficiently than men . All safety parameters remained within the reference ranges following the consumption of all formulations . CONCLUSION Both , the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials . The observed sex differences in curcumin absorption warrant further investigation The senescence-accelerated mouse prone 8 ( SAMP8 mice ) is known as a neurodegenerative model and may show age-related deficits of cognition . Curcumin , a major active component of spic turmeric , could increase the capacity of learning and memory in the aged rat . However , it is not known whether curcumin could improve cognitive deficits in SAMP8 mice . The present study was undertaken to evaluate the effect of curcumin on the learning and memory of SAMP8 mice and its possible mechanisms . Subjects were r and omly divided into four groups : SAMR1 mice , SAMP8 mice and two SAMP8 mice groups treated , intragastrically , with curcumin at the dose of 20 and 50mg/kg per day , respectively . After 25days , spatial memory , superoxide dismutase ( SOD ) activity , malondialdehyde ( MDA ) content , p-calcium/calmodulin-dependent kinase II ( p-CaMKII ) and p-N-methyl-d-aspartate receptor subunit 1 ( p-NMDAR1 ) expression in the hippocampus of mice were examined by using the Morris water maze , biochemical analysis , immunohistochemistry and Western blot . Compared with SAMR1 mice , SAMP8 mice had longer escape latency , higher MDA content , lower SOD activity in the hippocampus , and lower intensity of p-CaMKII in the stratum lucidum of hippocampal CA3 and p-NMDAR1 expression in the hippocampal membrane fraction . Both 20 and 50mg/kg curcumin administration significantly shortened the escape latencies and decreased the hippocampal MDA content in the SAMP8 mice . 50mg/kg curcumin administration significantly ameliorated the hippocampal SOD activity , and increased the intensity of p-CaMKII in the stratum lucidum of hippocampal CA3 and p-NMDAR1 expression in the hippocampal membrane fraction of the SAMP8 mice . The present study demonstrated that curcumin treatment could attenuate cognitive deficits of SAMP8 mice in a dose-dependent manner by decreasing the oxidative stress and improving the expression of p-CaMKII and p-NMDAR1 in the hippocampus . Thus treatment with curcumin may have a potential therapeutic agent for aging-related cognitive dysfunctions Background More and more pre clinical studies support the idea that curcumin , a plant-derived natural polyphenol , could be a promising anticancer drug . However , poor bioavailability has limited its efficacy in clinical trials , and plasma curcumin levels remain low despite patients taking gram doses of curcumin . Methods This study aim ed to evaluate the safety and pharmacokinetics of newly developed nanoparticle curcumin with increased water solubility ( named THERACURMIN ) . Six healthy human volunteers were recruited and received THERACURMIN at a single oral dose of 150 mg . After an interval of 2 weeks , the same subjects then received THERACURMIN at a single dose of 210 mg . Plasma curcumin levels were measured at 0 , 1 , 2 , 4 , 6 , and 24 h after THERACURMIN intake using high-performance liquid chromatography ( HPLC ) . Results One subject reported grade 1 diarrhea after intake of 150 mg THERACURMIN . No other toxicities were observed in this study . Cmax  for THERACURMIN at 150 and 210 mg was 189 ± 48 and 275 ± 67 ng/ml ( mean ± SEM ) , respectively , and the area under the curve for 24 h was estimated to be 2,649 ± 350 and 3,649 ± 430 ng/ml × h ( mean ± SEM ) , respectively . The t1/2 was estimated to be 9.7 ± 2.1 h for 150 mg and 13.0 ± 3.3 h for 210 mg . Conclusion THERACURMIN can safely increase plasma cur 
    Output:
    
Overall , animal research has shown very promising results in potentiating cognition , both physiologically and behaviourally .
Taking into account measurements of important inflammatory and antioxidant biomarkers , optimal dosages of curcumin , food interactions , and duration of treatment would increase our underst and ing on curcumin 's promising effects on cognition .