IntroductionThere are no empiric data to support guidelines for duration of therapy with antidementia drugs. This study examined whether persistent use of antidementia drugs slows clinical progression of Alzheimer disease (AD) assessed by repeated measures on serial tests of cognition and function.MethodsSix hundred forty-one probable AD patients were followed prospectively at an academic center over 20 years. Cumulative drug exposure was expressed as a persistency index (PI) reflecting total years of drug use divided by total years of disease symptoms. Baseline and annual testing consisted of Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Baylor Profound Mental Status Examination (BPMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Physical Self-Maintenance Scale (PSMS), and Instrumental Activities of Daily Living (IADL). Annual change in slope of neuropsychological and functional tests as predicted by follow-up time, PI, and the interaction of these two variables was evaluated.ResultsPI was associated with significantly slower rates of decline (with, without adjustment for covariates) on MMSE (P < 0.0001), PSMS (P < 0.05), IADL (P < 0.0001), and CDR-SB (P < 0.001). There was an insignificant trend (P = 0.053) for the PI to be associated with slower rate of decline on BPMSE. The association of PI with ADAS-Cog followed a quadratic trend (P < 0.01). Analysis including both linear and quadratic terms suggests that PI slowed ADAS-Cog decline temporarily. The magnitude of the favorable effect of a rate change in PI was: MMSE 1 point per year, PSMS 0.4 points per year, IADL 1.4 points per year, and CDR-SB 0.6 points per year. The change in mean test scores is additive over the follow-up period (3 ± 1.94 years).ConclusionsPersistent drug treatment had a positive impact on AD progression assessed by multiple cognitive, functional, and global outcome measures. The magnitude of the treatment effect was clinically significant. Positive treatment effects were even found in those with advanced disease.
Hydrocarbon contamination in soils may be toxic to plants and soil microorganisms and act as a source of groundwater contamination. The objective of this study was to evaluate the fate of diesel in soils with or without added nutrients. The soils examined either had or had not a previous history of hydrocarbon contamination. Particular aspects examined were soil respiration, changes in microbial population, breakdown of diesel hydrocarbons, and phytotoxicity to the germination of perennial ryegrass. Soil respiration was measured as evolved CO2. Bacterial population was determined as colony forming units in dilution plates and fungal activity was measured as hyphal length. The fate of individual hydrocarbons was determined by gas chromatography-mass spectrometry after extraction with dichloromethane. When diesel was added to soil with no previous history of hydrocarbon contamination at rates up to 50 mg/g, the respiration response showed a lag phase of 6 days and maximum respiration occurred at day 11. The lag phase was 2 days and maximum respiration occurred at day 3 in soil with a previous history of hydrocarbon contamination. After the peak, respiration decreased up to about 20 days in both soils. Thereafter, respiration become more or less constant but substantially greater than the control. N and P addition along with diesel did not reduce the lag phase but increased the respiration over the first 20 days of incubation. Diesel addition with or without N and P increased the bacterial population 10- to 100-fold but fungal hyphal length did not increase. Diesel addition at a rate of 136 mg/g did not increase the microbial population. Removal of inhibition to germination of perennial ryegrass was linked to the decomposition of nC10 and nC11 hydrocarbons and took from 11 to 30 days at diesel additions up to 50 mg/g depending on the soil. Inhibition to germination of perennial ryegrass persisted to more than 24 weeks at the 136 mg/g of diesel addition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.